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Cerebellum
Cerebellar Anatomyand Connectivity Cerebellum = “Little Brain”
• 10% of the volume of the total brain
• Contains more than half of all the brain’s neurons
History: Cerebellum and Volitional Movement
• 1809: Rolando first showed that cerebellar removal results in disturbances of posture and voluntary movement
• 1824: Fluorens showed cerebellum responsible for coordination of voluntary movements
• 1939: Holmes analyses of motor and speech deficits from cerebellar injury provided basis of modern terminology and neurological exams
Movement Disturbances
Early reports of cognitive disturbance
• Neuropsychological evaluation was primitive
• Most reports were somewhat anecdotal
• Consequently, cognitive contribution of cerebellum largely ignored
Schmahmann, J.D. (1997) Int Rev Neurobiol 41, 3-27.
Early Reports of Cognitive Disturbances
Early Evidence of Cerebellar Link to Sensory & Associative Cortex
• 1934: Abbie observed degeneration of human pontine nuclei following large lesions of parietal, temporal, occipital lobes
• 1942: Dow determined that dentate nucleus could be divided into older medial region and lateral neodentate
• 1942, 1958: Dow and Moruzzi, Snider & Stowell showed that proprioceptive, cutaneous, vagal, auditory and visual stimulation reaches the cerebellar cortex – Dow & Moruzzi: “…a hitherto unknown control may be exerted
by the cerebellum in the sensory sphere and on autonomic functions.”
– Snider: Concluded that cerebellum gets dual projections, one from sense organs and one from related sensory and motor cortical areas
• The cerebellum is “a great modulator of neurologic function.”– They note that large cerebellar lesions, especially in lateral
regions, produce little motor deficits
Trends in Cerebellar Research
• Pubmed Search:– Title contains *cerebell*, cerebrocerebell*, or cerebro-
cerebell*– Divide into Human and Animal– