Cerebellum, Psychiatric Aspects & Routine Disorders

1. 1
Cerebellum,Cerebellum,
Psychiatric AspectsPsychiatric Aspects
& Routine Disorders& Routine Disorders
Dr Khalid Mansour
Consultant Psychiatrist
Letterkenny General Hospital 2017

2. Index
1. Introduction: Some Basic Facts.
2. Anatomy.
3. Physiology: Models of Functioning.
4. Psychiatric Aspects of Cerebellar
Disorders.
5. Cerebellar Abnormities in Psychiatric
Disorders.
6. Cerebellar Mental Therapies.
7. Clinical Reflections:
a. Non-motor Dyspraxia
b. Routine Disorders.
c. Cerebellar Circuits and Mental Disorders. 2

3. Introduction
1- 10% of the weight of
the brain (Llinas et al, 2004) but
contains 80% of brain
neurones (Herculano-Houzel, 2010).
2- Traditional thinking is
that cerebellum involved
in posture, balance &
motor activity.
• Not involved in
initiating motor activity,
but coordinating them
(Flourens, 1824).

4. Introduction
3- Abundant connections >
non-motor brain regions >
involved in coordinating all
non-motor functions e.g.
perceptions, emotions,
cognition, speech,
personality, etc.
4- Cerebellar abnormalities
exist in most mental illnesses
and mental illnesses exist in
most cerebellar disorders.
4

5. Anatomy
5

6. Gross anatomy:
•Anterior lobe.
•Posterior lobe.
•Flocculonodular
lobe.
Cross sectional:
•Gray matter:
•White matter:
•Nerve fibre tracts
•Deep nuclei
6

7. Functional
Anatomy:
•Vestibulocerebellum
(flocculonodular
lobe).
•Spinocerebellum
(vermis &
paravermis).
•Cerebrocerebellum
(lateral cerebellar
hemispheres).
7

8. Deep
Cerebellar
Nuclei
•Dentate,
•Interposed
(Globose &
Emboliform)
•Fastigial
Nuclei.
8

9. Cerebellar Cortex
•Three layers:
•Molecular Layer,
•Dendrites of
Purkinje cells,
•Parallel Fibers
•Stellate cells and
Basket cells.
•Purkinje Layer
•Granular Layer,
Granule cells and
Golgi cells. 9

10. Purkinje Cells
Ramón y CajalJan Purkinje

11. Cerebellar Connections:
• Afferent:
• Brainstem, spinal cord
and cerebrum > Mossy
Fibers > Granular
cells> Parallel Fibers >
Purkinje Cells.
• Inferior Olivary
Nucleus > Climbing
Fibers > Purkinje cell.
• Efferent:
• Purkinje cell > Deep
Cerebellar Nuclei >
Inferior Olivary
Nucleus, Brainstem,
spinal cord and
cerebrum 11

12. Models of Cerebellar
Functioning
12

13. Marr & Albus Model for
Cerebellar Learning
(Eccles, Ito & Szentagothai,1967)
•Several theories about cerebellum
and learnt behaviour.
•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.
13
David Marr
James Albus

14. Marr & Albus Model for Cerebellar Learning
(Eccles, Ito & Szentágothai,1967)
1. Feedforward processing.
2. Divergence and Convergence.
3. Modularity / Compartmentalization.
4. Plasticity.
5. Adaptive Filtering.
14
Cerebellar Perceptron,
James Albus

15. (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.
15

16. (2) Divergence & Convergence:
(Llinas et al, 2004; Apps & Garwicz, 2005)
•200 million Moss F > 40
billion Granular Cells >
Parallel F > 15 million
Purkinje Cells
•100 million Parallel Fibers >
one microzone (1000
Purkinje cells) (over 200000
spines) > 50 Deep Nuclei
Cells.
•100 Moss Fibres > 2 billion
spines of Purkinje cells > 1 16

17. (3) 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. 17

18. (4) Plasticity
(Mial et al, 1998; Ohtsuki et al, 2009)
• Purkinje cells normally > high
rate action potentials : Simple
spike.
• Climbing fibers-Purkinje cell
synapses > Complex spike
• Parallel fibre-Purkinje cell
synapse > long-term
depression (LTD).
• Repetitive firing of parallel
fibres alone > long-term
potentiation (LTP).
18

19. 5-Adaptive Filtering(Fujita 1982; Dean & Porell, 2008; Dean et al, 2010)
•Elimination of noise
•Fine tuning
•Optimality / Coordination
•Execution not creativity
19

20. •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”. 20
Masao Ito
Kenji Doya
Cerebellar Learning: “Software Programmer”

21. Cerebellar Learning:
(Burguiere et al, 2010, Kalmbach et al, 2011)
Cerebellum > does not
initiate new learning.
> It develops frequently
needed learnt behaviour
into a Routine with:
1. Minimum Errors
2. Minimum Time
3. Minimum Effort
4. Minimum Attention /
awareness
5. Maximum Stability 21Chase Britton

22. Psychiatric Aspects of
Cerebellar Disorders
22

23. 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).
23
Chase Britton

24. 2 - Psychiatric Aspects of Cerebellar
Disorders: (Wolf et al, 2007)
24

25. 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).
25

26. 4 - Cerebellar Cognitive Affective Syndrome
(Schmahman et al, 2007; Tavano et al, 2007; Levisohn et al, 2000):
26
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:
General
27

28. 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)
28
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).

