Medical Hypotheses 83 (2014) 450–464

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Medical Hypotheses
journal homepage: www.elsevier.com/locate/mehy

‘‘Clinical brain profiling’’: A neuroscientific diagnostic approach

for mental disorders
Abraham Peled a,b,⇑, Amir B. Geva c
a
Sha’ar Menashe Mental Health Center, Hadera, Israel
b
Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel
c
Electrical and Computer Engineering Department, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel

a r t i c l e i n f o a b s t r a c t

Article history: Clinical brain profiling is an attempt to map a descriptive nosology in psychiatry to underlying constructs
Received 22 April 2014 in neurobiology and brain dynamics. This paper briefly reviews the motivation behind clinical brain pro-
Accepted 22 July 2014 filing (CBP) and presents some provisional validation using clinical assessments and meta-analyses of
neuroscientific publications.
The paper has four sections. In the first, we review the nature and motivation for clinical brain profiling.
This involves a description of the key aspects of functional anatomy that can lead to psychopathology.
These features constitute the dimensions or categories for a profile of brain disorders based upon path-
ophysiology. The second section describes a mapping or translation matrix that maps from symptoms
and signs, of a descriptive sort, to the CBP dimensions that provide a more mechanistic explanation.
We will describe how this mapping engenders archetypal diagnoses, referring readers to tables and fig-
ures. The third section addresses the construct validity of clinical brain profiling by establishing correla-
tions between profiles based on clinical ratings of symptoms and signs under classical diagnostic
categories with the corresponding profiles generated automatically using archetypal diagnoses. We then
provide further validation by performing a cluster analysis on the symptoms and signs and showing how
they correspond to the equivalent brain profiles based upon clinical and automatic diagnosis.
In the fourth section, we address the construct validity of clinical brain profiling by looking for associ-
ations between pathophysiological mechanisms (such as connectivity and plasticity) and nosological
diagnoses (such as schizophrenia and depression). Based upon the mechanistic perspective offered in
the first section, we test some particular hypotheses about double dissociations using a meta-analysis
of PubMed searches. The final section concludes with perspectives for the future and outstanding valida-
tion issues for clinical brain profiling.
Ó 2014 Elsevier Ltd. All rights reserved.

Motivation for clinical brain profiling
In this section, we review the clinical and theoretical literature
in neuroscience to motivate the pathophysiological basis of clinical
brain profiling. In brief, we will see that two cardinal dimensions or
axes emerge. The first is the degree of connectivity in the brain that
can be too high or too low. Variations in connectivity can then be
interpreted functionally in terms of false inference associated with
psychosis, in particular schizophrenia. The second key dimension is
plasticity that we will associate with abnormalities of mood, which
can be associated with aberrant neuromodulation and plasticity in
the brain.
⇑ Corresponding author at: Sha’ar Menashe Mental Health Center, Mobile Post
Hefer 37806, Israel. Tel.: +972 52 2844050.
E-mail address: neuroanalysis@gmail.com (A. Peled).
A common theme in this section will be abnormal connectivity
and its plastic changes that underlies perceptual inference and
learning respectively. This will be considered from a point of view
of graph theory and free energy formulations of the Bayesian brain
hypothesis. The latter is particularly pertinent for psychopathology
that usually can be reduced to some form of false believe or
inference.
The optimal brain probably assumes a small-world-network
organization [2]. This is an organization in which most units are
not neighbors of one another, but most units can be reached from
every other one through a small number of hops or steps (i.e., con-
nections). This entails optimal information transfer and thus opti-
mal brain organization. Such organization requires a certain
balanced connectivity between near-by clustered units and far-
away long-path connections when such a balance is disturbed then
the network can become unstable with different parts of the

