2. Introduction
•10% of the weight of
the brain (Llinas et al, 2004).
•80% of brain neurones
(Herculano-Houzel, 2010)
•Traditionally:
cerebellum only >
posture, balance &
motor control.
•Not involved in
initiating motor
activity, but
coordinating them
(Flourens, 1824).
3. Introduction
•Abundant connections > non-
motor brain regions.
•Involved in coordinating all
non-motor functions e.g.
perceptions, emotions,
cognition, speech,
personality, etc.
•Cerebellar abnormalities
exist in most mental
illnesses.
•Mental illnesses exist in most
cerebellar disorders. 3
12. Marr & Albus Model for
Cerebellar Learning
(Eccles, Ito & Szentagothai,1967)
•Several theories about cerebellum
and learning.
•Most theories about Cerebellar
functioning / learning are derived
from early models of David Marr
(1969) and James Albus (1971).
•Albus (1971) formulated his model
as a software algorithm: Cerebellar
Model Articulation Controller, which
has been tested in a number of
computer applications.
12
David Marr
James Albus
13. Marr & Albus Model for Cerebellar Learning
(Eccles, Ito & Szentágothai,1967)
1. Feedforward processing.
2. Divergence and Convergence.
3. Modularity / Compartmentalization
4. Plasticity.
13
Cerebellar Perceptron,
James Albus
14. (1) Feed-forward Processing:
(Eccles, Ito & Szentágothai,1967)
•Signals move uni-
directionally from
input to output,
with very little
recurrent internal
transmission > a
quick and clear
response with no
reverberation.
14
15. (2) Modularity / Compartmentalization
(Oscarsson, 1979; Apps & Garwicz, 2005)
•Cerebellar cortex >
zones and micr-
ozones (1000
Purkinje cells).
•Interactions
within a micro-
zone much
stronger than
interactions
between different
micro-zones. 15
18. Adaptive Filtering(Fujita 1982; Dean & Porell, 2008; Dean et al, 2010)
• Elimination of noise
•Fine tuning
• Optimality /
Coordination
• Execution not
creativity
18
1. Feedforward processing.
2. Divergence and
Convergence.
3. Modularity /
Compartmentalization
4. Plasticity.
19. •Kenji Doya (2000):
•“Neural computation”.
•Katz & Steinmetz (2002):
•“Regulates brain processes”.
•Boydon (2004):
•“Makes fine adjustments to the
way an action is performed”.
•Masao Ito (2005):
•“Matches intentions with actual
performance”.
•Reeber et al (2013):
“computational task … recognizing
neural patterns … predict optimal
movements”. 19
Masao Ito
Kenji Doya
Cerebellar Learning: “Software Programmer”
20. Cerebellar Learning:
(Burguiere et al, 2010, Kalmbach et al, 2011)
•Cerebellum > develops
learnt behaviour with >
1.Minimum Errors
2.Minimum Time
3.Minimum Effort
4.Minimum Attention /
awareness
5.Maximum stability
20Chase Britton
22. 1 - Psychological Studies of Normal
Individuals with Reduced Cerebellar
Volume
•Individuals with
reduced cerebellar
volume > higher
scores on scales of
anxiety, type A
personality,
phobia,
tenderness and
hostility (Chung et al, 2010).
22Chase Britton
23. 2 - Other Psychiatric Aspects of
Cerebellar Disorders: (Wolf et al, 2007)
23
24. 3 - Psychiatric Aspects of Anatomically
Specific Cerebellar Abnormalities
•Vermal Agenesis >
severe LD & Autism (Tavano
et al, 2007).
•Vermal lesions > affective
and relational disorders
(Schmahman et al, 2007).
•Spinocerebellar Ataxia >
impairment in attention,
memory, executive
functions and theory of
mind (Garard et al, 2008).
