POLITECNICO DI MILANO

SCHOOL OF INDUSTRIAL AND INFORMATION ENGINEERING

DEPARTMENT OF ELECTRONICS, INFORMATION AND BIOENGINEERING (DEIB)

Master's degree course in Biomedical Engineering

Effects of an EMG-based vibro-tactile biofeedback

training on motor learning in children and
adolescents with dystonia

Supervisor:
Dr. Emilia Ambrosini

Author:
Alessio Santambrogio
ID: 873109

Academic Year 2017/2018

Aknowledgements

I would like to say a few words of thanks to all the people who contributed to this work.

First of all I would like to thank Emilia, for her constant presence, for having always been close to me
and for the numerous suggestions that allowed me to carry on with the right autonomy.
Thanks to Prof. Pedrocchi, for giving me the opportunity to collaborate on this project.
I woul like to thank all the boys and girls of the NearLab.
And I thank the families and the children / teens who agreed to participate in the study.

A big thank you to my mom and dad, who always believed in me and who contributed to my personal
formation, with their support. I cannot but thank my sister, who really helped me so much. Without you
I would never have gotten this far! Love You so much!
I want to thank my grandparents, who have always been my number one fans.

Finally, I thank all the friends who shared the most important experiences with me over the past three
years. A special thanks to Dani, Rob, Davide, Ale and Jo, who were very close to me and gave me a
huge support during the heaviest moments, and Marco, friend for a lifetime. You cannot understand how
important you are!

Thank you all!

Alessio

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INDEX

Abstract.................................................................................................................................................................. 5

Sommario ............................................................................................................................................................ 13

CHAPTER 1. INTRODUCTION ........................................................................................................................ 21

1.1 General classification of the pathology ...................................................................................... 22
1.2 Characteristics of the pathology ................................................................................................... 24
1.3 Therapies ............................................................................................................................................. 25
1.4 Biofeedback treatments................................................................................................................... 26
1.5 Objective .............................................................................................................................................. 28

CHAPTER 2. MATERIALS AND METHODS ................................................................................................. 29

2.1 Study protocol ......................................................................................................................................... 29
2.2 Experimental apparatus ........................................................................................................................ 32
2.4 Participants .............................................................................................................................................. 36
2.5 Data analysis............................................................................................................................................ 37
2.5.1 Pre-processing ................................................................................................................................. 37
2.5.2 Post-processing............................................................................................................................... 41
2.5.2.1 Time-related outcome measures ......................................................................................... 42
2.5.2.2 Kinematic-related outcome measures................................................................................ 43
2.5.2.3 EMG-related outcome measures.......................................................................................... 46
2.5.3 Statistic analysis ............................................................................................................................. 48

CHAPTER 3. RESULTS .................................................................................................................................... 49

3.1 Characterization of the participants .................................................................................................. 49
3.2 Results ....................................................................................................................................................... 51
3.2.1 Movement Time ................................................................................................................................ 53
3.2.2 Index of Performance ..................................................................................................................... 58
3.2.3 Peaks .................................................................................................................................................. 62
3.2.4 Smoothness ...................................................................................................................................... 67
3.2.5 Movement Linearity ........................................................................................................................ 72
3.2.6 Movement repeatability.................................................................................................................. 77
3.2.7 Elbow Range of Motion .................................................................................................................. 81
3.2.8 Shoulder Translation ...................................................................................................................... 87
3.2.9 FCU/ECR co-contraction ............................................................................................................... 93
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 3.2.10 BIC/TRIC co-contraction.............................................................................................................. 98
3.2.11 AD/PD co-contraction ................................................................................................................ 103
CHAPTER 4. DISCUSSION, LIMITATIONS AND FUTURE DEVELOPMENTS ................................... 108
4.1 Discussion .......................................................................................................................................... 108
4.2 Limitations and future developments ......................................................................................... 111

CHAPTER 5 ....................................................................................................................................................... 112

CONCLUSION ................................................................................................................................................... 112

Appendix............................................................................................................................................................ 113

References ........................................................................................................................................................ 133

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Abstract

Introduction
Within the field of neuromotor rehabilitation, the aim of this thesis was to evaluate the efficacy of a vibro-
tactile biofeedback device based on electromyography, in improving motor learing in children and
adolescents with dystonia.

In 2013, an international committee formed by different personalities with years of experience in the field
of dystonia met to clarify terminological and classification aspects related to this pathology, which was
defined as follows (A. Albanese et al., 2013):

‘’Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions that

cause abnormal, often repetitive movements. Dystonic movements are typically stereotyped, torsional
and can be characterized by tremor. Dystonia is often initiated or worsened by voluntary actions and is
characterized by the activation of muscles that are not strictly functional to the motor gesture (overflow)’’

The most evident clinical manifestations of the pathology include abnormal postures, slow and not very
fluid gestures (sometimes spasmodic and characterized by tremor), increased resistance to passive
movement, activations of muscles not directly involved in the ongoing movement (T. D. Sanger et al.,
2003) (T. D. Sanger et al., 2010).
In terms of brain areas associated with the pathology, it should be emphasized that this is often
correlated with lesions at the level of the basal ganglia, in particular putamen and globus pallidus;
however, it is also possible to involve other, areas such as the cerebellum and the brainstem (V. K.
Neychev et al., 2011) (A. Tewari et al., 2017).
Sensory deficits have also been observed to be related to a deficit in the integration of afferent inputs at
the central level: this negatively affects the generation of the corresponding motor output (A. Berardelli
et al., 1998) (A. Quartarone and M. Hallett , 2013).
In terms of etiology, dystonia is classified as primary when it is the most important feature of an idiopathic
or an identified genetic disorder, while secondary dystonias are symptomatic disorders arising from
another underlying disease, such as cerebral palsy (CP) or acquired brain injury. The physiopathology
of dystonia is very variegate; there are evidences that subjects with primary dystonia do not show
sensory deficits, whereas, subjects with secondary dystonia are characterized by sensory abnormalities
entailing to motor impairments (F. M. Molloy et al., 2003) (T. D. Sanger and S. N. Kukke, 2007). Sensory
deficits lead to a lack of improvement in complex motor skills despite repeated practice.

The main treatment modalities range from physical and occupational therapy to the use of various types
of drugs (botulinum toxin, anticholinergic drugs, dopaminergic drugs, ...) and finally to surgery (Deep
Brain Stimulation, DBS): these are approaches exclusively based on the symptomatology presented by
the subject and, often, only partially effective in controlling it (A. Albanese et al., 2006) (J. Jankovic,
2013) (M. Bertucco and T. D. Sanger, 2015).
In this context, innovative and non-invasive treatment solutions that work at a higher level than the
symptomatic level are needed, with the aim of favoring the correct motor learning of the subject. In
general, biofeedback (BF) is a technique that consists in providing the subject with increased information
of a physiological process, allowing him/her to increase awareness of the process itself and to acquire
voluntary control over it (J. V. Basmajian, 1982).
The subject is provided with information on the state of a physiological variable (EMG, EEG, strength,
position, ...) through sensorial channels of different types (visual, auditory, tactile, ...).
The first studies on the use of BF-based treatments for the improvement of motor learning have shown
that the individual can acquire control at high levels on the neuromuscular system, even managing the
single muscle (J. V. Basmajian, 1963).
The neurological mechanisms underlying the BF training in dystonic subjects are not yet completely
clear; it is however known that such patients are potentially characterized by inefficiencies in terms of
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sensory information: a hypothesis is that the use of BF can improve neural plasticity by increasing,
thanks to the auxiliary information provided to the subject, the reliability of the incoming signal to
sensorimotor areas; the effect is that of reinforcing the correct neural circuits.
Rehabilitative tools that provide increased feedback, therefore, are potentially usable for improving
motor control in subjects with movement disorders.
In dystonic patients, the efficacy of the use of such a strategy has been demonstrated on several
occasions (S. J. Young et al., 2011) (C. Casellato et al., 2013).
However, to be effective a BF therapy should re-educate motor control during dynamic, functionally
purpose-oriented movements (H. Huang et al., 2006): to satisfy this demand, Sanger and Bloom
developed (2010), at SangerLab (University of Southern California (USC), Los Angeles, CA), a portable
and silent device that provides the subject with a mechanical vibration proportional to the activation of
the muscle on which it is positioned and which can therefore be easily used during daily life activities.

The present thesis work is part of a multi-center cross over study that involves, besides the Politecnico
of Milano, the Carlo Besta Neurological Institute, Milano (MI), the Scientific Institute Eugenio Medea,
Bosisio Parini (LC), and the Children's Hospital, Los Angeles (CA). The research project has been
approved and is supported by the United States Department of Health (NIH, National Institutes of
Health). The coordinator of the entire study is Dr. T. D. Sanger, professor at the University of Southern
California (USC, Los Angeles) and neurologist at the Children's Hospital of Los Angeles, who designed
and built a battery-powered wearable electromyographic (EMG) feedback device.
The objective of the present thesis work is to test the mechanism of action of this EMG-based vibro-
tactile biofeedback device and to quantify the effect of increased sensory information during motor
learning in children affected by primary and secondary dystonia while performing specific exercises in
in the laboratory/clinic, and to compare the effect it produces on patients with its influence on healthy
subjects.
Subjects suffering from primary dystonia are recruited at Carlo Besta Neurological Institute and acquired
at Laboratory of Neuroengineering and Medical Robotics (NearLab) of Politecnico di Milano, while the
secondary patients are recruited and acquired at Scientific Institute Eugenio Medea.
The aim is to prove that biofeedback improves motor function in children with secondary dystonia. On
the other hand, children with primary dystonia (without sensory deficits) are analyzed as a control to
show that the improvement is not due to a direct interaction between biofeedback and the motor
abnormality in dystonia, and we compare to healthy control subjects to quantify the degree of
normalization of function that can be achieved.
Hence, the working hypothesis is that a positive effect should be recorded only on the secondary
population, characterized by marked sensory deficits. In the case of subjects affected by primary
dystonia, the use of a biofeedback strategy should have no clear role in improving performance. At least,
the behavior of the tested primaries should be approximately consistent with the behavior of the healthy
participants.

Methods
The acquisition protocol is aimed at testing the effectiveness of the BF device in the short term (1 week)
in learning specific motor exercises to be performed in a controlled environment.
It consists of two weeks of data acquisition, with a break of at least one month in between. The subject
is asked to perform two defined motor exercises, the so-called Figure 8 Task and the Spoon Task, which
simulate, respectively, the act of writing and the act of self-feeding.
During this thesis work I participated in the entire experimental campaign, but the data analysis was
concentrated on the evaluation of the Spoon Task.
The subject is required to carry a marble in a spoon back and forth between two targets without dropping
the marble. The depth of the spoon defines the difficulty of the excercise and the request is to perform
10 movements (forward and backward) at the maximum possible speed.
Each week consists of two Testing sessions (day 1 and day5, which are, respectively, the baseline and
the end of the training), in which the motor task are always performed with different degrees of difficulty,
and three Training sessions, the intermediate days, during which the task is performed with only one

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difficulty level (the medium level). The subject wears the BF device (positioned on the dominant arm)
only during the Training sessions of one of the two weeks and the order of use of the BF device is
randomized between the two weeks.
Healthy subjects followed a simplified and more practicable protocol. Their presence in the laboratory
was required only during Testing days and they trained at home in the intermediate days.
The protocol was approved by both Besta and Medea. However a distinction must be made. Unlike the
PoliMi protocol, the Medea protocol provides four consecutive weeks of acquisition. In the first and third
weeks the subject plays Figure 8 Task, during the second and fourth weeks the subject plays Spoon
Task.

The quantitative analysis of the motor exercises is performed through the evaluation of:

• the electromyographic activity of eight muscles of the upper limb tested: Flexor Carpi Ulnaris (FCU),
Extensor Carpi Radialis (ECR), Bicep (BIC), Tricep (TRIC), Anterior Deltoid (AD), Lateral Deltoid (LD),
Posterior Deltoid (PD), Supraspinatus (SS);

• the kinematics of the shoulder joint, the elbow joint, the wrist joint and the spoon.

Figure 1 shows the experimental setup.

Figure 1: Experimental setup

The data analysis consisted of an initial pre-processing phase of the EMG signal and of the kinematic
signal, leading to obtain the EMG signal envelope for each of the 8 acquired muscles and the reprojected
kinematics on the main components plane of each joint.

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Then, the evaluation of the subject motor performance was based on quantitative indices that describe
various aspects of the task:

1) temporal indices:

• movement time;

• index of performance. Thus, deriving a speed-accuracy trade-off (SATO) is an important metric for
assessing motor impairments in dystonia (F. Lunardini et al., 2015). The SATO was examined by
changing the spoon size to create different difficulty levels, and the Index of Performance was computed,
which reflects the efficiency of the nervous / motor system in facing tasks of increasing difficulty;

2) kinematic descriptors of the final output and of the movements of the entire kinematic chain:

• movement speed;

• smoothness of the movement in three different formulations, i.e. number of peaks in the velocity profile,
the ratio between the mean velocity and the maximum velocity (H. Vikne et al., 2013), and a
dimensionless form of the jerk, the Normalized Mean Squared Jerk (N. Hogan, D. Sternad, 2009);

• movement linearity, an indirect measure of accuracy, calculated as the ratio between the amplitude of
the trajectory generated by the subject and the linear distance between the starting and the ending point
of the movement;

• movement repeatability, which provides an indication of the subject's ability to perform repeatable
movements throughout the trials;

• range of motion of the elbow joint. It gives an indication of the subject's upper limb flexion-extension
during the movement;

• displacement of the shoulder joint, which measures the movement of the shoulder joini in the anterior-
posterior direction;

3) indices of the electromyographic activity of three couples of agonist / antagonist muscles: Flexor Carpi
Ulnaris and Extensor Carpi Ulnaris, Bicep and Tricep, Anterior Deltoid and Posterior Deltoid.

In order to observe if the use of the biofeedback device during the Training impacted on these indices,
compared to the simple practice without additional instrumental feedback, a statistical analysis was
conducted: a subject-by-subject analysis was carried out to evaluate the effects of learning between day
1 and day 5 of the two weeks of treatment. The variability of each parameter was evaluated through a
2-way analysis of variance (ANOVA), including the condition (BF or noBF) and the day (day 1 and day
5) as fixed factors and the condition by day as interaction effect. A group-based statistical analysis was
not performed due to the heterogeneity of the subjects in terms of age and level of impairment.

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Results and discussion
A total of 15 patients were recruited: 9 primary dystonic subjects (5 boys and 4 girls from 7 to 19 years
old); 6 secondary dystonic subjects (4 boys and 2 girls from 6 to 16 years old).
A group of 12 age-matched healthy subjects were recruited and involved in the protocol: 5 boys and 7
girls from 6 to 19 years old.
All participants gave informed written consent for participation. In case of minors, parents were asked
to sign the informed consent and the authorization for use of protected health information, videos and
images.
Figure 2 shows the results of the analysis in terms of the percentage of the healthy, the primary and
secondary subjects that showed learning characteristics with the practice, regardless of the use of the
device, and better improvement when the BF device was used.

Figure 2: Learning / learning with interaction. MT=Movement Time, PEAKS=speed peaks, SMOOTHNESS=smoothness, ML=Movement
Linearity, ROM=elbow range of motion, ST=shoulder displacement, CC FCU / ECR=FCU / ECR co-contraction, CC BIC / TRIC=BIC / TRIC co-
contraction, CC AD / PD=AD / PD co-contraction. DAY is the day effect, INTER is the interaction effect. 9 panels are reported, related to
the outcomes for which the statystical analysis was performed. From left to right, the trend of the healthy (in blue), the primary (in black),
the secondary (in red) subjects is shown. For each group, the bar on the left shows the percentage of subjects who learned the task with
practice, the bar on the right shows the percentage of the subjects that showed a significant interaction effect in favour of the BF.

2 of the 12 the healthy subjects, 4 of the 9 primary subjects and 1 of the 6 secondary dystonic subjects
reduced the movement time with practice. 5 of the 12 healthy subjects, 2 of the 9 primary subjects and
1 of the 6 secondary dystonic subjects showed better improvement when the BF device was used.
3 of the 12 the healthy subjects, 3 of the 9 primary subjects and 1 of the 6 secondary dystonic subjects
reduced the number of the speed peaks with practice. 3 of the 12 healthy subjects, 2 of the 9 primary
subjects and 1 of the 6 secondary dystonic subjects showed better improvement when the BF device
was used.
None of the 12 the healthy subjects, 1 of the 9 primary subjects and none of the 6 secondary dystonic
subjects increased the smoothness of the movement with practice. 1 of the 12 healthy subjects, 1 of the
9 primary subjects and 1 of the 6 secondary dystonic subjects showed better improvement when the BF
device was used.
2 of the 12 the healthy subjects, 3 of the 9 primary subjects and 1 of the 6 secondary dystonic subjects
reduced the movement linearity with practice. 2 of the 12 healthy subjects, 1 of the 9 primary subjects
and 1 of the 6 secondary dystonic subjects showed better improvement when the BF device was used.
For what concerns the elbow ROM, a complete analysis was performed on 5 of the 6 secondary
subjects, since kinematic data concerning the spatial coordinates of the shoulder of the second testing
day of the second week were missing for one secondary dystonic subject.

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4 of the 12 the healthy subjects, none of the 9 primary subjects and 2 of the 5 secondary dystonic
subjects increased the elbow ROM with practice. 4 of the 12 healthy subjects, 3 of the 9 primary subjects
and 1 of the 5 secondary dystonic subjects showed better improvement when the BF device was used.
Even considering the shoulder displacement, a complete analysis was performed on 5 of the 6
secondary subjects, since kinematic data concerning the spatial coordinates of the shoulder of the
second testing day of the second week were missing for one secondary dystonic subject.
3 of the 12 the healthy subjects, 1 of the 9 primary subjects and 1 of the 5 secondary dystonic subjects
reduced the shoulder displacement during the movement with practice. 4 of the 12 healthy subjects, 3
of the 9 primary subjects and 2 of the 5 secondary dystonic subjects showed better improvement when
the BF device was used.
For what concerns EMG parameters, a complete analysiy was performed on 4 of the 6 secondary
subjects, because all the EMG data were missing, in one subject relating to the second testing day of
the first week, in the other secondary dystonic subject related to the first week.
1 of the 12 the healthy subjects, none of the 9 primary subjects and none of the 4 secondary dystonic
subjects reduced the FCU/ECR co-contraction with practice. 3 of the 12 healthy subjects, 2 of the 9
primary subjects and 1 of the 4 secondary dystonic subjects showed better improvement when the BF
device was used.4 of the 12 the healthy subjects, 2 of the 9 primary subjects and none of the 4
secondary dystonic subjects reduced the BIC/TRIC co-contraction with practice. 3 of the 12 healthy
subjects, 3 of the 9 primary subjects and 2 of the 4 secondary dystonic subjects showed better
improvement when the BF device was used.
1 of the 12 the healthy subjects, 1 of the 9 primary subjects and none of the 4 secondary dystonic
subjects reduced the AD/PD co-contraction with practice. None of the 12 healthy subjects, 4 of the 9
primary subjects and 2 of the 4 secondary dystonic subjects showed better improvement when the BF
device was used.

For what concerns time and speed of execution, the practice with the BF device influenced the behavior
of the primary subjects and the secondary patients almost in the same way, in fact the percentage of
the primary subjects for whom a significant interaction effect was found is about the same with respect
to the percentage of the secondary dystonic. It can be stated that for the movement time we see learning
trend mainly for the primary dystonic subjects. However, considering also the group of healthy subjects,
a great learning effect is not visible: less than half of people had a significant day effect. The
improvement trend observed looking at the IP is equal to that of the movement time. Thus, it can be
stated that the device affected the processing capabilities of the primary patients and the secondary
more or less in the same way. Even looking at the smoothness of the movement there’s no evidence to
confirm that the exercise performed with the BF produced better results on the secondary group: the
effect of the device on the task learning was comparable between patients; learning induced by the
practice was higher for the primary patients, but, overall, learning was not so evident, since only one
subjects over all the recruited subjects showed learning with the practice. The analysis on the movement
linearity confirms what has been said about the movement time and the smoothness.
Considering the elbow ROM and the displacement of the shoulder, the results show something different
with respect to the final output kinematic parameters. For what concerns the elbow ROM, there was no
learning for the primary dystonic patients, who, instead, improved their performance when the BF was
used, while, for the secondary patients, a greater percentage of them learned the task with the practice.
For what concerns the shoulder displacement, the behavior of the three groups was very similar: both
the healthy subjects and the patients (both primary dystonic and secondary dystonic) had better
improvement when the BF device was used. However, it is likely that these two parameters do not
identify so well the behavior of the subjects, who adopted different strategies that translated into a great
inter-sample variability in the movements of the entire kinematic chain: since the position of the wooden
block on the support table was not fixed, there were subjects who managed to perform the exercise
remaining firmly on the chair and positioning themselves closer to the block, and there were those who,
instead, preferred to stay less firmly on the chair and accompanied the movement with the trunk.
Initial values of the movement repeatability were more or less equal between primary distonic subjects
and secondary distonic patients. There was no clear trend towards learning among the primary subjects
and the healthy subjects. It is probably necessary to consider that the range of improvement was limited
by the already good performance on the first day of testing. The same type of analysis can be conducted
on the secondaries, which did not clearly reveal whether the device was actually effective. However, we

10
must consider that only in one case (S001BoLu) we there was an isolated learning in the week of non-
use of the device.
Even looking at the electromyographic parameters, there is no clear tendency in favour of the initial
hypotheses: indeed, for what concerns both the FCU/ECR muscles co-contraction and the AD/PD
muscles co-contraction, better improvement was evident when the BF device was used for both the
primary subjects and the secondary subjects; learning induced by the practice was null for the primary
patients and visible for only one secondary subjects. Focusing on the co-contraction of the muscles
primarly involved in the prono-supination of the wrist, the behavior of the three groups was similar: the
healthy subjects and the patients (primary subjects and secondary subjects) better improved their
performance when the sensory feedback was provided, while learning with the practice was shown by
only one subject (one healthy subject). The trend of the healthy subjects was to increase the FCU/ECR
co-contraction with the practice. It is not wrong to assume that only a greater simultaneous activation of
theese muscles reflects into greater stability of the wrist joint, and therefore greater control on the spoon.
This explains why, if the expected result was a decrease in the co-contraction levels, low levels of
learning were found. Finally, considering the BIC/TRIC co-contraction, the secondary subjects did not
reveal better improvement while using the BF. Rather, the practice induced a learning of the trained
task, but this was not influenced by the use of the device; moreover, for the primary subjects, the BF
device influenced the task learning more than the practice did.

In general, it can not be stated that an effect related to the use of the device is more pronounced in the
group of secondary dystonic: better improvement with the device was recorded for both the primary
subjects and the secondary subjects. Even for the healthy subjects the device accelerated learning
processes. This was particularly evident considering the time-related parameters and the FCU/ECR co-
contraction.
For what concerns the temporal paramaters and the parameters related to the final output kinematics,
learning in primary dystonic was not significantly stressed by the use of the device, but this trend was
not visible considering the parameters linked to the entire kinematic chain (ROM and ST) and the EMG
parameters, for which the device accelerated learning.

Hence, the results do not allow us to support the hypotheses the study is based on: even individuals
affected by secondary dystonia, which are characterized by marked sensory deficits that prevent their
improvement in the performance of complex motor tasks (despite repeated training), seem not to be so
much favored by using such a strategy; on the other hand, for the subjects affected by primary dystonia
and for the healthy subjects, in which there are no sensory deficits and the physiological learning
mechanisms linked to the training of a particular motor exercise are intact, the use of a biofeedback
strategy seems to have a role in improving performance.

However, we are not even in the position to refuse the initial hypotheses. Some limitations still need to
be overcome. The first limitation of the study lies in the fact that it does not currently take into
consideration cognitive variables that could lead to behavioral disorders and that can prevent the
secondaries from accessing sufficient sources for a correct learning.
A limitation derives from the lack of some fundamental data for the analysis of some secondary subjects.
Furthermore, the lack of a group statistic analysis and the scattered results do not allow for definitive
conclusions. This problem is added to the limited number of subjects, which make the sample power
limited and the comparison not always statistically robust.
However, the ongoing multi-center clinical trial will overcome this limitation and more dystonic subjects
will be recruited. Furthermore, the long-term effect of the use of the biofeedback device during daily life
activities (wearing the device at least 5 hours a day for one month) will be investigated.

Future developments of this work could be:

• definition of a set of criteria to guide the operator in choosing the most suitable muscles on which to
place the biofeedback; these could be selected, for example, after a clinical and quantitative evaluation
that clearly indicates the most compromised ones;

• test of simultaneous use of multiple feedback modalities;

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• test of the effects different sensory channels through which providing the feedback.

12
Sommario

Introduzione
Nel campo della riabilitazione neuromotoria, lo scopo di questa tesi è stato di valutare l'efficacia di un
dispositivo di biofeedback vibro-tattile basato sull'elettromiografia, nel miglioramento dell’
apprendimento motorio in bambini e adolescenti con distonia.
Nel 2013, un comitato internazionale formato da diverse personalità con anni di esperienza nel campo
della distonia si è incontrato per chiarire gli aspetti terminologici e di classificazione relativi a questa
patologia, che è stata definita come segue (A. Albanese et al., 2013):

"La distonia è un disturbo del movimento caratterizzato da contrazioni muscolari prolungate o

intermittenti che causano movimenti anormali, spesso ripetitivi. I movimenti distonici sono tipicamente
stereotipati, torsionali e possono essere caratterizzati da tremore. La distonia è spesso iniziata o
aggravata da azioni volontarie ed è caratterizzata dall'attivazione di muscoli che non sono strettamente
funzionali al gesto motorio (overflow) ".

Le manifestazioni cliniche più evidenti della patologia includono posture anormali, gesti lenti e non molto
fluidi (a volte spasmodici e caratterizzati da tremore), maggiore resistenza al movimento passivo,
attivazione di muscoli non direttamente coinvolti nel movimento (TD Sanger et al., 2003) (TD Sanger et
al., 2010).
In termini di aree cerebrali associate, va sottolineato che questa patologia è spesso correlata a lesioni
a livello dei gangli della base, in particolare putamen e globo pallido; tuttavia, è anche possibile
riscontrare un coinvolgimento di altre aree, quali il cervelletto e il tronco cerebrale (V. K. Neychev et al.,
2011) (A. Tewari et al., 2017).
È stato osservato che i deficit sensoriali sono correlati a un deficit nell'integrazione di input afferenti a
livello centrale: ciò influenza negativamente la generazione della corrispondente output motorio (A.
Berardelli et al., 1998) (A. Quartarone e M. Hallett, 2013).
In termini di eziologia, la distonia viene classificata come primaria quando è la caratteristica più
importante di una malattia genetica idiopatica, come secondaria quando deriva da cause pregresse, ad
esempio paralisi cerebrale (CP). Alcune evidenze provano che i soggetti affetti da distonia primaria non
mostrano deficit sensoriali; i soggetti affetti da distonia secondaria, invece, sono caratterizzati da
anomalie sensoriali che comportano alterazioni motorie (F. Molloy et al., 2003) (T. D. Sanger e S. N.
Kukke, 2007). Tali deficit sensoriali portano ad una mancanza di miglioramento nelle complesse abilità
motorie nonostante la pratica ripetuta.