http://dx.doi.org/10.1016/j.mehy.2014.07.013
0306-9877/Ó 2014 Elsevier Ltd. All rights reserved.
 A. Peled, A.B. Geva / Medical Hypotheses 83 (2014) 450–464
network becoming ‘‘disconnected’’ thus different units of the net-
work become statistically independent of each other (randomly).
Optimal integrated brain system can become disintegrated when
biased from the optimal small-world organization [2].
Small-world organization is characterized by ‘‘Hubs’’ that are
network junctions with numerous connections. Hubs allow for
brain hierarchy of information processing. ‘‘Unimodal’’ processors
(e.g., auditory visual somatosensory) integrate at ‘‘multimodal’’
levels (i.e., associative cortices) and these further integrate at
whole brain ‘‘transmodal’’ levels [3] to create the integrated con-
scious experience of a well-organized coherent familiarity. Thus,
hubs allow integration of multiple modalities and the higher-level
networks of hubs create integrated transmodal global whole-brain
organization.
With hierarchy comes bottom-up top-down hierarchical bal-
ance, and well organized sophisticated global integrations that
are both stable and changeable at the same time, offering the brain
its complexity, flexibility and adaptability required for its extre-
mely intricate activity [4].
The connectivity of the brain allows the brain to acquire ‘‘emer-
gent properties’’ that are synergistic. The system as a whole dem-
onstrates phenomena that are not achievable at the level of its
elements. For example, the brain realizes phenomena such as con-
sciousness, personality, mood and feelings. Single neurons, or
groups of neurons do not have such characteristics. Here we
approach the philosophical issue of ‘‘psychophysics’’; higher men-
tal phenomena implemented in mental disorders are emergent
properties from global brain organizations, and mental disorders
themselves are thus disturbances to the optimal global brain con-
figurations, i.e., ‘‘Globalopathies’’ [5].
Global workspace theory explains consciousness as an emer-
gent property of global transmodal brain organization [6]. Partial
parallel unconscious processes integrate into a momentary unitary
event of whole brain integration, each emerging as an instanta-
neous conscious experience. This is why consciousness is experi-
enced as a serial phenomenon in time, even though the brain is a
parallel processing machine [7]. Global organizations give con-
scious experience its integrity; it is always unitary complete, and
cannot disintegrate (e.g., Necker cube). One can conceive what
would happen to conscious experience if global brain organizations
were to disintegrate. We know that vast disintegration of brain
organization is accompanied by loss of consciousness, but milder
forms of disintegration can result in distortions and misrepresenta-
tions within the conscious experiencing of events.
Plasticity is another major organizational phenomena in the
brain. We know that the brain continually creates new connections
and loses old ones. This is implemented by synaptogenesis and
synaptic-deletion which is governed by incoming input stimuli,
i.e. governed by experience [8]. ‘‘Experience-dependent-plasticity’’
is the term used to indicate that brain connectivity is determined
by experience. Donald Hebb [9] stated the famous axiom of ‘‘fire
together wire together’’ implying that if within a certain experi-
ence (input) if two neurons are excited simultaneously repeatedly,
than the connection between them is strengthened. The opposite is
also correct, if they do not fire together (desynchronized) than the
connection between them is weakened.
This mechanism has been useful in embedding information
within neuronal network structures [10], implying that memories
in the brain are probably acquired by similar mechanisms of plas-
ticity increase of connection strength. If a certain experience is rep-
resented by activation of neuronal ensembles then the reactivation
of these units strengthens connectivity among the units of the
ensemble embedding the experience within the network connec-
tivity formation. Recall is achieved once some of the units of the
‘‘memory ensemble’’ are activated by input, activating the entire
451
memory construct by virtue of strong connections that excite all
the units strongly bounded by the strengthened connectivity.
This mechanism explains the acquisition of internal representa-
tions of the outer world archived by the brain. During develop-
ment, experiences of the individual are gradually embedded in
the developing brain by Hebbian mechanisms of plasticity. Thus,
an internal representation of experience is gradually developing;
the mature brain is capable of representing its external physical
and psychosocial environment.
Furthermore, the brain uses the internal representations as
guidance for action, i.e., the internal representations govern the
reactions and behaviors within the psychosocial world, thus it is
of utmost importance that the internal representations ‘‘match’’
and reliably represent the occurrences of the reality of one’s life.
The adaptability of the brain is achieved by plasticity using a
‘‘Bayesian brain’’ dynamics [11], the brain continually predicts
the patterns of incoming stimuli and acts to adapt to them contin-
ually reducing the differences, i.e., reducing the ‘‘free energy’’ the
diversity in terms of thermodynamic entropy calculation [12]. In
this context, free energy is a statistical measure of the goodness
of fit between sensory input and the brain’s best guess or hypoth-
esis about the causes of those inputs. Put simply, free energy can be
regarded as the amount of prediction error; where prediction error
is the actual sensory input minus the predicted sensory input.
The plastic brain achieves low free energy by increasing match-
ing capabilities [13]. Thus, it is adaptable and equipped with an
optimal reliable internal representation system that effectively
governs the individual in the constantly changing events of every-
day contemporary life. One can immediately conceive what would
happen if plasticity is impaired, internal representations are com-
promised, and if adaptability fails and the individual afflicted
begins to make erroneous actions and reactions to everyday
occurrences.
In this progression of plasticity and internal representations
there are two interdependent processes. The first is that of internal
configurations embedded in the form of strengthened connections,
the second is free-energy dynamics, which increases and decreases
based on both the plasticity and the degree of change in the envi-
ronment. If plasticity is impaired, the brain cannot adapt to the
dynamic environment and free energy increases; if plasticity is
not affected, but the alterations in the environment are abrupt
and large, the plastic brain does not have enough time to adapt
and free energy increases anyway. Thus, two interdependent pro-
cesses can increase free energy, aberrant plasticity, and environ-
mental changes. If both occur together, i.e., plasticity is
compromised and the environment changes substantially, free
energy will increase [5]. Disturbed plasticity, as well as stress
(abrupt changes) are correlated with depressed mood, thus it is
reasonable to conceive mood as an emergent property from global
free energy dynamics of the brain. With reduced plasticity and
increased stressful events free energy increases accompanied by
depressed mood, thus we can conceptualize depression as the
emergent property of free energy dynamics of the brain. Inversely
increased plasticity is at the basic mechanism of antidepressant
medications, thus reduced free energy due to plasticity-induced
environmental-matching is accompanied by the emergent prop-
erty of elevated mood [5].
Although it may sound a bit abstract to cast brain function in
terms of free energy minimisation, there is in fact a fairly simple
rationale for this. The minimisation of free energy referred to here
is a way of describing Bayesian inference. This is important
because one can cast many symptoms and signs in terms of false
inference or beliefs. This is obvious for things like delusions and
hallucinations; however, it also covers beliefs about movement
and agency that could even be relevant to things like Parkinson’s
452 A. Peled, A.B. Geva / Medical Hypotheses 83 (2014) 450–464
disease. Furthermore, there is a quantitative mapping between the
changes in free energy over different timescales and mood (see
[6]). This allows us to also accommodate a mechanistic explanation
for disorders of mood. Note that there is an alternative perspective
on emotional regulation, afforded by interoceptive inference and
its abnormalities that can be found in Seth [7].
The link between mood and personality can be conceived via
mal-adaptability of internal representations characterizing
personality disorders. Internal representations are non-matching,
non-adapting, to the occurrences in their surroundings, and such
non-adaptive dynamics increase free energy resulting in an emer-
gent property of depressed mood. Since these mismatches con-
tinue, those suffering from personality disorders typically
complain about long-lasting continuous depression (dysthymia).
To summarize; small-world network organization is a funda-
mental requisite for the stability of a hierarchal brain and thus of
coherent stable conscious experience. Plasticity is essential for
adaptability, development and learning. The adaptable brain devel-
ops mature internal representations capable of optimal psychoso-
cial achievements (i.e., mature adaptable personality). Thus the
high mental functions of ‘‘consciousness’’, ‘‘mood’’ and ‘‘personal-
ity’’ can be linked to ‘‘connectivity,’’ ‘‘on plasticity’’ and ‘‘Hebbian
internal representations’’. Mental disorders in the domains of con-
sciousness such as psychosis, mood such as depression, and per-
sonality such as personality disorders, can be linked to
disturbances of connectivity, plasticity and ‘‘Hebbian internal
representations’’.
Translation matrix
In the general sense, the conscious experience of the psychotic
patient is distorted and biased because of experiences such as
delusions hallucinations and owing to disorganization of thought
process with loosening of associations and disturbances of logic.
As explained above, coherent stable conscious experience is
related to optimal connectivity, then psychotic experience can be
related to disintegration of connectivity optimization. Here ‘‘Cs’’
connectivity segregation is the dimension of CBP related to pathol-
ogy of connectivity, with segregation and disconnection (see also
Table 1). For example, if auditory and speech-processing cortices
act independently from visual and the rest of the cortex then talk-
ing voices can be experienced even though there is no one around.
Thus a perception without stimulus occurs (i.e., hallucinations). If
concepts are activated as memories of neuronal ensembles linked
by pathways of associations, then a disintegrated brain will display
fragmented thought processes with loosening of associations and
Table 1
Clinical brain profiling – diagnoses.
Symbol Brain dynamic disturbance Assumed clinical correlate
DMN Undeveloped disturbed DMN Personality disorders
organization
Cs Disconnectivity dynamics Psychosis and positive signs
schizophrenia
Ci Overconnectivity dynamics Repetitive poverty ideation
perseverations
Hbu Hierarchical bottom-up Avolition and negative signs
insufficiency schizophrenia
Htd Hierarchical top-down shift Systemized organized delusions
D Deoptimization dynamic shift Symptoms and signs of
depression
O Hyper-optimization dynamic Symptoms and signs of mania
shift
CF Constrain frustration Symptoms and signs of anxiety
CFb Stimulus bound constrain Symptoms and signs of phobias
frustration
illogical references. Illogical thinking results in erroneous conclu-
sions leading to delusional ideation. Thus, one can conceive how
disintegrated cortical activity may lead to psychotic phenomenol-
ogy (Cs in Table 1).
In the post-psychotic progression of schizophrenia, negative
signs arise as the patient becomes deficient, with poverty of
thought and perseverative ideations. Overly connected networks
tend to converge into few repeated states reactivating the same
neuronal ensembles repeatedly due to the overly connected
mutual excitations [14]. ‘‘Ci’’ connectivity integration in Table 1
encodes this type of overly connected pathology. If initially the sys-
tem could activate multiple states, now with over-connectivity
taking hold, the system becomes constricted to those few repeat-
edly activated states. This description corresponds to the phenom-
enology of negative signs schizophrenia where poverty of speech
with perseveration occurs. Moreover if hierarchal connectivity dis-
rupts, as probably happens when connectivity is disturbed, then
higher mental functions, those of higher-level brain integration
(e.g., volition) fade and the debilitating loss of motivation and
‘‘zombie-like’’ schizophrenia phenomenology takes over [15]. This
is the hierarchal bottom up ‘‘Hbu’’ disturbance of CBP shown in
Table 1. Disturbances of hierarchical connectivity may also cause
top-down biased control with delusional ideations (schemata)
biasing experience leading to systemized delusions. This is the
CBP dimension of hierarchal top-down ‘‘Htd’’ shown in Table 1.
CBP describes schizophrenia spectrum phenomenology as
‘‘imbalanced connectivity’’ alternating between the two types of
dynamics, Cs and Ci, as the disease progresses from one psychotic
episode to the next. Over time the cortical organization is reduced
due to the repeated perturbation and in-between psychotic epi-
sodes deficiency syndrome increases. Thus the disease progresses
alternating between disconnection and over-connection imbalance
over time [15]. Such instability probably modifies brain hierarchy
destroying it and eliminating higher mental function and alterna-
tively fixating delusional ideations. The entire spectrum of the
schizophrenias phenomenology can be related to globally distrib-
uted connectivity and hierarchical brain pathology [5].
In mood disorders, other aspects of brain organization become
relevant. Currently the most effective antidepressant treatment is
the group of SSRI medications. These have been known to increase
plasticity [16]. Electro Convulsive Therapy ECT is also a known
effective antidepressant treatment, and increases plasticity [17].
Neuronal death and brain atrophy are also related to depression,
for example in dementia [18]. From the theoretical foundations
above, the plastic brain is adaptable in the sense that it reduces
free energy by executing its Bayesian function of predicting and
adapting to incoming stimuli. During development this process
generates the incorporation of experiences (as memories) that cre-
ate an internally represented model of reality (physical and psy-
chosocial). The model is dynamic as it changes and adapts to
incoming real-world environmental changes. The environment
offers continually changing stimuli because the environment is
highly dynamic. Thus there continued adjustment of optimization
of the internal configurations to the actual occurrences depends on
plasticity. When the optimization succeeds, elevated mood is
maintained but when the system is de-optimized because the dif-
ferences between the internal representations and environmental
occurrences increase (increased free energy) then deoptimization
occurs and depressed mood arises as an emergent property [5].
Thus ‘‘D’’ deoptimization is the CBP dimension for depressed
patients. Opposing, optimization dynamics causes elevated mood
thus ‘‘O’’ is the CBP dimension for manic phenomenology, see
Table 1 below.
Thus, two sources can contribute to initiate depression; plastic-
ity in general, when hampered causes depression, but also altered
internal representation when biased from (not matching) external
 A. Peled, A.B. Geva / Medical Hypotheses 83 (2014) 450–464
occurrences increases free energy and causes depression. This is
why personality disorders phenomenologically present in clinical
settings with complaints of depression [19].
Here personality disorders are presumed to occur when
developmental experiences create biased immature internal repre-
sentations which are non-adaptive and continually mismatch with
real-world occurrences. Thus there are elevated peaks of free-
energy that are expressed as depressive episodes. The internal rep-
resentations are embedded in the developed brain organization, or
in other words the basic ‘‘at rest’’ neuronal networks that are typ-
ically also called ‘‘Default Mode Networks’’ (DMN). They have
obtained this name because they are active as default when cogni-
tive-task-related networks are not active, i.e., at rest [20]. The
default mode resting-state network organization probably incor-
porates information in the form of memories using Hebbian-like
mechanisms, which create ‘‘attractor’’ formations to represent
the internal model of the outer world (i.e., attractors states to
which the system is attracted to when reactivating a memory). It
is probable that resting-state networks are also characterized by
SWN organization, and those suffering from personality disorders
will show altered SWN organization in addition to immature orga-
nization levels of attractor-formations [5]. The altered immature
biased resting state networks are easily destabilized leading to
deoptimization (depression) and even disruptions of the system
(tendencies to psychosis) as typically seen in patients with person-
ality disorders. As a CBP dimension such disturbance to the ‘‘DMN’’
is ironed for those suffering from personality disorders in Table 1
below.
The model of optimization dynamics for mood changes is also
useful to explain reactive depression from stressful events. A
stressful event always implies a massive abrupt change in the envi-
ronment, (e.g., losing a close family member, or being fired from
work). These changes in environmental occurrences will inevitably
mismatch the internal configurations that represented the pre-
stress environmental configurations. These major abrupt changes
in the environment cause an abrupt increase of free energy which
the brain struggles to avoid. Deoptimization dynamics are trig-
gered as the mismatch between the internal representations and
the altered environment increase drastically. The resulting emer-
gent property is depressed mood.
Using similar reasoning anxiety is conceptualized as an emer-
gent property of widespread whole-brain neural network pertur-
bation [5]. Normally during brain computation and organization
the neural networks are more or less stable. Such stability can be
conceptualized using the idea of ‘‘multiple constraint satisfaction.’’
Each unit in the system, in our case each neuron or group of neu-
rons, exerts connectivity constraints on all the other units con-
nected to it. Similarly it receives multiple constraints from all the
other neurons connected to it, thus each unit assumes activity val-
ues which can be defined as ‘multiple-constraint-satisfaction.’ As
such the entire network follows this law of constraint-satisfaction
which is in accord with the free energy principle. Any perturbation
to the network will inevitably increase the ‘‘values’’ of constraints
dissatisfaction as ‘surprises’ increased free-energy and spreads in
the network. Such destabilization and increases in free-energy is
assumed to emerge as a sensation of anxious mood. In the transla-
tion of Table 1 below CF (constraint frustration) is the dimension
preserved for generalized anxiety patient and when phobia arises
with ‘‘bounding’’ of fear to a recognized object stimuli CFb (‘‘b’’
for bound) is chosen, see Table 1.
Most, if not all types of perturbation presumably involve the
emergent-property of anxiety. We know from clinical experience
that most mental disorders are accompanied with concomitant
anxious and depressed mood. Patients suffering from personality
disorders, depression and psychosis frequently also suffer also
from anxiety and depression.
453
Table 1 proposes a novel outline where clinical manifestations
are translated to their presumed correlated brain-disturbances.
With the outline of Table 1, a ‘‘translating matrix’’ can be com-
posed where clinical phenomenology is translated to neuroscien-
tific brain disorders. The task is to assign to each clinical
descriptive phenomenology of mental disorders its presumed brain
disturbances. Thus in the CBP matrix, clinical evaluations are input
entries and the proposed neuroscientific brain disturbances are
outputs. The input item entries of clinical evaluations are repre-
sented by the left column in Table 2 and the proposed neuroscien-
tific brain disturbances are represented by values of the top row in
Table 2.
Assignment of symptoms to brain disturbances is made using
scores of ‘‘ones,’’ for example in the fourth row, motor slowness
is attributed to connectivity integration (Ci) Hierarchical bottom
up insufficiency (Hbu) and De-optimization dynamics (D), these
are the depressed and deficient, negative signs, of schizophrenia
patients. As evident the motor slowness is specifically assigned
to few predicted brain disturbances, other findings can be of a
more general attribute for example in the top row the finding of
a disorderly patient, is attributed to nearly all brain disturbances.
Even though the matrix uses only ‘‘ones’’ and ‘‘zeroes’’ it still
accounts also for the severity of symptoms, for example in the sec-
ond line of Table 2, finding the patient ‘‘very messy’’ which is a
degree worse than ‘‘disorderly’’ is manifested in the matrix by add-
ing an additional score to the relevant proposed brain disturbance.
The values of the first line in Table 2 indicating neuroscientific
brain disturbances are represented by accumulated scores of
‘‘ones’’ calculated as percentages of the total list of 54 signs, 18
symptoms and 14 history items, in all 86 of the items entries of
clinical evaluations represented at the left column in Table 2. Thus,
with the CBP format, the neuroscientific prediction is extracted as a
percentage value from the ‘‘phenomenological field’’ of 86 ‘‘phe-
nomenological entries’’ (Eq. (1)).
Equation 1 : phenomenological field
¼ phenomenological entries  100=86
The translation matrix actuated in Table 2 is faithful to the CBP
formulations of Table 1 as for example, all the signs and symptoms
of Psychosis and positive signs schizophrenia will be translated
into predicted ‘‘disconnection dynamics’’ with segregated global
brain organization as the presumed cause. The negative signs will
be translated to connectivity integration (Ci) Hierarchical bottom
up insufficiency (Hbu) and so on until all CBP predictions are
covered.
To summarize; the CBP translation uses binary 1, 0 scoring.
Going from top rows downward, the clinical findings are ordered
according to (1) signs, (2) symptoms and (3) clinical history of psy-
chiatric manifestations. Each clinical finding contributes a ‘one’
value score to its relevant correlated brain disturbance. The disor-
dered neuroscientific brain profile is a numerical vector constructed
by a set of values for ‘CSPD,’ ‘Cs,’ ‘Ci,’ ‘Hbu,’ ‘Htd,’ ‘D,’ ‘O,’ ‘CF’ and
‘CFb’ each composed of a summary of scores divided by the number
of all possible observations (i.e., the number of all clinical observa-
tion entries which is 87). As explained above, ‘‘grading’’ of clinical
findings is also incorporated in the CBP matrix, for example ‘Is the
patient very messy?’ is a higher degree finding than ‘Is the patient
disorderly?’ Thus if the patient is very messy rather than just disor-
derly, his score will be higher in the matrix. A web-based CBP pro-
gram is available open access at: http://neuroanalysis.org.il/?
page_id=114.
To increase the reliability of CBP, Table 3 describes each entry
for a consistent recording of patient’s phenomenology. As evident
the recording of phenomenology attempts to adhere to the current
descriptive consensual modes of diagnosing patients. Artificially
454 A. Peled, A.B. Geva / Medical Hypotheses 83 (2014) 450–464

