Cerebellum Flashcards
What are the ways to divide cerebellum anatomically?
-anatomy anterior, posterior, flocculonodular -phylogenesis (evolution) archicerebellum, paleocere, neocere -afferent vestibulocere, pontocere, spinocere -saggital/efferent medial, intermediate, lateral zone
For the efferent, which zone is connected to which nuclei?
medial: fastigial nucleus
intermediate: interposed nucleus
lateral zone:dentate nucleus
What are the function for each zone?
medial: Sitting, Stance/posture, gait, oculomotor/Eye movements
CLR (cerebellar locomotor region)
intermediate: Limb coordination/Foot placement,
motor speech, ongoing execution of movement
lateral zone: Limb coordination/motor planning,
Cognition, visual control
Flocculonodular lobe: oculomotor
control
What is limb ataxia
Involves symptoms such as
Dysmetria: lack of movement coordination
Intention tremor: Intention tremor (action/kinetic tremor)
Asynergia: jerky movement trajectory/Decomposition of
movement
Dysdiadochokinesis: inability to execute rapidly alternating movements, particularly of the limbs
Lesion in the right cerebellar hemisphere causes
limb ataxia on the right (Ipsilateral signs)
How is cerebellum organised?
Somatotopically
anterior lobe is in charge of fingers/foot etc
top posterior is empty (non-motor because it is cognition related);
Dysarthria
motor speech disorder; Lesion in region 6 of the cerebellum
Disease related to each zones
Medial zone:
Truncal, stance and gait ataxia
Nystagmus
Intermediate zone:
Dysmetria, intention tremor, dysdiadochokinesia, dysarthria
Lateral zone:
Asynergia, decomposition of movement
What are ataxias?
- Disorders of the cerebellum or it‘s pathways
- leading to chronic „ataxia“ (that is incoordination).
- Focal disorders of the cerebellum are not called Ataxias
Classification of ataxia
Focal cerebellar disorder disorders
- Stroke
- Tumour
- Multiple Sclerosis
Ataxia (degenerative disorder): 1) Hereditary Dominant = spinocerebellar ataxias (SCA) Recessive Most frequent: Friedreich‘s ataxia (FRDA)
2) Non-hereditary
a) SAOA
Sporadic/idiopathic adult onset
ataxia of unknown etiology
b) MSA-C
Multiple system atrophy
cerebellar type
+Parkinsonism
+autonomic dysfunction
3) Acquired
a) Alkoholic
cerebellar degeneration
b) Paraneoplastic
cerebellar degeneration
What are the causes of ataxia?
Stroke: acute
Tumour: subacute
MS: subacute
Hereditary and non-hereditary: chronic progressive
Acquired: subacute
What are the common age for ataxia?
Stroke: any age
Tumour: any age
MS: any age
Hereditary (dominant): SCA1-3 25-30 yrs, SCA6 50 yrs Hereditary (recessive): FRDA <20 yrs Non-hereditary: 50 yrs Acquired: any age
Differentiation between various SCA
All SCAs are Trinucleotide repeat disorders
SCA1: Pyramidal tract signs (spasticity)
SCA2: Slow saccades
SCA3: Ophthalmoplegia, pyramidal tract signs, dystonia, polyneuropathy (basal ganglia/brainstem)
SCA6: pure cerebellar, + migraine
FRDA
Autosomal recessive disorder Trinucleotide repeat disorder, Sensory (afferent) ataxia Affect: cerebellum, spinal cord, peripheral nerves Symptoms: -Macro square wave jerks -Dysarthria -Sensory ataxia -Areflexia -Pyramidal tract dysfunction -Blindness -Deafness -Cardiomyopathy -Scoliosis -Diabetes mellitus type 1 and/or 2 Atypical phenotypes: -Late onset and very late onset Friedreich‘s ataxia (VLOF) -With retained tendon reflexes -With cerebellar atrophy
Ataxia in MRI
OPCA = olivopontocerebellar atrophy (not a disease by itself but a pattern seen)
CA = cerebellar atrophy
Spinal atrophie
Focal cerebellar disorder
ischemic stroke: PICA = Posterior inferior cerebellar artery
and SCA = Superior cerebellar artery
tumour: Astrocytoma
1) Hereditary
SCA1,2,(3 only visible later): OPCA & CA
SCA6: CA
FRDA: spinal atrophy
2) Non-hereditary
SAOA: CA
MultipleSystemAtrophy-C: OPCA and
“hot cross bun sign”due to enlarged 4th ventricle
3) Acquired
Alkoholic: CA
most prominent: anterior lobe
Paraneoplic: no atrophy initially; long-term: CA
Which MRI shows the hot cross bun sign?