Le principali modalità di trattamento spaziano dalle terapie fisica ed occupazionale all'uso di vari tipi di
farmaci (tossina botulinica, farmaci anticolinergici, farmaci dopaminergici, ...) e al trattamento chirurgico
(Deep Brain Stimulation, DBS): si tratta di approcci basati esclusivamente sulla sintomatologia
presentata dal soggetto e, spesso, solo parzialmente efficaci (A. Albanese et al., 2006) (J. Jankovic,
2013) (M. Bertucco e TD Sanger, 2015).
In questo contesto, sono necessarie soluzioni di trattamento innovative e non invasive che agiscano ad
un livello superiore rispetto al livello sintomatico, con l'obiettivo di favorire il corretto apprendimento
motorio del soggetto. In generale, il biofeedback (BF) è una tecnica che consiste nel fornire al soggetto
una maggiore informazione di un processo fisiologico, consentendogli di aumentare la consapevolezza
del processo stesso e di acquisire il controllo volontario su di esso (J. V. Basmajian, 1982).
Al soggetto vengono fornite informazioni sullo stato di una variabile fisiologica (EMG, EEG, forza,
posizione, ...) attraverso canali sensoriali di diverso tipo (visivo, uditivo, tattile, ...).
I primi studi sull'uso di trattamenti basati sul BF per il miglioramento dell'apprendimento motorio hanno
dimostrato che l'individuo può acquisire il controllo ad alti livelli sul sistema neuromuscolare, gestendo
anche il singolo muscolo (J.Ve Basmajian, 1963).
I meccanismi neurologici alla base dell'allenamento con il BF nei soggetti distonici non sono ancora del
tutto chiari. Si ritiene che l'uso del BF possa migliorare la plasticità neuronale, aumentando, grazie alle

13
informazioni ausiliarie fornite al soggetto, l'affidabilità del segnale afferente, con l'effetto di rinforzare i
circuiti neurali.
Gli strumenti riabilitativi che forniscono un feedback sensoriale aumentato, quindi, sono potenzialmente
utilizzabili per migliorare il controllo motorio in soggetti con disturbi del movimento.
Nei pazienti distonici, l'efficacia dell'uso di tale strategia è stata dimostrata in diverse occasioni (S. J.
Young et al., 2011) (C. Casellato et al., 2013).
Tuttavia, per essere efficace, una terapia basata sull’uso del BF dovrebbe rieducare il controllo motorio
durante movimenti dinamici, orientati allo scopo (H. Huang et al., 2006): per soddisfare questa
necessità, Sanger e Bloom hanno sviluppato (2010), presso il SangerLab (University of Southern
California (USC), Los Angeles, CA), un dispositivo di BF portatile e silenzioso che fornisce al soggetto
una vibrazione meccanica proporzionale all'attivazione del muscolo su cui è posizionato e che può
quindi essere facilmente utilizzato durante le attività quotidiane.

Metodi
Il protocollo di acquisizione è finalizzato a testare l'efficacia del dispositivo di BF nel breve periodo (una
settimana) durante l’apprendimento di specifici esercizi motori da eseguire in un ambiente controllato.
Consiste in due settimane di acquisizione dati, con un'interruzione di almeno un mese. Al soggetto viene
chiesto di eseguire due esercizi motori ben definiti, il cosiddetto Figure 8 Task e lo Spoon Task, che
simulano, rispettivamente, l'atto della scrittura e l'atto del cibarsi.
Durante questo lavoro di tesi ho partecipato a tutta la campagna sperimentale, ma l'analisi dei dati si è
concentrata sulla valutazione del solo Spoon Task.
Al soggetto è chiesto di trasportare una biglia in un cucchiaio avanti e indietro rispetto a un blocco di
legno senza far cadere la pallina. La profondità del cucchiaio definisce la difficoltà dell'esercizio e la
richiesta è di eseguire 10 movimenti (avanti e indietro) alla massima velocità possibile.
Ogni settimana consiste in due sessioni di test (giorno 1 e giorno 5, che sono rispettivamente la baseline
e la fine dell'allenamento), in cui il compito motorio viene eseguito con diversi gradi di difficoltà, e tre
sessioni di allenamento, i giorni intermedi, durante i quali il task viene eseguito con un solo livello di
difficoltà (il livello medio). Il soggetto indossa il dispositivo di BF (posizionato sul braccio dominante, se
affetto) solo durante le sessioni di allenamento di una delle due settimane e l'ordine di utilizzo del
dispositivo è randomizzato tra le due settimane.
I soggetti sani hanno seguito un protocollo semplificato e più praticabile. La loro presenza in laboratorio
era richiesta solo durante i giorni di test e si allenavano a casa nei giorni intermedi.
Il protocollo è stato approvato da Besta e Medea. Tuttavia una distinzione deve essere fatta. A differenza
del protocollo PoliMi, il protocollo Medea prevede quattro settimane consecutive di acquisizione. Nella
prima e nella terza settimana il soggetto svolge il Figure 8 Task, durante la seconda e la quarta
settimana il soggetto svolge lo Spoon Task.

L'analisi quantitativa degli esercizi motori viene eseguita attraverso la valutazione:

• dell'attività elettromiografica di otto muscoli dell'arto superiore testato: Flessore Ulnare del Carpo
(FCU), Estensore Radiale del Carpo (ECR), Bicipite (BIC), Tricipite (TRIC), Deltoide Anteriore (AD),
Deltoide Laterale (LD), Deltoide Posteriore (PD), Sopraspinato (SS);

• della cinematica dell'articolazione della spalla, dell'articolazione del gomito, dell'articolazione del polso
e del cucchiaio.

14
La Figura 1 mostra il setup sperimentale.

Figura 1: Setup sperimentale

L'analisi dei dati è consistita in una fase iniziale di pre-processing sia del segnale EMG sia del segnale
cinematico, con l’obiettivo di ricavare l'inviluppo del segnale EMG per ciascuno degli 8 muscoli acquisiti
e la cinematica riproiettata sul piano delle componenti principali di ciascuna articolazione.
Quindi, la valutazione delle prestazioni del soggetto si è basata su indici quantitativi che descrivono vari
aspetti del gesto motorio:

1) indici temporali:

• tempo di movimento;

• Indice di Prestazione. Derivare un trade-off velocità-accuratezza (SATO) è importante per la

valutazione delle anomalie motorie nella distonia (F. Lunardini et al., 2015). Esso è stato esaminato
cambiando le dimensioni del cucchiaio per creare diversi livelli di difficoltà, e l'Indice di Prestazione è
stato calcolato. Esso riflette quindi l'efficienza del sistema nervoso/motorio nell'affrontare compiti di
difficoltà crescente;

2) descrittori cinematici dell'output finale e dei movimenti dell'intera catena cinematica:

• velocità di movimento;

15
• fluidità del movimento in tre diverse formulazioni, ovvero il numero di picchi nel profilo di velocità, il
rapporto tra la velocità media e la velocità massima (H. Vikne et al., 2013), e una forma adimensionale
del jerk, il Normalized Mean Squared Jerk (N. Hogan, D. Sternad, 2009);

• linearità del movimento, una misura indiretta di precisione, calcolata come rapporto tra l'ampiezza della
traiettoria generata dal soggetto e la distanza lineare tra i punti iniziale e finale del movimento;

• ripetibilità del movimento, che fornisce un'indicazione circa la capacità del soggetto di eseguire
movimenti ripetibili durante le prove;

• range di movimento dell'articolazione del gomito. Fornisce un'indicazione dell'estensione e della

flessione dell'arto superiore del soggetto durante il movimento;

• spostamento dell'articolazione della spalla, che misura il movimento della stessa nella direzione
antero-posteriore;

3) indici dell'attività elettromiografica di tre coppie di muscoli agonisti / antagonisti: Flessore Ulnare del
Carpo ed Estensore Radiale del Carpo, Bicipite e Tricipite, Deltoide anteriore e Deltoide posteriore.

Al fine di valutare se l'uso del dispositivo di biofeedback, rispetto alla sola pratica senza ulteriori
feedback strumentali, avesse impattato sugli indici poco fa descritti, è stata condotta un'analisi statistica:
un'analisi soggetto per soggetto è stata effettuata per valutare gli effetti di apprendimento tra il giorno 1
e il giorno 5 delle due settimane di trattamento. La variabilità di ciascun parametro è stata valutata
mediante un’analisi della varianza a 2 vie (ANOVA), scegliendo la condizione (BF o noBF) e il giorno
(giorno 1 e giorno 5) come fattori fissi. E’ anche stato valutato l’effetto interazione condizione-giorno.
Un'analisi statistica di gruppo non è stata invece eseguita a causa dell'eterogeneità dei soggetti in
termini di età e livello di compromissione.

16
Risultati e discussione
Sono stati reclutati 15 pazienti in totale: 9 soggetti distonici primari (5 maschi e 4 femmine dai 7 ai 19
anni) e 6 soggetti distonici secondari (4 maschi e 2 femmine dai 6 ai 16 anni).
Un gruppo di 12 soggetti sani di pari età è stato reclutato e coinvolto nel protocollo: 5 ragazzi e 7 ragazze
dai 6 ai 19 anni.
Tutti i partecipanti hanno dato il consenso informato per la partecipazione. In caso di minori, i genitori
sono stati invitati a firmare il consenso informato e l'autorizzazione per l'uso di informazioni, video e
immagini sanitarie protette.

La figura 2 mostra i risultati dell'analisi in termini di percentuale dei soggetti sani, primari e secondari
che hanno mostrato apprendimento con la pratica, indipendentemente dall'uso del dispositivo, e un
maggior apprendimento con l’utilizzo dispositivo.

Figura 2: Apprendimento / apprendimento con interazione. MT = Tempo di Movimento, PEAKS = picchi di velocità, SMOOTHNESS = fluidità,
ML = Linearità del Movimento, ROM = ROM del gomito, ST = Spostamento della Spalla, CC FCU / ECR = co-contrazione dei muscoli FCU /
ECR, CC BIC / TRIC = Co-contrazione dei muscoli BIC / TRIC, CC AD / PD = co-contrazione dei muscoli AD / PD. DAY indica l'effetto giorno,
INTER indica, invece, l'effetto di interazione. In figura sono riportati 9 pannelli, relativi a ciascun parametro su cui è stata eseguita l'analisi
statistica. Da sinistra a destra, viene mostrata la tendenza dei soggetti sani (in blu), dei primari (in nero), dei secondari (in rosso). Per ogni
gruppo, la barra di sinistra mostra la percentuale di soggetti che hanno appreso il task con la pratica, la barra di destra mostra la
percentuale di soggetti che hanno mostrato un'interazione significativa a beneficio della condizione BF.

2 dei 12 soggetti sani, 4 dei 9 soggetti primari e 1 dei 6 soggetti distonici secondari hanno ridotto il
tempo di movimento con la pratica. 5 dei 12 soggetti sani, 2 dei 9 soggetti primari e 1 dei 6 soggetti
distonici secondari hanno mostrato un maggior apprendimento grazie all’uso del dispositivo di BF.
3 dei 12 soggetti sani, 3 dei 9 soggetti primari e 1 dei 6 soggetti distonici secondari hanno ridotto il
numero dei picchi di velocità con la pratica. 3 dei 12 soggetti sani, 2 dei 9 soggetti principali e 1 dei 6
soggetti distonici secondari hanno mostrato un maggior apprendimento grazie all’uso del dispositivo di
BF.
Nessuno dei 12 soggetti sani, 1 dei 9 soggetti principali e nessuno dei 6 soggetti distonici secondari ha
aumentato la fluidità del movimento con la pratica. 1 dei 12 soggetti sani, 1 dei 9 soggetti primari e 1
dei 6 soggetti distonici secondari ha mostrato un maggior apprendimento grazie all’uso del dispositivo
di BF.
2 dei 12 soggetti sani, 3 dei 9 soggetti principali e 1 dei 6 soggetti distonici secondari hanno ridotto la
linearità del movimento con la pratica. 2 dei 12 soggetti sani, 1 dei 9 soggetti primari e 1 dei 6 soggetti
distonici secondari hanno mostrato un maggior miglioramento grazie all’uso del dispositivo di BF.

17
Per quanto riguarda il ROM del gomito e lo spostamento della spalla, è stata eseguita un'analisi
completa su 5 dei 6 soggetti secondari, poiché mancavano dati cinematici relativi alle coordinate spaziali
della spalla del secondo giorno di test della seconda settimana per un soggetto distonico secondario.
4 dei 12 soggetti sani, nessuno dei 9 soggetti principali e 2 dei 5 soggetti distonici secondari hanno
aumentato la ROM del gomito con la pratica. 4 dei 12 soggetti sani, 3 dei 9 soggetti primari e 1 dei 5
soggetti distonici secondari hanno mostrato un un maggior apprendimento grazie all’uso del dispositivo
di BF.
3 dei 12 soggetti sani, 1 dei 9 soggetti primari e 1 dei 5 soggetti distonici secondari hanno ridotto lo
spostamento della spalla durante il movimento con la pratica. 4 dei 12 soggetti sani, 3 dei 9 soggetti
primari e 2 dei 5 soggetti distonici secondari hanno mostrato un maggior apprendimento grazie all’uso
del dispositivo di BF.
Per quanto riguarda i parametri EMG, è stata eseguita un'analisi completa su 4 dei 6 soggetti secondari,
poiché mancavano tutti i dati EMG di due soggetti: in un soggetto quelli del secondo giorno di test della
prima settimana, nell'altro soggetto distonico secondario della prima settimana di acquisizioni.
1 dei 12 soggetti sani, nessuno dei 9 soggetti principali e nessuno dei 4 soggetti distonici secondari ha
ridotto la co-contrazione dei muscoli FCU/ECR con la pratica. 3 dei 12 soggetti sani, 2 dei 9 soggetti
primari e 1 dei 4 soggetti distonici secondari hanno mostrato un maggior apprendimento grazie all’uso
del dispositivo di BF.
4 dei 12 soggetti sani, 2 dei 9 soggetti primari e nessuno dei 4 i soggetti distonici secondari riducevano
la co-contrazione dei muscoli BIC/TRIC con la pratica. 3 dei 12 soggetti sani, 3 dei 9 soggetti primari e
2 dei 4 soggetti distonici secondari hanno mostrato un maggior apprendimento grazie all’uso del
dispositivo di BF.
1 dei 12 soggetti sani, 1 dei 9 soggetti primari e nessuno dei 4 soggetti distonici secondari ha ridotto la
co-contrazione AD / PD con la pratica. Nessuno dei 12 soggetti sani, 4 dei 9 soggetti primari e 2 dei 4
soggetti distonici secondari hanno mostrato un maggior apprendimento grazie all’uso del dispositivo di
BF.

Per quanto riguarda il tempo e la velocità di esecuzione, la pratica con il dispositivo ha influenzato il
comportamento dei soggetti primari e dei pazienti secondari quasi nello stesso modo, infatti la
percentuale dei soggetti primari per i quali è stato trovato un significativo effetto di interazione è circa
equivalente alla percentuale dei primari. Si può affermare che per il tempo di movimento ci sia stata una
tendenza all'apprendimento principalmente nei soggetti distonici primari. Tuttavia, considerando anche
il gruppo dei soggetti sani, non è risultato un così evidente apprendimento: meno della metà dei soggetti
reclutati ha mostrato un effetto giorno significativo. La tendenza al miglioramento osservata per l'IP è
uguale a quella del tempo di movimento. Pertanto, si può affermare che il dispositivo abbia influenzato
le capacità di elaborazione delle informazioni dei pazienti primari e dei secondari allo stesso modo.
Anche guardando alla fluidità del movimento non ci sono prove che confermino come l'esercizio
eseguito con il BF possa aver prodotto risultati migliori sul gruppo dei soggetti secondari. L'effetto del
dispositivo sull'apprendimento del compito è stato paragonabile tra i pazienti; l'apprendimento indotto
dalla pratica è stato maggiore per i pazienti primari, ma, nel complesso, esso non è stato così evidente,
dal momento che solo uno tra tutti i soggetti reclutati ha dimostrato di apprendere il task motorio con la
pratica. L'analisi sulla linearità del movimento conferma quanto è stato detto sul tempo di movimento e
sulla fluidità.
Considerando il ROM del gomito e lo spostamento della spalla, i risultati mostrano qualcosa di diverso
rispetto ai parametri cinematici dell'output finale. Per quanto riguarda il ROM del gomito, non è stato
riscontato alcun apprendimento nei pazienti distonici primari, che, invece, hanno migliorato le loro
prestazioni con l’uso del BF; considerando i secondari, una percentuale maggiore ha imparato con la
sola pratica. Per quanto riguarda lo spostamento della spalla, il comportamento dei tre gruppi è stato
molto simile: sia i soggetti sani sia i pazienti (distonici primari e distonici secondari) hanno avuto un
apprendimento migliore quando è stato utilizzato il dispositivo di BF. Tuttavia, è probabile che questi
due parametri non identifichino così bene il comportamento dei soggetti, che hanno adottato strategie
diverse che si sono tradotte in una grande variabilità inter-campione nei movimenti dell'intera catena
cinematica: poiché la posizione del blocco di legno sul tavolo di supporto non era fissa, alcuni soggetti
riuscivano a eseguire l'esercizio rimanendo fermamente sulla sedia e posizionandosi più vicino al
blocco, altri soggetti, invece, preferivano stare meno fermi sulla sedia e accompagnavano il movimento
con il busto.

18
I valori iniziali di ripetibilità del movimento sono più o meno uguali tra distonici primari e distonici
secondari. Non c’è stata una chiara tendenza verso l'apprendimento nè tra i soggetti primari né tra i
sani. Probabilmente è necessario considerare che le possibilità di miglioramento fossero già limitate in
partenza, date le buone prestazioni al primo giorno di test. Lo stesso tipo di analisi può essere condotto
sui secondari, che non hanno rivelato se il dispositivo fosse effettivamente efficace. Comunque, va
considerato che solo in un caso (S001BoLu) è stato riscontrato un apprendimento isolato nella
settimana di non utilizzo del dispositivo.
Anche guardando ai parametri elettromiografici, non vi è una chiara tendenza a favore delle ipotesi
iniziali: infatti, per quanto riguarda sia la co-contrazione dei muscoli FCU/ECR che la co-contrazione dei
muscoli AD/PD, è stato evidente un maggior apprendimento quando il BF è stato utilizzato sia per i
soggetti primari sia per soggetti secondari; l'apprendimento indotto dalla pratica è stato nullo per i
pazienti primari e visibile solo per un soggetto secondario. Concentrandosi sulla co-contrazione dei
muscoli primariamente coinvolti nella prono-supinazione del polso, il comportamento dei tre gruppi è
stato simile: i soggetti sani e i pazienti (soggetti primari e soggetti secondari) hanno migliorato le loro
prestazioni quando il feedback sensoriale è stato fornito, mentre l'apprendimento con la pratica è stato
mostrato da un solo soggetto (un soggetto sano). La tendenza dei soggetti sani è stata quella di
aumentare la co-contrazione dei muscoli FCU/ECR con la pratica. Non è sbagliato ipotizzare che solo
una maggiore attivazione simultanea di questi muscoli si rifletta in una maggiore stabilità
dell'articolazione del polso, e quindi un maggiore controllo sul cucchiaio. Questo spiega perché, se il
risultato atteso era una diminuzione dei livelli di co-contrazione, sono stati trovati bassi livelli di
apprendimento. Infine, considerando la co-contrazione dei muscoli BIC/TRIC, i soggetti secondari non
hanno rivelato maggior apprendimento durante l'utilizzo del BF. Piuttosto, la pratica ha indotto un
apprendimento del compito, ma questo non è stato influenzato dall'uso del dispositivo; inoltre, per i
soggetti primari, il dispositivo di BF ha influenzato l'apprendimento del compito più di quanto abbia fatto
la pratica.

In generale, non si può affermare che l’effetto correlato all'uso del dispositivo sia più pronunciato nel
gruppo di distonici secondari: è stato riscontrato un apprendimento accelerato dall’uso del dispositivo
sia nei soggetti primari sia nei pazienti secondari. Anche per i soggetti sani il BF ha accelerato i processi
di apprendimento. Ciò è stato particolarmente evidente considerando i parametri temporali e la co-
contrazione dei muscoli FCU/ECR.
Per quanto riguarda i parametri temporali e i parametri relativi alla cinematica dell'output finale,
l'apprendimento nei distonici primari non è stato significativamente influenzato dall'uso del dispositivo,
ma questa tendenza non è stata confermata considerando i parametri legati all'intera catena cinematica
(ROM e ST) e i parametri EMG, per i quali il dispositivo ha accelerato l'apprendimento.

Quindi, i risultati non ci permettono di supportare le ipotesi su cui si basa lo studio: anche individui affetti
da distonia secondaria, che sono caratterizzati da marcati deficit sensoriali che impediscono il loro
miglioramento nell'esecuzione di compiti motori complessi (nonostante l'allenamento ripetuto),
sembrano non essere così favoriti dall’uso di tale strategia; d'altra parte, per i soggetti affetti da distonia
primaria e per i sani, in cui non ci sono deficit sensoriali e i meccanismi di apprendimento fisiologico
legati alla formazione di un particolare esercizio motorio sono intatti, l'uso di una strategia di biofeedback
sembra avere un ruolo nel miglioramento delle prestazioni .

Tuttavia, non siamo neanche nella posizione di rifiutare le ipotesi iniziali. Alcune limitazioni devono
ancora essere superate. La prima limitazione dello studio risiede nel fatto che attualmente esso non
prende in considerazione variabili cognitive che potrebbero portare a disturbi comportamentali e che
potrebbero impedire ai secondari di accedere a risorse sufficienti per un apprendimento corretto.
Una limitazione deriva dalla mancanza di alcuni dati fondamentali per l'analisi di alcuni pazienti
secondari. Inoltre, la mancanza di un'analisi statistica di gruppo e i risultati molto variegati non
consentono conclusioni definitive. Questo problema si aggiunge al numero limitato di soggetti, che rende
la potenza del campione limitata e il confronto non sempre statisticamente robusto.
Tuttavia, lo studio clinico multicentrico in corso supererà questa limitazione ed è previsto il reclutamento
di ulteriori soggetti distonici. Inoltre, sarà studiato l'effetto a lungo termine dell'uso del dispositivo di
biofeedback durante le attività quotidiane (indossando il dispositivo almeno 5 ore al giorno per un mese).

19
I futuri sviluppi di questo lavoro potrebbero essere:

• definizione di una serie di criteri per guidare l'operatore nella scelta dei muscoli più adatti su cui
collocare il biofeedback; questi potrebbero essere selezionati, ad esempio, dopo una valutazione clinica
e quantitativa che indica chiaramente i più compromessi;

• test di utilizzo simultaneo di più modalità di feedback;

• test degli effetti di diversi canali sensoriali attraverso i quali fornire il feedback.

20
CHAPTER 1
INTRODUCTION

Dystonia is defined as “a movement disorder characterized by sustained or

intermittent muscle contractions that cause abnormal, often repetitive
movements. Dystonic movements are typically stereotyped, torsional and can be
characterized by tremor. Dystonia is often initiated or worsened by voluntary
actions and is characterized by the activation of muscles that are not strictly
functional to the motor gesture (overflow)’’ (A. Albanese et al., 2013).

Childhood dystonia is defined as a “movement disorder in which involuntary

sustained or intermittent muscle contractions cause twisting and repetitive
movements, abnormal postures, or both” (T. D. Sanger et al., 2003).

Dystonia is a chronic disease and only rarely affects the cognition of the affected
patient. It is unlikely that dystonia is directly related to a decrease in an individual's
life expectancy. In any case, it is important to remember that dystonia, when it
manifests itself as a symptom of an other pathology, could still generate short or
long-term complications, so as to seriously compromise the quality of life of the
affected subject.

21
1.1 General classification of the pathology
Definition of dystonia in childhood is complicated by the fact that it is a symptom and not a disease.
Another complication in childhood dystonia is the frequent association with other movement disorders.
For example, many children with cerebral palsy have components of both spasticity and dystonia
presented in the same limb. When hypertonia is present it can be very important to distinguish between
spasticity and dystonia, since surgical intervention can have different outcomes depending on the type
of disorder (T. D. Sanger, 2005).

Dystonia is classified along two axes: clinical characteristics, including age of onset, body distribution,
temporal pattern and associated features (additional movement disorders or neurological features),
and etiology, which includes nervous system pathology and inheritance (A. Albanese et al., 2013).
Clinical features are specified through the use of 5 descriptors:

1. Age of onset of the pathology. A classification by age is of great importance both in diagnostic and
prognostic terms and the following categories can be distinguished:

• early Childhood (from birth to 2 years);

• childhood (3 to 12 years);

• adolescence (from 13 to 20 years);

• early adulthood (21 to 40 years);

• late adulthood (over 40).

2. Body distribution. This classification is of great interest in the diagnostic and therapeutic field and
allows to evaluate the possible spread of the pathology across areas not previously involved; the
following categories are distinguished:

• focal dystonia, if it affects a single body part;

• segmental: involves two or more contiguous body regions;

• multifocal dystonia, if it affects two or more non-contiguous body parts;

• generalized dystonia, if it affects one leg and the trunk plus one other body part, or both legs plus one
other body part;

• hemidystonia, if it affects only one half of the body.

3. Temporal patterns. Temporal aspects assume great relevance since they allow to distinguish static
forms from progressive forms and to have an idea concerning the occurrence of dystonic phenomena
during the course of the day; the following categories are distinguished:

• persistent, if dystonia persists throughout the day;

• action-specific, if dystonia occurs only during the course of a particular action or a particular task;

• diurnal fluctuations, if dystonia varies during the day in terms of occurrence, severity and
phenomenology;

• paroxysmal, if sudden dystonic episodes re-entry to the starting conditions.

22
4. Coexistence of other movement disorders: dystonia can be alone or in combination with other
movement disorders; the following categories are distinguished:

• isolated dystonia, if it is the only motor feature (with the exception of tremors);

• combined dystonia, if it is combined with other movement disorders.

5. Other neurological manifestations. The presence of other neurological or systemic manifestations

facilitates the pathology characterization.

The etiological classification of dystonia has evolved over time. Fahn and Eldridge first distinguished
primary dystonia (with or without a hereditary pattern) from secondary dystonia (with other hereditary
neurological conditions or due to known environmental cause), and psychological forms of dystonia.
Later, the classification was expanded to include four subgroups of dystonia syndromes: primary,
dystonia-plus, secondary, and heredodegenerative. Bressman further refined the etiological
classification and proposed a dichotomous distinction between primary (autosomal dominant or other
genetic causes), and secondary dystonia syndromes (including dystonia-plus and degenerative,
complex/unknown, and acquired forms). These proposed changes are due in part to increased
understanding of etiology, but also to differences in opinion regarding how the growing number of
different etiological mechanisms should be lumped or split in relation to the varied clinical phenotypes.
The etiology of many forms of dystonia is still not fully understood. At the present time, two
complementary characteristics may be useful for classification: identifiable anatomical changes and
pattern of inheritance. Anatomical causes can be investigated using brain imaging or by pathology.
Inheritance differentiates inherited from acquired conditions by means of metabolic, genetic or other
tests.
Several difficulties in currently employed etiological classifications for dystonia are identified. One of
them involves terminology. The term “primary” dystonia, although historically most consistently used,
carries some inherent implications. For other disorders, the term “primary” most often is used either for
the first condition in some type of ordering system, to indicate the most prevalent subgroup, or to refer
to the absence of other detectable abnormalities. The term “secondary” dystonia also lacks clarity, as it
is antithetical to primary and may indicate non-isolated dystonia, a defined pathology or more generally
a known etiology.
These varied meanings have led to confusion, with the term “secondary dystonia” sometimes referring
to any dystonia that is not primary, sometimes to any dystonia with a known cause, and sometimes only
to acquired dystonias. The dichotomous usage of “primary” and “secondary” has led to some confusion
and the expression “non primary” has been also introduced.
Although it is possible to propose definitions with a greater degree of detail, for the purpose of the
present work we will exploit a classification that divides dystonia into primary and secondary, with the
following meaning:

• primary dystonia, if dystonia is the only disorder characterizing the patient (of genetic origin, idiopathic,
...)

