Disease mechanisms Showcase: Spatial Attention and Spatial Neglect

 Spatial neglect
o Can come from stroke or in Alzheimer’s disease
o Those with spatial neglect are not even aware that they are missing part of
the space in their vision
 Case Story
o Vigilance reduced
o Visual fields were normal – no visual impairment relating to blindness
o Always looked to right first and denied the presence of object on the left
o He explored mainly the right side of the table
o Touches to the left hand were inconsistently detected
o Motor function was normal
o Head MRI showed a diffusion restriction in the right inferior and middle
frontal gyrus and anterior insula, consistent with an acute ischemic stroke
 Definition of spatial neglect
o Neglect is a failure to report, respond, or orient to novel pr meaningful
stimuli presented to the side opposite to the brain lesion, when this failure
cannot be attributed to either sensory or motor deficits (Heilman and
Valenstein 1979)
 Not very well understood
 Spatial neglect: disease burden
o Occurs in about 33% of patients with a stroke (Hammerbeck et al., 2019)
o About 3-5 million new cases per year worldwide
o Decreases the ability to carry out everyday tasks like eating, reading ot
crossing a road
o 1/3 of the patients have the disease 1 year after a stroke
o Currently no efficient treatment
 How do we assess spatial neglect?
o Differential diagnostic – are motor and visual functions adequate? Is there a
visual field defect?
o Standardised tests for spatial attention
 Mos of them are visual search tasks
 Does the test show a lateral bias?
o Neuroanatomical assessment – is there evidence for a brain lesion in a critical
area?
o Differential diagnosis
 Look for differences between for example Visuospatial neglect and
homonymous hemianopia
o Behavioural assessments for spatial neglect
 Line bisection task
 Mark the mid-point on a line
 Patients asked to circle full circles and cross out half-circles
 Patient circle half-circles as they neglect the left side of the
circle
 Draw a house
  People draw more to the right – objects are not accurately
represented spatially in drawing recreation
 Identify a letter when there are 2 – one right and one left
o Do neglect tests measure the same thing?
 Some correlations are higher than others
 Line bisection correlates least with other things
o Activity of daily living assessment (CBS rating scale)
 10 questions assessing everyday function
 Higher the score = more severe spatial neglect
 what is the critical lesion in spatial neglect? (VLBM results in 54 stroke patients)
o Find brain areas that correlate positively or negatively with test scores
 The critical lesion depends on the assessment method (meta-analysis of 20 VLBM
studies)
o Depending on the task we use to score neglect severity the lesion sight varies
 Cancellation we see temporal, parietal, frontal lesions
 Different tasks = different lesions
o Spatial neglect is not a homogeneous syndrome
o There are different disease mechanisms
 What is the critical lesion in spatial neglect?
o The hemisphere contralateral to the neglected side, around the perisylvian
(lateral) sulcus
o The exact location depends on the assessment method
 Spatial neglect – disease mechanisms
o Neglect = inattention
o What is attention?
 Attention implies withdrawal from some things in order to deal
effectively with others (James, 1890)
 Attention: we are unaware of more than 99% of visual input
o Human retina receives about 100 megabytes (MB) per second (s) of visual
input data, from about 107 cones. 100MB can store about 40,000 pages of
text uncompressed
o Human retina sends about 1MB/s of visual data to the central brain from 10 6
retinal ganglion cells. This rate is lower than the retinal input data rate largely
by efficient encoding or compression of retinal inputs
o Human attentional bottleneck is about 40 bits/second. This was measured by
Pierce and Karlin (1957) using the speed of reading aloud lists of words. 40
bits can store one to two short sentence of English text
o This suggests that we are unaware of more than 99% of the visual input
 Spatial neglect – Hypotheses of disease mechanism
o 1. Attention hypotheses
 The bias in attention is caused by a lesion of the brain areas that
control the allocation of attention. There is a separate, stand-alone
functional module in the brain
o 2. Transformation Hypotheses
  The brain areas involved in the allocation of attention around the
body are unimpaired. The bias in attention is caused by an error in
perceiving the midline of the body
o Other hypotheses
 Premotor hypothesis – a deficit in planning eye movements (Rizzolatti
and Berti, 1990)
 Representation hypothesis – a deficit in memory representations
(Biasch et al., 1978)
 Limited impact on rehabilitation and assessment so far
 Attention Hypothesis
o Interhemispheric competition
 Opponent processor model (Kinsbourne, 1977)
 If right hemisphere is taken out of competition due to lesion then
attention will be oriented to right hand of space
 There is evidence for this
o Right hemisphere control attention in both visual hemispaces, whereas left
hemisphere control attention in the right hemispace only (Heilman and Van
Den Abell, 1980; Mesulam, 1981)
 No evidence that right hemisphere controls both hemispaces
o The spatial attention bias is worsened by a reduced alertness to new stimuli.
This non-spatial component of attention is represented in the right
hemisphere (Corbetta and Shulman, 2011)
 Circuit-breaker mechanism in brain
 How does the brain implement spatial attention?
o Meta-analysis of 4 experiments
o Perisylvian regions involving spatial neglect are not in this slide
o The symmetry of the representation of attended locations in both
hemispheres refutes the hypothesis that the R brain hemisphere controls
attention in both visual hemispaces, whereas the L brain hemisphere
controls attention in right hemispace only
 Interhemispheric competition in spatial attention – evidence from transcranial
magnetic stimulation (TMS) in healthy participants
o One can reduce legions and activity of focal brain area
o Superior parietal lobe
o Look into TMS use
 Can alleviate spatial neglect
 When TMS is on the right side of the brain – stops function of right
side of brain
 Happened on left side to lesser extent
o Asymmetry between the two hemispheres: the effects are stronger after rTS
over the right brain hemisphere (Hilgetag)
o Problems with the attention hypothesis?
 One problem is that the brain areas that control attention in the healthy brain
differ from those that are lesioned in spatial neglect
 Some observations cannot be easily explained by the lesion of an encapsulated
attention system
 o Sensorimotor interventions influence the severity of spatial neglect
 Neck muscle vibration
 Muscle vibration = person has feeling that muscle elongates
 Sensation is that head is moving to right when left head
muscle is vibrated
 Caloric vestibular stimulation
 Prism adaptation
 Somatosensory cortex lesion
 Transformation hypotheses
o Error in transforming sensory input into a supra-modal frame of reference
that allows us to perceive the midline of our bodies (or egocenter).
o The bias in attention in spatial neglect is caused by ipsilesional shift of the
subjective egocenter
o Jeannerod and Biguer, 1987; Karnath, 1994)
 Participants struggled identifying their actual body midpoint
 Neglect is a disorder of perceived egocenter (body midline)
o Problems
 It assumes a deviation of the egocenter in neglect patients. This is not
always the case
 If the deviation of the egocenter is causal in neglect, one would
expect a positive correlation between this deviation and neglect signs.
This is not the case
 The restoration of the egocenter should improve neglect signs. This is
not always the case
 An experimental deviation of the egocenter in healthy people should
cause neglect. This is not the case
 Different mechanisms may cause spatial neglect in different patients
 Rehabilitation methods
o Attention hypothesis
 TMS/TDCS induces virtual lesion of the healthy hemisphere
o Transformation hypothesis
 Prism adaptation; caloric vestibular stimulation, neck muscle vibration
 The efficacy of rTMS in stroke rehabilitation
o A randomised controlled trial
 30 patients with a R hemisphere stroke and spatial neglect
 Randomised to the intervention (rTMS over the posterior parietal
cortex of the l, intact hemisphere) or the control intervention (sham-
TMS which is an intervention that resembles TMS but has no effect on
the brain)
 Mean score on CBS improved more in the TMS group vs sham. 3
moths after intervention
 How do we assess the efficacy of a treatment?
o Levels of evidence (from lowest to highest)
 One randomised controlled trial (RCT)
 Controlled = effect of the treatment is examined relative to a
control intervention for instance a placebo drug
  Systematic reviews are systematic reviews of all relevant RCTs
o These are the highest levels of evidence available
o Cochrane is an international charity that aims to
produce systematic reviews of treatment efficacy
 Is the treatment efficient in spatial neglect?
o Systematic reviews of 20+ RCTs of cognitive rehabilitation specifically aimed
at spatial neglect
o Some individual studies show a beneficial effect
o Newest review highlights smooth pursuit eye movement training as the most
promising intervention
 Current directions in rehabilitation research
o Investigating the reason for the inter-individual variability in the response to
treatment, which is a step towards individualisation of treatment
 Non-responders to TMS therapy vs responders had a corpus callosum lesion
o In these patients, the competition between brain hemispheres is unlikely to
explain spatial neglect
 We need to have a better understanding of the disease mechanisms