MultipleSystemAtrophy-C in addition to OPCA
Diagnosis of ataxia
In addition to MRI
1) Hereditary
Genetics
SCA1,2,3,6, FRDA = trinucleotide-repeat-disorders
2) Non-hereditary
by exclusion of hereditary and acquired ataxias
3) Acquired
Alkoholic: liver enzymes, blood count, carbodeficient transferrin CDT; lack of vitamine B1
Paraneoplastic: CSF, antineuronal antibodies, tumor workup
Clinical ratings for ataxia
Scale for the Assessment and Rating of Ataxia (SARA)
for gait and stance; most common
International Cooperative Ataxia Rating Scale (ICARS)
eye movement
For cognitive function: Schmahmann scale (the guy who discovered Cerebellar cognitive affective syndrome)
Treatment of ataxia
There is no anti-ataxic drug except Aminopyridines (fampridine) for nystagmus and episodic ataxia
Currently, Physiotherapy, speech therapy, occupational
therapy is the approach
-The more you do the better for you.
-2 x 20 minutes a week is not enough.
-Daily home based training in addition to
physiotherapy.
-In an ideal world: In-patient rehabilitation every six month, at least every 2 years
For future, genetic treatment is being investigated and looking promising in animals
Hypotheses about cerebellar function
- Timing device (like a clock)
- Sensory analyzer (many input via peduncle)
- Predictive device for motor control (planning)
- Learning machine (error-based learning)
Histology: output cell of cerebellum
Purkinje cells
input -> cerebellar cortex -> purkinje cells -> cerebellar nuclei -> output
Purkinje to cerebellar nuclei is INHIBITORY (masao ito)
Cerebellar nuclei
excitatory output back to the body (controlled by inhibitory purkinje cells)
Histology: input cell of cerebellum
- climbing fibre from inferior olive
2. mossy fibre from mainly pons -> granule cells
Why do researchers think cerebellum is in charge of timing?
Tidal wave timing theory
Because of parallel fibres (axon of granule cells) in the molecular layers, connected perpendicularly to purkinje cells
Hypermetria
測定過大-四肢の随意運動が目的の位置を行き過ぎてしまうこと
Cerebellar dysfunction
Cerebellar hypermetria
Timing (speech perception) - rabbit vs rapid
Which is most likely function of cerebellum?
Predictive device for motor control (planning)
- cerebellum function as a “comparator” to adjust the motor planning by sending error message to brain if edit needs to be made
- works by comparing the planned movement to the previous movement experience
- adjust the current movement to the accurate speed
Explain the Predictive device for motor control (planning)
Internal model of prediction error
Planning and programming of movement (Feedforward)
sensory association cortex -> BG and lateral zone of cere. hemisphere -> premotor cortical area (controller)
Movement execution (feedback) premotor cortical area (controller) -> motor cortex ->movement -> sensory feedback -> intermediate zone of cere. hemisphere -> ADJUSTMENT -> motor cortex
Proof:
cooling/temporal lesion of dentate have caused dysmetria and intention tremor
How to test cerebellar motor prediction?
