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Cerebellum, Psychiatry& Routine Disorders
Dr Khalid Mansour
Locum Consultant PsychiatristNorthgate Hospital
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Cerebellum and Psychiatric
Disorders: Introduction
Traditionally: cerebellum > posture, balance,motor control (Flourens, 1824).
Recently: cerebellum > perceptions,emotions, cognition, speech & personality(Chung et al, 2010; Konarski et al, 2005; Roskies et al, 2001;Schmahmann, 1991; schmahmann and Sherman, 1989; Papez, 1937)
Cerebellar abnormalities have been found ofmost of the major psychiatric disorders(Hoppenbrouwers et al, 2008)
Cerebellum > automation of brainperformances like a computer(Eccles, 1973):software programmer of the brain.
Some clinical implications
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Contents:
1. Cerebellar Anatomy, Histology &
Physiology
2. Cerebellar Abnormalities in
Psychiatric Disorders.
3. Psychiatric Aspects of Cerebellar
Disorders.
4. Clinical applications > RoutinesDisorders
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Cerebellar Anatomy, histology &
Physiology
Cerebellar Anatomy Structural Anatomy
Functional Anatomy
Deep Cerebellar Nuclei
Cerebellar Histology and Physiology Cerebellar Cortex
Mossy Fibers & Granule Cells
Climbing Fibers & Purkinje Cells
Compartmentalization
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Cerebellum Anatomy
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Cerebellar Anatomy
Structural anatomy: Cortex and White matter
Cortex (Gross Anatomy):
Anterior lobe (3 lobules),
Posterior lobe (6 lobules) &
Flocculonodular lobe (2 lobules).
White matter:
Nerve fibre tracts
Deep nuclei
Dentate,
Interposed (Globose & Emboliform)
Fastigial nuclei.
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Cerebellar Anatomy
Functional Anatomy:
Vestibulocerebellum(flocculonodular lobe).
Spinocerebellum(vermis & paravermis).
Cerebrocerebellum (lateral cerebellarhemispheres).
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Deep Cerebellar Nuclei
They receive inhibitory final output from the
cerebellar cortex (Purkinje calls).
They also receive afferent projections from
excitatory inputs from
Mossy fibers
Climbing fibers
provide feedback control of the cerebellarcortex.
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Deep Nuclei
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Cerebellum Anatomy
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Cerebellar Cortex:
Three layers:
Bottom thick granular layer, densely packed
with Granule cells and Golgi cells.
Middle Purkinje layer Top molecular layer,
Dendrite trees of Purkinje cells,
Parallel Fibers
Stellate cells and Basket cells
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Micrograph of the cerebellar cortex showing its three layers
(molecular layer, Purkinje cells layer and granule cell layer) and its
meningeal coverings (pia materand arachnoid mater). H&E stain.
http://localhost/var/www/apps/conversion/tmp/scratch_5//lhfs03/wiki/Pia_materhttp://localhost/var/www/apps/conversion/tmp/scratch_5//lhfs03/wiki/Arachnoid_materhttp://localhost/var/www/apps/conversion/tmp/scratch_5//lhfs03/wiki/H&E_stainhttp://localhost/var/www/apps/conversion/tmp/scratch_5//lhfs03/wiki/H&E_stainhttp://localhost/var/www/apps/conversion/tmp/scratch_5//lhfs03/wiki/Arachnoid_materhttp://localhost/var/www/apps/conversion/tmp/scratch_5//lhfs03/wiki/Pia_mater7/29/2019 Cerebellum and Psychiatric Disorders 22
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Mossy Fibers & Granule Cells
Mossy Fibers arise from brainstemspinal cord and cerebrum (about 200million in humans) >
A single mossy fiber makes contact withan estimated 400600 granule cells.
Granule cells> Parallel Fiber.
A Parallel fiber > 80100 synapticconnections with Purkinje cell dendriticspines.
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Climbing Fibers
Spinal cord, brainstem, and cerebral cortex >Inferior Olivary nucleus > Climbing fibers >
deep cerebellar nuclei and Purkinje cell.
A single climbing fibre > 3000 contacts with 10different Purkinje cell > Axons travel into deep
cerebellar nuclei (1000 contacts each).