24
25. 4 - Cerebellar Cognitive Affective Syndrome
(Schmahman et al, 2007; Tavano et al, 2007; Levisohn et al, 2000):
25
Cerebellar Syndromes > motor
impairments +
Cognitive impairments:
Executive dysfunctions, visuo-
spatial abnormalities, linguistic
dysfunction.
Affective impairments: Anxiety,
lethargy, depression, lack of
empathy, ruminativeness,
perseveration, anhedonia and
aggression.
Jeremy
Schmahmann
27. Cerebellar Abnormalities in
Psychiatric Disorders
•Bipolar Affective
Disorder: e.g.
reduced Cerebellar /
Vermis volume (Glaser
et al, 2006)
•Anxiety: e.g.
cerebellar-vestibular
dysfunction (Levinson,
1989)
•Depression: e.g.
reduced posterior
cerebellar activities
(Fitzgerald et al, 2009)
27
ADHD:
•Smaller cerebellar
volume (Berquin et al 1998;
Giedd et al, 2001).
•Abnormalities in post-
inferior cerebellar
hemispheres and vermis
(Casey et al, 2007; Steinlin,
2007).
•Reduction in the activity
of cerebellum and
vermis (Mackie et al, 2007).
28. Cerebellar Abnormalities in
Psychiatric Disorders:
•Post Traumatic
Stress Disorder:
e.g. altered
function of the
vermis (Anderson et al,
2002)
•Alcohol abuse:
e.g. induced
reduction in
Cerebellar /
Vermis volume
(Glaser et al, 2006) 28
•Gender differences:
(Dean & McCarthy, 2008)
•Antisocial
Personality
Disorder: e.g.
reduced Cerebellar
volume (Barkataki et al, 2006).
•Alzheimer
Dementia: e.g.
cerebellar atrophy
(Wegiel et al, 1999)
30. (1) Cerebellum & Dyslexia:
•Developmental Dyslexia:
(Stoodley & Stein, 2011; Nicolson et al,
2001; Pernet et al, 2009)
•Dyslexia > cerebellar
structural and functional
abnormalities in 80% of
cases.
•Dyslexia > impairment
in the ability to perform
skills automatically.
•Cerebellar syndromes >
impairments in reading
and writing characteristic
of dyslexia.
30
The Cerebellar
Deficit
Hypothesis of
Dyslexia: (Nicolson &
Fawcett, 1990; Nicolson et al,
2001): dyslexia is an
impaired
automatization of
high-order
sensory-motor
procedures in
reading.
31. (2) Cerebellum & Schizophrenia:
General Studies
• ↑ Imaging studies >
cerebellar abnormalities in
schizophrenia (Vernas et al,
2007):
• ↑ Cerebellar-Motor
Dysfunction in
Schizophrenia and
Psychosis-Risk (Bernard &
Mittal, 2014).
• ↓ Cerebellar volume (Bottmer
et al, 2005)
• ↓ Blood flow on PET scan
(Andreasen et al, 1996).
31
• ↓ Level of N-acetylaspartate
in Magnetic Resonance
Spectroscopy Imaging
(MRSI) studies (marker of
neurone density and viability) in
vermis and cerebellar cortex (Ende
et al, 2005).
• ↓ Volume in the cerebello-
thalamic-cortical network
(Rusch et al, 2007).
• Neuronal disorganisation in
the superior peduncle on
Diffusion Tensor Imaging
(DTI) studies (Okugawa et al,
2006).
32. (2) Cerebellum & Schizophrenia:
Specific Symptoms (Picard et al, 2008)
•Hallucinations (Shergill et al,
2003; Neckelman et al, 2006)
•Formal Thought Disorder
(Kircher et al, 2001; Levitt et al, 1999)
•Affect symptoms (Stip et al,
2005; Paradiso et al, 2003; Abel et al,
2003)
•Cognition (Szesko et al 2003;
Toulopoulou et al 2004)
•Attention (Eyler et al, 2004; Honey
et al, 2005; Aasen et al, 2005)
•Language (Shergill et al, 2003;
Boksman et al 2005; Kircher et al 2005)
•Memory (all types) (Mendrek et
al, 2005; Whyte et al 2006)
32
33. (2) Cerebellum &
Schizophrenia:
Cerebellar Glutamate
Theory
33
•Hypo-
functioning of
the Glutamate
NMDA receptors
in cerebellum >
cognitive
dysmetria >
schizophrenia.