-Coupling between grip and load (up and down movement) forces
If cerebellum is functioning, person grip force will increase when moving up and down to prevent dropping the object
-Coupling between shoulder movement and arm extension (Prediction of interaction torques)
If cerebellum is functioning, one can catch a ball above their head
Classic experiment for cerebellar learning
Prism adaptation
Task: Throw a darts
Catch? You wear a prism glass (which shifts your vision)
If cerebellum is functioning, the participants learn to adjust to the shift and re-start hitting the target again.
Cerebellar dysfunction patient will not learn.
Reach adaptation
Task: Move a Manipulandum (a machine with a rotatable lever)
Catch? The lever can give force preventing you to move the lever to the target
If healthy, they learn to adjust to the force
Visual threat eyeblink response (VTER)
a naturally conditioned response acquired in early childhood
Eyeblink in response to airpuff is to be learned by cerebellum as it is not seen in cerebellum agnesis patients (both learning and storage of memory is done in cerebellum)
What are in charge of learning in cerebellum?
The purkinje cell
Many simple spike via mossy fibre cause LTD reducing the Purkinje cell firing -> less inhibition
Cerebellum agnesis
individual without cerebellum
Explain the VTER mechanism
Visual threat eyeblink response
Air puff: error via climbing fibre
Tone: efference copy via mossy fibre
LTD caused decrease purkinje cell firing, leading to less inhibition -> Long term potentiation?
What are the complication of cerebellar learning?
1) Inhibitory interneurons most likely also playing a role and learning occurs w/o LTD as well
2) Although the wiring of the cerebellar cortex appears to be uniform, the neurons in this region of the brain behave more differently from each other than previously thought
Having the protein “zebrin” seems to be related to LTP leading to learning
3) Connection between basal ganglia (reinforcement learning from reward) and cerebellum (supervised learning from error)
Evolution
parallel increase of the frontal lobe and neocerebellum
How did understanding of cerebellum change from an anatomical perspective?
Before: reciprocal/efferent cerebellocerebral connections primarily to primary motor cortex
New: reciprocal cerebellocerebral connections to many, including cognitive cerebral areas
How were the findings for cerebellum being efferent to lots of cortical cerebral areas discovered?
This leads to supporting cerebellum being important for cognitive functions
• FMRI studies in healthy subjcets
• Human lesion studies
• Findings in neuropsychiatric and developmental disorders
Why is “cerebellum and cognition” an ongoing matter f discussion?
- Motor performance deficits e.g. oculomotor disorders and attention (How can we purely measure cerebellar function?)
- Extracerebellar lesion
- Depression influence cognitive functions
- Influence of disordered motor development on cognitive development
Cerebellar cognitive affective syndrome
aka Schmahmann Syndrome
(i) Disturbances of executive function. This includes
deficient planning, set-shifting, abstract reasoning,
working memory, and decreased verbal fluency.
(ii) Impaired spatial cognition, including visuospatial
disorganization and impaired visuospatial memory.
(i) Personality change, characterized by flattening or
blunting of affect, and disinhibited or inappropriate
behavior.
(ii) Linguistic difficulties, including dysprosodia,
agrammatism and mild anomia
According to Schmahmann, there is lateralisation of cerebellum function
Left
Executive function
Visual-spatial
function
Right
Executive function
Language
Vermis
Affect, behaviour attention
Cognitive abnormalities in children with cerebellar disease
• Cerebellar malformations e.g. Congenital agenesia/ Partial agenesie • Focal lesions of the cerebellum e.g. Hemorrhage, ischemia, tumours • Cerebellar degeneration e.g. Ataxia telangiectasia • Developmental disorders Preterm children, autism, dyslexia, ADHD
diaschisis
機能解離
Importance of cerebellum in cognitive development
Motor related develop earlier than cognitive in cerebellum
typical cerebellar signs
Dysmetria Intentiontremor Ataxia Nystagmus Dysarthria Asynergia
NOT
paresis
akinesia