• secondary dystonia, if dystonia is a consequence of a previous event (infantile cerebral palsy, ...)

23
1.2 Characteristics of the pathology
Dystonia has long been associated with three physiologic phenomena (T. D. Sanger, 2005):

• Activation of muscles that are not directly involved in the movement (overflow). Overflow occurs during
attempts of voluntary movements when muscles that would not normally be involved in that movement
are activated involuntarily. Given the inability to correctly focus on the single motor action, the activity of
the muscles is not adequately inhibited, resulting in an overabundance of muscles used.

• Agonist / antagonist muscles co-contraction. This must be seen as the subject voluntary compensation
to a typical dystonic posture attitude.

• Involuntary activation of muscles during passive handling. The innervated muscle is characterized by
visco-elastic resistive properties, so the action of a stretching force with respect to the rest position is
required. In dystonic subjects there is an anomalous increase in the resistance to the imposed
movement.

As seen, a clinical feature of dystonia is represented by the excess of movement (extremely prolonged
EMG activity, agonist / antagonist co-contractions, overflow on muscles not directly involved in the task
execution): this can be potentially explained by the presence of alterations at the level of spinal and
cortical inhibition circuits. These alterations are not specific for dystonia, but have also been reported
for other neurological disorders; consequently it is not possible to establish a univocal link between
these alterations and the pathology under study: how, then, can a non-specific deficit in cortical inhibition
translate into excessive and typical little-focused dystonic subject movements? The hypothesis is that,
in producing a specific voluntary movement, our brain suppresses all possible remaining movements.
By doing so, the motor cortex should be able to generate a more accurate movement; the lack of such
inhibitory mechanisms is responsible for the failure in focusing the motor command, which results in
overflow, co-contractions, ...
In terms of neuroanatomical structures, the interpretation that justifies these phenomena is linked to an
unbalance, in the basal ganglia area, between the activity of direct pathways (which control voluntary
movement) and that of indirect pathways (which inhibit undesired movements): this unbalance causes
problems of focusing on the movement. It is also thought that the cerebellum, whose activity influences
cortical excitability, can play an important role.

The second topic of interest is related to deficits in the sensorimotor integration process: although
dystonia is a disorder with predominantly motor characterization, it is accompanied by sensory deficits
(T. D. Sanger et al., 2001) (F. M. Molloy et al., 2003), typically extended to body segments not directly
involved by the pathology; the involvement of sensory aspects can also be demonstrated by the fact
that through sensory input it is possible to modulate the symptoms of the pathology: a tactile or
proprioceptive sensory input improves postural abnormalities of the subject;. The physiological
mechanisms underlying the sensory trick are not known, but it is assumed that the additional sensory
stimulus is able to correct the incorrect connection between sensory input and movement parameters,
allowing motor commands to be more effectively generated (M. Naumann et al., 2001).
With regard to the neuroanatomical aspects, also in this case the basal ganglia play an important role,
in particular through the activity of cholinergic interneurons; the latter therefore play a central role both
in the control of voluntary movement and, precisely, in the pathogenesis of diseases such as Parkinson's
disease and dystonia.

Third and final aspect to be underlined is related to deficits of synaptic plasticity processes, which are
the founding basis of learning mechanisms: the excessive training of a particular movement, for
example, is responsible for changes in connectivity at the motor and sensory level (cortical
reorganization) and, consequently, it ends up creating incorrect correlations between sensory inputs
and motor outputs that result in errors in the execution of the movement.
Again, these alterations can be associated with potential anomalies both at the level of the basal ganglia
and at the cerebellum level (A. Quartarone and M. Hallett , 2013).
24
Another physiological aspect of interest is linked to the fact this pathology is typically associated with
the presence of noise and disturbances on neural control signals: although the origin of these disorders
is unclear, they grow with increasing value signal average; consequently, the execution of a rapid
movement, which requires high control signals, is characterized by a large noise component, which will
increase the variability of the executed movements. The increase in noise on the control signals makes
the subject to slow down in the execution of the movement itself, which will be not only slow, but also
variable (C. M. Harris and D. M. Wolpert, 1998) (T. D. Sanger, 2006) (F. Lunardini et al., 2015).

1.3 Therapies
Given the probabilities of complete and definitive recovery are almost nil, therapies aim at spastic
symptomatology correction, pain reduction, allowing the subject to assume less incorrect postures and,
above all, the improvement of the patient's quality of life.
Considering secondary forms, which result from specific diseases, the patient responds more
satisfactorily to therapies, precisely because the triggering cause is known. The only approach to
primary dystonia remains symptomatic therapy, i.e. treatment based solely on symptoms.

The most commonly used treatment options are either only partially sufficient to control the symptoms
(pharmacological therapies and complementary treatments) or invasive (surgical therapies).

The most used pharmacological therapies are summarized below:

• oral administration of targeted pharmacological specialties, such as anticholinergic drugs (triesifenidile)

which have proved to be useful in cases of segmental and generalized dystonia and well tolereted (R.
E. Burke et al., 1986) (A. H. Hoon Jr, 2001), and dopaminergic drugs (levodopa). Although many patients
do not report substantial improvements, a small percentage typically shows excellent results, even until
complete resolution of the dystonia. From these cases the name dopa-responsive dystonia was born
(S. A. Schneider, 2006). Instead, for what concerns antidopaminergic drugs, although these can
potentially guarantee beneficial effects, their use is extremely limited (and usually discouraged) due to
the development of various side effects (B. I. Karp, 1999);

• intrathecal administration of muscle relaxants;

• botulinum toxin injections. Botulinum toxin is the first choice drug not only for the treatment of dystonia,
but also for all forms of dyskinesia. It guarantees excellent results in the treatment of hypertonia
connected to dystonia (J. Jankovic, 2006). The beneficial effects of botulinum toxin are substantially
linked to its primary mechanism of action, which blocks the release of acetylcholine in the neuromuscular
junction, temporarily inducing chemodenervation and muscular paralysis; several clinical studies
demonstrated significant improvements in quality of life for subjects (J. Jankovic et al., 2004). Botulinum
toxin is injected directly into the affected muscle and the effect is almost rapid in most patients (positive
outcomes after 10 days). Although the effects of the drug generally cover a time span of 3 to 6 months,
sometimes it is possible that these are prolonged.

The only option for patients who do not respond to pharmacological treatments is surgical therapy. In
particular, a neurosurgery intervention is performed: Deep Brain Stimulation (DBS) exploits the
implantation of electrodes that send high frequency electrical impulses to specific parts of the brain,
usually the inner pale globe (GPi). The internal pale globe is a site of implantation that guarantees
effectiveness in improving the symptoms of primary and secondary dystonia (E. L. Air et al. , 2011).
Being a highly invasive treatment, complexity, cost and risks mean that it’s applied only if all other
treatment options are unusable. Still with regard to surgical treatments, possible alternatives (actually
hardly used) are linked to radiofrequency ablations of the thalamus or pale globe and to selective
peripheral denervation procedures.

25
Non-pharmacological therapies are recommended in conjunction with targeted pharmacological
treatments. Non-pharmacological therapy means a particular approach, based on physical
(physiotherapy) or verbal (logopedic) therapies, aimed at acquiring greater awareness and self-control
by the patient. Obviously, physical therapy is not able to cure dystonia, since it is a mostly neurological
disorder. However, physical therapy is still a valid option, useful for the patient to monitor and self-
manage the secondary symptoms caused by dystonia. Clearly, physical therapy can not replace the
pharmacological, but physical therapy can be helpful in speeding up subject improvement. Many
clinicians suggest physical and occupational therapy in addition to actual medical treatment, with the
aim of maintaining a full range of motion, improving posture and preventing contractures.
The use of customized braces can promote postural improvements, but it is little tolerated, especially by
children.

1.4 Biofeedback treatments

One of the most innovative non-invasive complementary treatment options is biofeedback (BF).
BF is a technique that consists in providing the subject with increased information of a physiological
process through sensory channels of different types, allowing him to increase his awareness of it and
to acquire voluntary control over it (J. V. Basmajian, 1982).
This is a treatment strategy that provides the patient with real-time information regarding the value of a
biological variable. Typically, we refer to this information with the term of increased feedback (or extrinsic
feedback), to indicate an additional contribution that is added to what is already available; it is customary
to separate the afferent information into intrinsic and extrinsic: the first is linked to sensory and
perception aspects that arise in response to the performance of a movement, the second, instead, is
provided by an external source; ultimately, this additional information should help integration at the
central level by promoting motor learning (C. Casellato et al., 2013).
The BF mechanism is generally linked to the measurement of a target variable which is then provided
to the user through one of the following strategies:

• direct feedback inherent to the measured variable, for example showing its value on a display;

• transformation of the measured variable, which is used to modulate an auditory, visual or tactile signal.

The biofeedback methodologies traditionally used in the clinical-rehabilitative field can be divided into
two distinct categories:

• physiological. Physiological biofeedback is based on measurements relating to the neuromuscular

system, the cardiovascular system and the respiratory system.
Neuromuscular biofeedback strategies include electromyography-based biofeedback (EMG) and real-
time ultrasound-based (RTUS) imaging.
EMG-based biofeedback uses surface electrodes to read the signal related to the activity of skeletal
muscle: this signal is then supplied to the patient in a different form (tactile, visual, auditory, ...); this can
allow, for example, an increase in the activity of weak or paretic muscles as well as a reduction in the
tone of the spastic musculature.
RTUS-based biofeedback, on the other hand, sends short ultrasonic pulses to the body, then uses the
reflected signal from the interfaces between tissues to generate internal structures images; this type of
BF modality is able to provide an immediate visual feedback of the state of the structure under
investigation (for example a muscle) through the monitor display of the shape / length variations of the
structure itself.
Cardiovascular biofeedback uses heart rate and heart rate variability measurements, which are provided
to the patient in numeric format, usually on the screen of a wearable device (a special watch, for
example).

26
The biofeedback related to the respiratory system, on the other hand, is linked to measures correlated
to the subject's breathing that are obtained through sensors placed at the level of the abdomen; these
measures will then be converted into visual / auditory signals;

• biomechanical. Biomechanical biofeedback exploits movement measurements, postural control and

force, obtained via dynamometric platforms, inertial sensors, electrogoniometers.
Inertial sensors (implementing accelerometers and 3D gyroscopes) provide us with an estimate of the
kinematic parameters of a body segment in 3D space (position, orientation, speed, ...); these parameters
are then used as inputs of a feedback mechanism that provides the subject with a visual or auditory
signal.
The dynamometric platforms measure the reaction force to the ground generated by the subject and
can be used to provide feedback relating to balance, movement and walking; this feedback is visually
provided visually through a monitor that, of course, modulates its activity in relation to the value of the
force, read by the platform.
The electrogoniometers allow measurements of joint kinematics; as soon as the kinematics is changed,
a feedback signal (auditory or visual) is provided.

The first studies on the use of BF-based treatments for the improvement of motor learning have shown
that the individual can acquire control at high levels on the neuromuscular system, even managing the
single muscle (J. V. Basmajian, 1963). It was found individuals are able to reduce their co-contraction
significantly when visual biofeedback is provided (S. J. Young, 2010). These results indicate that
children with dystonia are able to control co-contraction, at least to a certain extent, provided attention
can be directed to the excess muscle activation. Such considerations are confirmed in literature:
reduction of the levels of agonist / antagonist muscles activation is an obtainable outcome, if augmented
sensory feedback is guaranteed, without incurring an excessive increase in the performance error (S.
J. Young et al., 2012). Successful preliminary results on the use of EMG-based vibro-tactile biofeedback
training have been shown in children with secondary dystonia due to dyskinetic CP during the execution
of a figure 8 writing task relevant to daily life (F. Lunardini et al., 2016). Moreover, prolonged use of EMG
biofeedback can improve function in children with upper extremity motor disorders (R. Bloom, 2010):
changes of the use of the upper extremity in children with cerebral palsy and upper extremity motor
deficits can be assessed using an individualized Goal Attainment Scale. The mechanism of
improvement is not known, but it could be related to increased attention to the affected arm, enhanced
sensation of muscle contraction mimicking proprioception, or magnification of the perceived effect of
previously ineffective attempts at movement.

These studies aimed at analyzing the most common dystonic disorders have highlighted why increased
sensory feedback can actually be beneficial for subjects suffering from dystonia in terms of motor
rehabilitation and learning motor skills. However, significant further tests are needed and some
limitations still need to be overcome:

• some of the studies employed a visual biofeedback which acts as an extrinsic feedback via external
pathways in contrast to intrinsic feedback which develops through proprioceptive pathways during
movement. Furthermore, a visual feedback cannot be implemented in a wearable device, thus
preventing the use outside clinical or laboratory settings, such as school or domestic environments;

• in some of the studies the effectiveness of the biofeedback techniques was assessed on few subjects
or using only qualitative interviews and clinical scales, without any quantitative measures able to capture
small motor changes;

• comparisons about the effect of biofeedback training on subjects with primary and secondary dystonia
were not reported so far;

• comparisons between prolonged feedback to intermittent or short-term biofeedback, nor to other

interventions such as robot-assisted rehabilitation, constraint-induced movement therapy, or high
occupational therapy or physical therapy were not investigated.

27
1.5 Objective
The present thesis work is part of a multi-center cross over study that involves, besides the Politecnico
of Milano, the Carlo Besta Neurological Institute, Milano (MI), the Scientific Institute Eugenio Medea,
Bosisio Parini (LC), and the Children's Hospital, Los Angeles (CA). The research project has been
approved and is supported by the United States Department of Health (NIH, National Institutes of
Health). The coordinator of the entire study is Dr. T. D. Sanger, professor at the University of Southern
California (USC, Los Angeles) and neurologist at the Children's Hospital of Los Angeles, who designed
and built a battery-powered wearable electromyographic (EMG) feedback device. The person wearing
the device is alerted to muscle activity by smooth changes in the speed of a silent vibration motor.
Proportional tactile sensory feedback is achieved by driving the motor with a signal proportional to the
estimated EMG power, and the vibration is provided at the site of the active muscle. The mechanism of
motor improvement using EMG biofeedback could be related to increased attention and enhanced
sensation of muscle contraction mimicking proprioception. Another possible mechanism for
improvement is the induction of Hebbian plasticity associated with increased correlation between a
motor action and its sensory result. By increasing the sensation associated with muscle contraction, BF
can further enhance cortical or subcortical representations of movement (M. Bertucco and T. D. Sanger,
2015).

The entire study is based on a broad protocol aimed both at testing the effectiveness of the biofeedback
device in terms of motor learning of specific exercises performed in the clinic / laboratory, hypothesizing
a faster and facilitated motor learning in presence of increased sensory information, and at verifying the
effectiveness of the device at home level, during daily activity, assuming that increased sensory
information will allow the acquisition of skills related to the child's natural environment. This comparison
between short- term to prolonged biofeedback allows to determine which aspects of the device are most
helpful, the minimum required amount of time to see benefits, and the particular deficits that are most
improved by this intervention.
In particular, the objective of the present work is to test the mechanism of action of the EMG-based
vibro-tactile biofeedback device and to quantify the effect of increased sensory information during motor
learning in children affected by primary and secondary dystonia while performing specific exercises in
the clinic / laboratory, and to compare the effect it produces on patients with its influence on healthy
subjects.
Subjects suffering from primary dystonia were recruited at Besta and performed the acquisition protocol
at Politecnico, while the secondary patients were recruited and performed the exercises at Medea.
In the case of subjects with secondary dystonia, characterized by sensory deficits (F. M. Molloy et al.,
2003) (T. D. Sanger and S. N. Kukke, 2007), the use of BF techniques can be useful to drive attention
to specific sensory representations, focusing on errors that would otherwise have gone unnoticed.
Instead, in the case of subjects with primary dystonia, not characterized by sensory deficits (F. M. Molloy
et al., 2003) (T. D. Sanger and S. N. Kukke, 2007), and healthy subjects, the use of such a strategy
could be useful in accelerating motor learning rather than in obtaining finer movements.
This suggestion translates into an important work hypothesis:

• In the case of subjects affected by primary dystonia, in which there are no sensory deficits and the
physiological learning mechanisms linked to the training of a particular motor exercise are intact, the
use of a biofeedback strategy should have no clear role in improving performance. At least, the behavior
of the tested primaries should be approximately consistent with the behavior of the healthy participants;

• Individuals with secondary dystonia, which are characterized by marked sensory deficits that prevent
their improvement in the performance of complex motor tasks (despite repeated training), should be
favored by using such a strategy.

28
CHAPTER 2
MATERIALS AND METHODS

2.1 Study protocol

The entire acquisition protocol consists of two distinct phases:

• Phase A: to test the effectiveness of the BF device in the short term (1 month) during the execution of
two activities that each of us do habitually and daily, such as writing and eating, to be carried out in a
controlled environment. In the first case, the subject is required to perform Figure 8 Task, i.e. to trace,
on the iPad, the figure of an 8; in order to replicate the activity of feeding, the subject is required to
complete the so-called Spoon Task, i.e. to move a marble in a spoon from a certain initial position to a
target position, spaced by a wooden block;

• Phase B: aimed at testing the effectiveness of the BF device in the long term, during the performance
of daily activities (school, play, domestic, ...), to be carried out at home.

The present thesis work focused on the analysis of Spoon Task, performed during the first phase of the
protocol.

This phase involves two weeks (blocks) of data acquisition, with a wash-out period of a minimum of four
weeks in between. At the beginning of the first block, patients are involved in a baseline assessment to
quantify dystonia severity in the dominant upper limb. Video shots were performed allowing the evaluator
to assign a score to the subject according to a clinical evaluation scale, the Barry-Albright dystic scale
(BAD), characterized by an evaluation in 5 points (from 0, i.e. absent, to 4, i.e. severe) to be assigned
to 8 body regions: eyes, mouth, neck, trunk, upper extremities (left and right side), lower extremities (left
and right side).
Each block consists of five consecutive days of data collection, from Monday (day 1, baseline) to Friday
(day 5, end of training). Day 1 and day 5 are defined as Testing sessions, while intermediate days (day
2, day 3 and day 4) are Training sessions. During the Testing sessions, the subject performs exercises
on several difficulty levels (different speeds for Figure 8 Task, different spoon depths for Spoon Task);
during the Training sessions, on the other hand, the subject executes the exercises on one difficulty
level (the intermediate level).
The patient wears the BF device only during the Training days in only one of the 2 weeks. The order of
the the two weeks is randomized among subjects.

Figure 1 shows a representation of the protocol.

Figure 1: Study protocol

29
Spoon Task consists of carrying a marble inside a spoon from one side to the other of a 20 cm x 10 cm
x 7 cm wooden block. During each trial the subject is given the opportunity to stop at the end of the
forward movement (or the backward movement), trying to complete the movement as quickly as possible
(Figure 2).

Figure 2: Experimental apparatus

During the Testing sessions the subject performs the exercise at 3 different levels of difficulty, which
derive from as many concavities of the spoon. The available spoons are 12, numbered from 1 to 12 for
increasing depths, from 3 mm (for spoon number 1) up to 36 mm (for spoon number 12).
During Training sessions, the subject performeed 3 blocks of 3 sets of trials, each one made of 10
movements with the intermediate spoon.

30
At the end of each day, the subject is made to perform additional tests to ensure a more complete
assessment that also takes into account cognitive and sensory aspects.
In particular, the following tests are performed:

• Day 1 (D1)

✓ Handwriting Task: the subject is asked to write a sentence while the examiner times the time needed
to complete the task;

✓ Star Task: the subject is asked to design a star on the iPad, by connecting five numerically labeled
points in ascending order. The patient performs the exercise 10 times with the tested limb and 10 times
with the contralateral limb; also in this case the examiner keeps track of the time needed by the
participant to complete the task;

• Day 2 (D2)

✓ Peg Board Task: the subject is asked to fill, with plastic bars, 9 holes ordered on a 3x3 grid; the bars
must be taken one at a time and, once the grid is filled, always one at a time must be removed from the
holes, in order to return the grid to its initial configuration. The exercise is performed both with the tested
limb and with the contralateral, and, again, the examiner times the time taken;

✓ Button Press Task: the participant must select, one at a time, a pair of targets, positioned at opposite
ends of the iPad screen, moving from one side to the other as quickly as possible; the number of
correctly hit targets and the number of errors (missing targets) are tracked. The exercise is performed
both with the compromised limb and with the contralateral arm and with two different sizes of targets;

• Day 3 (D3)

✓ Test Of Nonverbal Intelligence, 4th Edition (TONI – 4): through a set of questions it allows to evaluate
cognitive aspects. The purpose of the test is to measure abstract reasoning and the ability to solve
problems (problem solving);

• Day 4 (D4)

✓ JVP Domes Sensitivity Test: it allows to obtain a measure of the subject's tactile acuity; it is therefore
an indication of the participant's ability to discriminate two stimuli;

• Day 5 (D5). Day 1 tests are repeated to evaluate the training effect

✓ Handwriting Task;

✓ Star Task.

Healthy subjects followed a simplified and more practicable protocol. Their presence in the laboratory
was required only during Testing days and they trained at home in the intermediate days. Moreover, the
only sensory and cognitive tests they performed were those relating to Testing sessions, i.e. Handwriting
Task and Star Task.

The protocol was approved by both Besta and Medea. However a distinction must be made. Unlike the
PoliMi protocol, which provides two weeks of acquisition, in which the subject performs both Figure 8
Task and Spoon Task, the Medea protocol provides four consecutive weeks of acquisition. In the first
and third weeks the subject plays Figure 8 Task, during the second and fourth weeks the subject plays
Spoon Task.

31
2.2 Experimental apparatus
The experimental setup includes the devices to acquire kinematic and electromyographic signals: an
optoelectric motion analysis system and an electromyograph. Different commercial systems were used:
at Politecnico di Milano POLARIS VICRA and Porti 32 TMSi were used, at Medea Institute OEP System
and BTS Free EMG were adopted.

Polaris Vicra System

The Polaris Vicra System is an optical measurement system that measures the 3D positions of passive
markers attached to application-specific tools with a sampling frequency of 20 Hz.
The Position Sensor (Figure 3) is the main component of the Polaris Vicra System.

Figure 3: Polaris Vicra System

The Position Sensor emits infrared (IR) light from its illuminators, placed at a distance of about 20 cm
on a concave surface. These illuminators are accompanied two sensors, which collect IR light that is
reflected from the passive sphere markers; the Position Sensor then measures the positions of the
markers, and calculates the transformations (the positions and orientations) of the tools to which the
markers are attached; finally, the Position Sensor transmits the transformation data to the host computer
for collection, display, or further manipulation.
Passive tools incorporate passive sphere markers. The passive sphere markers have a retroreflective
coating that reflects IR light back to its source, instead of scattering it. Markers can be attached to an
object such that the markers are fixed with respect to one another, to form a tool. The Polaris Vicra
System can track the tools positions and orientations, and can also report the positions of individual
passive spheres. The system can track up to 6 compatible tools simultaneously. Obviously, the Position
Sensor requires a tool definition file for each tool, which defines the tool’s marker geometry.

For the purpose of the present study, 5 different tools were developed:

• one to detect the movements of the shoulder joint;

• one to trace the kinematics of the elbow;

• one to measure the displacements and rotations of the wrist;

• one to be positioned on the finger during the execution of the Figure 8 Task;

• one mounted on the spoon used by the subject to complete the Spoon Task.

32
The position and orientation of tools are determined only if they are placed within a specific
measurement volume, as shown in Figure 4.

Figure 4: Polaris Vicra measurement volume

If the field of view is the total volume in which the Polaris Vicra System can detect a marker, regardless
of accuracy, the characterized measurement volume is a subset of the field of view, and represents the
volume where data were collected and used to characterize the Polaris Vicra System Position Sensor.
Within the characterized measurement volume, the system can measure a single marker with an
accuracy of 0.25 mm. A tool is flagged as out of volume if all of its markers are outside of it, but the
system can still detect the tool. By default, the system reports tools with markers that are outside of the
characterized measurement volume as missing.

TMSi
Figure 5 shows the device used at Politecnico to record the EMG signals.

Figure 5: TMSi 32 Porti

The EMG signal is acquired using the TMSi Porti system, a 32-channel electromyograph that allows
sampling at a frequency of 2048 Hz by useing a pair of Ag / AgCl surface electrodes, which are
attached on the skin.

33
These bipolar surface EMG electrodes are positioned on 8 muscles of the upper limb: Flexor Carpi
Radialis (FCR), Extensor Carpi Radialis (ECR), Biceps Brachii (BIC), Triceps Brachii (TRIC), Anterior
Deltoid (AD), Lateral Deltoid (LD), Posterior Deltoid (PD), and Supraspinatus (SS).

OEP SYSTEM
The kinematics at Medea is acquired through the Optoelectronic Plethysmography System (sampling
frequency of 60Hz). It consists of 8 infrared cameras positioned inside the laboratory, concentric to
cameras with sensors for optoelectronic transduction.
Markers are placed on the tip of the index (Figure 8 Task) or on the spoon (Spoon Task), on the knuckle
of the index, on the styloid processes of ulna and radius, on the lateral epicondyle of the elbow, on right
and left acromion, on C7, on the breastbone and on the left and right rib margin using an elastic band.

FREEMG
At Medea the EMG signal is acquired through the FREEMG system by BTS Bioengineering, an 8-
channel electromyograph made of wireless probes that sample the signal at a frequency of 1000 Hz
(Figure 6). The accuracy of the signal, the complete absence of cables, lightness and extremely reduced
size of the probes allow to perform analysis of any type of movement, for each body district, without
altering in any way the motor gesture of the examined subject. The probes hook directly to the electrodes
pre-loaded for signal pick-up, without the need for additional fastenings, ensuring a quicker setup
preparation.

Figure 6: FREEMG by BTS Bioengineering

34
Biofeedback device
During the Training days of the BF block, the subject is asked to wear the EMG-based vibro-tactile
biofeedback device on a target muscle of the tested arm. For each patient, based on a clinical
examination, the target muscle is selected as the most significant contributor to poor motor performance
during upper limb tasks. The device is shown in Figure 7.

Figure 7: EMG-based vibro-tactile biofeedback device

The device, with a total weight of 80g, is basically made up of two elements: a terminal for the recording
of the electromyographic activity and for the generation of a proportional somatosensory stimulus (4.5
x 2.6 x 0.4 cm) and a control block consisting of a microcontroller with an amplifier and a filtering circuit
(8.5 x 6 x 1 cm).
The terminal includes:

• an active differential electrode of the SX230 type (Biometrics Ltd, Ladysmith, Virginia, 20-460 Hz
bandpass filter, 1000x amplification, 10 Mohm input impedance, compliant with the Medical Device
Directive 93/42 / EEC) for the detection of electromyographic activity of the target muscle;

• Low-power Analog-Digital converter (ADS1251, Texas Instruments Inc., Dallas, Texas, USA, 24-Bit,
20kHz);

• Vibrating motor (C1234B016F, Jinlong Machinery, Zhejiang, China, 10-55 Hz vibration frequency)
placed on the skin of the target muscle, to perform a somatosensory stimulation, whose vibration
frequency is proportional to the electromyographic activation of the muscle itself.