Table 2
CBP translation matrix.

Detected CSPD Cs Ci Hbu Htd D O CF CF (b)

Is the patient disorderly? 1 1 1 1 1 1 1 0
Is the patient very messy 0 1 1 1 0 1 0 0 0
Is the patient with excessive jewelry makeup and colored clothing? 0 0 0 0 0 0 1 0 0
Moves slowly? 0 0 1 1 0 1 0 0 0
Stiff frozen? 0 0 1 1 0 1 0 0 0
Restless moves a lot? 0 1 0 0 0 0 1 1 0
Agitated looks as on verge of blowing up? 0 1 0 0 0 0 1 1 0
Bizarre unexplainable movement 0 1 0 0 0 0 0 0 0
Repetitive stereotype movements? 0 0 1 0 0 0 0 0 0
Speaks slowly? 0 0 1 1 0 1 0 0 0
Speaks little, gives short responses? 0 0 1 1 0 1 0 0 0
Speaks little, few words only or non at all 0 0 1 1 0 1 0 0 0
Speech at low tone or whisper 0 0 1 1 0 1 0 0 0
Speaks fast? 0 0 0 0 0 0 1 0
Speaks a lot, gives long spontaneous responses? 0 1 0 0 0 0 1 1
Speaks without stopping jumping from one issue to another? 0 1 0 0 0 0 0 0 0
Speech with elevated tone? 0 1 0 0 0 0 1 1
Speech associations are loose; jumps from one sentence to another each different topic? 0 1 0 0 0 0 0 0 0
Words are unrelated within sentences ‘word salad’? 0 1 0 0 0 0 0 0 0
Repeating same topics of conversation? 0 0 1 0 0 0 1
Repeating perseverating the same sentences? 0 0 1 0 0 0 0 0 0
Responding to previous question? 0 0 0 0 0 0 0 0 0
Obsessions and compulsions? 0 0 1 0 0 0 1
Delusion, false unshakable belief? 0 1 1 1 1 0 0 0 0
Systemized delusion? 0 0 0 0 1 0 0 0 0
Illogical conclusions are non logical? 0 1 1 0 1 0 0 0 0
Mood incongruent delusion? 0 1 0 0 0 0 0 0 0
Flight of ideas 0 1 0 0 0 0 1
Speech content includes mainly issues of despair, hopelessness, and pessimism 1 0 0 0 0 1 0 0 0
Speech content includes mainly issues of megalomania, over empowerment and unrealistic optimism (and plans) 0 0 0 0 0 0 1 0 0
Bizarre or overly abstract response to categorization (proverbs) and abstraction? 0 1 0 0 0 0 0 0 0
Concrete interpretation of proverbs and low abstraction? 0 0 1 1 0 0 0 0 0
Auditory hallucinations? 0 1 0 0 0 0 0 0 0
Visual tactile olphactory hallucinations? 0 0 0 0 0 0 0 0 0
Hypomimic affect 0 0 1 1 0 1 1 0
Blunt affect? 0 0 1 1 0 1 0 0 0
Expansive mood elevated affect? 0 0 0 0 1 1 1
Dysphoric (suffering) affect? 0 0 0 0 0 1 0 0 0
Depressed affect? 0 0 0 0 0 1 0 0 0
Anxious affect? 1 1 0 0 1 1 1
Detached from examiner? 0 0 1 1 0 1 0 0 0
Perplex ambivalent? 0 1 0 0 0 0 0 0 0
Inappropriately close to examiner (no boundaries)? 0 1 0 0 0 0 1 0 0
Suspicious with examiner? 1 1 1 0 1 0 0 0 0
Threatening to examiner? 1 1 0 0 1 0 0 0 0
Seductive toward examiner (theatrical)? 1 0 0 0 0 1 0 0
Sensitive easily offended? 1 0 0 0 0 0 0 0 0
Childish dependent regressive? 1 0 0 0 0 0 0 0 0
Manipulating demanding? 1 0 0 0 0 0 0 0 0
Stubborn obsessive non adaptable? 1 0 0 0 0 0 0 0 0
Tend to idealize or devaluate examiner? 1 0 0 0 0 0 0 0 0
Egocentric un-empathic? 1 0 0 0 0 0 0 0 0
Distractible? 0 1 0 0 0 0 1 1 1
Disoriented? 0 1 0 0 0 0 0 0 0
Memory lose? 0 1 0 0 0 0 0
Complaining of insomnia or hypersomnia? 0 1 1 1 0 1 1 1 0
Complaining of early insomnia? 0 0 0 0 0 0 0 1 0
Complaining of late insomnia? 0 0 0 0 0 1 0 0
Complaining of anorexia wight loss 0 0 0 0 0 1 1 0 0
Complaining of palpitations, dizziness, abdominal cramps and tingling 0 0 0 0 0 0 0 1 0
Complaining of anxiety fear of dying or loosing control panic 0 0 0 0 0 0 0 1 0
Complaining of fear of dying or loosing control panic in specific conditions 0 0 0 0 0 0 0 0 1
Complaining of tension restlessness and agitation 0 1 0 0 0 0 1 1 0
Complaining of avolition indifference apathy anhedonia 0 0 1 1 0 1 0 0 0
Complaining of depressed mood 0 0 0 0 0 1 0 0 0
Complaining of depressed mood especially in the morning 0 0 0 0 0 1 0 0
Complaining about flight of ideas? 0 1 0 0 0 0 1 0 0
Complaining that thing are strange unfamiliar changing not as usual (dereism depersonalization) 0 1 0 0 0 0 0 0 0
Complaining of external control, mind reading, bugging, persecution (about delusions) 0 1 1 0 0 0 0 0 0
Complaining related to systemized delusion 0 0 0 0 1 0 0 0 0
Complaining of low self esteem 1 0 0 0 0 1 0 0 0
Complaining about being easily offended, oversensitive? 1 0 0 0 0 0 0 0 0
Complaining of being impulsive, over imposing? 1 0 0 0 0 0 0 0 0
History of delusions? 0 1 1 0 0 0 0 0 0
 A. Peled, A.B. Geva / Medical Hypotheses 83 (2014) 450–464 455