• Yeganeh-Doost et al,
2011):
34. (2) Cerebellum & Schizophrenia:
Cognitive Dysmetria Theory
(Andreasen et al, 1998)
•The Cortico-Cerebellar-
Thalamo-Cortical circuit is
dysfunctional > poor
mental coordination >
(Cognitive Dysmetria) >
Schizophrenia.
•The theory has been
criticised by other
researchers (e.g. Kaprinis et al,
2002, Kaprinis et al, 2002; Shanagher et
al, 2006) Nancy
Andreasen
35. (2) Cerebellum & Schizophrenia:
Secondary Cerebellar Abnormalitites
•Schizophrenia >
increased dopaminergic
activities > cerebellar
disorder > motor
disorders in
schizophrenia (even
neuroleptics naïve)
(Mittleman et al, 2008;
Hoppenbrouwers et al, 2008;
Varambally et al, 2006; Picard et al,
2007).
35
36. (3) Cerebellar & Autism:
General Studies
•One of the most consistent
abnormalities found in ASD (DiCicco-Bloom
et al, 2006).
•95% of post mortem examinations of
autistic individuals (Delong, 2005)
•Consensus related to cerebellar
involvement in autism (Fatemi et al, 2012):
• Abnormal cerebellar anatomy,
• Abnormal neurotransmitter systems,
• Oxidative stress,
• Cerebellar motor and cognitive deficits,
• Neuro-inflammation
36
S. Hossein
Fatemi
37. (3) Cerebellum & Autism:
Cerebral Involvement
•Associated with mal-development of the frontal
lobe and any other brain regions > ASD (Carper &
Courchesne, 2000; Kuemerle et al, 2006; Reeber et al, 2013).
•Loss of modulatory control of Frontal Cortex >
ASD, (Catani et al, 2008).
•Cerebellum malfunction hinders neural development
(Wang et al, 2014).
Sam Wang
41. Cerebellar Transcranial Magnetic
Stimulation (TMS) (Schmahmann, 2010)
•Demirtas-Tatlidede et al (2010): stimulation of the
vermis in 8 schizophrenic patients > improvements in
mood, alertness, memory, attention, visual-spatial
skills and energy.
•Very early stages (Minks et al, 2010)
•No RCT
41
43. Cerebellum: Clinical Reflections
Introduction
•Best way to make clinical judgment
> follow the model of motor
cerebellar functioning:
• Well studied
• Must be linked physiologically to non-
motor functioning.
•Two main fields:
• Cerebellar connections to mental
disorders specially dyslexia,
schizophrenia and Autism > very
promising and interesting but slow and
small impact .
• Mental equivalent to praxis and
dyspraxia > clearer and more promising 43
44. (1) Motor Learning vs Non-motor / Mental
Learning
Cerebellum > “motor”
and “non-motor / mental”
coordination.
a) Motor coordination
> “Motor Learning /
Praxis”.
b) Mental coordination
> Non-motor
coordination /
Mental
Coordination”
44
45. •Cerebellum failing in motor
coordination >
• (Motor) dyspraxia,
• Developmental Coordination
Disorder (DCD),
• Clumsy Child Syndrome, etc.
•Cerebellum failing in non-
motor / mental coordination >
• ? Mental Dyspraxia,
• ? Developmental Mental
Coordination Disorder (DMCD),
• ? Mentally Clumsy Child
Syndrome, or
• ? Mental Routine Disorder (MRD)
45
(2) Motor Dyspraxia vs Non-motor Dyspraxia
46. (3) Mental Routine Disorders (MRD):
A new chapter in psychopathology?!