The control block includes:

• microcontroller (TMS320C5515, Texas Instruments Inc., Dallas, Texas, USA), mainly responsible for
the non-linear filtering of the electromyographic signal transmitted to it. Proportionally to the amplitude
of the filtered signal, the microcontroller sets the frequency value to command the vibrating motor;

• customizable gain amplifier (0.03-30x secondary amplification);

• 3.3V lithium ion battery (900mAh) and related battery recharging circuit (LTC4062, LINEAR
Technology Inc., Milpitas, California, USA);

• Bluetooth serial port (ESD200, SENA Inc., San Jose, California, USA).

35
Compatible and hypoallergenic materials were used for the device. The terminal is made of plastic and
stainless steel. The microcontroller, the amplification and filtering circuits that make up the control block
are suitably connected and enclosed in a plastic case. The wire that interconnects the two parts is made
of insulating material, highly flexible PVC.

The device is an instrument designed to provide a cutaneous vibration proportional to the activation of
a particular muscle. The terminal is positioned by the operator on the skin surface of the target muscle.
During the execution of appropriate movements, the active differential electrode detects the
electromyographic activity of the target muscle. The signal is sent to the microcontroller in the control
unit, which performs a non-linear filtering of the signal. Proportionally to the activation level of the target
muscle, the microcontroller calculates the vibration frequency, which is used to control the motor, in
order to return to the subject a skin vibration whose magnitude is proportional to his muscular activation.

The action of the device, as already discussed in the introduction, aims to increase awareness related
to muscle recruitment and attention to electromyographic activity through a cutaneous vibration
proportional to the detected activity. The aim is to achieve an improvement in motor control and learning
in children with sensory deficits.

The main innovation of the biofeedback device realized by Dr. Terence Sanger is related to the type of
feedback signal used, that is a sensory stimulation provided by cutaneous vibration to the patient. In
fact, previous devices used visual or auditory feedback. These feedbacks require attention from the
subject and can distract nearby people, preventing their prolonged use outside the lab. In contrast, this
device provides a skin vibration and is silent. It has also been designed and built to be wearable. These
two characteristics allow the device to be worn for several consecutive hours during the regular daily
activities, maximazing the transparency for the subject.

2.4 Participants
A total of 15 patients were recruited:

• 9 primary dystonic subjects (5 boys and 4 girls from 7 to 19 years old), recruited at Carlo Besta
Neurological Institute and acquired at Laboratory of Neuroengineering and Medical Robotics (NearLab)
of Politecnico di Milano;

• 6 secondary dystonic subjects (4 boys and 2 girls from 6 to 16 years old), recruited and acquired at
Scientific Institute Eugenio Medea.

Inclusion criteria were:

• primary or secondary dystonia affecting the dominant arm;

• developmental age (6-20 years);

• no cognitive impairment that could prevent understanding of instructions;

• a stable drug therapy during the investigation;

• no treatment with botulinum toxin in the testedt arm in the six months prior to recruitment.

A group of 12 age-matched healthy subjects were recruited and involved in the protocol: 5 boys and 7
girls from 6 to 19 years old.

36
All participants gave informed written consent for participation. In case of minors, parents were asked
to sign the informed consent and the authorization for use of protected health information, videos and
images.

2.5 Data analysis

The analysis of the acquired data, made through Matlab (R2018a), was carried out starting from a pre-
processing phase, leading to obtain the EMG signal envelope for each of the 8 acquired muscles and
the reprojected kinematics on the main components plane of each joint, and to divide the overall
movement into a ssequence of repetitions, followed by a post-processing phase, aimed at extracting the
outcome measures necessary to evaluate the effect of the training.
On post-processed data a statistical analysis was performed with IBM SPSS Statistics, to assess the
influence of the device and practice on learning.

2.5.1 Pre-processing
The preliminary processing of the acquired electromyographic data consisted first of all in eliminating
any spurious peaks of the signal, which were not related to the actual muscular activity of the subject.
Then, a high pass filter, a signal rectification, and a low pass filter were applied one after the other. In
one exceptional case, which occours for the data analysis of a patient treated with DBS, another filter
was applied, in order to eliminate the noise resulting from the deep brain stimulation. Figure 8 shows
the rectified EMG and the envelope resulting after the LP filter.

Figure 8: Rectification and envelope of the electromyographic signal related to the 8 tested muscles. The rectified EMG is represented in
blue, the envelope is in red

37
The normalization of EMG data was done on the median of the maxima EMG signal envelopes. It has
to be emphasized that, since it is not a normalization methodology with respect to the maximum
contraction values expressed by the subject, the normalized signal result in a limited range of values,
but not necessarily between 0 and 1 (Figure 9).

Figure 9: Normalization of the EMG signal

For what concerns kinematic data, the pre-processing first performed an interpolation of missing data,
that occour when the motion acquisition system has lost track of a tool for short instants (Figure 10).

Figure 10: Raw and interpolated data for kinematics of the 4 tested joints

38
The second step consisted in the downsampling of the kinematic signal. This was necessary because
the C++ acquisition program over-samples the kinematic signal to synchronize it with the EMG signal.
In Figure 11 a double plot of the kinematics of the spoon and the EMG signal of the anterior deltoid and
the bicep is reported.

Figure 11: Double plot after downsampling of kinematic data. Top: AD envelope is shown in blue, kinematic signal of the spoon is shown
in red. Bottom: BIC envelope is shown in blue, kinematic signal of the spoon is shown in red

Therefore, on the wrist signal, which represents the main component of the movement, maxima and
minima were identified, eliminating any maxima below the average value of the signal and any minima
above the mean value of the signal (Figure 12). This procedure was fundamental for the division of the
entire movement into forward movements and backward movements.

Figure 12: Maxima and minima of the kinematics signal of the wrist

39
The pre-processing phase ended up with the processed data saving. For each tested subject, 2
structures were created, respectively corresponding to the outward movements and the return
movements, each containing 9 fields, relative to:

• the raw EMG signals;

• HP filtered EMG signals;

• the EMG envelopes;

• the normalized EMG data;

• the cquisition time of the EMG data;

• the kinematic data;

• the acquisition time of the kinematic data;

• the size of the used spoon;

• the depth of the spoon.

An example of the post-processing structure is reported in Figure 13.

Figure 13: Sample pre-processing structure of a tested subject: each field contains 10 matrices because 10 are the movements performed

The available Medea data had undergone an initial pre-processing, carried out by the examiners of the
Eugenio Medea Institute, which generated a structure of 7 fields:

• spoon size;

• spoon depth;

• kinematic data;

• raw EMG data;

• time vector related to the kinematic data;

• time vector linked to the EMG data;

• vector Tcut, time vector which indicates the temporal instants in correspondence of which all the data
were cut, if a movement was disregarded due to the fell of the marble.
40
In order to adapt Medea data to the post-processing code, it was essential to save pre-processed Medea
data in the same way as PoliMi data.
Among the values of Tcut, the extremes of the time interval of greater length (the interval including the
greatest number of movements performed without marble falling) were identified. These allowed to
determine the initial point and the final point at which cutting the data saved in the Medea structure, and
then to extrapolate, both from the kinematic and the electromyographic data, only the section related to
the sequence of movements that were to be analyzed in the post- processing.
Then the same steps adopted for the pre-processing of PoliMi data were performed. The generated
structure of Medea data was thus standardized to PoliMi data structure.

2.5.2 Post-processing

The post-processing code managed both the PoliMi data and the Medea data, with the aim of extracting
from the pre-processed data a series of parameters useful for evaluating the subject's motor learning
abilities.

The first part of the code allowed to load the pre-processed data into structures that contain, for each
subject, the data of the forward and backward movements related to all the spoons used for the test.
Thus, the extraction of the outcome measures consisted of a 3-way analysis:

• temporal analysis;

• kinematic analysis;

• electromyographic analysis.

Once the post-processing was completed, the final data were saved into a structure that contains, for
each subject, all the outcome values measured for the forward and backward movements during the
Testing days: W1D1 (Day 1 of Week 1), W1D5 (Day 5 of Week 1), W2D1 (Day 1 of Week 2), W2D5
(Day 5 of Week 2).

41
2.5.2.1 Time-related outcome measures
Time-related analysis was based on the evaluation of two parameters:

• Movement Time (MT). It is defined as the time interval used by the subject to complete a single
forward or backward movement. It was calculated as the difference between the temporal instant
at the end of the movement (for a forward movement, when the spoon touches the table after
passing over the wooden block) and the temporal instant at the beginning of movement (for a
forward movement, when the spoon is still and ready to start the movement).
𝑀𝑇 = [𝑡(𝑒𝑛𝑑) − 𝑡(1)]
As the spoon depth decreases, or the difficulty of the task increases, the movement time
increases, indicating that to perform the exercise with good accuracy it is inevitable to lose in
terms of speed of execution. We expect the movement time to decrease with learning.
• Index of Performance (IP). This parameter is an indicator of the information processing capacity
of the subject. It reflects the efficiency of the nervous / motor system in facing tasks of increasing
difficulty. Movement speed and accuracy are both affected in childhood dystonia. Thus, deriving
a speed-accuracy function is an important metric for assessing motor impairments in dystonia
(F. Lunardini et al., 2015). The speed-accuracy trade-off (SATO) was examined by changing the
spoon size to create different difficulty levels. Then, the IP was calculated as the inverse of the
linear regression between the movement time (MT) and the Index of Difficulty (ID), the latter
defined as the ratio between the characteristic size of the marble and the depth of the spoon (F.
Lunardini et al., 2015).
1
𝐼𝑃 =
(∆𝑀𝑇⁄∆𝐼𝐷 )

Figure 14 shows SATO and highlights the positive slope of the MT-ID trade-off. We expect the
IP to increase with learning.

Figure 14: Sample MT-ID linear regression

42
2.5.2.2 Kinematic-related outcome measures
The kinematic analysis concerned the evaluation of the accuracy, through parameters that are linked to
the geometry of the movement:

• Velocity. It was calculated as the square root of the velocity components along the spatial
coordinates of the wrist joint.

(𝑥𝑖 − 𝑥𝑖−1 )2 (𝑦𝑖 − 𝑦𝑖−1 )2 (𝑧𝑖 − 𝑧𝑖−1 )2

𝑉𝐸𝐿 = √ + +
𝑑𝑡 𝑑𝑡 𝑑𝑡

Obviously, the information provided by the aforementioned parameter confirms the evaluations
made on the time, and we expect the movement velocity to increase with learning.

• Movement fluidity. Smoothness is widely regarded as a hallmark of skilled and coordinated

movement (F. Lunardini et al., 2015).
The first index that allows to evaluate the fluidity of the movement is the number of peaks in the
velocity profile: it is evident that a velocity profile in which a large number of peaks is found is an
indication of an uncontrolled movement. In practice, however, a greater number of peaks was
typical for those tests where more effort was required by the examiner. We expect this value
decreases gradually with the simplification of the task.

A second measure of smoothness was expressed as the ratio, instant by instant, between the
average and the maximum speed of the wrist joint coordinates (H. Vikne et al., 2013):
𝑣𝑚𝑒𝑎𝑛
𝑆𝑀𝑂𝑂𝑇𝐻𝑁𝐸𝑆𝑆 =
𝑣𝑚𝑎𝑥

A fluid movement is a movement whose smoothness tends to unity, and we expect the
smoothness to increase with leaning.

Another empirical measure of the ability to perform a highly qualified motor gesture is the
derivative of acceleration, the jerk. If we want to have a measure of the shape of the movement,
without any dependence on duration and width, this measure must necessarily be
dimensionless. This is the reason why we evaluated the fluidity of the movement by adopting the
Normalized Mean Squared Jerk (N. Hogan, D. Sternad, 2009):
𝐼

𝑁𝑆𝐽𝑒𝑟𝑘 = 𝑐 {∑[𝑥⃛2 (𝑖) + 𝑦⃛2 (𝑖) + 𝑧⃛2 (𝑖)]}

𝑖=1

X, y, z are the spatial coordinates of the wrist.

The constant c is the dimensionless factor, which takes into account the acquisition time interval
(∆t), the movement time (MT), and the movement amplitude (A):

∆𝑡 ∗ 𝑀𝑇 5
𝑐=
𝐴2

A fluid movement, in this case, is a less jerky movement. Hence, we expect the Normalized
Mean Squared Jerk to decrease with learning.

43
 • Movement Linearity (ML). It is an indirect measure of accuracy, which gives an indication of the
individual's ability to not exaggerate in the generation of a parabolic trajectory that goes too far
from the wooden block.
It was calculated as the ratio between the amplitude of the trajectory generated by the subject
and the linear distance between the starting and the ending point of the movement.

∑𝐼𝑖=1 √(𝑥𝑖+1 − 𝑥𝑖 )² + (𝑦𝑖+1 − 𝑦𝑖 )² + (𝑧𝑖+1 − 𝑧𝑖 )²

𝑀𝐿 =
√(𝑥𝐼 − 𝑥1 )² + (𝑦𝐼 − 𝑦1 )² + (𝑧𝐼 − 𝑧1 )²

Index of a correct execution of the exercise is a Movement Linearity as low as possible,

considering that the minimum limit is one, which ccould not be achieved because it would have
meant to complete the task without the presence of the wooden hindrance. A dicreasing
movement linearity is expected with learning.

• Spacial repeatability of the movement. This measure provides an indication of the subject's
ability to perform repeatable movements throughout the test. It was computed as the variance
(%) explained by the first principal component (PC) applied on the 3D wrist trajectories of each
trial, after time-normalization on the mean duration across all the repetitions. With learning, this
index should increase.
Qualitatively, it is possible to evaluate the parameter of interest by mapping, in the same graph,
the trend of all the repetitions completed within the same test (Figure 15).

Figure 15: Example Spatial repeatability in y direction for each spoon. The more these trends are superimposable, the more the
subject has been able to perform similar movements in terms of kinematic characteristics

• Range of motion (ROM) of the elbow joint. It gives an indication of the subject's upper limb
flexion-extension during the movement, and it was computed, for each repetition of each test, as
the difference between the elbow angle at the end of the movement and the elbow angle at the
beginning of the movement. A further evaluation was carried out on the maximum ROM of the
elbow, calculated as the difference between the maximum and the minimum elbow angle. ROM
should increase with practice;

• Displacement of the shoulder joint (ST). It measures the movement of the shoulder joint in the
anterior-posterior direction. It was calculated as the difference between the position of the
shoulder at the end of the movement and its position at the beginning of the movement. Also in
this case, a further evaluation was carried out on the maximum displacement of the shoulder,
44
calculated as the difference between the maximum value and the minimum value of the shoulder
position.
This evaluation refers to the main direction of the movement, which coincides with the y-direction
of the absolute reference system centered on the shoulder joint. This is underlined by the fact
that the trend of the scores relative to the PC of the movement almost completely coincides with
the kinematic signal of the y-coordinate of the shoulder joint (Figure 16).

Figure 16: Scores of the PC in blue, shoulder coordinates in y–direction in red

45
2.5.2.3 EMG-related outcome measures

The electromyographic analysis was exclusively focused on the assessment of the level of simultaneous
activation of 3 couples of agonist / antagonist muscles: Flexor Carpi Ulnaris and Extensor Carpi Ulnaris,
Bicep and Tricep, Anterior Deltoid and Posterior Deltoid. Co-contraction (CC) of agonist / antagonist
muscles is a typical parameter of interest in dystonia, because excessive co-contractions are considered
to be typical features of some types of dystonia.

The co-contraction was evaluated in two different ways. The first measure used computes, for each time
frame, the ratio between the lowest value and the highest value of the normalized EMG envelope of a
couple of agonist / antagonist muscles normalized with respect to the sum of the two, averaged over
each forward and backward movement (F. Lunardini et al., 2016):

𝐼
1 𝐿𝑜𝑤𝑒𝑟 𝐸𝑀𝐺𝑖
𝐶𝐶 = ∑( (𝐿𝑜𝑤𝑒𝑟 𝐸𝑀𝐺𝑖 + 𝐻𝑖𝑔ℎ𝑒𝑟 𝐸𝑀𝐺𝑖 ))
𝐼 𝐻𝑖𝑔ℎ𝑒𝑟 𝐸𝑀𝐺𝑖
𝑖=1

The co-contraction was evaluated also as the minimum value of the normalized EMG envelope between
a couple of agonist / antagonist muscles for each time sample, averaged over each forward and
backward movement (Q. Qian, 2017):

𝐼
1
𝐶𝐶 = ∑ min[𝐸𝑀𝐺1𝑖 , 𝐸𝑀𝐺2𝑖 ]
𝐼
𝑖=1

Figure 18 shows the normalized EMG envelopes of a subject for each pairs of agonist / antagonist
muscles under investigation for the forward movements performed with the most difficult spoon.

Figure 17: Normalized EMG envelopes. Top position: In red the normalized EMG envelopeof FCU, in blue the normalized EMG envelopeof
ECR. Intermediate position: In red the normalized EMG envelopeof BIC, in blue the normalized EMG envelopeof TRIC. Bottom position: In
red the normalized EMG envelopeof AD, in blue the normalized EMG envelopeof PD.

46
If for the other parameters the direction of changes in case of effective learning can be easily
hypothesized, for co-contraction it is more difficult to make preliminary evaluations, since the selected
task is quite complex, and requires stability of the joints, guaranteed by a good muscle activation of the
couple of agonist and antagonist muscles. In this regard, it is therefore essential to observe the general
behavior of the healthy population, in order to have an indication about the direction of change in case
of learning.

47
2.5.3 Statistic analysis
For each subject involved in the study, a two-way Analysis of Variance (ANOVA) model was used
separately for each outcome measures. The two factors implemented in the model were the condition
(BF or noBF) and the day (D1 or D5). The primary objective of this statistical analysis was to understand
if there was a significant effect of the day, suggesting a motor learning regardless of the use of the
device (Figure 19). We also observed the presence of a significant interaction effect, which indicates a
different learning effect when the training was performed with or without the device (Figure 20).
Estimated marginal averages

Figura 18: Typical case of a subject for whom a significant day effect is detected. Condition 1 is BF condition, condition 2 is noBF condition.
The outcome mean value on day 5 between condition noBF and BF is significantly lower than the mean value of the outcome on day 1
between the same conditions. Considering that the expected result from the analysis of the movement time is a decrease in the value of
the parameter, in this specific case there is a learning trend thanks to the practice.
Estimated marginal averages

Figure 19: Typical case of a subject for which a significant interaction effect is detected. Condition 1 is BF condition, nondition 2 is noBF
condition. The mean value of the outcome on day 1 and day 5 between the two conditions is more or less the same, so there is no general
learning of the task. However, the two curves have completely opposite trends, and we can therefore conclude that the practice with the
device, in this specific case, produces learning.

A group-based statistical analysis was not performed due to the heterogeneity of the subjects in terms
of age and level of impairment.
48
CHAPTER 3
RESULTS

3.1 Characterization of the participants

Table 1 shows clinical and demographic details as well as training parameters of the primary patients
recruited for the study.

ID Age Sex Dystonia Tested BAD Spoon depth Target

arm arm Muscle
S01_BiSo 10 F I Right 1 3 mm 9 mm 15 mm AD
S02_FeRo 10 F I Right 1 12 mm 18 mm 24 mm FCU
S03_VaAn 16 M I Right 1 3 mm 9 mm 15 mm AD
S04_FaMa 17 F I Right 1 3 mm 9 mm 15 mm FCU
S05_ToMa 19 M I Right 1 3 mm 9 mm 15 mm ECR
S06_MoAl 8 M I Right 1 6 mm 12 mm 18 mm FCU
S07_BeMa 8 M I Right 1 3 mm 9 mm 15 mm FCU
S08_CaLe 15 M I Right 1 3 mm 9 mm 15 mm LD
S09_DaVe 7 F I Right 3 6 mm 9 mm 12 mm LD
Table 1. Clinic and treatment parameters - Primary

Table 2 shows clinical and demographic details as well as training parameters of the secondary patients
recruited for the study.

ID Age Sex Dystonia Tested BAD Spoon depth Target

arm arm Muscle
S001BoLu 14 M II Right 2 12,5 15 mm 20 mm LD
mm
S002MoLu 10 M II Right 2 10 mm 15 mm 20 mm ECR
S004FoAl 8 M II Right 1 7,5 mm 12,5 mm 20 mm ECR
S005MaDa 16 F II Right 3 20 mm (no marble) BIC
S009LeMa 13 M II Left 3 7,5 mm 12,5 mm 20 mm LD
S011ZoDe 8 F II Right 1 20 mm (no marble) AD
Table 2. Clinic and treatment parameters - Secondary

49
Table 3 shows clinical and demographic details as well as training parameters of the age-matched
healthy subjects recruited for the study.

ID Age Sex Tested Spoon depth Target

arm Muscle
C10_DeMa 11 M Left 3 mm 9 mm 15 mm AD
C11_DeLu 8 F Left 3 mm 9 mm 15 mm AD
C12_FaLu 12 M Right 3 mm 6 mm 9 mm LD
C13_FaCa 6 F Right 3 mm 6 mm 9 mm LD
C14_BaCa 9 F Right 3 mm 6 mm 9 mm LD
C15_LaAn 11 F Left 3 mm 6 mm 9 mm AD
C16_LaEl 7 F Right 3 mm 6 mm 9 mm LD
C17_LaGi 17 M Left 3 mm 6 mm 9 mm AD
C18_LaMa 15 F Right 3 mm 6 mm 9 mm LD
C21_GeTo 10 M Right 3 mm 6 mm 9 mm AD
C22_AnAn 19 M Right 3 mm 6 mm 9 mm AD
C23_GeLu 8 F Right 3mm 6 mm 9 mm LD
Table 3. Clinic and treatment parameters - Healthy

Clearly, less deep spoons were used for the healthy subjects to test their learning abilities. It can be
seen how the most difficult spoon chosen for the primary dystonic corresponds, in most cases, to the
one adopted by the control subjects. The BAD values highlight the fact that the severity of dystonia for
the primary subjects is higher than that of the secondary subjects. This explains why the participants
affected by secondary dystonia were tested on deeper spoons.

50
3.2 Results
This section reports the results obtained through an analysis carried out on each subject.
This analysis is made exclusively on the most challenging condition for the subjects, that is on the
deepest spoon. Obviously the only exception is the Index of Performance, which is by definition a
parameter that takes into consideration all the tested spoons.

For each parameter the absolute values of the outcomes calculated on the first testing day of both weeks
are reported in a bar chart. Then, both healthies and patients outcomes are normalized with respect to
day 1 of both weeks, in order to derive the overall behavior trend of all the healthy subjects and the
behavior trend of each patient.
Considering healthy subjects, the normalization is made considering the average value over all the
repetitions of the outcome for each subject:

• for day 1, we divide the average value of the outcome by itself, for each subject (i), in order to compute
the mean and the standard deviation over all the subjects (which are respectively always equal to one
and always null).

𝐷1𝑚𝑒𝑎𝑛𝑣𝑎𝑙𝑢𝑒𝑖 𝐷1𝑚𝑒𝑎𝑛𝑣𝑎𝑙𝑢𝑒𝑖 𝐷1𝑚𝑒𝑎𝑛𝑣𝑎𝑙𝑢𝑒𝑖

→ 𝑚𝑒𝑎𝑛 ( ) , 𝑠𝑑 ( )
𝐷1𝑚𝑒𝑎𝑛𝑣𝑎𝑙𝑢𝑒𝑖 𝐷1𝑚𝑒𝑎𝑛𝑣𝑎𝑙𝑢𝑒𝑖 𝐷1𝑚𝑒𝑎𝑛𝑣𝑎𝑙𝑢𝑒𝑖

• for day 5, for each subject (i), the ratio between the second testing day (day 5) average value of the
outcome and the first day average value of the outcome is computed, so as to make the mean and the
standard deviation over all subjects.

𝐷5𝑚𝑒𝑎𝑛𝑣𝑎𝑙𝑢𝑒𝑖 𝐷5𝑚𝑒𝑎𝑛𝑣𝑎𝑙𝑢𝑒𝑖 𝐷5𝑚𝑒𝑎𝑛𝑣𝑎𝑙𝑢𝑒𝑖

→ 𝑚𝑒𝑎𝑛 ( ) , 𝑠𝑑 ( )
𝐷1𝑚𝑒𝑎𝑛𝑣𝑎𝑙𝑢𝑒𝑖 𝐷1𝑚𝑒𝑎𝑛𝑣𝑎𝑙𝑢𝑒𝑖 𝐷1𝑚𝑒𝑎𝑛𝑣𝑎𝑙𝑢𝑒𝑖

Considering patients, the normalization with respect to the first day of acquisitions is made considering
all the repetitions:

• for day 1, the outcome mean value over all the repetitions (j) outcome values is calculated, then the
outcome value of each repetition is divided for the calculated average, so as to compute the mean
(which is always equal to one) and the standard deviation.

𝐷1𝑣𝑎𝑙𝑢𝑒𝑗 𝐷1𝑣𝑎𝑙𝑢𝑒𝑖 𝐷1𝑣𝑎𝑙𝑢𝑒𝑖

𝑛𝑅𝐸𝑃 → 𝑚𝑒𝑎𝑛 ( 𝑛𝑅𝐸𝑃 ) , 𝑠𝑑 ( 𝑛𝑅𝐸𝑃 )
(∑𝑗 𝐷1𝑣𝑎𝑙𝑢𝑒𝑗 ) (∑𝑗 𝐷1𝑣𝑎𝑙𝑢𝑒𝑗 ) (∑𝑗 𝐷1𝑣𝑎𝑙𝑢𝑒𝑗 )
𝑛𝑅𝐸𝑃 𝑛𝑅𝐸𝑃 𝑛𝑅𝐸𝑃

• for day 5, the outcome value of each repetition (j) is divided by the average of the outcome values of
day 1, and the mean and the standard deviation are calculated.

𝐷5𝑣𝑎𝑙𝑢𝑒𝑖 𝐷5𝑣𝑎𝑙𝑢𝑒𝑖 𝐷5𝑣𝑎𝑙𝑢𝑒𝑖

𝑛𝑅𝐸𝑃 → 𝑚𝑒𝑎𝑛 ( 𝑛𝑅𝐸𝑃 ) , 𝑠𝑑 ( 𝑛𝑅𝐸𝑃 )
(∑𝑗 𝐷1𝑣𝑎𝑙𝑢𝑒𝑗 ) (∑𝑗 𝐷1𝑣𝑎𝑙𝑢𝑒𝑗 ) (∑𝑗 𝐷1𝑣𝑎𝑙𝑢𝑒𝑗 )
𝑛𝑅𝐸𝑃 𝑛𝑅𝐸𝑃 𝑛𝑅𝐸𝑃

The normalization procedure permits a graphical representation that allows to have an idea of the
improvement (or of the worsening) the patient undergoes with the practice using and not using the
device, and at the same time to evaluate if his behavior is diverged (or not) from that of the healthy
population.

51
Hence, for each parameter of interest, three figures are plotted. The first figure contains the trends of all
the healthy subjects, superimposed in the same graph. The other figures are dedicated to the patients:
each figure is made of panels, 9 for the first, because 9 are the primary patients recruited for the study,
6 for the second, as 6 are the secondaries included in the experiment.
Each panel shows the trend of the parameter of interest of the corresponding subject, on the left between
day 1 and day 5 of the week of noBF, on the right between day 1 and day 5 of the week of BF,
superimposed on the area containing the variability of the healthy subjects.