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Purkinje Cells (Plasticity)(Mial et al, 1998; Ohtsuki et al, 2009 )
Purkinje cells normally emit action potentials at ahigh rate even in the absence of synaptic input:
Simple spike > single action potential followed by arefractory period of about 10 msec
Complex spike > stereotyped sequence of actionpotentials with very short inter-spike intervals anddeclining amplitudes
Parallel fiber-Purkinje cell synapse can undergo long-term depression (LTD) in response to the coincident
firing of both parallel and climbing fibers1. Repetitive firing of parallel fibers alone can induce
long-term potentiation (LTP) at the same synapses.in controlling this balance.
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Compartmentalization
Each body part maps to specific points in
the cerebellum.
Cerebellar cortex is compartmentalized into
zones and microzones.A Microzones were found to contain on the
order of1000 Purkinje cells.
Cellular interactions within a microzone aremuch stronger than interactions between
different microzones.
S h ti Ill t ti f Th St t f Z d Mi i Th
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Schematic Illustration of The Structure of Zones and Microzones in The
Cerebellar Cortex(Apps & Garwicz, 2005).
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Cerebellar Learning
1. Marr & Albus model
2. Modern Views
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Cerebellar Functional Organisation
Cerebellum functional structures are largely
suitable for regulating brain processes (Katz
& Steinmetz, 2002; Ito, 2008)
10% of the weight of the brain 4 times number of neurones in the cerebral
cortex.
50% of brain neurones
Fewer types of neurones
Different systems of interconnections
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Marr & Albus Model for Cerebellar learning
Most theories that assign learning to the
circuitry of the cerebellum are derived from
early ideas ofDavid Marr(1969) and James
Albus (1971).Albus (1971) formulated his model as a
software algorithm he called a CMAC
(Cerebellar Model Articulation Controller),
which has been tested in a number ofapplications.
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Marr & Albus model for Cerebellar learning
Eccles, Ito & Szentagothai (1967);
Feedforward processing: signals moveunidirectionally through the system from input tooutput, with very little recurrent internal transmission> a quick and clear response.
Divergence and convergence: In the humancerebellum, information from 200 million Mossy fibersinputs is expanded to 40 billion granule cells, whoseparallel fibers outputs then converge onto 15 millionPurkinji cells.
Modularity: The cerebellar system is functionallydivided into more or less independent modules.
Plasticity: The synapses between parallel fibers andPurkinje cells, and the synapses between mossyfibers and deep nuclear cells, are both susceptible to
modification of strength LTP and LTD.
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Model of Cerebellar Perceptron, James Albus 1971
M d l f C b ll f ti i J Alb 1971
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Model of Cerebellar functioning; James Albus, 1971
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Cerebellar Learning:
? Software programmer Cerebellar dysfunction > continue to be able
to generate motor activity, but uncoordinated.
Boydon (2004): Cerebellum is involved inmotor learning to make fine adjustments tothe way an action is performed.
Kenji Doya (2000): function of thecerebellum is best understood as neural
computation. Ito (2005):A modulator role of motor and
non-motor functions: matches intentions withactual performance.
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(3) Cerebellar Abnormalities in
Psychiatric Disorders(Hoppenbrouwers et al, 2008)
A- Psychological Studies of Normal Individuals
with Reduced Cerebellar VolumeB- Cerebellar Abnormalities in Schizophrenia:
C- Cerebellar Abnormalities in Autism:
D- Cerebellar Abnormalities in other psychiatric
disorders:
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Cerebellar Studies in Psychiatric
Disorders:General Observations
The most common studies but not the mostevident.
Significant number of studies have positivefindings.
Findings are not always consistent andconclusions are debatable.
Cerebellar abnormalities can also be
secondary / compensatory pathology e.g.increased dopamine in schizophrenia causeboth psychosis and cerebellar pathology.
Best studied; autism and schizophrenia.
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A - Psychological Studies of Normal
Individuals with Reduced Cerebellar Volume
Normal individuals with reduced cerebellar
volume > higher scores on scales of anxiety,
type A personality, phobia, tenderness and
hostility (Chung et al, 2010):
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B- Cerebellar Abnormalities in
Schizophrenia: General
Large part of imaging studies (Varnas et al, 2007) support
cerebellar malformation in schiz.
Smaller cerebellar volume (Bottmer et al, 2005)
Reduced blood flow on PET scan (Andreasen et al, 1996).
Reduced level of N-acetylaspartate (marker of neurone
density and viability) in vermis and cerebellar cortex in
Magnetic Resonance Spectroscopy Imaging (MRSI)
studies (Ende et al, 2005).
Volume reduction in the cerebello-thalamic-corticalnetwork (Rusch et al, 2007).
Neuronal disorganisation in the superior peduncle on
Diffusion Tensor Imaging (DTI) studies (Okugawa et al,2006).
B Cerebellar Abnormalities in
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B- Cerebellar Abnormalities in
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 disorder in schiz Stip et al, 2005; Paradiso et al, 2003; Abel et al, 2003
Cognitive function in schiz
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
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B- Cerebellar Abnormalities in
Schizophrenia: Clinical Studies
Increased prevalence of motor impairment in
schizophrenic patients even drug nave ones,
could suggest possible cerebellar
abnormalities (Hoppenbrouwers et al, 2008; Varambally et al,2006).
However, these motor abnormalities could be
secondary to schizophrenia e.g. increased
dopaminergic activities affect the cerebellarfunctioning or morphology (Mittleman et al, 2008).
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B- Cerebellar Abnormalities in Schizophrenia:
Cognitive Dysmetria Theory: (Andreasen et al, 1998)
A dysfunctional Cortico-cerebellar-thalamo-
cortical circuit > poor mental coordination
(cognitive dysmetria) > Schizophrenia.
Some disagreed e.g. Kaprinis et al, 2002:split between positive & negative symptoms >
different psychopathologies.
Others support the theory e.g. Schmahman,
2004 & Honey et al, 2005: Dysmetria also
affect affective and motivational aspects of
brain functioning.
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C- Cerebellar Abnormalities in Autism One of the most consistent abnormalities
found in ASD are cerebellar degenerative
changes, especially Reduced Purkinji cells,
especially in vermal lobules I & II(DiCicco-Bloomet al, 2006).
Theory: cerebellar malfunction > loss of
modulatory control of frontal cortex >ASD,
(catani et al, 2008).
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D- Cerebellar Abnormalities in Psychiatric
Disorders:Others
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) ADHD: e.g. reduced Cerebellar volume(Glaser et al, 2006)
Post Traumatic Stress Disorder: e.g. altered functionof the vermis (Anderson et al, 2002)
Alcohol abuse: e.g. induced reduction in Cerebellar /Vermis volume(Glaser et al, 2006)
Gender differences:(Dean & McCarthy, 2008)
Antisocial Personality Disorder: e.g. reducedCerebellar volume(Barkataki et al, 2006).
Alzheimer Dementia: e.g. cerebellar atrophy(Wegiel et al,
1999)
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(4) Psychiatric Aspects of
Cerebellar Disorders
(1) Cerebellar Cognitive Affective Syndrome
(2) Anatomically Specific Psychiatric Aspects of
Cerebellar Disorders
(3) Other Psychiatric Aspects of Cerebellar Disorders
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(1) Cerebellar Cognitive Affective
Syndrome(Schmahman & Shermen, 1998). Cerebellar lesions in general e.g. acquired lesions, congenital
cerebellar malformations, cerebellar tumour resection, etc can
cause motor impairments plus the following (Schmahman etal, 2007; Tavano et al, 2007; Levisohn et al, 2000)
Cognitive impairments:
Executive dysfunctions e.g. in working memory and planning
Visuo-spatial abnormalities e.g. in visual memory and visuo-
spatial organisation
Linguistic dysfunction e.g. dysprosodia, agrammatism and
anomia
Affective impairments:
anxiety, lethargy, depression, lack of empathy, ruminativeness,
perseveration, anhedonia and aggression
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(2) Anatomically Specific Psychiatric
Aspects of Cerebellar Disorders
Vermal Agenesis > severe LD, Autism &
abnormal motor development (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).
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(3) Other Psychiatric Aspects of Cerebellar Disorders:(Wolfet al, 2007)
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Clinical Implications
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Clinical Implications:
Assessment:
(1) Motor disorders in psychiatric disorders as
signs of cerebellar dysfunctioning
(2) Non-motor symptoms equivalent to motorsymptoms related to cerebellum
Treatments:
(3) Cerebellar exercises
(4) Transcranial Magnetic Stimulation (TMS) (5) Routine disorders
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(1) Motor disorders in psychiatric patients:
signs of cerebellar dysfunctioning E.g. Poor saccadic eye movement, Motor
clumsiness, Gait abnormalities, Stuttering,
cluttering, stammering, etc
Used mainly in research as markers and/orassociations
Not highly specific to cerebellum but to the
motor brain circuits which include the
cerebellum
? Clinical significance
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(2) Non-motor symptoms equivalent to
motor symptoms related to cerebellum
Usage of Non-motor Dysmetria (Andreasen et al,1998) as clinical concepts in assessment andtreatment of psychiatric disorders (Schmahmann,2010): e.g.