Table 2 (continued)

Detected CSPD Cs Ci Hbu Htd D O CF CF (b)

History of hallucinations? 0 1 0 0 0 0 0 0 0
History of thought disorders loosening of associations 0 1 0 0 0 0 0 0 0
History of thought disorders perseverations poverty of thought? 0 0 1 0 0 0 0 0 0
History of depressions? 0 0 0 0 0 1 0 0 0
History of mania? 0 0 0 0 0 0 1 0 0
History of anxiety 0 0 0 0 0 0 0 1 0
History of phobias 0 0 0 0 0 0 0 0 1
History of disturbed upbringing, parental loose 1 0 0 0 0 0 0 0 0
History of behavioral problems 1 0 0 0 0 0 0 0 0
History of coping deficiency work and social? 1 0 0 0 0 0 0 0 0
History of instable interpersonal relationships 1 0 0 0 0 0 0 0 0
History of psychosocial or other stress (regular life stressors) 0 0 0 0 0 1 0 1 1
History of trauma (stressor exceeding regular life stress) 0 1 1 0 0 1 0 1 1

Table 3
Scoring criteria for reliability.

Detected Description for scoring

Is the patient untidy? Appearance is somewhat disheveled i.e., greasy hair, dirty clothes as in ‘Grooming and Hygiene’
section (1)
Is the patient very messy Subject’s clothes, body and environment are dirty and foul smelling as in ‘Grooming and Hygiene
section’ (1)
Is the patient with excessive jewelry makeup and colored It is evident that the clothing makeup and jewelry are grossly exaggerated. Excessiveness is the
clothing? criteria. This score should not be assigned to people who are well groomed
Moves slowly? Obvious decrease of motor activity at interview as described in level ‘2’ of retardation on the
Hamilton Depression Scale (3) together with reduction of usage of expressive body gestures as in
‘marked’ level of ‘paucity of expressive gestures’ in the section of ‘affective flattening’ (1)
Stiff or frozen? Subject never gesticulates as in ‘severe’ rating of ’paucity of expressive gestures’ in the section of
‘affective flattening’ (1). In addition motor activity is reduced as rated for ‘stupor’ in the
‘retardation’ item of the Hamilton Depression Scale
Restless, moves a lot? As in ‘fidgets’ in the ‘behavior at interview’ score according to the Hamilton Anxiety scale (4) the
patient finds it difficult to remain seated during the interview, moves a lot in the chair, moves arms
legs, changes position often, he is ‘Restless’ as in the ‘Tension’ score (4)
Agitated looks as if on verge of ‘‘exploding’’? As in ‘Paces’ in the ‘behavior at interview’ score according to Hamilton Anxiety scale (4) looks as if
making the effort to restrain himself from becoming violent. Finds it hard to remain seated during
the interview
Bizarre unexplainable movement Makes movements that are bizarre and non-purposeful, to the extent that they must be effortlessly
noticed as such by interviewer and others. If the movements are explainable and their oddity is
questionable then this item must not be scored as ‘present’
Repetitive stereotype movements? Movements that are repeated in the same (similar) manner; they can be ‘repetitive stereotyped
behavior’ at the ‘marked’ level of the SANS (1)
Speaks slowly? Speech is slow, words are pronounced slowly and pauses between words are longer than usual,
speech must be slower than those who speak slowly. It should be easily and readily evident for the
examiner, if there is doubt then this item must not be scored
Limited verbal communication, gives short responses? Restriction in the amount of spontaneous speech as in ‘Alogia’ section of the SANS (1) answers in
single words or very short sentences, no spontaneous speech; the interview takes the form of
investigation where the examiner repeatedly asks questions and the patient responds only briefly
Limited verbal communication, few words only or non at all Restriction in the amount of spontaneous speech as in ‘Alogia’ section of the SANS (1) Subject says
almost nothing and frequently fails to answer
Speech at low tone or whisper ‘Lack of Vocal inflection’ speaks in monotone, as in ‘affective flattening’ section of SANS (1). In
addition voice is distinguishably weak
Speaks fast? Sentences are uttered rapidly – word follows word immediately. All speech is distinguishably fast
more than the regular higher spectrum of normal speech. It should be easily and readily evident for
the examiner, if there is doubt, this item should not be scored
Speaks a lot, gives long spontaneous responses? Here the emphasis is on the volume of speech (rather than speed, the patient starts to speak
continuously even when not asked any questions, once starting he never ends and it is difficult to
stop him or insert a question while he is speaking)
Speaks without stopping, jumps from one issue to another? In addition to the description of the above previous score, here the patient is practically
unstoppable and speech content is disturbed in the sense that jumping from one concept to
unrelated (or loosely related) concepts is the rule
Speech with elevated tone? Tone is elevated to the extent that the patient seems to be shouting. The tone is higher than the
normal range of voice tones, if there is doubt then this item should not be scored
Speech associations are loose; jumps from one sentence to As in ‘marked derailment’ of the SAPS (2) ‘Frequent instances of derailment: subject is often
another each a different topic? difficult to follow’ only ‘marked’ levels warrant a score here, ‘moderate’ and ‘mild’ do not
Words are unrelated within sentences ‘word salad’? As in ‘severe derailment’ of the SAPS (2) ‘derailment so frequent and/or extreme that the subject’s
speech is almost incomprehensible’ here also the ‘marked and severe incoherence’ items of the
SAPS (2) apply, ‘at least half of the subject’s speech is incomprehensible’
Repeating same topics of conversation? The patient is pre-occupied by a set of thoughts and repeatedly expresses them in speech. Typically
this is expressed in conversation; no matter where the examiner takes the topics of discussion, the
patient inevitably returns to his set of concerns. The examiner cannot divert the patient from his
repeated issues for long and the patient returns to his original thoughts
Repeating/perseverating the same sentences? Here sentences are concretely repeated over and over again

(continued on next page)

456 A. Peled, A.B. Geva / Medical Hypotheses 83 (2014) 450–464

Table 3 (continued)