Visually, the trend of the outcome for patients is represented by a broken, dashed line, if related to the
first week of acquisitions, with a continuous line if related to the second week. It is in black for the primary
dystonic, in red for the secondary dystonic. The area representing the variability of healthy subjects is
in light blue color.
To take into account, also graphically, the statistical analysis, the panels relating to those patients that
record a statistically significant day effect (pValue<0.05) have a larger board thickness, the panels
relating to those patients that detect a statistically significant condition-day interaction effect
(pValue<0.05) have a gray background: these are the subjects that most give us an indication about the
effectiveness of the BF device.

52
3.2.1 Movement Time
As already mentioned in chapter 3, movement time and execution speed provide the same type of
information on the subjects learning abilities, therefore only the graphs relating to MT are reported.
Figure 20 shows the mean value of the parameter calculated during the 1st day of acquisitions,
considering both the noBF and the BF weeks, for each healthy subject.

Figure 20: Movement Time. On the left, in a lighter blue, mean and standard deviation values are reported for the noBF, on the right, in a
darker blue, mean and standard deviation values are drawn for the BF week

Figure 21 shows the mean and the standard deviation values of the parameter calculated during the
first testing day, considering both the noBF and the BF weeks, for each primary subject.

Figure 21: Movement Time. On the left, in a lighter black, mean and standard deviation values are reported for the noBF, on the right, in
a darker black, mean and standard deviation values are drawn for the BF week
53
Figure 22 shows the mean and the standard deviation values of the parameter calculated during the
first testing day, considering both the noBF and theBF weeks, for each secondary subject.

Figure 22: Movement Time. On the left, in a lighter red, mean and standard deviation values are reported for the noBF week, on the
right, in a darker red, mean and standard deviation values are drawn for the BF week.

Figure 23 shows the overall behavior of the healthy subjects group. All the data are normalized with
respect to Day1 of each week, so at to visualize weather the subject has improved or worsened.

Figure 23: Movement Time. On the left, normalized values are reported for the noBF week, on the right, normalized values are drawn for
the BF week. Each color is assigned to a single subject. Each color is assigned to a subject, the dotted line indicates that the week was the
first week of acquisitions, the solid line indicates that it was the second week.

54
Ideally, we expect a decrease in the parameter, since with the practice associated with the use of the
device the subject should be able to spend less time performing the task.
The interaction effect was significant for 8 of the 12 healthy subjects: in 5 subjects (C11_DeLu,
C13_FaCa, C16_LaEl, C18_LaMa and C21_GeTo) the interaction effect was in favour of the BF; in the
other 3 subjects, (C15_LaAn, C17_LaGi and C22_AnAn) this effect was instead against the use of the
BF.
5 subjects showed a significant day effect: for 2 of them (C14_BaCa and C15_LaAn) it translates into
improved performance in both weeks.

Considering now patients, Figure 24 shows the results relative to primary subjects.

Figure 24: Movement Time. The figure consists of 9 panels, because 9 are the primary subjects. Each panel shows, on the left, the trend of
improvement/worsening during the noBF week, on the right, the trend relative to the BF week. Both trends are superimposed on the
general behavior of healthy subjects, also divided between noBF week, on the left, and BF week, on right. Subjects showing a significant
interaction effect are indicated by the gray background color of the panel. Subjects showing a significant day effect are indicated by the
thicker edge of the panel. The dotted line indicates the first week of training, the solid line indicates the second week of training.

The interaction effect was significant for 4 of the 9 primary dystonic participants: for 2 subjects
(S02_FeRo and S07_BeMa), the interaction effect was in favour of the BF; for the other 2 subjects
(S03_VaAn and S08_BeMa), this effect was instead against the use of the BF.
5 subjects showed a significant day effect: for 4 of these (S01_BiSo, S02_FeRo, S06_MoAl and
S08_CaLe) the practice induced a learning of the trained task, but this was not influenced by the use of
the device.

55
Figure 25 shows the results relative to secondary subjects.

Figure 25: Movement Time. The figure consists of 6 panels, because 6 are the secondary subjects. Each panel shows, on the left, the trend
of improvement/worsening during the noBF week, on the right, the trend relative to the BF week. Both trends are superimposed on the
general behavior of healthy subjects, also divided between noBF week, on the left, and BF week, on right. Subjects showing a significant
interaction effect are indicated by the gray background color of the panel. Subjects showing a significant day effect are indicated by the
thicker edge of the panel. The dotted line indicates the first week of training, the solid line indicates the second week of training.

The interaction effect was significant only for 1 of the 6 secondary dystonic participants, i.e. S002_MoLu,
for whom it was in favour of the BF.
The remaining 5 subjects did not show a significant interaction effect; S004_FoAl instead showed a
significant day effect, and improved the performance in approximately the same way in the two weeks
of exercise.

56
Finally, in Figure 26 the percentage of how many subjects, considering the 3 analyzed populations,
show a significant improvement with practice and an significant interaction effect in favor of the BF
device are reported.

Figure 26: Movement Time. From left to right, the trend of the healthy (in blue), the primary (in black), the secondary (in red) is shown. For
each group, the bar on the left shows the percentage of subjects who have learning, the bar on the right shows the percentage of subjects
that show a significant interaction for the benefit of the BF condition.

17% of healthy subjects show learning with practice, and 42% of healthy subjects shows better
improvement when the BF device was used.

44% of the primary dystonic show learning with practice, while 22% of the primary subjects shows better
improvement when the BF device was used.

17% of the secondary subjects show learning with practice, while 17% of secondary participants shows
better improvement when the BF device was used.

57
3.2.2 Index of Performance

Figure 27 shows the mean value of the parameter calculated during the first day of training, considering
both the noBF and the BF weeks, for each healthy subject.

Figure 27: IP. On the left, in a lighter blue, mean values are reported for the noBF, on the right, in a darker blue, mean values are drawn
for the BF week

Figure 28 shows the mean value of the parameter calculated during the first day of training, considering
both the noBF and the BF weeks, for each primary subject.

Figure 28: IP. On the left, in a lighter black, mean values are reported for the noBF, on the right, in a darker black, mean values are drawn
for the BF week. S9 (S09_DaVe) has a negative value of IP on day 1 of BF week because the slope of the MT-ID curve is negative. This means
the subject has been able to perform the task faster with the harder spoon than he did with the other spoons.

58
Figure 29 shows the mean value of the parameter calculated during the first day of training,
considering both the noBF and the BF weeks, for each secondary subject.

Figure 29: IP. On the left, in a lighter black, mean values are reported for the noBF, on the right, in a darker black, mean values are drawn
for the BF week. S4 (S005MaDa) and S6 (S011ZoDe) have not reported the relative graphs as they used only one spoon.

In this case, we do not have an outcome value for each repetition, but an overall value that includes all
the repetitions of each spoon. Therefore, no statistical analysis was performed.
Figure 30 shows the overall behavior of healthy subjects. All the data are normalized with respect Day1
of each week, so at to visualize weather the subject has improved or worsened.

Figura 30: IP. On the left, normalized values are reported for the noBF week, on the right, normalized values are drawn for the BF week.
Each color is assigned to a subject, the dotted line indicates that the week was the first week of acquisitions, the solid line indicates that it
was the second week

59
The subjects that improved their performance only / to a greater extent during the week of use of the
device are 7 out of 12: C11_DeLu, C12_FaLu, C13_FaCa, C14_BaCa, C16_LaEl, C18_LaMa,
C21_GeTo and C23_GeLu. C10_DeMa, C15_LaAn, C17_LaGi, C22_AnAn, on the other hand,
improved only / to a greater extent in the week of non-use of the BF treatment.

Considering now patients, Figure 31 shows the results relative to primary subjects.

Figure 31: IP. The figure consists of 9 panels, because 9 are the primary subjects. Each panel shows, on the left, the trend of
improvement/worsening during the noBF week, on the right, the trend relative to the BF week. Both trends are superimposed on the
general behavior of healthy subjects, also divided between noBF week, on the left, and BF week, on right. The dotted line indicates the first
week of training, the solid line indicates the second week of training.

The subjects that showed an improvement in performance only / to a greater extent during the week of
use of the device are S02_FeRo, S04_FaMa, S06_MoAl and S07_BeMa. The subjects that instead
improved only / to a greater extent during the week of non-use of the device are S01_BiSo, S03_VaAn,
S05_ToMa, S08_CaLe and S09_DaVe.
The IP trend is comparable to the MT trend: where there is a trend of improvement in the movement
time during the execution of the task with the deeper spoon, there is also an increase in the IP, and vice
versa.

60
Figure 32 shows the results relative to secondary subjects. Trends for S005MaDa and S011ZoDe are
missing because they used only one spoon.

Figure 32: IP. The figure consists of 4 panels, because 4 are the secondary subjects a complete analysis is performed on. Each panel shows,
on the left, the trend of improvement/worsening during the noBF week, on the right, the trend relative to the BF week. Both trends are
superimposed on the general behavior of healthy subjects, also divided between noBF week, on the left, and BF week, on right. The dotted
line indicates the first week of training, the solid line indicates the second week of training.

The subjects that showed a performance improvement trend only / to a greater extent during the week
of use of the device are S002MoLu, S004FoAl and S009LeMa, while there were no subjects that
improved only during the week of non-use of the device. Even if no statistical analysis has been done,
this is indicative of the fact that the device may have helped patients to better face the task with
increasing difficulty. S001BoLu worsens in both weeks.

61
3.2.3 Peaks

Figure 33 shows the mean value of the parameter calculated during the first day of training, considering
both the noBF and the BF weeks, for each healthy subject.

Figure 33: PEAKS. On the left, in a lighter blue, mean values are reported for the noBF, on the right, in a darker blue, mean values are
drawn for the BF week

Figure 34 shows the mean value of the parameter calculated during the first day of training, considering
both the noBF and the BF weeks, for each primary subject.

Figura 34: PEAKS. On the left, in a lighter black, mean values are reported for the noBF, on the right, in a darker black, mean values are
drawn for the BF week

62
Figure 35 shows the mean value of the parameter calculated during the first day of training, considering
both the noBF and the BF weeks, for each secondary subject.

Figura 35: PEAKS. On the left, in a lighter red, mean values are reported for the noBF, on the right, in a darker red, mean values are
drawn for the BF week

Figure 36 shows the overall behavior of healthy subjects. All the data are normalized with respect Day1
of each week, so at to visualize weather the subject has improved or worsened.

Figure 36: PEAKS. On the left, normalized values are reported for the noBF week, on the right, normalized values are drawn for the BF
week. Each color is assigned to a single subject. Each color is assigned to a subject, the dotted line indicates that the week was the first
week of acquisitions, the solid line indicates that it was the second week

63
The interaction effect is significant for 5 of the 12 healthy subjects tested: for 3 subjects (C13_FaCa,
C18_LaMa and C21_GeTo) the interaction effect was in favour of the BF; in the other 2 subjects
(C17_LaGi and C22_AnAn), this effect was against the BF.
For 3 subjects (C11_GeLu, C14_BaCa and C21_GeTo) the practice induced a learning of the trained
task, but this was not influenced by the use of the device.

Considering now patients, Figure 37 shows the results relative to primary subjects.

Figure 37: PEAKS. The figure consists of 9 panels, because 9 are the primary subjects. Each panel shows, on the left, the trend of
improvement/worsening during the noBF week, on the right, the trend relative to the BF week. Both trends are superimposed on the
general behavior of healthy subjects, also divided between noBF week, on the left, and BF week, on right. Subjects showing a significant
interaction effect are indicated by the gray background color of the panel. Subjects showing a significant day effect are indicated by the
thicker edge of the panel. The dotted line indicates the first week of training, the solid line indicates the second week of training.

The interaction effect was significant for 3 of the 9 primary dystonic subjects: for 2 subjects (S02_FeRo
and S06_MoAl), the interaction effect was in favour of the BF; for S08_CaLe, however, this effect was
against the BF.
6 subjects showed a significant day effect; in 3 of these (S01_BiSo, S04_FaMa, S06_MoAl), the practice
induced a learning of the trained task, but this was not influenced by the use of the device.

64
Figure 38 shows the results relative to secondary subjects.

Figure 38: PEAKS. The figure consists of 6 panels, because 6 are the secondary subjects. Each panel shows, on the left, the trend of
improvement/worsening during the noBF week, on the right, the trend relative to the BF week. Both trends are superimposed on the
general behavior of healthy subjects, also divided between noBF week, on the left, and BF week, on right. Subjects showing a significant
interaction effect are indicated by the gray background color of the panel. Subjects showing a significant day effect are indicated by the
thicker edge of the panel. The dotted line indicates the first week of training, the solid line indicates the second week of training.

The interaction effect was significant for 2 of the 6 dystonic secondary participants: for S002MoLu the
interaction effect was in favour of the BF, for S005MaDa it was abainst both conditions, even if it is to
note how the better performance in the week of use of the device compared to the noBF condition.
2 subjects showed a significant day effect: for S004FoAl the practice induced a learning of the trained
task, but this was not influenced by the use of the device.

65
Finally, in Figure 39 the percentage of how many subjects, considering the 3 analyzed populations,
shaw learning skills with practice and an interaction effect to the advantage of the device are reported.

Figure 39: PEAKS. From left to right, the trend of the healthy (in blue), the primary (in black), the secondary (in red) is shown. For each
group, the bar on the left shows the percentage of subjects who have learning, the bar on the right shows the percentage of subjects that
show a significant interaction for the benefit of the BF condition.

25% of the healthy subjects show learning with practice, and 25% of healthy subjects shows better
improvement when the BF device was used.

33% of the primariy patients show learning with practice, while 22% of the primary subjects shows better
improvement when the BF device was used.

17% of the secondary subjects show learning with practice, while 17% of the secondary group shows
better improvement when the BF device was used.

66
3.2.4 Smoothness
The NSJerk analysis confirms the one made on speed peaks and smoothness, therefore only the results
relating to smoothness are reported.
Figure 40 shows the mean value of the parameter calculated during the first day of training, considering
both the noBF and the BF weeks, for each healthy subject.

Figure 40: SMOOTHNESS. On the left, in a lighter blue, mean and standard deviation values are reported for the noBF week, on the right,
in a darker blue, mean and standard deviation values are drawn for the BF week

Figure 41 shows the mean value of the parameter calculated during the first day of training, considering
both the noBF and the BF weeks, for each primary subject.

Figure 41: SMOOTHNESS. On the left, in a lighter black, mean and standard deviation values are reported for the noBF week, on the
right, in a darker black, mean and standard deviation values are drawn for the BF week.

67
Figure 42 shows the mean value of the parameter calculated during the first day of training, considering
both the noBF and the BF weeks, for each secondary subject.

Figure 42: SMOOTHNESS. On the left, in a lighter red, mean and standard deviation values are reported for the noBF week, on the right,
in a darker red, mean and standard deviation values are drawn for the BF week.

Figure 43 shows the overall behavior of healthy subjects. All the data are normalized with respect Day1
of each week, so at to visualize weather the subject has improved or worsened.

Figure 43: SMOOTHNESS. On the left, normalized values are reported for the noBF week, on the right, normalized values are drawn for the
BF week. Each color is assigned to a single subject, the dotted line indicates that the week was the first week of acquisitions, the solid line
indicates that it was the second week.

Ideally, we expect an increase in the parameter, since with the practice associated with the use of the
device the subject should be able to be more fluid.

68
The interaction effect was significant only for 1 of the 12 healthy subjects, i.e. C16_LaEl, and it was in
favour of the BF.

Considering now patients, Figure 44 shows the results relative to primary subjects.

Figure 44: SMOOTHNESS. The figure consists of 9 panels, because 9 are the primary subjects. Each panel shows, on the left, the trend of
improvement/worsening during the noBF week, on the right, the trend relative to the BF week. Both trends are superimposed on the
general behavior of healthy subjects, also divided between noBF week, on the left, and BF week, on right. Subjects showing a significant
interaction effect are indicated by the gray background color of the panel. Subjects showing a significant day effect are indicated by the
thicker edge of the panel. The dotted line indicates the first week of training, the solid line indicates the second week of training.

The interaction effect was significant only for 2 of the 9 primary dystonic subjects: for S05_ToMa it was
in favour of the BF, for S06_MoAl this effect was instead against the BF condition.
2 subjects showed a significant day effect, which translates into a learning trend in both weeks of use
of the device for S08_CaLe.

69
Figure 45 shows the results relative to secondary subjects.

Figure 45: SMOOTHNESS. The figure consists of 6 panels, because 6 are the secondary subjects. Each panel shows, on the left, the trend of
improvement/worsening during the noBF week, on the right, the trend relative to the BF week. Both trends are superimposed on the
general behavior of healthy subjects, also divided between noBF week, on the left, and BF week, on right. Subjects showing a significant
interaction effect are indicated by the gray background color of the panel. Subjects showing a significant day effect are indicated by the
thicker edge of the panel. The dotted line indicates the first week of training, the solid line indicates the second week of training.

The interaction effect was significant only for 1 of the 6 dystonic secondary subjects, that is S002MoLu,
for which this effect was in favour of the BF.

70
Finally, in Figure 46 the percentage of how many subjects, considering the 3 analyzed populations,
shaw learning skills with practice and an interaction effect to the advantage of the device are reported.

Figure 46: SMOOTHNESS. From left to right, the trend of the healthy (in blue), the primary (in black), the secondary (in red) is shown. For
each group, the bar on the left shows the percentage of subjects who have learning, the bar on the right shows the percentage of subjects
that show a significant interaction for the benefit of the BF condition.

None of healthy subjects show learning with practice, while 8% of the healthy subjects shows better
improvement when the BF device was used.

11% of the primary subjects show learning with practice, and 11% of the primary subjects shows better
improvement when the BF device was used.

None of the secondary participants show learning with practice, while 17% of the secondary subjects
shows better improvement when the BF device was used.

71
3.2.5 Movement Linearity
Figure 47 shows the mean value of the parameter calculated during the first day of training, considering
both the noBF and the BF weeks, for each healthy subject.

Figure 47: Movement Linearity. On the left, in a lighter blue, mean and standard deviation values are reported for the noBF week, on the
right, in a darker blue, mean and standard deviation values are drawn for the BF week

Figure 48 shows the mean value of the parameter calculated during the first day of training, considering
both the noBF and the BF weeks, for each primary subject.

Figure 48: Movement Linearity. On the left, in a lighter black, mean and standard deviation values are reported for the noBF week, on
the right, in a darker black, mean and standard deviation values are drawn for the BF week

72
Figure 49 shows the mean value of the parameter calculated during the first day of training, considering
both the noBF and the BF weeks, for each secondary subject.

Figure 49: Movement Linearity. On the left, in a lighter red, mean and standard deviation values are reported for the noBF week, on the
right, in a darker red, mean and standard deviation values are drawn for the BF week

Figure 50 shows the overall behavior of healthy subjects. All the data are normalized with respect Day1
of each week, so at to visualize weather the subject has improved or worsened.

Figure 50: Movement Linearity. On the left, normalized values are reported for the noBF week, on the right, normalized values are drawn
for the BF week. Each color is assigned to a single subject, the dotted line indicates that the week was the first week of acquisitions, the
solid line indicates that it was the second week

73
Ideally, we expect a decrease in the parameter, since with the practice associated with the use of the
device the subject should be able to be more accurate in the production of a trajectory not too far from
the wooden block.
The interaction effect was significant for 4 of the 12 healthy subjects: in 2 subjects (C11_DeLu and
C18_LaMa) it was in favour of the BF; in the other 2 subjects (C17_LaGi and C21_GeTo) this effect was
against the BF.
5 subjects show a significant day effect; in 2 subjects (C14_BaCa and C18_LaMa) the practice induced
a learning of the trained task, but this was not influenced by the use of the device.

Considering now patients, Figure 51 shows the results relative to primary subjects.

Figure 51: Movement Linearity. The figure consists of 9 panels, because 9 are the primary subjects. Each panel shows, on the left, the trend
of improvement/worsening during the noBF week, on the right, the trend relative to the BF week. Both trends are superimposed on the
general behavior of healthy subjects, also divided between noBF week, on the left, and BF week, on right. Subjects showing a significant
interaction effect are indicated by the gray background color of the panel. Subjects showing a significant day effect are indicated by the
thicker edge of the panel. The dotted line indicates the first week of training, the solid line indicates the second week of training.

The interaction effect was significant for 4 of the 9 primary dystonic participants: in 1 subject
(S07_BeMa) it was in favour of the BF; in 2 subjects (S05_ToMa and S06_MoAl) this effect was instead
against the BF; in the last subject (S03_VaAn) it was against both conditions.
8 subjects had a significant day effect: 3 of them (S02_FeRo, S04_FaMa, S08_CaLe) revealed a
learning trend due to training in both weeks.

74
Figure 52 shows the results relative to secondary subjects:

Figure 52: Movement Linearity. The figure consists of 6 panels, because 6 are the secondary subjects. Each panel shows, on the left, the
trend of improvement/worsening during the noBF week, on the right, the trend relative to the BF week. Both trends are superimposed on
the general behavior of healthy subjects, also divided between noBF week, on the left, and BF week, on right. Subjects showing a significant
interaction effect are indicated by the gray background color of the panel. Subjects showing a significant day effect are indicated by the
thicker edge of the panel. The dotted line indicates the first week of training, the solid line indicates the second week of training.

The interaction effect was significant only for 1 of the 6 dystonic secondary subjects, that is S001BoLu,
for which it was in favour of the BF. This subject also showed a significant day effect: this means the
practice induced a learning of the trained task, but this was not influenced by the use of the device.
Hence, the BF device accelerated the learning.

75
Finally, in Figure 53 the percentage of how many subjects, considering the 3 analyzed populations,
shaw learning skills with practice and an interaction effect to the advantage of the device are reported.

Figure 53: Movement Linearity. From left to right, the trend of the healthy (in blue), the primary (in black), the secondary (in red) is shown.
For each group, the bar on the left shows the percentage of subjects who have learning, the bar on the right shows the percentage of
subjects that show a significant interaction for the benefit of the BF condition.

17% of healthy subjects show learning with practice, and 17% of healthy subjects shows better
improvement when the BF device was used.

33% of the primary dystonic show learning with practice, and 11% of the primary subjects shows better
improvement when the BF device was used.

17 % of the secondary subjects show learning with practice, and 17% of the secondary subjects shows
better improvement when the BF device was used.

76
3.2.6 Movement repeatability
Figure 54 shows the mean value of the parameter calculated during the first day of training, considering
both the noBF and the BF weeks, for each healthy subject.

Figure 54: Movement Repeatability. On the left, in a lighter blue, mean values are reported for the noBF, on the right, in a darker blue,
mean values are drawn for the BF week

Figure 55 the mean value of the parameter calculated during the first day of training, considering both
the noBF and the BF weeks, for each primary subject.

Figure 55: Movement Repeatability. On the left, in a lighter black, mean values are reported for the noBF, on the right, in a darker black,
mean values are drawn for the BF week

77
Figure 56 shows the mean value of the parameter calculated during the first day of training,
considering both the noBF and the BF weeks, for each secondary subject.

Figure 56: Movement Repeatability. On the left, in a lighter black, mean values are reported for the noBF, on the right, in a darker black,
mean values are drawn for the BF week

In this case, we do not have an outcome value for each repetition, but an overall value that includes all
the repetitions of each spoon. Therefore, no statistical analysis was performed.
Figure 57 shows the overall behavior of healthy subjects. All the data are normalized with respect Day1
of each week, so at to visualize weather the subject has improved or worsened.

Figure 57: Movement Repeatability. On the left, normalized values are reported for the noBF week, on the right, normalized values are
drawn for the BF week. Each color is assigned to a subject, the dotted line indicates that the week was the first week of acquisitions, the
solid line indicates that it was the second week.

78
The subjects that improved their performance only / to a greater extent during the week of use of the
device are 4 out of 11: C13_FaCa, C14_BaCa, C18_LaMa, C21_GeTo. C11_DeLu, C12_FaLu,
C16_LaEl, C22_AnAn, instead, improved only / to a greater extent in the week of non-use of the BF
treatment. C10_DeMa, C15_LaAn, C17_LaGi and C23_GeLu got worse in both weeks.

Considering now patients, Figure 58 shows the results relative to primary subjects.

Figure 58: Movement Repeatability. The figure consists of 9 panels, because 9 are the primary subjects. Each panel shows, on the left, the
trend of improvement/worsening during the noBF week, on the right, the trend relative to the BF week. Both trends are superimposed on
the general behavior of healthy subjects, also divided between noBF week, on the left, and BF week, on right. The dotted line indicates the
first week of training, the solid line indicates the second week of training.

Subjects that showed a tendency to improve performance only / to a greater extent during the BF week
are S04_FaMa, S05_ToMa, S06_MoAl. The subjects that improved only / to a greater extent during the
week of non-use of the device are S01_BiSo, S02_FeRo, S03_VaAn, S07_BeMa, S08_CaLe.
S09_DaVe worsened in both weeks.

79
Figure 59 shows the results relative to secondary subjects.

Figure 59: Movement Repeatability. The figure consists of 6 panels, because 6 are the secondary subjects. Each panel shows, on the left,
the trend of improvement/worsening during the noBF week, on the right, the trend relative to the BF week. Both trends are superimposed
on the general behavior of healthy subjects, also divided between noBF week, on the left, and BF week, on right. The dotted line indicates
the first week of training, the solid line indicates the second week of training.

The subjects that showed an improved performance trend only / to a greater extent during the week of
device use are S004FoAl and S005MaDa. The subjects that instead improved only / to a greater extent
during the week of non-use of the device are S001BoLu and S009LeMa. S002MoLu and S011ZoDe got
worse in both weeks.

80
3.2.7 Elbow Range of Motion
Generally, the angular positions of the elbow joint at the beginning and at the end of the movement
coincide with the minimum and maximum angular positions. If there are differences, they do not produce
inconsistencies in the results of the two parameters (Figure 60). Therefore, the results reported in this
section are related to the ROM, and not to the maximum ROM.

Figure 60: ROM. On the top the trend of the angle of the elbow is shown. On the bottom, on the left side, it is shown how the minimum
and maximum coincide with the beginning and end of the forward movement. On the bottom, on the left side, it is shown how the minimum
does not coincide with the start of the movement, but the difference in terms of angle with the beginning of the movement is paltry.

Figure 61 shows the mean value of the parameter calculated during the first day of training, considering
both the noBF and the BF weeks, for each healthy subject.

Figure 61: ROM. On the left, in a lighter blue, mean and standard deviation values are reported for the noBF week, on the right, in a
darker blue, mean and standard deviation values are drawn for the BF week

81
Figure 62 shows the mean value of the parameter calculated during the first day of training, considering
both the noBF and the BF weeks, for each primary subject.

Figure 62: ROM. On the left, in a lighter black, mean and standard deviation values are reported for the noBF week, on the right, in a
darker black, mean and standard deviation values are drawn for the BF week

Figure 63 shows the mean value of the parameter calculated during the first day of training, considering
both the noBF and the BF weeks, for each secondary subject.

Figure 63: ROM. On the left, in a lighter red, mean and standard deviation values are reported for the noBF week, on the right, in a
darker red, mean and standard deviation values are drawn for the BF week

82
Figure 64 shows the overall behavior of healthy subjects. All the data are normalized with respect Day1
of each week, so at to visualize weather the subject has improved or worsened.