Cognitive dysmetria,
Emotional dysmetria,
Social dysmetria,
Speech/Communication dysmetria,
? No available publications
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(3) Cerebellar Training(Schmahmann, 2010)
Physical exercises that combine movement
and balance, designed to improve the slow
information processing with dyslexia and
ADHD; claimed to speed up informationprocessing and improve cerebellar
functioning >
Controversial treatments for which there is no
known published scientific literature.
C b ll T i l M ti
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Cerebellar Trancranial 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
No RCT
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Routine Disorders
Follow the established neurological models
for Motor Behavioural Routines
Function of brain circuits involving cerebrum,
striatum, cerebellum and thalamus. The cortico-cereller-thalamo-cortical circuit
The cortico-striato-thalamo-cortical circuit
M t L i M d l
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Motor Learning Models:
(Doya, 2000)
The cerebellum, is best understood as a
device forsupervised learning (also
Imamizu et al, 2000)
in contrast to the basal ganglia, whichperform reinforcement learning
and the cerebral cortex, which performs
unsupervised learning
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Differences Between Routines, Habits and
Compulsions
When brain wants to learn a behaviour for a frequent
use: > Cerebellum then provides the software
programme >
Gradually learn the most efficient way to do the task
with least effort > a successful Routine (functionalRoutine)
if the process fails > Routine Disorder
Diff b R i H bi
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Differences between Routines, Habits
and Compulsions
When brain wants to learn a behaviour for a
frequent use: > Basal Ganglia > Checking /
Feedback System:
Checks that the learnt behaviour is consistent with
the data from the Reward System (via NucleusAccumbens+ Dopamine) (thermostat)> if rewardSystem is dysfunctional > Habits Disordere.g.
addiction, gambling > (dysfunctional routines)
Avoid anxiety provoking errors (via lateralamygdala + serotonin) (alarm) > if gives faulty
checking > OCD and/orcompulsive disorder >
(functional routine unnecessarily repeated)
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Routine Disorders
Problems with clinical uses: Multiple systems involved: striatum, frontal
lobe, limbic system as well as environmentalfactors
Complex system of assessment
Advantages:
Following a system which is a product of abrain circuit is more neurologically meaningfulthat monitoring symptoms related to a single-brain-centre.
More clinically relevant
Examples of Routine Habit and
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Examples of Routine, Habit and
Compulsion Disorders
Want to learn how to drive the car from home to
work:
Cerebellum > software for smooth and quick drive, if
still struggling to drive smoothly or efficiently > Routine
disorder Basal ganglia: checks your routine if achieving the
target > if you develop the habit of drive fast to attract
attention > Habit Disorder
Basal ganglia: checks your routine if no errors
committed > if it keeps giving you unjustified signal that
tyres and you have to stop to check time after time >
Compulsion.
Seven Stages of a successful
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Seven Stages of a successful
Behavioural Routines
1. Identifying the data relevant to the routine
2. Process (analyse) these data
3. Developing a partial routine
4. Learn from ones mistakes as well as fromothers
5. Develop an efficient routine
6. Routine works well even in unfamiliarcircumstances
7. Routine works well even under pressure
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Routine Disorders Can not detect the relevant data to the routine
Can not understand them properly
Can not formulate a routine
Can not learn from others how to improve or develop
the routine
Can only formulate partially functional (mechanical)
routines
Can not use the routine under pressure
Can not use the routine in unfamiliar situations
Applying the Seven Stages of
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Applying the Seven Stages of
Social Routines in Autism Can not detect the relevant social data: severe
Autism
Can do the above but can not understand them
well: severe Autism
Can do the above but can not formulate a even
partially functional routines: e.g. High Functioning
Autism
Can do the above but can not imitate routines of
other people: High Functioning Autism.
Can do the above but can not use the routine in an
unfamiliar situations: Asperger Syndrome
Can do the above but can not use the routine under
pressure: Asperger Syndrome
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