Detected Description for scoring

Responding to previous question? The patient is ‘stuck’ answering the first question although other additional questions were already
asked. For example what is your name? John, where do you live? John. . . and so on
Obsessions and compulsions? As in DSM
Delusion, false unshakable belief? As in all delusions of the ‘delusions’ chapter of the SAPS (2) rated ‘moderated’ ‘marked’ or ‘severe’
Systemized delusion? Delusion is non-bizarre stable over time tends to grow incorporating new events in the experience
of the patient. As in the delusional disorder of the DSM
Illogical conclusions? As in ‘illogicality’ SAPS (2) rated ‘moderated’ ‘marked’ or ‘severe’
Inappropriate affect? As in ‘inappropriate affect’ SAPS (2) rated ‘moderate’ ‘marked’ or ‘severe’
Flight of ideas As in ‘pressure of speech ‘ SAPS (2) rated ‘moderate’ ‘marked’ or ‘severe’
Speech content includes mainly issues of despair, hopelessness, As in Hamilton Depression Scale (3) items ‘guilt’, ‘helplessness,’ ‘hopelessness’ and ‘worthlessness’
and pessimism – scores 1–4
Speech content includes mainly issues of megalomania, over The subject is concerned with issues of megalomania, over empowerment and unrealistic
empowerment and unrealistic optimism (and plans) optimism (and plans). This must be self-evident and obvious
Bizarre or overly abstract response to categorization (proverbs) Bizarre or overly abstract response to categorization (proverbs) and abstraction
and abstraction?
Concrete interpretation of proverbs? Concrete interpretation of proverbs for example the common characteristic of table chair and
cupboard are that they are made of wood instead of that they are all furniture. Concrete responses
are given even after assisting the patient with examples of abstraction from related issues – for
example ‘‘apple banana orange are fruit’’
Auditory hallucinations? As in ‘auditory hallucinations’ including voices commenting and conversing of the SAPS (2) rated
’mild’ ‘moderate’ ‘marked’ or ‘severe’
Visual tactile olphactory hallucinations? As in the other ‘hallucinations’ Visual tactile and olphactory of the SAPS (2) rated ’mild’ ‘moderate’
‘marked’ or ‘severe’
Constricted affect As in ‘unchanging facial expression’ in the SANS (1) ‘moderate: subject’s expressions are dulled
overall, but not absent’ and ‘‘marked: subject’s face has a flat ‘set’ look, but flickers of affect arise
occasionally’’
Blunt affect? As in ‘unchanging facial expression’ in the SANS (1) ‘‘severe: subject’s face looks ‘wooden’ and
changes little, if at all throughout the interview’’
Expansive mood elevated affect? The subject seems elated overly happy, mood is excessive in a self-evident unquestionable manner
Dysphoric (suffering) affect? Facial expression of suffering; uneasy as in an uncomfortable state of mind. Must be evident, if
questionable no score is applied
Depressed affect? Facial expression is of painful sadness (typical triangle form of eyebrow). Must be evident, if
questionable no score is applied
Anxious affect? Facial expression is of anxious form, constricted facial muscles, and bulging eye expression.
Startled and/or crying expression. Must be evident, if questionable no score is applied
Detached from examiner? The patient behaves as if the examiner (and others), are not there, seems to be reflecting on inner
thoughts and is not available for whatever is occurring in the interview or around him. Must be
evident, if questionable no score is applied
Perplexed, ambivalent? Face expression is similar to that of a person seeing something extraordinary for the first time, and
seems to be lost, not knowing where to turn. Must be evident, if questionable no score is applied
Inappropriately close to examiner (no boundaries)? Attitude toward the examiner is as if he were a ‘buddy’ of the patient or a close intimate relative.
Asks intimate embarrassing intruding questions, sits close to the examiner (may touch or hug him).
Must be evident, if questionable no score is applied
Suspicious with examiner? Suspicious attitude toward the examiner as if the examiner is a threat, or wants to harm the
patient. Must be evident, if questionable no score is applied
Threatening to examiner? Seems as if about to get up and hit the examiner. Must be evident, if questionable no score is
applied
Seductive toward examiner (theatrical)? Attitude toward the examiner is as if he were a ‘buddy’ of the patient or a close intimate relative
but with a seducing actively probing attitude. Must be evident, if questionable no score is applied
Sensitive easily offended? Overly reactive easily offended, tends to respond to regular instructions as if they were harsh
criticism. Must be evident, if questionable no score is applied
Childish dependent regressive? Attitude of the patient gives an impression of a little child, with childish facial expression and
intonation of speech. Needs instructions and guidance even for simple tasks. Must be evident, if
questionable no score is applied
Manipulating demanding? The examiner senses a constant uneasy feeling of being pressed or utilized to say, feel or do
uncomfortable things. Must be evident, if questionable no score is applied
Stubborn, obsessive non adaptable? Attitude to examiner and other events are obstinate, inflexible, and repeatedly insisted upon. Must
be evident, if questionable no score is applied
Tend to idealize or devaluate examiner? Attitude to the examiner as if he is the most wonderful and best therapist in the world, or the worst
person ever; these attitudes can interchange frequently. Must be evident, if questionable no score
is applied
Egocentric un-empathic? Thinks of no one but himself, unable to see the view point of others, cannot put himself in ‘‘others
shoes’’ Must be evident, if questionable no score is applied
Distractible? Every stimulus from the environment causes the subject to turns his attention from the main
course of the interview. Must be evident, if questionable no score is applied
Disoriented? Unable to orient himself, does not know the time and day, may not recognize faces of relatives
Memory loss? Unable to remember things of recent past days and weeks. Recall is typically preserved and long
term memory is typically present
Complaints of Insomnia or hypersomnia? Insomnia or hypersomnia
Complaints of Early insomnia? Early insomnia, hard to fall asleep
Complaints of Late insomnia? Late insomnia, early wake
Complaints of Anorexia Wight loss Anorexia, weight loss
Complaints of palpitations, dizziness, and/or abdominal cramps Palpitations, dizziness, and/or abdominal cramps and/or tingling
and/or tingling
Complaints of anxiety fear of dying or loosing control panic Fear of dying or loosing control panic
 A. Peled, A.B. Geva / Medical Hypotheses 83 (2014) 450–464 457

Table 3 (continued)

Detected Description for scoring

Complaints of fear of dying or loosing control panic in specific Fear of dying or loosing control; panic in specific conditions
conditions
Complaints of tension, restlessness and agitation Tension, restlessness and agitation
Complaints of avolition indifference apathy anhedonia Avolition, indifference, apathy, anhedonia
Complaints of depressed mood Being sad as in the Hamilton Depression Scale items and major depression
Complaints of depressed mood especially in the morning Being sad as in the Hamilton Depression scale items and major depression especially in the
morning
Complaints about Flight of ideas? Head full of racing thoughts
Complaints that things are strange and unfamiliar – changing not A sense that something is not usual, there are hidden meanings to things, there are forces acting
as usual (dereism? depersonalization) behind things, things are connected in a meaningful way to the individual. Must be evident, if
questionable no score is applied
Complaints of external control, mind reading, bugging, Feeling as if controlled by external sources, others can read his mind; he is being persecuted.
persecution (about delusions) Others intend and plan to hurt him. Must be evident, if questionable no score is applied
Complaints related to Systemized delusion There is a dominating non-bizarre false idea that gradually grows and incorporates all occurrences
and aspects of life. Must be evident, if questionable no score is applied
Complaints of low self esteem Feeling worthless
Complaints bout being easily offended, oversensitive? Easily offended, oversensitive to criticism and insinuations. Interprets even the slightest
inattention from others as rejection and humiliation. Must be evident, if questionable no score is
applied
Complaints of being impulsive, over imposing? Reacts immediately without giving it another thought, unable to change the decision or reaction
once taken. Must be evident, if questionable no score is applied
History of Delusions? As above
History of Hallucinations? As above
History of thought disorders loosening of associations As above
History of thought disorders perseverations poverty of thought? As above
History of depressions? As in DSM criteria
History of mania? As in DSM criteria
History of anxiety As in DSM criteria
History of phobias As in DSM criteria
History of disturbed upbringing, parental loose Parents were not available (or orphan) the family history is of turmoil, instability and frequent
changes. Subject deprived of needed attention care and love, or/and abused maltreated. Must be
evident from anamnesis, if questionable no score is applied
History of behavioral problems Problems at school, patient often reprimanded in school because of misbehavior, must be more
than regular child’s mischief; later problems with the law are typical. Must be evident from
anamnesis, if questionable no score is applied
History of inability to maintain employment and social Unable to remain employed for an extended period of time, interpersonal relationships. Are
relationships? generally short and unstable; and frequently changes partners. Must be evident from anamnesis, if
questionable no score is applied
History of unstable interpersonal relationships Interpersonal relationships chaotic, characterized by turmoil. Must be evident from anamnesis, if
questionable no score is applied
History of psychosocial or other stress (regular life stressors) As in Holmes–Rahe life changes scale (5): changes to different line of work, change in number of
arguments with spouse, mortgage over $100,000, foreclosure of mortgage or loan, change in
responsibilities at work, son or daughter leaving home, trouble with in-laws, outstanding personal
achievement, wife begins or stops work, begin or end school, change in living conditions, revision
in personal habits, trouble with boss, change in work hours or conditions, change in residence,
change in schools, change in recreation, change in church activities, change in social activities,
mortgage or loan less than $30,000, change in sleeping habits, change in number of family get-
togethers, change in eating habits, vacation, christmas alone, Minor violations of the law
History of trauma (stressor exceeding regular life stress) As in Holmes-Rahe life changes scale (5): death of spouse, divorce, martial separation, jail term,
death of close family member, personal injury or illness, marriage, fired at work, marital
reconciliation, retirement, change in health of a family member, pregnancy, sex difficulties, gain of
new family member, business readjustment, change in financial state, death of close friend

Appendix references:
(1) Andreasen N.C., The scale for the assessment of negative symptoms (SANS). Iowa City: University of Iowa, 1983.
(2) Andreasen N.C., The scale for assessment of positive symptoms (SAPS). Iowa City: University of Iowa, 1984.
(3) Hamilton M. Development of a rating scale for primary depressive illness. Br J Clin Soc Psychol 1967;6:278–296.
(4) Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32(1):50–5.
(5) Holmes & Rahe (1967). Holmes–Rahe life changes scale. J Psychosom Res, vol. 11, pp. 213–218.

generated archetypes are used to demonstrate how the CBP trans-
lation can be manifested in the clinical setting (Fig. 1) and to exem-
plify CBP in an intuitive manner. These are prototypes of ideal
cases where symptoms and signs where limited to the typical,
‘‘by the book,’’ clinical consensus for each of the phenomenological
disease-entity.
The archetypes (Fig. 1) are chosen to represent major diagnostic
phenomenological classification that every clinician uses when try-
ing to assign diagnosis to his patient. Schizophrenia of positive
symptoms (psychosis), schizophrenia of negative (deficiency)
symptoms, depression, mania, anxiety disorder, and personality
disorder are chosen for archetypes and are listed in Fig. 1. The first
(left 1A) column lists the CBP entries. The middle graph column
(1B) shows the graph morphology of the CBP results. Fig. 1C gives
a short explanation of the graphs in terms of brain disturbances.
Validation and metanalysis of CBP
The computer program of CBP (linked above) was introduced to
4000 clinicians using ‘‘LinkedIn’’: web-based social network, asking
them to diagnose their patients, using CBP. 642 CBP diagnostic pro-
files (vectors) were collected. The computer program was designed
458 A. Peled, A.B. Geva / Medical Hypotheses 83 (2014) 450–464