Figure 64: ROM. On the left, normalized values are reported for the noBF week, on the right, normalized values are drawn for the BF week.
Each color is assigned to a single subject, the dotted line indicates that the week was the first week of acquisitions, the solid line indicates
that it was the second week

Ideally, we expect an increase in the parameter, since with the practice associated with the use of the
device the subject should be able to better extend the elbow joint.
The interaction effect was significant for 5 of the 12 healthy subjects: in 4 subjects (C10_DeMa,
C12_FaLu, C14_BaCa and C23_GeLu) it was in favour of the BF; in C22_AnAn this effect was instead
against the BF.
8 subjects showed a significant day effect: for 4 of these (C13_FaCa, C15_LaAn, C18_LaMa and
C22_AnAn) the practice induced a learning of the task, but this was not influenced by the use of the
device.

83
Considering now patients, Figure 65 shows the results relative to primary subjects.

Figure 65: ROM. The figure consists of 9 panels, because 9 are the primary subjects. Each panel shows, on the left, the trend of
improvement/worsening during the noBF week, on the right, the trend relative to the BF week. Both trends are superimposed on the
general behavior of healthy subjects, also divided between noBF week, on the left, and BF week, on right. Subjects showing a significant
interaction effect are indicated by the gray background color of the panel. Subjects showing a significant day effect are indicated by the
thicker edge of the panel. The dotted line indicates the first week of training, the solid line indicates the second week of training.

The interaction effect was significant for 5 of the 9 primary dystonic pasrticipants: in 3 subjects
(S06_MoAl, S07_BeMa and S08_CaLe) it was in favour of the BF; in the other 2 subjects (S01_BiSo
and S05_ToMa) this effect was instead against the BF.
4 subjects had a significant day effect, but for none of them the practice induced a learning of the trained
task.

84
Figure 66 shows the results relative to secondary subjects. Trend of S001BoLu is missing: it is not
possible to perform a complete analysis as we do not have the kinematic data concerning the spatial
coordinates of the shoulder of the second testing day of the second week, which corresponds to the
week of non-use of the BF.

Figure 66: ROM. The figure consists of 5 panels, because 5 are the secondary subjects a complete analysis is done on. Each panel shows,
on the left, the trend of improvement/worsening during the noBF week, on the right, the trend relative to the BF week. Both trends are
superimposed on the general behavior of healthy subjects, also divided between noBF week, on the left, and BF week, on right. Subjects
showing a significant interaction effect are indicated by the gray background color of the panel. Subjects showing a significant day effect
are indicated by the thicker edge of the panel. The dotted line indicates the first week of training, the solid line indicates the second week
of training.

The interaction effect was significant for 2 of the 6 dystonic secondary pasrticipants tested: for
S002MoLu it was in favour of the BF, for S009LeMa this effect was against both conditions.
3 subjects showed a significant day effect: for 2 of these (S002MoLu and S005MaDa) the practice
induced a learning of the trained task, but this was not influenced by the use of the device.

85
Finally, in Figure 67 the percentage of how many subjects, considering the 3 analyzed populations,
shaw learning skills with practice and an interaction effect to the advantage of the device are reported.

Figure 67: ROM. From left to right, the trend of the healthy (in blue), the primary (in black), the secondary (in red) is shown. For each group,
the bar on the left shows the percentage of subjects who have learning, the bar on the right shows the percentage of subjects that show
a significant interaction for the benefit of the BF condition.

33% of healthy subjects show learning with practice, and 33% of healthy subjects shows better
improvement when the BF device was used.

None of the primary patients show learning with practice, while 33% of the primary subjects better
improvement when the BF device was used.

40 % of the secondary subjects show learning with practice, while 20% of the secondary subjects shows
better improvement when the BF device was used.

86
3.2.8 Shoulder Translation
Generally, the positions of the shoulder joint at the beginning and at the end of the movement coincide
with the minimum and maximum angular positions. If there are differences, they do not produce
inconsistencies in the results of the two parameters (Figure 68). Therefore, the results reported in this
section are related to the ST, and not to the maximum ST.

Figure 68: Shoulder Translation. On the top the trend of the position of the shoulder is shown. On the bottom, both figures show how the
maximum does not coincide with the start of the movement, but the difference in terms of position with the beginning of the movement
is not significant

Figure 69 shows the mean value of the parameter calculated during the first day of training, considering
both the noBF and the BF weeks, for each healthy subject.

Figure 69: Shoulder Translation. On the left, in a lighter blue, mean and standard deviation values are reported for the noBF week, on the
right, in a darker blue, mean and standard deviation values are drawn for the BF week

87
Figure 70 shows the mean value of the parameter calculated during the first day of training, considering
both the noBF and the BF weeks, for each primary subject.

Figure 70: Shoulder Translation. On the left, in a lighter black, mean and standard deviation values are reported for the noBF week, on
the right, in a darker black, mean and standard deviation values are drawn for the BF week

Figure 71 shows the mean value of the parameter calculated during the first day of training, considering
both the noBF and the BF weeks, for each secondary subject.

Figure 71: Shoulder Translation. On the left, in a lighter red, mean and standard deviation values are reported for the noBF week, on the
right, in a darker red, mean and standard deviation values are drawn for the BF week

88
Figure 72 shows the overall behavior of healthy subjects. All the data are normalized with respect Day1
of each week, so at to visualize weather the subject has improved or worsened.

Figure 72: Shoulder Translation. On the left, normalized values are reported for the noBF week, on the right, normalized values are drawn
for the BF week. Each color is assigned to a single subject, the dotted line indicates that the week was the first week of acquisitions, the
solid line indicates that it was the second week

Ideally, we expect a decrease in the parameter, since with the practice associated with the use of the
device the subject should be able to better stabylize the shoulder joint.
The interaction effect was significant for 6 of the 12 healthy subjects: in 4 subjects (C12_FaLu, 13_FaCa,
C21_GeTo and C23_GeLu) it was in favour of the BF; in 1 subject (C17_LaGi) this effect was instead
against the BF; in C16_LaEl it was against both conditions.
9 subjects show a significant day effect: for 3 subjects (C13_FaCa, C18_LaMa and C22_AnAn) the
practice induced a learning of the trained task, but this was not influenced by the use of the device.

89
Considering now patients, Figure 73 shows the results relative to primary subjects.

Figure 73: Shoulder Translation. The figure consists of 9 panels, because 9 are the primary subjects. Each panel shows, on the left, the trend
of improvement/worsening during the noBF week, on the right, the trend relative to the BF week. Both trends are superimposed on the
general behavior of healthy subjects, also divided between noBF week, on the left, and BF week, on right. Subjects showing a significant
interaction effect are indicated by the gray background color of the panel. Subjects showing a significant day effect are indicated by the
thicker edge of the panel. The dotted line indicates the first week of training, the solid line indicates the second week of training.

The interaction effect was significant for 6 of the 9 primary dystonic subjects tested: in 3 subjects
(S07_BeMa, S08_CaLe and S09_DaVe) it was in favour of the BF; in the other 3 subjects (S01_BiSo
S02_FeRo and S06_MoAl) this effect was instead against the BF condition.
6 subjects showed a significant day effect: for S06_MoAl the practice induced a learning of the trained
task, but this was not influenced by the use of the device.

90
Figure 74 shows the results relative to secondary subjects. The panel for S001BoLu is missing: it is not
possible to perform a complete analysis, as we do not have the kinematic data concerning the spatial
coordinates of the shoulder of the testing day of the second week, which corresponds to the noBF week.

Figure 74: Shoulder Translation. The figure consists of 5 panels, because 5 are the secondary subjects a complete analysis is performed on.
Each panel shows, on the left, the trend of improvement/worsening during the noBF week, on the right, the trend relative to the BF week.
Both trends are superimposed on the general behavior of healthy subjects, also divided between noBF week, on the left, and BF week, on
right. Subjects showing a significant interaction effect are indicated by the gray background color of the panel. Subjects showing a
significant day effect are indicated by the thicker edge of the panel. The dotted line indicates the first week of training, the solid line
indicates the second week of training.

The interaction effect was significant for 3 of the 6 dystonic secondary subjects: for 2 subjects
(S002MoLu and S005MaDa) it it was in favour of the BF, for S009LeMa this effect was against both
conditions.
3 subjects had a significant day effect: only for S002MoLu the practice induced a learning of the trained
task, but this was not influenced by the use of the device.

91
Finally, in Figure 75 the percentage of how many subjects, considering the 3 analyzed populations,
shaw learning skills with practice and an interaction effect to the advantage of the device are reported.

Figura 75: Shoulder Translation. From left to right, the trend of the healthy (in blue), the primary (in black), the secondary (in red) subjects
is shown. For each group, the bar on the left shows the percentage of subjects who have learning, the bar on the right shows the percentage
of subjects that show a significant interaction for the benefit of the BF condition.

25% of healthy subjects show learning with practice, while 33% of healthy subjects shows better
improvement when the BF device was used.

11% of the primary patients show learning with practice, while 33% of the primary subjects shows better
improvement when the BF device was used.

20% of the secondary patients show learning with practice, while 40% of secondary subjects shows
better improvement when the BF device was used.

92
3.2.9 FCU/ECR co-contraction

Figure 76 shows the mean value of the parameter calculated during the first day of training,
considering both the noBF and the BF weeks, for each healthy subject.

Figure 76: FCU / ECR co-contraction. On the left, in a lighter blue, mean and standard deviation values are reported for the noBF week,
on the right, in a darker blue, mean and standard deviation values are drawn for the BF week

Figure 77 shows the mean value of the parameter calculated during the first day of training,
considering both the noBF and the BF weeks, for each primary subject.

Figure 77: FCU / ECR co-contraction. On the left, in a lighter black, mean and standard deviation values are reported for the noBF week,
on the right, in a darker black, mean and standard deviation values are drawn for the BF week

93
Figure 78 the mean value of the parameter calculated during the first day of training, considering both
the noBF and the BF weeks, for each secondary subject.

Figure 78: FCU / ECR co-contraction. On the left, in a lighter red, mean and standard deviation values are reported for the noBF week, on
the right, in a darker red, mean and standard deviation values are drawn for the BF week. For S6 (S011ZoDe) EMG data for the firs day of
BF condition are missing

Figure 79 shows the overall behavior of healthy subjects. All the data are normalized with respect Day1
of each week, so at to visualize weather the subject has improved or worsened.

Figure 79: FCU / ECR co-contraction. On the left, normalized values are reported for the noBF week, on the right, normalized values are
drawn for the BF week. Each color is assigned to a single subject, the dotted line indicates that the week was the first week of acquisitions,
the solid line indicates that it was the second week

94
Ideally, we expect a decrease in the parameter, since with the practice associated with the use of the
device the subject should be able to better contol muscles activation.
The interaction effect was significant for 5 of the 12 healthy subjects tested: for 3 subjects (C14_BaCa,
C18_LaMa and C21_GeTo) it was in favour of the BF; in the other 2 (C12_DeLu and C15_LaAn) this
effect was instead against the BF.
9 subjects had a significant day effect; in 6 subjects of these (C10_DeMa, C11_DeLu, C12_DeLu
C13_FaCa, C17_LaGi and C22_AnAn) the practice induced an increase of the parameter; in 1 subject
(C18_LaMa) the practice induced a learning of the trained task, but this was not influenced by the use
of the device.
This evaluation shows that the trend of healthy behavior is more aimed at increasing the levels of co-
contraction of the FCU / ECR muscles.

Considering now patients, Figure 80 shows the results relative to primary subjects.

Figure 80: FCU / ECR co-contraction. The figure consists of 9 panels, because 9 are the primary subjects. Each panel shows, on the left, the
trend of improvement/worsening during the noBF week, on the right, the trend relative to the BF week. Both trends are superimposed on
the general behavior of healthy subjects, also divided between noBF week, on the left, and BF week, on right. Subjects showing a significant
interaction effect are indicated by the gray background color of the panel. Subjects showing a significant day effect are indicated by the
thicker edge of the panel. The dotted line indicates the first week of training, the solid line indicates the second week of training.

The interaction effect was significant for 7 of the 9 primary dystonic subjects tested: for 2 subjects
(S06_MoAl and S09_DaVe) it was in favour of the BF; in 3 subjects (S01_BiSo, S02_FeRo and
S05_ToMa) this effect was against the BF; in the other 2 subjects (S03_VaAn and S07_BeMa) it was
against both conditions.
4 subjects showed a significant day, but for none of them the practice induced a learning of the trained
task.

95
Figure 81 shows the results relative to secondary subjects. Panels for S004FoAl and S011ZoDe are not
shown: it is not possible to perform a complete analysis, because all the electromyographic data are
missing, in the first case relating to the second testing day of the first week, which corresponds to the
noBF week, in the second case related to the first week, which corresponds to the BF week.

Figure 81: FCU / ECR co-contraction. The figure consists of 4 panels, because 4 are the secondary subjects a complete analysis is performed
on. Each panel shows, on the left, the trend of improvement/worsening during the noBF week, on the right, the trend relative to the BF
week. Both trends are superimposed on the general behavior of healthy subjects, also divided between noBF week, on the left, and BF
week, on right. Subjects showing a significant interaction effect are indicated by the gray background color of the panel. Subjects showing
a significant day effect are indicated by the thicker edge of the panel. The dotted line indicates the first week of training, the solid line
indicates the second week of training.

The interaction effect was significant for 3 of the 6 dystonic secondary tested subjects: in 1 subject,
(S001BoLu) it was in favour of the BF; in the other 2 subjects (S002MoLu and S009LeMa) this effect
was against the BF.

96
Finally, in Figure 82 the percentage of how many subjects, considering the 3 analyzed populations,
shaw learning skills with practice and an interaction effect to the advantage of the device are reported.

Figure 82: FCU / ECR co-contraction. From left to right, the trend of the healthy (in blue), the primary (in black), the secondary (in red) is
shown. For each group, the bar on the left shows the percentage of subjects who have learning, the bar on the right shows the percentage
of subjects that show a significant interaction for the benefit of the BF condition

8% of healthy subjects show learning with practice, and 25% of healthy subjects shows better
improvement when the BF device was used.

None of the primary subjects show learning with practice, while 22% of the primary patients shows better
improvement when the BF device was used.

None of the secondary subjects show learning with practice, while 25% of the secondary subjects shows
better improvement when the BF device was used.

97
3.2.10 BIC/TRIC co-contraction
Figure 83 shows the mean value of the parameter calculated during the first day of training, considering
both the noBF and the BF weeks, for each healthy subject.

Figure 83: BIC / TRIC co-contraction. On the left, in a lighter blue, mean and standard deviation values are reported for the noBF week,
on the right, in a darker blue, mean and standard deviation values are drawn for the BF week.

Figure 84 shows the mean value of the parameter calculated during the first day of training, considering
both the noBF and the BF weeks, for each primary subject.

Figure 84: BIC / TRIC co-contraction. On the left, in a lighter black, mean and standard deviation values are reported for the noBF week,
on the right, in a darker black, mean and standard deviation values are drawn for the BF week

98
Figure 85 shows the mean value of the parameter calculated during the first day of training, considering
both the noBF and the BF weeks, for each secondary subject.

Figure 85: BIC / TRIC co-contraction. On the left, in a lighter red, mean and standard deviation values are reported for the noBF week, on
the right, in a darker red, mean and standard deviation values are drawn for the BF week. For S6 (S011ZoDe) EMG data for the firs day of
BF condition are missing

Figure 86 shows the overall behavior of healthy subjects. All the data are normalized with respect Day1
of each week, so at to visualize weather the subject has improved or worsened.

Figure 86: BIC / TRIC co-contraction. On the left, normalized values are reported for the noBF week, on the right, normalized values are
drawn for the BF week. Each color is assigned to a single subject, the dotted line indicates that the week was the first week of acquisitions,
the solid line indicates that it was the second week

99
Ideally, we expect a decrease in the parameter, since with the practice associated with the use of the
device the subject should be able to better contol muscles activation.
The interaction effect was significant for 11 of the 12 healthy tested subjects: in 3 subjects (C11_DeLu,
C21_GeTo and C14_BaCa) it was in favour of the BF; in 5 subjects (C12_DeLu, C13_FaCa, C16_LaEl,
C18_LaMa and C23_GeLu) this effect was instead against the BF; in the last 3 subjects (C10_DeMa,
C17_LaGi and C22_AnAn) it it was against both conditions.
10 subjects had a significant day effect: for 4 of these (C13_FaCa, C14_BaCa, C18_LaMa and
C23_GeLu) the practice induced a learning of the trained task, but this was not influenced by the use of
the device.

Considering now patients, Figure 87 shows the results relative to primary subjects.

Figure 87: BIC / TRIC co-contraction. The figure consists of 9 panels, because 9 are the primary subjects. Each panel shows, on the left, the
trend of improvement/worsening during the noBF week, on the right, the trend relative to the BF week. Both trends are superimposed on
the general behavior of healthy subjects, also divided between noBF week, on the left, and BF week, on right. Subjects showing a significant
interaction effect are indicated by the gray background color of the panel. Subjects showing a significant day effect are indicated by the
thicker edge of the panel. The dotted line indicates the first week of training, the solid line indicates the second week of training.e

The interaction effect was significant for 7 of the 9 primary dystonic participants: in 3 subjects
(S03_VaAn, S04_FaMa and S06_MoAl) it was in favour of the BF; in 1 subject (S01_BiSo) this effect
was instead against; finally, in the other 3 subjects (S05_ToMa, S07_BeMa and S08_CaLe) this effect
was against both conditions. Of these 7 subjects, S03_VaAn, S04_FaMa, S05_ToMa, S07_BeMa and
S08_CaLe also show a significant day effect.
5 subjects showed a significant day effect: for 2 subjects (S03_VaAn and S04_FaMa) the practice
induced a learning of the trained task, but this was not influenced by the use of the device.

100
Figure 88 shows the results relative to secondary subjects. Panels for S004FoAl and S011ZoDe are not
shown: it is not possible to perform a complete analysis, because all the electromyographic data are
missing, in the first case relating to the second testing day of the first week, which corresponds to the
noBF week, in the second case related to the first week, which corresponds to the BF week.

Figure 88: BIC / TRIC co-contraction. The figure consists of 4 panels, because 4 are the secondary subjects a complete analysis is performed
on. Each panel shows, on the left, the trend of improvement/worsening during the noBF week, on the right, the trend relative to the BF
week. Both trends are superimposed on the general behavior of healthy subjects, also divided between noBF week, on the left, and BF
week, on right. Subjects showing a significant interaction effect are indicated by the gray background color of the panel. Subjects showing
a significant day effect are indicated by the thicker edge of the panel. The dotted line indicates the first week of training, the solid line
indicates the second week of training.

The interaction effect was significant for 2 of the 6 dystonic secondary participants (S002MoLu and
S009LeMa): in both cases it was against the BF.
3 subjects showed a significant day effect: in 2 of theese (S001BoLu and S002MoLu) the practice
induced a learning of the trained task, but this was not influenced by the use of the device.

101
Finally, in Figure 89 the percentage of how many subjects, considering the 3 analyzed populations,
shaw learning skills with practice and an interaction effect to the advantage of the device are reported.

Figure 89: BIC / TRIC co-contraction. From left to right, the trend of the healthy (in blue), the primary (in black), the secondary (in red) is
shown. For each group, the bar on the left shows the percentage of subjects who have learning, the bar on the right shows the percentage
of subjects that show a significant interaction for the benefit of the BF condition

33% of the healthy subjects show learning with practice, and 25% of healthy subjects shows better
improvement when the BF device was used.

22% of the primary subjects show learning with practice, and 33% of the primary patients shows better
improvement when the BF device was used.

50% of the secondary subjects show learning with practice, while none of the secondary patients shows
better improvement when the BF device was used.

102
3.2.11 AD/PD co-contraction
Figure 90 shows the mean value of the parameter calculated during the first day of training, considering
both the noBF and the BF weeks, for each healthy subject.

Figure 90: AD / PD co-contraction. On the left, in a lighter blue, mean and standard deviation values are reported for the noBF week, on
the right, in a darker blue, mean and standard deviation values are drawn for the BF week

Figure 91 shows the mean value of the parameter calculated during the first day of training, considering
both the noBF and the BF weeks, for each primary subject.

Figure 91: AD / PD co-contraction. On the left, in a lighter black, mean and standard deviation values are reported for the noBF week, on
the right, in a darker black, mean and standard deviation values are drawn for the BF week

103
Figure 92 shows the mean value of the parameter calculated during the first day of training, considering
both the noBF and the BF weeks, for each secondary subject.

Figure 92: AD / PD co-contraction. On the left, in a lighter red, mean and standard deviation values are reported for the noBF week, on the
right, in a darker red, mean and standard deviation values are drawn for the BF week. For S6 (S011ZoDe) EMG data for the first day of BF
condition are missing

Figure 93 shows the overall behavior of healthy subjects. C16_LaEl trend is not shown: it is not possible
to make an assessment because we do not have electromyographic data of the posterior deltoid of the
testing day of the first week, which corresponds to the noBF week. All the data are normalized with
respect to Day1 of each week, so at to visualize weather the subject has improved or worsened.

Figure 93: AD / PD co-contraction. On the left, normalized values are reported for the noBF week, on the right, normalized values are drawn
for the BF week. Each color is assigned to a single subject, the dotted line indicates that the week was the first week of acquisitions, the
solid line indicates that it was the second week

104
Ideally, we expect a decrease in the parameter, since with the practice associated with the use of the
device the subject should be able to better contol muscles activation.
The interaction effect was significant for 5 of the 12 healthy subjects: in 4 subjects (C12_FaLu,
C13_FaCa, C15_LaAn and C23_GeTo) it was against the BF; in the other subject (C11_DeLu) this
effect was against both conditions.
6 subjects showed a significant day effect; for 1 subject (C18_LaMa) the practice induced a learning of
the trained task, but this was not influenced by the use of the device.

Considering now patients, Figure 94 shows the results relative to primary subjects.

Figure 94: AD / PD co-contraction. The figure consists of 9 panels, because 9 are the primary subjects. Each panel shows, on the left, the
trend of improvement/worsening during the noBF week, on the right, the trend relative to the BF week. Both trends are superimposed on
the general behavior of healthy subjects, also divided between noBF week, on the left, and BF week, on right. Subjects showing a significant
interaction effect are indicated by the gray background color of the panel. Subjects showing a significant day effect are indicated by the
thicker edge of the panel. The dotted line indicates the first week of training, the solid line indicates the second week of training.

The interaction effect was significant for 8 of the 9 primary dystonic participants: in 4 subjects
(S03_VaAn, S04_FaMa, S07_BeMa and S09_DaVe) it was in favour of the BF; in 2 subjects (S01_BiSo
and S08_CaLe) this effect was instead against the BF condition; in the other 2 subjects (S02_FeRo and
S05_ToMa) it was against both weeks.
7 subjects showed a significant day effect: only for 1 subject (S06_MoAl) the practice induced a learning
of the trained task, but this was not influenced by the use of the device.

105
Figure 95 shows the results relative to secondary subjects. Panels for S004FoAl and S011ZoDe are not
shown: it is not possible to perform a complete analysis, because all the electromyographic data are
missing, in the first case relating to the second testing day of the first week, which corresponds to the
noBF week, in the second case related to the first week, which corresponds to the BF week.

Figure 95: AD / PD co-contraction. The figure consists of 4 panels, because 4 are the secondary subjects a complete analysis is performed
on. Each panel shows, on the left, the trend of improvement/worsening during the noBF week, on the right, the trend relative to the BF
week. Both trends are superimposed on the general behavior of healthy subjects, also divided between noBF week, on the left, and BF
week, on right. Subjects showing a significant interaction effect are indicated by the gray background color of the panel. Subjects showing
a significant day effect are indicated by the thicker edge of the panel. The dotted line indicates the first week of training, the solid line
indicates the second week of training.

The interaction effect was significant for 3 of the 6 dystonic secondary participants: in 2 subjects
(S001BoLu and S009LeMa) it was in favour of the BF; in 1 subject (S002MoLu) this effect was instead
against the BF.
4 subjects had a significant day effect, but for none of them the practice induced a learning of the trained
task, but this was not influenced by the use of the device.

106
Finally, in Figure 96 the percentage of how many subjects, considering the 3 analyzed populations,
show learning skills with practice and an interaction effect to the advantage of the device are reported.

Figure 96: AD / PD co-contraction. From left to right, the trend of the healthy (in blue), the primary (in black), the secondary (in red) is
shown. For each group, the bar on the left shows the percentage of subjects who have learning, the bar on the right shows the percentage
of subjects that show a significant interaction effect for the benefit of the BF condition.

8% of the healthy subjects show learning with practice, while none of the healthy subjects shows better
improvement when the BF device was used.

11% of the primary subjects show learning with practice, and 44% of the primary subjects shows better
improvement when the BF device was used.

None of the secondary participants show learning with practice, while 50% of the secondary subjects
shows better improvement when the BF device was used.

107
CHAPTER 4
DISCUSSION, LIMITATIONS AND FUTURE
DEVELOPMENTS

4.1 Discussion
An overall evaluation of the results allows us to draw conclusions about this work.

Figure 97 shows the percentage of healthy, primary and secondary subjects that show learning
characteristics with the practice, regardless of the use of the device, and better improvement when the
BF device was used. Obviously, panels showing the Index of Performance and the Movement
Repetability are missing, since theese are indices measured on all repetitions and not for each repetition.

Figure 97: Learning / learning with interaction. MT=Movement Time, PEAKS=speed peaks, SMOOTHNESS=smoothness, ML=Movement
Linearity, ROM=elbow range of motion, ST=shoulder displacement, CC FCU / ECR=FCU / ECR co-contraction, CC BIC / TRIC=BIC / TRIC co-
contraction, CC AD / PD=AD / PD co-contraction. DAY is the day effect, INTER is the interaction effect. 9 panels are reported, each one
related to each outcome for which the statystical analysis is carried out. From left to right, the trend of the healthy (in blue), the primary
(in black), the secondary (in red) subjects is shown. For each group, the bar on the left shows the percentage of subjects who have learning,
the bar on the right shows the percentage of subjects that show a significant interaction for the benefit of the BF condition.