29. 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) 29
•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. Cerebellar Abnormalities
in Psychiatric Disorders:
Dyslexia, Schizophrenia & Autism
30

31. (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.
31
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.

32. (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).
32
• ↓ 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).

33. (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)
33

34. (2) Cerebellum &
Schizophrenia:
Cerebellar Glutamate
Theory
34
•Hypo-
functioning of
the Glutamate
NMDA receptors
in cerebellum >
cognitive
dysmetria >
schizophrenia.
• Yeganeh-Doost et al,
2011):

35. (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

36. (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).
36

37. (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
37
S. Hossein
Fatemi

38. (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

39. Cerebellar Mental
Therapies
39

40. Cerebellar Exercises / Training
(Schmahmann, 2010)
• Some claims (e.g. DORE) > Physical exercises (movement +
balance) > speed up information processing and improve
cerebellar functioning > improve dyslexia, ADHD and
Asperger’s syndrome:
• ? Could improve some mental illnesses like schizophrenia .
• No known scientific studies.
• Controversial treatments (Reynolds & Nicolson, 2007; Bishop,
2007; Rack, 2007)
40

41. Dance & Movement Therapy
(Levi, 1988; Jeong et al, 2005)
41

42. 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
42

43. Cerebellum:
Clinical Reflections
43

44. Non-motor Dyspraxia
44

45. Non-motor Dyspraxia
•Clumsy expression of, well
developed, emotional,
social, communication
interactions due to
difficulties in expression.
•Possible examples:
dyslexia and dyscalculia.
•Primarily an “Ideomotor or
Executive Dyspraxia” rather
than “Ideational or Planning
Dyspraxia” (Gibbs et al 2007). 45

46. Routine Disorders
46

47. Routine Disorders vs Dyspraxia
•Dyspraxia does not usually include
complex behavioural patterns that,
coordinated by cerebellum, e.g.
“Habits” and “Routines”.
•This seems to be the case with
other similar clinical conditions as
they are manly describe motor
performance problems e.g.
• The Clumsy Child Syndrome
• Minimal Brain Dysfunction (MBD)
• Developmental Apraxia
• Specific developmental disorder of
motor function (ICD-10)
• Developmental Coordination Disorder
(DCD) (DSM-5). 47

48. •Most of daily behaviour for
adults are made of learnt
routines (habits) (Betsch et al, 2001; Beach &
Potter, 1992).
•biologically, Routines are the
main product or expression of
the brain and cerebellum
functioning.
•Explain many aspects of learning,
coping, health, pathology, future
choices and therapy (Bernacer & Murillo,
2014). 48
Routines : Clinical Perspectives

49. Routines : Clinical Perspectives
“Routines” are written in a book
designed by cerebrum and written
by cerebellum.
The book contain thousands if not
millions of routine > defining the
individual.
•Neurological (motor) disorders >
like misprints of the book.
•Routine disorders > like
discovering wrong chapters in the
book.
49

50. Healthy Routines vs Routine Disorders
50
Functional Routines Dysfunctional Routines
Meaningful > Serve useful
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

51. Cerebellar Circuits and Mental
Disorders
51

52. Cerebellar Circuits of Learnt Behaviour
•Best way to
understand Cerebellar
Circuits of Learnt
Behaviour > follow
motor cerebellar
learning:
•Well studied
•Must be linked
physiologically to non-
motor functioning.
52

53. Doya’s Model of Motor Learning (Doya, 2000)
(also Imamizu et al, 2000; Hikosaka et al, 2002, Bosch-Bouju et al, 2013)
Kenji DoyaFerreira et al, 2008

54. Routines : Components
(Following modified Doya’s model)
•Cognitive (neocortical)
•Satisfaction (septal nuclei)
•Emotional (amygdala)
•Impulse control
(striatum).
•Coordination
(cerebellum).
•Processing Capacity
(diencephalon /
thalamus).
•Autonomic (diencephalon
/ hypothalamus). 54

55. Development of pathological behaviour: examples
•1 faulty > failure to learn
(problem solving, adapting,
planning, etc.) e.g. LD.
•2/5 faulty > failure to eliminate
anxiety (threat) > e.g. OCD.
•3/5 faulty > failure to reach
satisfaction e.g. habit disorder
•1, 2 & 5 faulty > rigid (ego
syntonic) obsessional routines.
•5 faulty > disinhibition disorder
e.g. Tourette Syndrome.
•4 faulty > primary coordination
disorder (clumsiness).

56. Development of Biological Disorders
from Stress
- Stress effects on the brain
> Cerebellum to create
circuits that enhance
pathological responses.
- This explain how stress
reactions turn by cerebellum
into biologically based
pathology.
- Also explains how originally
stress related behaviours can
later become treatable by
psychiatric medications through
changing brain chemistry. 56

57. 57
Thank you
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