A B C
Archetype CBP Graph Explanaon of
Phenomenology CBP translaon

Archetype Schizophrenia Posive Signs

The paent is undy
Is the paent restless, in constant moon?
Does the paent look agitated, on the verge of exploding
Does the paent exhibit bizarre unexplainable movements?
Does the paent speak without stopping jumping from one subject to another?
“Cs” is dominant meaning connecvity
Are the paent’s speech associaons loose?
segregaon, or in other words
Delusion, false unshakable beliefs
disconnecon syndrome spread in the
Inappropriate affect
brain with unstable disrupted brain
Bizarre or overly abstract response to categorizaon (proverbs) and abstracon
organizaon causing fragmentaon of
Auditory hallucinaons
consciousness with psychosis
Detached from examiner
Perplex ambivalent
Complains that things are strange, unfamiliar, changing, not as usual
Complaints of external control, mind reading, bugging, persecuon (about delusions)
History of Delusions
History of Hallucinaons
History of thought disorders loosening of associaons

Archetype Schizophrenia Negave Signs

Is the paent undy? “Ci” connecvity integraon, over-
Is the paent very messy connected brain network organizaon and
Does the paent move slowly “Hbu” boom-up hierarchal insufficiency
Does he paent have limited verbal communicaon e.g., short responses are dominant, the brain organizaon is
Does the paent answer with only a few words or none at all? fixated, and few states can be acvated
The paent repeats the same topics of conversaon repeatedly because of the over-
Concrete interpretaon of proverbs and low abstracon connecvity. In addion, due to boom-
Constricted affect up hierarchal insufficiency higher-level
Blunt affect hierarchical brain organizaon is
Detached from examiner hampered resulng in reducon of high
Complains of avolion, indifference, apathy and anhedonia mental funcons such as volion and
movaon

Archetype Schizoaffecve
Does the paent move slowly
Does the paent speak slowly
Are the paent’s speech associaons loose “Cs,” “Ci” and “Hbu” are all dominant
Delusion, false unshakable beliefs destabilizing the brain to create
Inappropriate affect schizophrenia spectrum phenomenology
Speech content includes mainly issues of despair, hopelessness, and pessimism. (see above). With connecvity unbalanced
Auditory hallucinaons and hierarchy unstable the brain cannot
Constricted affect opmize adapve acvity, thus
Depressed affect deopmizaon, high “D” values, results
Complaints of depressed mood with increase of free energy and emergent
Complains that things are strange, unfamiliar, changing, not as usual property of depressed mood is dominant.
History of Delusions
History of Depression

Archetype Depression
Is the paent undy? “D” is dominant indicang that De-
Does the paent move slowly opmizaon dynamics takes over brain
Does the paent speak in a low tone or whisper organizaon, either due to plascity
Speech content includes mainly issues of despair, hopelessness, and pessimism. reducon, or to stressful events, or both,
Depressed affect brain adaptability is hampered and cannot
Complaints of depressed mood “match” dynamic requirements of
Complains of late insomnia adaptability thus, free energy increases
History of Depression and the emergent property of depressed
mood ensues.

Archetype Mania
Is the paent wearing excessive jewelry makeup and eccentric
clothing?
Is the paent restless, in constant moon “O” is dominant indicang that
Does the paent speak fast Opmizaon dynamics takes over brain
Does the paent speak with an elevated tone organizaon, due to increased plascity,
Speech content includes mainly issues of megalomania, over brain adaptability is improved and
empowerment and unrealisc opmism (and plans). matching dynamic requirements of
Expansive mood elevated affect adaptability are increased, free energy
Inappropriately close to examiner (no boundaries) decreases and the emergent property of
Complaints of tension restlessness and agitaon elevated mood ensues.
Complaints about flight of ideas
History of mania

Archetype Anxiety
Is the paent restless, in constant moon
Anxious affect
Complaints of early insomnia “CF” is dominant, frustraon of
Complains of palpitaons, dizziness, abdominal cramps and ngling constraints destabilize the corcal
Complaints of anxiety fear of dying or losing control, panic neural network organizaon with
Complaints of tension restlessness and agitaon resulng emergent property of
History of anxiety anxiety.

Archetype Personality Disorder

Is the paent restless, in constant moon
Disphoric (suffering)
Depressed affect “DMN” the default-mode-network in
Inappropriately close to examiner (no boundaries) these paents is disturbed,
Seducve toward examiner undeveloped unstable and immature,
Sensive easily offended thus inevitably unable to adapt and
Childish dependent regressive match to ongoing alternang
Manipulang demanding circumstances. Connuous mismatch
Stubborn non obsessive non adaptable results in endured increases of free-
Tends to idealize or devaluate examiner energy and destabilizaon (frustraon)
Egocentric not empathic of constraints, thus a certain degree of
Complaints of depressed mood D” and “FC” always also present with
History of disturbed upbringing and parental lose depression and anxiety typical to
History of behavioral problems personality disorders created by the
History of deficiencies in coping at work and in social situaons biased disturbed Default Mode
History of unstable interpersonal relaonships Network
History of psychosocial or other stress (regular life stressors)

Fig. 1. CBP of archetypes.

 A. Peled, A.B. Geva / Medical Hypotheses 83 (2014) 450–464
so that it does not collect identifiable information of clinician and
patient alike, thus, all gathered information is anonymous. The
Internal Review Board of Sha’ar Menashe Mental Health Center in
Israel approved the study.
The average age of diagnosed patients was 36 (SD ± g10.6).
There were 400 men and 242 women. On average education of
patients reached 11.1 (SD ± n3.8). Sixty-seven patients suffered
acute illness and 150 were chronic patients the remaining 425,
had fluctuating changing manifestations. 379 patients received
antipsychotic medications, 84 patients received Selective Seroto-
nin Reuptake Inhibitors (SSRI’s), 100 patients were not taking med-
ication on the day of diagnosis was done. Seventy-nine patients
had combined treatment of whom 19 were treated with common
mood stabilizers.
Three hundred and four patients were diagnosed with schizo-
phrenia; 34 patients with Schizoaffective Disorder; 59 patients
received the diagnosis of depression, 94 suffered from Anxiety;
40 received the diagnosis of personality disorders. Of those diag-
nosed with schizophrenia 27 seemed to be psychotic with positive
symptoms but most of the schizophrenia sample was not divided
into subtypes; 111 patients were grouped as others due to small
numbers of different diagnoses. For example there were only two
manic patients, and four with ‘‘organic brain syndromes’’ and
‘‘drug abuse’’. ‘‘PTSD,’’ ‘‘conversion disorders’’ and ‘‘autism’’ were
grouped as ‘‘others’’ because there were not enough patients with
each diagnosis to create specific groups.
Two interdependent features in the results were expected from
the diagnostic data collected, grouping of diagnosis in the form of
clinically-relevant archetypes. Fig. 2 compares the artificially gen-
erated CBP diagnosis from Fig. 1 to the diagnostic data for both
adherence and grouping given by the clinicians.
The archetypes are listed in Fig. 2A (left column), the archetype
for mania is excluded due to missing data for comparison. In the
middle column, in Fig. 2B diagnostic results are shown when
grouped according to the diagnosis given by the clinicians. Com-
parison, i.e., correlation statistics, of the results to the archetypes
is given and listed in-between the archetype column A, and the
results data of column B. Most comparisons show good correla-
tions (0.56–0.9) between the archetypes and the actual results in
the data, best correlations were between diagnosed personality
disorders and the archetype of ‘‘personality disorder’’ (0.9). The
weakest correlation was between ‘‘positive signs schizophrenia’’
archetype and the data diagnosed as schizophrenia. This lower cor-
relation results is probably because clinicians grouped schizophre-
nia diagnosis in one group, which seems to correlate better with
negative signs schizophrenia (0.8). From Fig. 2A and B it seems that
CBP complies with adherence to DSM-like phenomenological
archetypes.
For assessment of grouping, we chose to apply Unsupervised
Fuzzy Clustering (UFC; 24–25) to the data. UFC is a method for car-
rying out fuzzy classification without a priori assumptions regard-
ing the number of clusters in the data set. Assessment of cluster
validity is based on performance measures using hypervolume
and density criteria. The algorithm is derived from a combination
of the fuzzy K-means algorithm and the fuzzy maximum likelihood
estimation (FMLE). The UFP-ONC (unsupervised fuzzy partition-
optimal number of classes) algorithm performs well in situations
of large variability of cluster shapes, densities, and number of data
points in each cluster. It has been tested on a number of simulated
and real data sets [21].
Cluster analysis is based on partitioning a collection of data
points into a number of subgroups, where the objects inside a clus-
ter (a subgroup) show a certain degree of closeness or similarity.
Hard clustering assigns each data point (feature vector) to one
and only one of the clusters, with a degree of membership equal
to one, assuming well defined boundaries between the clusters.
459
This model often does not reflect the description of real data,
where boundaries between subgroups might be fuzzy, and where
a more nuanced description of the object’s affinity to the specific
cluster is required.
We chose UFC because it captures the internal structure of the
grouping providing support to the linkage with archetypes. Interest-
ingly, the UFC algorithm cluster validity criteria were recommend-
ing mainly two preferred partitions, the first of two clusters and the
second of seven clusters. As such we first investigate the clinical
usefulness of UFC application to the CBP data divided it into two
clusters and then into seven clusters. Fig. 3 shows the results UFC
of the patients into very symptomatic schizophrenia psychotic
patients in one group, and milder, less-symptomatic, non-
psychotic non-schizophrenic in the other group. Accordingly, the
first cluster was composed of 97% schizophrenia patents while the
second cluster was composed of 80% mixture of milder psychiatric
disorders personality disorders and anxiety depression patients.
When UFC clustered the data into 7 groups they represented
good resemblance to both the archetypes as well as to the actual
diagnostic groups of the data. Fig. 2C shows the resembling graphs
and percentages of diagnosis given by the clinicians. As evident
clusters 6, and 1, readily correlated with the archetypes of person-
ality disorders and anxiety disorders respectively. Clusters 3 and 2
correlated with the archetypes of depression and schizoaffective as
well as schizophrenia of negative signs, but in effect cluster 3 had
only 30% of the patients diagnosed with depression. Thus, the UFC
separation was not good at differentiating depression from schizo-
affective and negative-signs schizophrenia. However clusters 5 and
7 achieved good correlations with the archetype of positive-signs
schizophrenia, something that clinicians did not separate, thus, it
had the capability of separating the two subtypes of schizophrenia
from the data, where this information was concealed by the ten-
dency of clinicians to group all types of schizophrenia in one group.
From these results, it seems that the CBP diagnostic format
when used by clinicians using the CBP computer-program in the
clinical settings has generated concordance diagnostic prototypes.
Larger samples of diagnosis are required to evaluate if more diag-
noses such as those currently grouped as ‘‘Others’’ (Fig. 2B) can
become included in specific CBP profiles. However, as a prelimin-
ary result it seems that CBP ‘‘carves psychiatric nature at its clinical
joints.’’ It seems to concord with the currently descriptive psychi-
atry as reflected by clinical practice (archetypes) as well as DSM-
like approaches; it seems also, that CBP can reach reliability levels,
which are similar to those currently characterizing the descriptive
DSM like approach. With such reliability the advantage of CBP in
comparison to the DSM-approach is manifest within its brain-
related formulation, one that can now be validated (or refuted)
to discover the pathophysiological underlying disease mechanisms
of mental disorders.
Discussion
In the first part of this discussion we will provide a brief review
of the literature that substantiates the associations and mappings
established in the previous two sections. In particular, we will be
looking for empirical evidence that ties abnormalities of connectiv-
ity to psychosis and schizophrenia on the one hand, and disorders
of plasticity to mood disorders on the other. We base this discus-
sion on a survey of relevant publications over the past few years.
In the case of CBP only large-scale imaging studies with large-
data analyses and signal processing can begin to validate the test-
able predictions generated by CBP. Thus, an initial validation can
be attempted using the currently available scientific literature, or
in other words using PUBMED literature searches. Assuming that
published work is typically reporting positive results, the number
460 A. Peled, A.B. Geva / Medical Hypotheses 83 (2014) 450–464