2 of the 12 healthy subjects, 4 of the 9 primary subjects and 1 of the 6 secondary dystonic subjects
reduced the movement time with practice. 5 of the 12 healthy subjects, 2 of the 9 primary subjects and
1 of the 6 secondary dystonic subjects showed better improvement when the BF device was used.
3 of the 12 healthy subjects, 3 of the 9 primary subjects and 1 of the 6 secondary dystonic subjects
reduced the number of the speed peaks with practice. 3 of the 12 healthy subjects, 2 of the 9 primary

108
subjects and 1 of the 6 secondary dystonic subjects showed better improvement when the BF device
was used.
None of the 12 healthy subjects, 1 of the 9 primary subjects and none of the 6 secondary dystonic
subjects increased the smoothness of the movement with practice. 1 of the 12 healthy subjects, 1 of the
9 primary subjects and 1 of the 6 secondary dystonic subjects showed better improvement when the BF
device was used.
2 of the 12 healthy subjects, 3 of the 9 primary subjects and 1 of the 6 secondary dystonic subjects
reduced the movement linearity with practice. 2 of the 12 healthy subjects, 1 of the 9 primary subjects
and 1 of the 6 secondary dystonic subjects showed better improvement when the BF device was used.
For what concerns the elbow ROM and shoulder displacement, a complete analysis was performed on
5 of the 6 secondary subjects, since kinematic data concerning the spatial coordinates of the shoulder
of the second testing day of the second week were missing for one secondary dystonic subject.
4 of the 12 healthy subjects, none of the 9 primary subjects and 2 of the 5 secondary dystonic subjects
increased the elbow ROM during the movement with practice. 4 of the 12 healthy subjects, 3 of the 9
primary subjects and 1 of the 5 secondary dystonic subjects showed better improvement when the BF
device was used.
3 of the 12 healthy subjects, 1 of the 9 primary subjects and 1 of the 5 secondary dystonic subjects
reduced the shoulder displacement during the movement with practice. 4 of the 12 healthy subjects, 3
of the 9 primary subjects and 2 of the 5 secondary dystonic subjects showed better improvement when
the BF device was used.
For what concerns the EMG parameters, a complete analysiy was performed on 4 of the 6 secondary
subjects, because all the EMG data were missing, in one subject relating to the second testing day of
the first week, in the other secondary dystonic subject related to the first week.
1 of the 12 healthy subjects, none of the 9 primary subjects and none of the 4 secondary dystonic
subjects reduced the FCU/ECR co-contraction with practice. 3 of the 12 healthy subjects, 2 of the 9
primary subjects and 1 of the 4 secondary dystonic subjects showed better improvement when the BF
device was used.
4 of the 12 healthy subjects, 2 of the 9 primary subjects and none of the 4 secondary dystonic subjects
reduced the BIC/TRIC co-contraction with practice. 3 of the 12 healthy subjects, 3 of the 9 primary
subjects and 2 of the 4 secondary dystonic subjects showed better improvement when the BF device
was used.
1 of the 12 healthy subjects, 1 of the 9 primary subjects and none of the 4 secondary dystonic subjects
reduced the AD/PD co-contraction with practice. None of the 12 healthy subjects, 4 of the 9 primary
subjects and 2 of the 4 secondary dystonic subjects showed better improvement when the BF device
was used.

For what concerns time and speed of execution, the practice with the BF device influenced the behavior
of the primary subjects and the secondary patients almost in the same way, in fact the percentage of
the primary subjects for whom a significant interaction effect was found is about the same with respect
to the percentage of the secondary dystonic. It can be stated that for the movement time we see learning
trend mainly for the primary dystonic subjects. However, considering also the group of healthy subjects,
a great learning effect is not visible: less than half of people had a significant day effect. The
improvement trend observed looking at the IP is equal to that of the movement time. Thus, it can be
stated that the device affected the processing capabilities of the primary patients and the secondary
more or less in the same way. Even looking at the smoothness of the movement there’s no evidence
confirming that the exercise performed with the BF produced better results on the secondary group: the
effect of the device on the task learning was comparable between patients; learning induced by the
practice was higher for the primary patients, but, overall, learning was not so evident, since only one
subjects over all the recruited subjects showed learning with the practice. The analysis on the movement
linearity confirms what has been said about the movement time and the smoothness.
Considering the elbow ROM and the displacement of the shoulder, the results show something different
with respect to the final output kinematic parameters. For what concerns the elbow ROM, there was no
learning for the primary dystonic patients, who, instead, improved their performance when the BF was
used, while, for the secondary patients, a greater percentage of them learned the task with the practice.
For what concerns the shoulder displacement, the behavior of the three groups was very similar: both
the healthy subjects and the patients (both primary dystonic and secondary dystonic) had better
improvement when the BF device was used. However, it is likely that these two parameters do not
109
identify so well the behavior of the subjects, who adopted different strategies that translated into a great
inter-sample variability in the movements of the entire kinematic chain: since the position of the wooden
block on the support table was not fixed, there were subjects who managed to perform the exercise
remaining firmly on the chair and positioning themselves closer to the block, and there were those who,
instead, preferred to stay less firmly on the chair and accompanied the movement with the trunk.
Initial values of the movement repeatability were more or less equal between primary distonic subjects
and secondary distonic patients. There was no clear trend towards learning among the primary subjects
and the healthy subjects. It is probably necessary to consider that the range of improvement was limited
by the already good performance on the first day of Testing. The same type of analysis can be conducted
on the secondaries, which did not clearly reveal whether the device was actually effective. However, we
must consider that only in one case (S001BoLu) there was an isolated learning in the week of non-use
of the device.
Even looking at the electromyographic parameters, there is no clear tendency in favour of the initial
hypotheses: indeed, for what concerns both the FCU/ECR muscles co-contraction and the AD/PD
muscles co-contraction, better improvement was evident when the BF device was used for both the
primary subjects and the secondary subjects; learning induced by the practice was null for the primary
patients and visible for only one secondary subject. Focusing on the co-contraction of the muscles
primarly involved in the prono-supination of the wrist, the behavior of the three groups was similar: the
healthy subjects and the patients (primary subjects and secondary subjects) better improved their
performance when the sensory feedback was provided, while learning with the practice was shown by
only one subject (one healthy subject). It was already discussed in paragraph 3.2.9 the fact that the
tendency of the healthy subjects was to increase the FCU/ECR co-contraction with the practice. It is not
wrong to assume that only a greater simultaneous activation of theese muscles reflects into greater
stability of the wrist joint, and therefore greater control on the spoon. This explains why, if the expected
result was a decrease in the co-contraction levels, low levels of learning were found. Finally, considering
the BIC/TRIC co-contraction, the secondary subjects did not reveal better improvement while using the
BF. Rather, the practice induced a learning of the trained task, but this was not influenced by the use of
the device; moreover, for the primary subjects, the BF device influenced the task learning more than the
practice did.

In general, it can not be stated that an effect related to the use of the device is more pronounced in the
group of secondary dystonic: better improvement with the device was recorded for both the primary
subjects and the secondary subjects. Even for the healthy subjects the device accelerated learning
processes. This was particularly evident considering the time-related parameters and the FCU/ECR co-
contraction.
For what concerns the temporal paramaters and the parameters related to the final output kinematics,
learning in primary dystonic was not significantly stressed by the use of the device, but this trend was
not visible considering the parameters linked to the entire kinematic chain (ROM and ST) and the EMG
parameters, for which the device accelerated learning.

Hence, the results do not allow us to support the hypotheses the study is based on: even individuals
affected by secondary dystonia, which are characterized by marked sensory deficits that prevent their
improvement in the performance of complex motor tasks (despite repeated training), seem not to be so
much favored by using such a strategy; on the other hand, for the subjects affected by primary dystonia
and for the healthy subjects, in which there are no sensory deficits and the physiological learning
mechanisms linked to the training of a particular motor exercise are intact, the use of a biofeedback
strategy seems to have a role in improving performance.

110
4.2 Limitations and future developments
From the comparison between the three groups, it results that learning in the secondary subjects is
lower than learning of the primary dystonic, as well as of the healthies: the percentage of the secondary
subjects for whom the day effect leads to a general learning trend is lower for all the analyzed outcomes,
with the sole exception of the elbow ROM and the BIC/TRIC muscles co-contraction. This impairment
of the ability to learn in the subjects affected by secondary dystonia is identifiable as the fact that, despite
the training with the BF, they may not learn the task.This introduces a first limitation of the study, which
does not currently take into consideration cognitive variables that could lead to behavioral disorders and
that can prevent the secondary subjects from accessing sufficient sources for a correct learning.
A limitation derives from the lack of some fundamental data for the analysis of some secondary subjects.
Furthermore, the lack of a group statistic analysis and the scattered results do not allow for definitive
conclusions. This problem is added to the limited number of subjects, which make the sample power
limited and the comparison not always statistically robust.
However, the ongoing multi-center clinical trial will overcome this limitation and more dystonic subjects
will be recruited. Furthermore, the long-term effect of the use of the biofeedback device during daily life
activities (wearing the device at least 5 hours a day for one month) will be investigated. Indeed, while,
on the short-term, biofeedback may bring about improved awareness of the ongoing movement, on the
long-term such technique has the potential to facilitate plasticity of the neural pathways that encode
motor commands.
Future developments of this work could be:

• definition of a set of criteria to guide the operator in choosing the most suitable muscles on which to
place the biofeedback; these could be selected, for example, after a clinical and quantitative evaluation
that clearly indicates the most compromised ones;

• test of simultaneous use of multiple feedback modalities;

• test of the effects different sensory channels through which providing the feedback;

• evaluation of the effectiveness of the device in the long term.

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CHAPTER 5
CONCLUSION

Overall, this work highlights the potential effectiveness of a biofeedback training in helping children and
adolescents with dystonia to gain improved control over specific muscles during voluntary motion.
Theese preliminary results do not allow us to support or to refute the hypotheses the study is based on:
some limitations still need to be overcome and the whole project is still far from an end.
Symptoms of dystonia are highly-disabling and strongly influence the everyday life, from school activities
to social interaction. Therefore, these results could pave the way for effective non-invasive interventions
in secondary dystonias, for whom deep brain stimulation is very often not effective in improving motor
control.

112
Appendix
The mean and the standard deviation values of the measured outcomes for each of the Testing days
are reported for each subject. Moreover, pValues for each outcome are reported in this section. In each
table the tested healthy subjects are highlighted in blue, the primary subjects are in black, the secondary
patients in red.
For what concerns the Index of Performance and the Movement Repetability, only the mean values are
reported, since theese are indices measured on all repetitions and not for each repetition.

SUBJECTS noBFD1 noBFD5 BFD1 BFD5

Mean SD Mean SD Mean SD Mean SD
C10_DeMa 1.953 0.334 1.960 0.357 2.358 0.234 2.280 0.313
C11_DeLu 2.145 0.280 2.215 0.289 2.786 0.199 1.928 0.322
C12_FaLu 2.265 0.359 2.133 0.138 2.453 0.189 2.375 0.703
C13_FaCa 3.688 0.772 4.389 0.827 2.790 0.318 2.273 0.266
C14_BaCa 2.991 0.689 2.180 0.115 2.818 0.376 2.019 0.178
C15_LaAn 2.388 0.598 1.578 0.236 1.478 0.118 1.464 0.200
C16_LaEl 1.940 0.228 2.057 0.246 2.636 0.464 1.933 0.162
C17_LaGi 1.425 0.090 1.268 0.107 1.406 0.122 1.535 0.114
C18_LaMa 1.425 0.099 1.493 0.253 1.908 0.142 1.505 0.150
C21_GeTo 1.829 0.157 1.829 0.157 1.696 0.222 1.413 0.101
C22_AnAn 1.700 0.143 1.436 0.094 1.770 0.149 2.058 0.403
C23_GeLu 1.910 0.260 1.919 0.131 1.782 0.175 1.660 0.138
S01_BiSo 6.489 1.753 3.713 0.619 5.275 1.441 3.710 0.749
S02_FeRo 1.010 0.174 0.873 0.072 2.063 0.289 1.188 0.142
S03_VaAn 1.605 0.305 1.353 0.066 1.604 0.176 1.956 0.144
S04_FaMa 1.773 0.261 1.993 0.288 2.165 0.283 2.036 0.312
S05_ToMa 1.175 0.080 1.105 0.175 1.700 0.329 1.575 0.266
S06_MoAl 1.538 0.122 1.270 0.132 1.523 0.172 1.153 0.126
S07_BeMa 1.768 0.143 2.040 0.122 2.184 0.330 1.681 0.152
S08_CaLe 3.025 0.275 1.417 0.097 1.444 0.082 1.245 0.042
S09_DaVe 1.692 0.190 2.000 0.279 1.665 0.105 2.103 0.278
S001BoLu 1.432 0.205 1.373 0.107 1.818 0.323 1.929 0.417
S002MoLu 1.262 0.172 1.991 0.181 1.738 0.358 1.132 0.153
S004FoAl 1.919 0.376 1.244 0.153 1.875 0.259 1.308 0.000
S005MaDa 2.342 0.934 3.769 2.334 1.409 1.001 1.597 0.560
S009LeMa 2.528 0.503 3.036 0.875 3.112 0.657 3.295 0.598
S011ZoDe 0.711 0.273 0.768 0.347 0.756 0.222 0.945 0.393
Table 4: Mean and standard deviation values for the Movement Time.

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 SUBJECTS pValues
Condition Day Interaction
C10_DeMa 0.003 0.750 0.702
C11_DeLu 0.055 <0.001 <0.001
C12_FaLu 0.151 0.476 0.852
C13_FaCa <0.001 0.640 0.004
C14_BaCa 0.214 <0.001 0.964
C15_LaAn <0.001 0.001 0.001
C16_LaEl 0.032 0.029 0.003
C17_LaGi 0.005 0.728 0.002
C18_LaMa <0.001 0.004 <0.001
C21_GeTo 0.001 0.089 0.039
C22_AnAn <0.001 0.869 0.001
C23_GeLu 0.004 0.374 <0.001
S01_BiSo 0.131 <0.001 0.133
S02_FeRo <0.001 <0.001 <0.001
S03_VaAn <0.001 0.478 <0.001
S04_FaMa 0.023 0.622 0.065
S05_ToMa <0.001 0.306 0.770
S06_MoAl 0.157 <0.001 0.271
S07_BeMa 0.660 0.083 <0.001
S08_CaLe <0.001 <0.001 <0.001
S09_DaVe 0.662 <0.001 0.457
S001BoLu <0.001 0.769 0.348
S002MoLu 0.031 0.475 <0.001
S004FoAl 0.952 0.002 0.746
S005MaDa <0.001 0.069 0.167
S009LeMa 0.158 0.243 0.578
S011ZoDe 0.378 0.326 0.598
Table 5: Results of the 2-way ANOVA for the Movement Time.

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 SUBJECTS noBFD1 noBFD5 BFD1 BFD5
Mean Mean Mean Mean
C10_DeMa 3.176 3.341 2.728 2.489
C11_DeLu 3.065 2.695 2.109 3.733
C12_FaLu 3.342 3.373 2.613 7.190
C13_FaCa 1.231 1.074 1.788 4.251
C14_BaCa 1.748 3.113 1.822 4.926
C15_LaAn 2.363 7.726 7.582 6.289
C16_LaEl 4.817 5.001 2.729 5.390
C17_LaGi 6.740 8.900 6.942 7.776
C18_LaMa 6.181 5.630 3.084 5.214
C21_GeTo 3.706 3.706 4.231 7.024
C22_AnAn 6.590 7.441 4.836 2.910
C23_GeLu 4.949 3.985 4.211 6.691
S01_BiSo 0.748 2.103 0.951 1.923
S02_FeRo 3.114 8.297 0.784 1.926
S03_VaAn 5.024 7.689 5.335 3.510
S04_FaMa 5.342 3.518 2.917 3.387
S05_ToMa 6.408 7.790 3.886 4.191
S06_MoAl 2.402 3.447 2.450 3.872
S07_BeMa 3.494 3.043 2.801 4.165
S08_CaLe 1.996 6.332 7.169 11.532
S09_DaVe 3.169 1.692 -10.209 1.609
S001BoLu 14.861 2.396 1.695 1.318
S002MoLu 8.654 0.581 0.812 2.301
S004FoAl 3.230 4.378 1.947 30.000
S009LeMa 1.708 0.874 0.854 1.016
Table 6: Mean values for the Index of Performance.

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 SUBJECTS noBFD1 noBFD5 BFD1 BFD5
Mean SD Mean SD Mean SD Mean SD
C10_DeMa 7.778 2.575 8.350 2.646 15.000 2.608 13.900 2.492
C11_DeLu 12.300 2.741 9.050 1.771 16.667 2.398 11.800 2.541
C12_FaLu 15.100 2.460 12.600 1.853 15.111 2.607 14.625 4.033
C13_FaCa 25.583 4.042 28.643 6.349 16.550 3.337 12.500 3.197
C14_BaCa 18.500 4.683 14.000 1.453 19.050 3.140 13.063 2.821
C15_LaAn 9.250 4.252 8.400 2.591 7.833 1.521 7.500 1.958
C16_LaEl 12.400 2.434 12.143 3.224 16.714 2.706 12.583 2.538
C17_LaGi 8.643 1.749 6.500 1.080 7.000 2.000 9.300 2.139
C18_LaMa 7.400 1.390 8.200 1.619 12.150 2.161 8.250 1.768
C21_GeTo 9.667 0.983 9.667 0.983 10.214 3.592 5.063 1.782
C22_AnAn 10.750 1.875 8.000 1.521 9.800 1.513 12.333 3.961
C23_GeLu 11.300 2.927 10.889 2.147 9.214 2.464 6.550 1.536
S01_BiSo 31.571 12.448 16.550 4.232 22.222 9.169 16.900 8.037
S02_FeRo 2.900 2.012 3.250 1.704 8.875 5.706 3.250 2.092
S03_VaAn 6.700 1.859 3.700 2.689 8.167 1.663 8.438 4.136
S04_FaMa 10.000 2.896 7.700 2.946 10.250 3.974 7.667 2.411
S05_ToMa 4.357 2.304 5.900 1.084 4.917 1.563 6.375 3.114
S06_MoAl 7.188 1.831 7.100 1.853 9.550 1.950 5.100 2.025
S07_BeMa 10.050 1.691 8.300 1.358 9.250 2.521 9.722 2.399
S08_CaLe 17.750 4.699 7.611 0.741 5.444 1.810 6.700 1.398
S09_DaVe 9.889 1.710 11.150 1.780 10.500 2.646 13.350 2.698
S001BoLu 7.100 1.868 7.091 1.841 12.050 3.157 12.800 3.882
S002MoLu 5.100 1.194 14.250 2.648 11.700 3.882 5.800 1.636
S004FoAl 14.250 4.252 7.000 1.299 11.250 1.061 6.500 0.000
S005MaDa 20.115 9.689 64.136 55.692 7.900 8.003 8.000 3.542
S009LeMa 13.400 4.955 17.333 7.816 19.800 4.778 16.150 5.442
S011ZoDe 4.071 1.988 4.650 2.925 4.667 2.443 4.900 2.945
Table 7: Mean and standard deviation values for the PEAKS.

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 SUBJECTS pValues
Condition Day Interaction
C10_DeMa <0.001 0.769 0.355
C11_DeLu <0.001 <0.001 0.299
C12_FaLu 0.333 0.160 0.338
C13_FaCa <0.001 0.745 0.025
C14_BaCa 0.856 0,000 0.486
C15_LaAn 0.235 0.540 0.788
C16_LaEl 0.046 0.064 0.099
C17_LaGi 0.375 0.903 0.002
C18_LaMa <0.001 0.008 <0.001
C21_GeTo 0.006 0.001 0.014
C22_AnAn 0.037 0.890 0.002
C23_GeLu 0,000 0.057 0.158
S01_BiSo 0.129 0.001 0.102
S02_FeRo 0.019 0.036 0.019
S03_VaAn 0.003 0.170 0.102
S04_FaMa 0.915 0.020 0.888
S05_ToMa 0.578 0.116 0.964
S06_MoAl 0.774 0.001 0.001
S07_BeMa 0.642 0.342 0.103
S08_CaLe <0.001 <0.001 <0.001
S09_DaVe 0.084 0.014 0.321
S001BoLu <0.001 0.675 0.667
S002MoLu 0.343 0.101 <0.001
S004FoAl 0.305 0.003 0.459
S005MaDa <0.001 0.012 0.012
S009LeMa 0.313 0.956 0.149
S011ZoDe 0.684 0.695 0.868
Table 8: Results of the 2-way ANOVA for the speed PEAKS.

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 SUBJECTS noBFD1 noBFD5 BFD1 BFD5
Mean SD Mean SD Mean SD Mean SD
C10_DeMa 0.508 0.046 0.481 0.079 0.560 0.018 0.542 0.060
C11_DeLu 0.500 0.051 0.498 0.070 0.559 0.034 0.522 0.051
C12_FaLu 0.499 0.075 0.532 0.053 0.521 0.030 0.521 0.053
C13_FaCa 0.533 0.094 0.472 0.081 0.510 0.075 0.502 0.051
C14_BaCa 0.521 0.056 0.559 0.025 0.533 0.023 0.529 0.034
C15_LaAn 0.487 0.053 0.487 0.047 0.507 0.037 0.508 0.038
C16_LaEl 0.576 0.032 0.552 0.024 0.540 0.035 0.580 0.026
C17_LaGi 0.565 0.030 0.570 0.043 0.564 0.040 0.594 0.018
C18_LaMa 0.552 0.025 0.545 0.047 0.532 0.034 0.542 0.042
C21_GeTo 0.568 0.068 0.568 0.068 0.554 0.045 0.570 0.043
C22_AnAn 0.589 0.037 0.604 0.046 0.551 0.032 0.514 0.047
C23_GeLu 0.537 0.050 0.548 0.026 0.529 0.021 0.534 0.043
S01_BiSo 0.477 0.071 0.443 0.040 0.492 0.057 0.486 0.091
S02_FeRo 0.584 0.081 0.577 0.038 0.491 0.078 0.557 0.071
S03_VaAn 0.565 0.042 0.604 0.064 0.566 0.024 0.543 0.053
S04_FaMa 0.547 0.033 0.590 0.058 0.572 0.060 0.575 0.040
S05_ToMa 0.602 0.062 0.576 0.063 0.405 0.051 0.522 0.081
S06_MoAl 0.462 0.034 0.513 0.041 0.556 0.053 0.532 0.032
S07_BeMa 0.531 0.041 0.539 0.041 0.497 0.057 0.495 0.033
S08_CaLe 0.466 0.115 0.534 0.023 0.549 0.033 0.578 0.022
S09_DaVe 0.533 0.053 0.467 0.024 0.490 0.033 0.457 0.049
S001BoLu 0.588 0.057 0.553 0.040 0.553 0.050 0.559 0.067
S002MoLu 0.615 0.069 0.564 0.066 0.559 0.062 0.634 0.041
S004FoAl 0.545 0.020 0.601 0.056 0.608 0.014 0.582 0.000
S005MaDa 0.358 0.097 0.299 0.168 0.501 0.112 0.431 0.095
S009LeMa 0.520 0.080 0.514 0.065 0.414 0.103 0.488 0.108
S011ZoDe 0.539 0.123 0.560 0.105 0.551 0.055 0.541 0.094
Table 9: Mean and standard deviation values for the SMOOTHNESS.

118
 SUBJECTS pValues
Condition Day Interaction
C10_DeMa 0.009 0.279 0.822
C11_DeLu 0.020 0.255 0.301
C12_FaLu 0.766 0.393 0.411
C13_FaCa 0.898 0.204 0.317
C14_BaCa 0.447 0.163 0.082
C15_LaAn 0.229 0.956 0.975
C16_LaEl 0.744 0.515 0.013
C17_LaGi 0.430 0.205 0.386
C18_LaMa 0.358 0.883 0.507
C21_GeTo 0.657 0.267 0.751
C22_AnAn <0.001 0.408 0.058
C23_GeLu 0.421 0.558 0.840
S01_BiSo 0.213 0.384 0.553
S02_FeRo 0.045 0.282 0.178
S03_VaAn 0.101 0.652 0.090
S04_FaMa 0.722 0.160 0.214
S05_ToMa <0.001 0.102 0.014
S06_MoAl <0.001 0.304 0.008
S07_BeMa 0.010 0.802 0.727
S08_CaLe 0.001 0.008 0.249
S09_DaVe 0.092 0.003 0.304
S001BoLu 0.401 0.391 0.231
S002MoLu 0.739 0.585 0.005
S004FoAl 0.510 0.651 0.229
S005MaDa <0.001 0.084 0.845
S009LeMa 0.155 0.455 0.384
S011ZoDe 0.920 0.883 0.702
Table 10: Results of the 2-way ANOVA for the SMOOTHNESS.

119
 SUBJECTS noBFD1 noBFD5 BFD1 BFD5
Mean SD Mean SD Mean SD Mean SD
C10_DeMa 1.204 0.048 1.212 0.041 1.241 0.032 1.223 0.032
C11_DeLu 1.194 0.028 1.218 0.036 1.230 0.029 1.163 0.024
C12_FaLu 1.158 0.036 1.193 0.041 1.169 0.030 1.207 0.083
C13_FaCa 1.225 0.033 1.209 0.047 1.242 0.031 1.254 0.040
C14_BaCa 1.284 0.023 1.278 0.047 1.260 0.033 1.207 0.029
C15_LaAn 1.202 0.091 1.162 0.033 1.131 0.021 1.130 0.032
C16_LaEl 1.206 0.036 1.212 0.037 1.220 0.028 1.195 0.013
C17_LaGi 1.223 0.034 1.182 0.026 1.169 0.030 1.408 0.061
C18_LaMa 1.137 0.012 1.122 0.017 1.209 0.024 1.153 0.016
C21_GeTo 1.156 0.017 1.156 0.017 1.178 0.041 1.203 0.051
C22_AnAn 1.215 0.036 1.205 0.042 1.161 0.027 1.181 0.031
C23_GeLu 1.221 0.040 1.276 0.053 1.172 0.025 1.198 0.027
S01_BiSo 1.287 0.047 1.261 0.037 1.146 0.019 1.158 0.030
S02_FeRo 1.214 0.044 1.141 0.036 1.245 0.034 1.168 0.043
S03_VaAn 1.229 0.033 1.230 0.023 1.204 0.010 1.242 0.021
S04_FaMa 1.245 0.031 1.213 0.026 1.209 0.030 1.182 0.014
S05_ToMa 1.213 0.038 1.207 0.027 1.166 0.035 1.259 0.068
S06_MoAl 1.256 0.036 1.174 0.033 1.204 0.022 1.208 0.036
S07_BeMa 1.249 0.045 1.322 0.053 1.199 0.029 1.187 0.018
S08_CaLe 1.205 0.035 1.188 0.012 1.214 0.029 1.192 0.012
S09_DaVe 1.174 0.042 1.221 0.048 1.145 0.038 1.210 0.051
S001BoLu 1.264 0.048 1.189 0.075 1.516 0.106 1.303 0.096
S002MoLu 1.429 0.108 1.425 0.082 1.310 0.086 1.422 0.075
S004FoAl 1.270 0.045 1.318 0.076 1.347 0.093 1.313 0.000
S005MaDa 2.635 1.229 2.427 1.499 2.592 1.165 2.121 0.656
S009LeMa 1.325 0.069 1.449 0.123 1.467 0.081 1.452 0.147
S011ZoDe 1.667 0.138 1.669 0.248 1.457 0.157 1.594 0.119
Table 11: Mean and standard deviation values for the Movement Linearity.

120
 SUBJECTS pValues
Condition Day Interaction
C10_DeMa 0.094 0.717 0.350
C11_DeLu 0.314 0.027 <0.001
C12_FaLu 0.511 0.066 0.924
C13_FaCa 0.029 0.865 0.313
C14_BaCa <0.001 0.018 0.053
C15_LaAn 0.004 0.198 0.239
C16_LaEl 0.923 0.440 0.217
C17_LaGi <0.001 <0.001 <0.001
C18_LaMa <0.001 <0.001 0.001
C21_GeTo 0.777 0.120 0.005
C22_AnAn 0.001 0.678 0.200
C23_GeLu <0.001 0.004 0.276
S01_BiSo <0.001 0.520 0.109
S02_FeRo 0.093 0,000 0.895
S03_VaAn 0.500 0.031 0.041
S04_FaMa <0.001 0.001 0.771
S05_ToMa 0.903 0.030 0.015
S06_MoAl 0.381 0.001 <0.001
S07_BeMa <0.001 0.026 0.003
S08_CaLe 0.422 0.021 0.738
S09_DaVe 0.222 0.002 0.594
S001BoLu <0.001 <0.001 0.012
S002MoLu 0.051 0.081 0.063
S004FoAl 0.472 0.887 0.407
S005MaDa 0.543 0.289 0.813
S009LeMa 0.200 0.328 0.217
S011ZoDe 0.064 0.356 0.370
Table 12: Results of the 2-way ANOVA for the Movement Linearity.