1. Better understanding of a
major part of human
behaviour.
2. Widespread problem >
marked suffering > needs
attention.
3. Good room for effective
interventions
4. Enhance therapies for
major mental disorders
e.g. ASD.
46
47. (4) Prevalence of MRDs
• Motor Dyspraxia : 6-10 % in school children (Gibbs et al, 2007).
• Dyscalculia: 5-7% (Butterworth et al, 2011)
• Developmental Coordination Disorder (DCD): 5–6% (Blank et al, 2012;
Zwicker et al, 2012).
• Dyslexia: 5% - 17% of school-age children (USA) (Shaywitz & Shaywitz,
2003).
• Symptom: 40% reading below grade level (Shaywitz & Shaywitz,
2003).
• Special groups: 80% of individuals with LD (Shaywitz & Shaywitz,
2003).
• Complications: lower self-esteem and more emotional and
behavioural difficulties than those without dyslexia (Terras et al, 2009).
• comorbidity : 95% (Pauc 2005).
47
48. 3- Assessment of MRDs:
(A) Doya’s Model of Motor Learning (Doya, 2000)
(also Imamizu et al, 2000; Hikosaka et al, 2002, Bosch-Bouju et al, 2013)
•Brain circuits:
•The cortico-cerebeller-thalamo-cortical
circuit
•The cortico-striato-thalamo-cortical
circuit
•Learning paradigms
•Cerebral cortex > unsupervised
learning
•Basal ganglia > reinforcement
learning
•Cerebellum > supervised learning
Kenji Doya
51. (B) The Four Primary Components
1. Failure to learn (problem
solving, adapting, planning,
etc.) e.g. LD.
2. Failure to eliminate anxiety
(threat) > marked disturbance
of functioning e.g. OCD.
3. Failure to reach satisfaction
without causing marked
disturbance of functioning
e.g. habit disorder
4. Failure to have smooth
functioning without errors e.g.
dyspraxia
51
52. (C)The Four Components Mixed
•Complex routine
abnormalities.
•1, 3 & 4 okay but 2
faulty > OCD with
inner resistance.
•3 & 4 okay but 1 & 2
faulty > rigid
obsessional routines
without inner
resistance. 52
53. Functional
Routines
Dysfunctional
Routines
Meaningful > Serves a
purpose
Bizarre (counting lamp posts /
eating flies).
Resilient (to stress):
stress > little disruption
Unstable: stress >
marked disruption
Adaptive (with novelty):
new data > little
disruption
Rigid: new data >
significant disruption
53
(4) Classification of MRDs:
a- Dysfunctional Routines
54. (4) Classification of MRDs:
b- Simple vs. Complex MRD
54
Simple Complex
− Single faulty
component (e.g.
OCD or drug
addiction)
− Highly functional
individuals
‒ Multiple faulty
components e.g.
routine problems in
Autism.
‒ Less functional
individuals
55. (4) Classification of MRDs:
c- Primary vs. Secondary MRD
55
e.g. primary
clumsiness
Secondary
clumsiness
− Clumsiness due to
faulty cerebellar
component
(Performance
clumsiness)
‒ Clumsiness due to
faulty cerebral
(cognitive)
component.
(Mentation
Clumsiness)
56. (5) Treatment of MRDs:
The Methods
• General Lines:
1. Medications.
2. Educational.
3. CBT.
4. Behavioural.
5. Others: e.g.
• GORE or Movement
Therapies
•Process-oriented approach
•Task-oriented approach
• Transcranial Magnetic
Stimulation (TMS)
• Specific:
• Depends on specific
conditions
56
57. “3 Dimensions” is not
the same as “2
Dimensions”:
•Integrating the
psychiatric dimension
into the
neuropsychological and
OT therapies for
dyspraxia > extra depth
and sophistications but
needs resources and
time.
(5) Treatment of MRDs :
The Strategy