A B C
Archetype Diagnosis results N=642 (Averages ) Fuzzy Clustering and cluster percentage

Archetype schizophrenia Cluster 7

posive signs 80% Schizo
15% Depp

5% Drug
9 8 7 6 5 4 3 2 1
Corr = 0.56
9 8 7 6 5 4 3 2 1 Schizophrenia N= 304 Cluster 5
23% psych
Archetype schizophrenia 53% Schizo
Negaves signs
9 8 7 6 5 4 3 2 1 15% Others

9 8 7 6 5 4 3 2 1

Corr = 0.8
9 8 7 6 5 4 3 2 1

Schizoaffecve N=34 Cluster 2

Archetype Schizoaffecve
99% Schizo
1% Other

9 8 7 6 5 4 3 2 1 9 8 7 6 5 4 3 2 1 9 8 7 6 5 4 3 2 1
Corr = 0.87

Archetype Depression Depression N=59 Cluster 3

70% Schizo
30% Depp

9 8 7 6 5 4 3 2 1
9 8 7 6 5 4 3 2 1
9 8 7 6 5 4 3 2 1
Corr = 0.63

Anxiety N=94 Cluster 1

Archetype Anxiety

96% Anxiety
4% Depp

9 8 7 6 5 4 3 2 1 9 8 7 6 5 4 3 2 1
9 8 7 6 5 4 3 2 1
Corr = 0.66

Archetype Personality
disorder Personality
Disorders N=40 Cluster 6

69% PD
15% Adjust
15% other
9 8 7 6 5 4 3 2 1
9 8 7 6 5 4 3 2 1

Corr = 0.9 9 8 7 6 5 4 3 2 1
LEGEND:
Y axis = % percentage
Corr = Correlaons
Schizo = Schizophrenia
Psych = psychosis Others N=111
Cluster 4
Dep+Anx Depression and Anxiety
PD= Personality disorder 45% PD
Depp= Depression 28% Anxiety
Adjust = Adjustment disorder
Cluster = results of fuzzy clustering 27% Dep+Anx
9 8 7 6 5 4 3 2 1
1 = DMN Default Mode Network 9 8 7 6 5 4 3 2 1
2= D De-opmizaon
3 = O Opmizaon
4 = CF Constraint Frustraon
5= CF Constraint Frustraon bound
6 = Cs Connecvity segregaon
7= Ci Connecvity integraon
8= Hbu Hierarchical boom-up
9 = Htd Hierarchical top- down

Fig. 2. Comparison of results to archetypes.