121
 SUBJECTS noBFD1 noBFD5 BFD1 BFD5
Mean Mean Mean Mean
C10_DeMa 93.921 91.387 97.025 95.335
C11_DeLu 96.680 97.191 98.479 94.100
C12_FaLu 93.578 95.781 91.848 90.624
C13_FaCa 90.328 91.168 87.063 92.883
C14_BaCa 94.068 94.538 92.269 94.726
C15_LaAn 88.534 85.834 98.030 97.825
C16_LaEl 91.650 93.304 92.844 89.794
C17_LaGi 97.902 97.286 98.280 97.221
C18_LaMa 95.649 98.841 92.237 97.892
C21_GeTo 94.835 94.835 97.770 97.929
C22_AnAn 98.100 98.123 98.427 97.145
C23_GeLu 97.241 96.004 98.907 98.742
S01_BiSo 96.756 97.078 96.335 96.107
S02_FeRo 87.778 98.006 95.754 94.047
S03_VaAn 96.125 98.936 98.542 98.330
S04_FaMa 98.090 96.813 97.282 97.600
S05_ToMa 99.214 99.013 89.959 97.138
S06_MoAl 96.838 94.782 96.819 97.304
S07_BeMa 91.622 96.001 96.255 97.643
S08_CaLe 83.136 97.446 95.460 98.250
S09_DaVe 95.281 84.900 88.196 83.307
S001BoLu 76.312 81.605 80.008 74.859
S002MoLu 89.247 79.165 87.524 83.767
S004FoAl 92.477 87.627 96.129 100.000
S005MaDa 69.234 66.694 71.695 72.065
S009LeMa 84.747 81.958 77.322 81.011
S011ZoDe 74.485 74.520 83.495 77.794
Table 13: Mean values for the Movement Repeatability.

122
 SUBJECTS noBFD1 noBFD5 BFD1 BFD5
Mean SD Mean SD Mean SD Mean SD
C10_DeMa 41.790 3.618 36.173 4.489 37.919 3.828 38.311 4.216
C11_DeLu 27.409 3.105 27.689 5.309 34.992 3.168 37.578 2.602
C12_FaLu 24.743 5.083 15.048 3.154 19.723 2.883 20.534 3.585
C13_FaCa 26.236 2.847 34.853 6.171 19.303 4.241 33.019 5.133
C14_BaCa 49.642 3.043 45.867 7.687 24.666 2.784 35.225 4.105
C15_LaAn 27.041 2.278 32.369 3.947 22.579 3.023 31.710 3.425
C16_LaEl 47.532 3.695 42.409 4.302 37.075 2.933 32.974 2.319
C17_LaGi 35.671 1.892 36.368 2.212 38.754 3.270 35.828 2.318
C18_LaMa 17.062 2.922 25.515 1.926 31.432 5.305 40.986 1.830
C21_GeTo 39.924 3.803 39.924 3.803 54.958 9.999 47.495 2.097
C22_AnAn 27.342 2.342 38.549 3.094 33.799 2.793 34.229 1.641
C23_GeLu 64.187 3.320 41.052 3.183 25.960 3.604 34.060 2.168
S01_BiSo 50.241 10.213 57.523 4.931 70.799 8.417 40.306 11.831
S02_FeRo 65.031 4.057 67.381 3.389 61.489 6.973 60.689 3.491
S03_VaAn 39.485 3.994 39.929 3.276 31.879 4.576 34.090 0.894
S04_FaMa 39.894 4.652 41.362 5.335 33.239 4.132 32.236 3.839
S05_ToMa 29.527 3.172 36.326 2.161 45.982 2.008 38.966 4.774
S06_MoAl 67.193 9.158 65.620 3.135 43.744 3.340 58.976 4.132
S07_BeMa 41.271 2.098 40.591 2.845 22.973 2.682 47.057 2.068
S08_CaLe 35.522 6.393 33.223 1.844 28.470 1.621 45.311 2.727
S09_DaVe 39.493 9.737 33.753 8.780 32.326 2.320 41.358 7.172
S001BoLu 20.514 2.744 NaN NaN 24.560 1.746 24.030 5.484
S002MoLu 38.469 3.559 39.272 4.314 25.956 3.633 37.289 1.612
S004FoAl 55.597 3.498 49.222 4.659 55.550 0.084 51.284 0.000
S005MaDa 42.398 5.604 50.515 6.843 45.444 4.901 47.220 6.097
S009LeMa 42.887 0.374 30.987 3.613 43.737 3.379 42.864 3.156
S011ZoDe 56.558 12.043 54.503 10.497 50.651 1.571 46.891 5.197
Table 14: Mean and standard deviation values for the elbow ROM.

123
 SUBJECTS pValues
Condition Day Interaction
C10_DeMa 0.545 0.074 0.042
C11_DeLu <0.001 0.236 0.339
C12_FaLu 0.859 0.002 <0.001
C13_FaCa 0.016 <0.001 0.147
C14_BaCa <0.001 0.049 <0.001
C15_LaAn 0.063 <0.001 0.161
C16_LaEl <0.001 0.003 0.714
C17_LaGi 0.188 0.247 0.065
C18_LaMa <0.001 <0.001 0,602
C21_GeTo 0.002 <0.001 0.719
C22_AnAn 0.202 <0.001 <0.001
C23_GeLu <0.001 <0.001 <0.001
S01_BiSo 0.591 0.001 <0.001
S02_FeRo 0.009 0.670 0.389
S03_VaAn <0.001 0.277 0.467
S04_FaMa <0.001 0.874 0.402
S05_ToMa <0.001 0.937 <0.001
S06_MoAl <0.001 <0.001 <0.001
S07_BeMa <0.001 <0.001 <0.001
S08_CaLe <0.001 <0.001 <0.001
S09_DaVe 0.940 0.571 0.015
S002MoLu <0.001 <0.001 <0.001
S004FoAl 0.730 0.087 0.718
S005MaDa 0.535 0.013 0.151
S009LeMa <0.001 <0.001 0.001
S011ZoDe 0.069 0.421 0.812
Table 15: Results of the 2-way ANOVA for the elbow ROM.

124
 SUBJECTS noBFD1 noBFD5 BFD1 BFD5
Mean SD Mean SD Mean SD Mean SD
C10_DeMa 175.318 10.225 186.086 21.851 174.146 12.985 189.025 14.963
C11_DeLu 177.742 8.059 201.693 16.899 167.841 7.205 200.648 11.622
C12_FaLu 204.198 15.596 210.819 9.809 247.873 15.480 213.705 14.950
C13_FaCa 220.999 11.965 213.113 21.784 260.140 23.769 201.058 18.959
C14_BaCa 85.768 8.641 92.262 31.944 182.436 14.172 179.974 9.723
C15_LaAn 155.879 6.627 170.379 15.677 138.083 8.870 138.212 8.488
C16_LaEl 172.575 11.457 177.307 13.804 164.051 6.508 204.123 7.831
C17_LaGi 117.924 10.817 97.535 17.917 103.233 15.843 152.026 7.127
C18_LaMa 205.504 10.384 171.716 7.252 141.968 28.858 107.272 9.137
C21_GeTo 96.097 18.185 96.097 18.185 104.143 19.913 76.400 6.488
C22_AnAn 91.483 13.248 68.763 9.564 89.081 10.270 62.569 7.323
C23_GeLu 57.173 12.904 124.863 12.534 187.690 14.957 148.671 7.706
S01_BiSo 94.670 13.487 65.196 10.410 122.733 9.173 188.000 28.218
S02_FeRo 68.681 6.567 49.892 15.305 58.603 14.124 79.320 9.755
S03_VaAn 108.047 14.829 104.493 6.621 130.009 11.686 139.335 4.987
S04_FaMa 70.728 21.748 125.571 13.763 129.062 7.866 175.429 15.018
S05_ToMa 114.029 5.591 127.058 5.493 116.178 9.333 131.720 5.437
S06_MoAl 88.214 13.557 72.083 7.539 132.747 10.015 130.360 6.365
S07_BeMa 68.454 7.770 91.556 12.276 173.800 17.825 112.199 13.538
S08_CaLe 120.544 12.333 138.434 10.173 142.249 9.757 88.559 8.741
S09_DaVe 139.834 27.733 203.082 30.216 189.833 14.741 158.301 19.236
S001BoLu 76.909 15.443 NaN NaN 79.057 13.660 67.870 20.847
S002MoLu 38.844 6.142 36.430 11.012 80.688 9.662 24.549 7.417
S004FoAl 53.553 6.955 76.271 14.761 33.290 3.767 50.336 0.000
S005MaDa 15.078 4.269 25.318 6.858 22.030 5.881 16.887 6.647
S009LeMa 33.400 4.070 79.275 9.484 20.721 8.999 37.241 3.471
S011ZoDe 44.491 17.103 43.581 19.363 55.067 10.065 79.191 8.324
Table 16: Mean and standard deviation values for the Shoulder Translation.

125
 SUBJECTS pValues
Condition Day Interaction
C10_DeMa 0.875 0.028 0.714
C11_DeLu 0.153 <0.001 0.246
C12_FaLu <0.001 0.011 <0.001
C13_FaCa 0.071 <0.001 0.001
C14_BaCa <0.001 0.760 0.499
C15_LaAn <0.001 0.112 0.118
C16_LaEl 0.039 <0.001 <0.001
C17_LaGi 0.001 0.016 <0.001
C18_LaMa <0.001 <0.001 0.931
C21_GeTo 0.454 0.383 <0.001
C22_AnAn 0.213 <0.001 0.579
C23_GeLu <0.001 0.001 <0.001
S01_BiSo <0.001 0.005 <0.001
S02_FeRo 0.085 0.859 0.001
S03_VaAn <0.001 0.434 0.087
S04_FaMa <0.001 <0.001 0.397
S05_ToMa 0.207 <0.001 0.636
S06_MoAl <0.001 0.005 0.033
S07_BeMa <0.001 <0.001 <0.001
S08_CaLe 0.001 <0.001 <0.001
S09_DaVe 0.771 0.085 <0.001
S002MoLu <0.001 <0.001 <0.001
S004FoAl 0.020 0.039 0.747
S005MaDa 0.551 0.198 <0.001
S009LeMa <0.001 <0.001 <0.001
S011ZoDe 0.001 0.070 0.052
Table 17: Results of the 2-way ANOVA for the Shoulder Translation.

126
 SUBJECTS noBFD1 noBFD5 BFD1 BFD5
Mean SD Mean SD Mean SD Mean SD
C10_DeMa 0.598 0.096 0.710 0.093 0.445 0.064 0.515 0.085
C11_DeLu 0.412 0.132 0.995 0.129 0.474 0.074 1.078 0.138
C12_FaLu 0.281 0.183 0.760 0.079 0.480 0.046 0.536 0.088
C13_FaCa 0.371 0.096 0.489 0.062 0.455 0.064 0.479 0.076
C14_BaCa 0.776 0.108 1.017 0.106 0.345 0.083 0.301 0.066
C15_LaAn 0.561 0.039 0.701 0.033 0.454 0.069 0.921 0.154
C16_LaEl 0.828 0.118 0.818 0.248 0.634 0.123 0.538 0.113
C17_LaGi 0.385 0.045 0.498 0.162 0.410 0.060 0.577 0.075
C18_LaMa 0.604 0.099 0.575 0.025 0.815 0.161 0.547 0.190
C21_GeTo 0.578 0.072 0.578 0.072 0.616 0.176 0.389 0.087
C22_AnAn 0.408 0.142 0.564 0.154 0.897 0.055 1.018 0.053
C23_GeLu 0.322 0.013 0.228 0.080 0.575 0.198 0.645 0.157
S01_BiSo 0.654 0.050 0.471 0.079 0.535 0.151 0.746 0.121
S02_FeRo 0.498 0.191 0.381 0.168 0.584 0.120 0.773 0.110
S03_VaAn 0.622 0.162 1.431 0.113 0.845 0.071 0.872 0.067
S04_FaMa 0.808 0.203 0.890 0.140 0.468 0.071 0.453 0.077
S05_ToMa 0.634 0.293 0.365 0.204 0.688 0.117 1.119 0.087
S06_MoAl 0.614 0.139 0.721 0.076 0.960 0.081 0.538 0.059
S07_BeMa 0.162 0.018 0.166 0.053 0.156 0.048 0.259 0.070
S08_CaLe 0.835 0.075 0.946 0.045 1.119 0.046 0.942 0.363
S09_DaVe 0.648 0.078 0.987 0.110 0.474 0.133 0.432 0.077
S001BoLu 1.007 0.085 1.050 0.154 0.880 0.038 0.706 0.131
S002MoLu 0.419 0.059 0.314 0.027 0.213 0.106 0.274 0.031
S004FoAl 0.434 0.074 NaN NaN 0.556 0.013 0.603 0.000
S005MaDa 0.434 0.218 0.517 0.091 0.735 0.165 0.854 0.169
S009LeMa 0.662 0.085 0.460 0.008 0.498 0.103 0.730 0.115
S011ZoDe 0.863 0.299 0.832 0.238 NaN NaN 0.948 0.485
Table 18: Mean and standard deviation values for the FCU / ECR muscles co-contraction.

127
 SUBJECTS pValues
Condition Day Interaction
C10_DeMa <0.001 0.005 0.490
C11_DeLu 0.072 <0.001 0.778
C12_FaLu 0.734 <0.001 <0.001
C13_FaCa 0.172 0.011 0.085
C14_BaCa <0.001 0.003 <0.001
C15_LaAn 0.105 <0.001 <0.001
C16_LaEl 0.002 0.439 0.529
C17_LaGi 0.208 0.002 0.510
C18_LaMa 0.038 0.001 0.008
C21_GeTo 0.004 0.044 <0.001
C22_AnAn <0.001 0.001 0.631
C23_GeLu <0.001 0.781 0.070
S01_BiSo 0.044 0.709 <0.001
S02_FeRo 0,002 0.592 0.030
S03_VaAn <0.001 0,000 <0.001
S04_FaMa <0.001 0.443 0.273
S05_ToMa <0.001 0.299 <0.001
S06_MoAl 0.009 <0.001 <0.001
S07_BeMa 0.013 0.003 0.005
S08_CaLe 0.090 0.683 0.080
S09_DaVe <0.001 <0.001 <0.001
S001BoLu <0.001 0.073 0.004
S002MoLu <0.001 0.350 0.001
S005MaDa <0.001 0.097 0.600
S009LeMa 0.260 0.752 <0.001
Table 19: Results of the 2-way ANOVA for the FCU / ECR muscle co-contraction.

128
 SUBJECTS noBFD1 noBFD5 BFD1 BFD5
Mean SD Mean SD Mean SD Mean SD
C10_DeMa 0.473 0.048 0.801 0.056 0.315 0.039 0,431 0.031
C11_DeLu 0.303 0.030 0.604 0.107 0.524 0.045 0.506 0.068
C12_FaLu 0.675 0.068 0.528 0.092 0.495 0.108 0.675 0.190
C13_FaCa 0.574 0.085 0.320 0.021 0.374 0.035 0.365 0.022
C14_BaCa 0.737 0.038 0.703 0.064 0.707 0.055 0.520 0.064
C15_LaAn 0.519 0.035 0.459 0.048 0.755 0.104 0.799 0.117
C16_LaEl 0.725 0.035 0.695 0.063 0.395 0.070 0.814 0.066
C17_LaGi 0.369 0.036 0.727 0.110 0.700 0.128 0.706 0.038
C18_LaMa 0.353 0.035 0.027 0.002 0.607 0.078 0.200 0.075
C21_GeTo 0.249 0.024 0.249 0.024 0.447 0.124 0.195 0.019
C22_AnAn 0.362 0.029 0.337 0.121 0.186 0.056 0.650 0.132
C23_GeLu 0.298 0.047 0.082 0.016 0.401 0.033 0.396 0.118
S01_BiSo 0.703 0.073 0.583 0.103 0.591 0.050 0.618 0.119
S02_FeRo 0.825 0.172 0.721 0.131 0.686 0.091 0.640 0.167
S03_VaAn 0.311 0.046 0.293 0.070 0.759 0.036 0.598 0.040
S04_FaMa 0.698 0.108 0.576 0.042 0.545 0.044 0.232 0.022
S05_ToMa 0.207 0.061 0.239 0.045 0.481 0.098 0.747 0.044
S06_MoAl 0.307 0.036 0.338 0.037 0.601 0.114 0.464 0.078
S07_BeMa 0.174 0.018 0.552 0.057 0.106 0.019 0.311 0.050
S08_CaLe 0.534 0.035 0.780 0.098 0.760 0.087 0.853 0.089
S09_DaVe 0.902 0.075 0.789 0.110 0.798 0.134 0.649 0.145
S001BoLu 1.006 0.130 0.884 0.164 0.795 0.087 0.491 0.218
S002MoLu 1.017 0.048 0.382 0.027 0.551 0.034 0.405 0.043
S004FoAl 0.832 0.045 NaN NaN 0.388 0.107 0.294 0.000
S005MaDa 0.630 0.057 0.665 0.160 0.601 0.136 0.756 0.121
S009LeMa 1.021 0.030 0.878 0.012 0.832 0.106 0.938 0.090
S011ZoDe 0.475 0.208 0.530 0.173 NaN NaN 0.712 0.339
Table 20: Mean and standard deviation values for the BIC / TRIC muscles co-contraction.

129
 SUBJECTS pValues
Condition Day Interaction
C10_DeMa <0.001 <0.001 <0.001
C11_DeLu 0.009 <0.001 <0.001
C12_FaLu 0.714 0.726 0.001
C13_FaCa <0.001 <0.001 <0.001
C14_BaCa <0.001 <0.001 <0.001
C15_LaAn <0.001 0.801 0.133
C16_LaEl <0.001 <0.001 <0.001
C17_LaGi <0.001 <0.001 <0.001
C18_LaMa <0.001 <0.001 0.028
C21_GeTo <0.001 0.004 <0.001
C22_AnAn 0.029 <0.001 <0.001
C23_GeLu <0.001 <0.001 <0.001
S01_BiSo 0.224 0.145 0.025
S02_FeRo 0.086 0.234 0.641
S03_VaAn <0.001 <0.001 <0.001
S04_FaMa <0.001 <0.001 <0.001
S05_ToMa <0.001 <0.001 <0.001
S06_MoAl <0.001 0.037 0.002
S07_BeMa <0.001 <0.001 <0.001
S08_CaLe <0.001 <0.001 0.028
S09_DaVe 0.007 <0.001 0.668
S001BoLu <0.001 <0.001 0.074
S002MoLu <0.001 <0.001 <0.001
S005MaDa 0.307 0.009 0.172
S009LeMa 0.096 0.628 0.003
Table 21: Results of the 2-way ANOVA for the BIC / TRIC muscles co-contraction.

130
 SUBJECTS noBFD1 noBFD5 BFD1 BFD5
Mean SD Mean SD Mean SD Mean SD
C10_DeMa 0.611 0.091 0.853 0.095 0.412 0.048 0.694 0.099
C11_DeLu 0.322 0.051 0.688 0.054 0.467 0.051 0.665 0.100
C12_FaLu 0.754 0.119 0.628 0.092 0.451 0.084 0.555 0.145
C13_FaCa 0.460 0.230 0.484 0.047 0.596 0.080 0.400 0.068
C14_BaCa 0.829 0.145 0.965 0.043 0.549 0.100 0.573 0.054
C15_LaAn 0.604 0.055 0.512 0.104 0.984 0.082 1.070 0.053
C16_LaEl 0.841 0.042 NaN NaN 0.667 0.047 0.848 0.068
C17_LaGi 1.325 0.106 1.411 0.148 1.264 0.102 1.508 0.131
C18_LaMa 0.863 0.077 0.795 0.049 1.239 0.055 1.094 0.123
C21_GeTo 0.956 0.159 0.956 0.159 0.746 0.132 0.664 0.108
C22_AnAn 0.645 0.138 0.769 0.125 1.225 0.244 0.987 0.153
C23_GeLu 0.842 0.094 0.652 0.057 1.021 0.118 1.033 0.187
S01_BiSo 0.575 0.064 0.566 0.051 0.563 0.098 0.781 0.094
S02_FeRo 0.630 0.076 0.903 0.058 0.705 0.106 0.774 0.120
S03_VaAn 0.590 0.109 1.020 0.045 1.145 0.082 0.776 0.056
S04_FaMa 0.601 0.063 0.608 0.125 0.726 0.039 0.449 0.036
S05_ToMa 0.798 0.124 1.000 0.152 0.550 0.117 1.031 0.086
S06_MoAl 0.602 0.078 0.349 0.024 0.664 0.056 0.424 0.055
S07_BeMa 0.288 0.022 0.351 0.079 0.523 0.079 0.495 0.033
S08_CaLe 1.027 0.113 0.593 0.086 0.861 0.040 0.988 0.045
S09_DaVe 0.855 0.260 0.888 0.086 1.084 0.021 0.642 0.142
S001BoLu 0.556 0.069 0.560 0.098 0.636 0.068 0.475 0.141
S002MoLu 0.649 0.030 0.510 0.046 0.302 0.065 1.060 0.058
S004FoAl 0.670 0.067 NaN NaN 0.632 0.176 0.455 0.000
S005MaDa 0.490 0.220 0.688 0.181 0.735 0.162 0.800 0.200
S009LeMa 0.844 0.023 0.839 0.032 0.943 0.042 0.621 0.155
S011ZoDe 0.573 0.177 0.547 0.172 NaN NaN 0.921 0.529
Table 22: Mean and standard deviation values for the AD / PD muscles co-contraction.

131
 SUBJECTS pValues
Condition Day Interaction
C10_DeMa <0.001 <0.001 0.526
C11_DeLu 0.008 <0.001 0.001
C12_FaLu <0.001 0.794 0.008
C13_FaCa 0,524 0.045 0.012
C14_BaCa <0.001 0.015 0.082
C15_LaAn <0.001 0.923 0.009
C16_LaEl 0.391 0.391 0.391
C17_LaGi 0.710 0.002 0.103
C18_LaMa <0.001 <0.001 0.140
C21_GeTo <0.001 0.422 0.332
C22_AnAn <0.001 0.318 0.003
C23_GeLu <0.001 0.047 0.025
S01_BiSo 0.001 <0.001 <0.001
S02_FeRo 0.477 <0.001 0.012
S03_VaAn <0.001 0.274 <0.001
S04_FaMa 0.483 <0.001 <0.001
S05_ToMa 0.030 <0.001 0.007
S06_MoAl 0.001 <0.001 0.726
S07_BeMa <0.001 0.369 0.026
S08_CaLe <0.001 <0.001 <0.001
S09_DaVe 0.889 0.001 <0.001
S001BoLu 0.937 0.015 0.011
S002MoLu <0.001 <0.001 <0.001
S005MaDa 0.002 0.014 0.170
S009LeMa 0.251 0.004 0.005
Table 23: Results of the 2-way ANOVA for the AD / PD muscles co-contraction.

132
References
A. Albanese et al. (2006). A systematic review on the diagnosis and treatment of primary (idiopathic) dystonia
and dystonia plus syndromes: report of an EFNS/MDS‐ES Task Force.

A. Albanese et al. (2013). Phenomenology and classification of dystonia: A consensus update.

A. Berardelli et al. (1998). The pathophysiology of primary dystonia.

A. H. Hoon Jr. (2001). Age-dependent effects of trihexyphenidyl in extrapyramidal cerebral palsy.

A. Quartarone and M. Hallett . (2013). Emerging concepts in the physiological basis of dystonia.

A. Tewari et al. (2017). It's not just the basal ganglia: Cerebellum as a target for dystonia therapeutics.

B. I. Karp. (1999). An open trial of clozapine for dystonia.

C. Casellato et al. (2013). EMG-Based Visual-Haptic Biofeedback: A Tool to Improve Motor Control in Children
With Primary Dystonia.

C. M. Harris and D. M. Wolpert. (1998). Signal-dependent noise determines motor planning.

E. L. Air et al. . (2011). Deep brain stimulation in children: experience and technical pearls.

F. Lunardini et al. (2015). Increased task-uncorrelated muscle activity in childhood dystonia.

F. Lunardini et al. (2015). Speed-Accuracy Trade-Off in a Trajectory-Constrained Self-Feeding Task: A

Quantitative Index of Unsuppressed Motor Noise in Children With Dystonia.

F. Lunardini et al. (2016). EMG-based vibro-tactile biofeedback improves motor control in children with
secondary dystonia: two case reports.

F. Lunardini et al. (2016). Robustness and Reliability of Synergy-Based Myocontrol of a Multiple Degree of
Freedom Robotic Arm.

F. M. Molloy et al. (2003). Abnormalities of spatial discrimination in focal and generalized dystonia.

H. Huang et al. (2006). Recent developments in biofeedback for neuromotor rehabilitation.

H. Vikne et al. (2013). The smoothness of unconstrained head movements is velocity-dependent.

J. Jankovic. (2006). Treatment of dystonia.

J. Jankovic. (2013). Medical treatment of dystonia.

J. Jankovic et al. (2004). Evidence-Based Review of Patient-Reported Outcomes With Botulinum Toxin Type A.

J. V. Basmajian. (1963). Control and Training of Individual Motor Units.

J. V. Basmajian. (1982). Clinical use of biofeedback in rehabilitation.

M. Bertucco and T. D. Sanger. (2015). Current and emerging strategies for treatment of childhood dystonia.

M. Naumann et al. (2001). Sensory tricks in cervical dystonia: Perceptual dysbalance of parietal cortex
modulates frontal motor programming.

133
N. Hogan, D. Sternad. (2009). Sensitivity of Smoothness Measures to Movement Duration, Amplitude and
Arrests.

Q. Qian. (2017). Assisted with an Electromyography-Driven Neuromuscular Electrical Stimulation-Robotic Arm.

R. Bloom. (2010). Prolonged Electromyogram Biofeedback Improves Upper Extremity Function in Children With
Cerebral Palsy.

R. E. Burke et al. (1986). Torsion dystonia. A double‐blind, prospective trial of high‐dosage trihexyphenidyl.

S. A. Schneider. (2006). Familial dopa-responsive cervical dystonia.

S. J. Young. (2010). Visual Feedback Reduces Co-contraction in Children With Dystonia.

S. J. Young et al. (2011). Visual Feedback Reduces Co-contraction in Children With Dystonia.

S. J. Young et al. (2012). Finger Muscle Control in Children with Dystonia.

T. D. Sanger. (2005). Toward a definition of childhood dystonia.

T. D. Sanger. (2006). Arm Trajectories in Dyskinetic Cerebral Palsy Have Increased Random Variability.

T. D. Sanger and S. N. Kukke. (2007). Abnormalities of Tactile Sensory Function in Children With Dystonic and
Diplegic Cerebral Palsy.

T. D. Sanger et al. (2001). Abnormalities of spatial and temporal sensory discrimination in writer's cramp.

T. D. Sanger et al. (2003). Classification and Definition of Disorders Causing Hypertonia in Childhood.

T. D. Sanger et al. (2010). Definition and classification of hyperkinetic movements in childhood.

V. K. Neychev et al. (2011). The functional neuroanatomy of dystonia.

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