 A. Peled, A.B. Geva / Medical Hypotheses 83 (2014) 450–464
12
10
Axis Y= Percentages
4
Axis X : Cluster 2= 80% others
1 = DMN Default Mode Network Personality disorders Anxiety
2= D De-opmizaon
3 = O Opmizaon
4 = CF Constraint Frustraon 2
5= CF Constraint Frustraon bound
6 = Cs Connecvity segregaon
7= Ci Connecvity integraon
8= Hbu Hierarchical boom-up 0
9 = Htd Hierarchical top- down 1 2
Fig. 3. Clustering of data into two groups.
of papers with relevant combinations of keywords would reflect
findings linking evidence for those relevant keywords. For exam-
ple, a large number of publications resulting from a search of
‘‘plasticity’’ and ‘‘depression’’ compared to ‘‘plasticity’’ and
‘‘schizophrenia’’ would indicate that in the literature mechanisms
of plasticity are associated more with depression than with schizo-
phrenia, thus pointing to more relevance of plasticity in depression
than in schizophrenia. One major postulation predicted by the CBP
theory is that schizophrenia-spectrum disorders are related to
findings of disturbed connectivity within brain neural network
while depression (mood disorders) are more relevant to brain plas-
ticity dynamics and the Bayesian brain. A literacy search was con-
ducted in this respect. Fig. 4 shows the results of numbers of
publications resulting from different combination of searches.
It is evident that combined search of keywords ‘‘connectivity’’
and ‘‘schizophrenia’’ yielded 1000 publications in comparison to
a search of the keywords ‘‘connectivity’’ and ‘‘depression’’ that
have yielded only about half, 615 publications. On the other hand
when keywords ‘‘plasticity’’ and ‘‘schizophrenia’’ were searched
only 1041 publications were found in comparison to 4784 for key-
words ‘‘plasticity’’ and ‘‘depression,’’ more than fourfold the publi-
cations related plasticity to depression than to schizophrenia. As
evident in Fig. 4 the cross over between schizophrenia and depres-
sion occurs when searching ‘‘connectivity disturbances’’ and
‘‘Bayesian’’ this indicates that more publications related connectiv-
ity disturbances to schizophrenia and more papers related Bayes-
ian evaluations to depression. Assuming, as already mentioned,
that publications typically inform about positive findings than
the number of publications probably signifies positive relation-
ships between these keyword concepts, indicating the relevant
trend in the literature. In other words, if we use the literature
search as an initial indicator for validation, than these results pro-
pose a preliminary validation for the general prediction of CBP that
relates schizophrenia spectrum disorders to disturbances of neuro-
nal network connectivity, while mood disorders are related to
dynamics of plasticity and entropy parameters within the neuronal
networks of the brain.
Specific publications may increase the resolution of predicting
validation of a CBP search of ‘‘connectivity schizophrenia review’’
yields 237 papers with the most recent by van den Heuvel and For-
nito [22] who reviewed the explanatory finding about ‘‘brain disor-
ders such as schizophrenia arising from abnormal brain network
461
HFC 2 groups
Cluster 1 = 97% schizophrenia
3 4 5 6 7 8 9
wiring and dynamics’’ while most papers talk about connectivity
alterations meaning mostly disconnections there are also papers
mentioning over-connectivity in the disease [23,24]. Altered hier-
archical organization has also been found to be disturbed. For
example Zhang and colleagues [25] used imaging graph analysis
in un-medicated first-episode schizophrenias patients and found
that most of the regions that showed significantly decreased nodal
parameters belonged to the top-down control systems. Sharma
and colleagues [26] found that impaired cognitive control in
schizophrenia might be driven by disrupted communication
between the frontal and posterior brain areas, long-range connec-
tivity being a more consistent deficit in schizophrenia as compared
to locally evoked activity. This reflects altered hierarchy because
frontal brain areas relate to higher-level processing thus consisting
of higher hierarchical levels.
Hampered plasticity and neuronal degeneration have been
repeatedly found to correlate with depression [27–30]. A review
by Masi and Brovedani [31] describes recent studies indicating that
an impairment of synaptic plasticity (neurogenesis, axon branch-
ing, dendritogenesis and synaptogenesis) in specific areas of the
CNS, particularly the hippocampus, may be a core factor in the
pathophysiology of depression. Accordingly they proposed that
new possible targets for the pharmacotherapy of depression could
involve agents such as neurotrophic factors, their receptors and
related intracellular signaling cascades; agents counteracting the
effects of stress on hippocampal neurogenesis (including antago-
nists of corticosteroids, inflammatory cytokines and their recep-
tors); and agents facilitating the activation of gene expression
and increasing the transcription of neurotrophins in the brain. Sim-
ilarly, according to Hayley and Litteljohn [32] the ‘‘next wave’’ of
antidepressant treatments, whether used alone or in combination,
is at least partially tied to their ability to modulate neuroplasticity.
The CBP theory argues that plasticity alteration generates mood
alteration by optimization and de-optimization dynamics that can
be estimated by entropy and Bayesian measurements of neuronal
networks spread in the brain. In the case of personality disorders
the validity of the disturbed resting-state network can be divided
into (1) relationships to psychoanalytic theory and (2) initial liter-
ature linking resting-state networks to personality and personal-
ity-related phenomena. As for relationships to psychoanalytic
theory, in effect the internal map of representations has been well
described for many years by ‘‘object relationship’’ psychologists
462 A. Peled, A.B. Geva / Medical Hypotheses 83 (2014) 450–464
PUBMED Search January 2014
"4784
Adaptability Brain Dynamics Plascity Bayesian
schizophrenia
Bayesian
schizophrenia
Fig. 4. Partial validation of CBP based on PUNMED publication search.
[33] who described the internal representations of others, such as
parents, teachers friends as, ‘‘objects’’. In this case objects relate to
memories and these are embedded in attractors. The individual
also has a representation of himself in his brain that is composed
of his experiences toward himself, and was termed ‘‘self-object’’
by object relationship psychologists. Thus one can see how even
higher coding ‘‘maps’’ of social occurrences are represented in
the brain as dynamic attractor formations in state-space. Object
relationship theories have been useful in explaining why and
how individuals experience, adapt and react to the psychosocial
surrounding. These individual adaptation behavioral reactions
have been related to personality styles, showing that internal rep-
resentations shape our personality. Additionally Carl Rogers [34]
described internal maps ‘‘organismic maps’’ as internal representa-
tions that determine the way we interpret experiences and react to
psychosocial occurrences. These descriptions link internal repre-
sentations and configurations to ‘‘personality’’ because personality
is typically defined as the individual’s set of interpretations, expe-
riences and reactions to psychosocial occurrences.
Based on these insights the link between development of
default mode network and the maturation of personality is created.
The default mode network encodes internal representations as
attractor configurations of state-space and these in turn determine
and guide our psychosocial adaptation and psychological behav-
ioral reactions, related to our experience-dependent individual
style, i.e., personality traits.
A direct prediction from these insights is that individuals suffer-
ing from personality disorders will demonstrate altered default
2500
2000
1500
1000
500
0
Connecvity Brain connecvity Connecvity
disturbances
depression PD
180
160
140
120
100
80
60
40
20
0
connecvity disturbances
depression
mode network development which will manifest as biased organi-
zation in terms of altered small-world network organization. Initial
validation for such alterations is beginning to appear in the litera-
ture. Lei et al. [35] provide evidence for an association between
individual differences in personality and scaling dynamics in the
default mode network. Default mode network of rsfMRI in 20
healthy individuals was significantly associated with the extraver-
sion score of the revised Eysenck Personality Questionnaire. Specif-
ically, longer memory in default mode network corresponded to
lower extraversion. Wei et al. explored brain disturbances underly-
ing extraversion and neuroticism in 87 healthy individuals using
fractional amplitude of low-frequency fluctuations on resting-state
functional magnetic resonance imaging, they showed a positive
correlation between low-frequency fluctuations amplitude at
Slow-5 waves and extraversion in medial prefrontal cortex and
precuneus, (important portions of the default mode network), thus
suggesting a link between default network activity and personality
traits. Overall, these findings suggest the important relationships
between personality and low-frequency fluctuations. Amplitude
dynamics depend on specific frequency bands.
Patients with borderline personality disorder demonstrate an
increase in functional connectivity in the left frontopolar cortex
and the left insula, whereas decreased connectivity was found in
the left cuneus. Within a network comprising predominantly right
lateral prefrontal and bilateral parietal regions, patients with bor-
derline personality disorder showed decreased connectivity of
the left inferior parietal lobule and the right middle temporal cor-
tex compared with healthy controls. Correlations between
 A. Peled, A.B. Geva / Medical Hypotheses 83 (2014) 450–464
functional connectivity of the frontopolar cortex and measures of
impulsivity as well as between connectivity of the insula/cuneus
and dissociation tension were found. These data suggest that
abnormal functional connectivity of temporally coherent resting-
state networks may underlie certain symptom clusters in patients
with borderline personality disorder.
Tang et al. [36] designed an exploratory data-driven classifier
based on machine learning to investigate changes in functional
connectivity in the brains of patients with antisocial personality
disorder. They used resting state functional magnetic resonance
imaging (fMRI) data for 32 subjects with antisocial personality dis-
order and 35 controls. The results showed that the classifier
achieved satisfactory performance (86.57% accuracy, 77.14% sensi-
tivity and 96.88% specificity) and could extract stable information
regarding functional connectivity that could be used to discrimi-
nate antisocial personality disorder individuals from normal con-
trols. More important, they found that the greatest change in the
antisocial personality disorder subjects was uncoupling between
the default mode network and the attention network. A voxel-
based morphometry analysis showed that the gray matter volumes
in the parietal lobule and white matter volumes in the precuneus
were abnormal in antisocial personality disorder compared to con-
trols. In summary, this study used resting-state fMRI to identify
abnormal functional connectivity in antisocial personality disorder
patients. The authors suggest that their analysis can be used to
improve the diagnosis of antisocial personality disorder, and eluci-
date the pathological mechanism of antisocial personality disorder
from a resting-state functional integration viewpoint.
Servaas et al. [37] showed that individuals scoring higher on neu-
roticism showed altered functional connectivity between the clus-
tered seed regions and brain areas involved in the appraisal,
expression and regulation of negative emotions. The seed-based
functional connectivity method and subsequent clustering were
used to analyze the resting state data, thus linking personality traits
such as being more self-critical and overly sensitive to criticism by
others.
To summarize this section, it can be concluded, that the emerg-
ing literature of the past and recent years consistently conforms to
the CBP conceptualizations promising an initial potential for a gen-
eral-literature validation, one that can be sufficient to begin a
detailed comprehensive research program, to fully validate CBP
in a focused manner as explained in the next section.
Future directions and implications
‘‘Personalized medicine’’ is an important trend in modern med-
icine, CBP is personalized because it is constructed from the per-
sonal clinical profile of the specific patient, however it is also
classifiable phenomenologically allowing it to become relevant to
knowledge about treatments and readily available for research.
We show that in addition to being a personalized diagnosis, CBP
has the chance to become a reliable diagnostic approach thus
becoming ‘‘as good as’’ the DSM-like approach. However, the CBP
format has the advantage of being readily available for a neurosci-
entific validation. This is in accord with Nick Craddock’s recom-
mendations for a system that ‘‘better reflects the underlying
functions and dysfunctions of the brain and that, hence, maps more
readily the experiences of patients’’ [1].
CBP strives to bridge the current descriptive diagnosis with
future neuroscientific diagnosis, believing that science advances
in evolution rather than revolution, i.e., building the future diag-
nostic system without discarding the current one, but rather build-
ing on it. This is why the CBP entries are formulated based on the
currently in-use, mental status, signs, symptoms and history. Obvi-
ously, the critical future of CBP lays in the challenge of validation
(or refutation). Validity of CBP will be obtained simply by following
463
Table 4
Signal processing needed to validate CBP.
Brain signal processing
DMN Age-related changes of all of the below (especially to normal controls)
Cs Correlations, synchrony, granger causality mutual information,
dimension estimation Bayesian statistics dynamic causal modeling
independent components analysis, neural complexity (correlation
matrix) graph assessment of overall small wordiness
Ci ‘‘
Hbu Estimating hierarchy with hub composition K-shell decomposition,
fractal geometry estimations, integrated information theory
estimations
Htd ‘‘
D Whole brain matching complexity, estimations. Free energy
estimations. Entropy measurements
O ‘‘
CF ‘‘
CFb ‘‘
the testable predictions. Such a study will inevitably require large
data, from multiple centers, and will require extensive collabora-
tion of many imaging labs synchronized in their assessment meth-
odologies. Results of all signal processing methods will be
classified into indicators of CBP predictions, for example for the
signal processing methods such as correlation analysis and sensi-
tive to connectivity dynamics that could indicate disconnection
or over-connection in the brain. Those signal processing methods
sensitive to dynamics of entropy alterations can become indicative
to optimization dynamics, and so on. Table 4 proposes possible
classification for signal processing methods relevant for validating
specific CBP predations.
Validation of CBP will offer a brain-related pathophysiological
psychiatric diagnosis, ridding psychiatry of the current descriptive
diagnostic system, thus adjoining psychiatry to the medical com-
munity of pathophysiological diagnosis. Validation of CBP paves
the way to cure mental disorders by offering the blue-print, or
road-map, for new therapeutic interventions in the brain. Cur-
rently multiple neuromodulation technologies are being developed
and tested. Deep Brain Stimulation technology is already in use for
severe Parkinson disease, and tested for depression [38]. Transcra-
nial Magnetic (TMS) and Direct Current (tDCS), and Alternating
Current Stimulations (tACS) are noninvasive methods being tested
[39]. Optogentic is another promising technology [40] able to
selectively and precisely control neuronal activations. Focused
Ultrasound technology is also developing to intervene precisely
in neuronal tissue [41]. Any neuromodulator technology will even-
tually require the knowledge about the disease-specific distur-
bance in order to try and correct it. Such knowledge will require
specific to the resolution of sub-millimeter in space and millisec-
ond in time in addition to the multiple parallel and time-related
synchronizations, or other divergent, complicated stimulus-algo-
rithms that shall be required to rebalance neuronal networks and
re-optimize brain functions, for eliminating symptoms and defi-
ciencies of mental disorders.
Thus, with these upcoming novel brain-stimulating technolo-
gies. It is hard to envision progress in psychiatry without a validation
of a CBP-like system or a similar research track, prior to designing
interventions [42]. This said, it is important to emphasize that the
CBP conceptualization is a preliminary starting point, a pointer of
direction, rather than an advanced or finite schema. As such it has
a heuristic value for future research in the field of neuroscientific
psychiatry.
Conflict of interest
No conflict of interest of any sort commercial or other is
declared.
464 A. Peled, A.B. Geva / Medical Hypotheses 83 (2014) 450–464

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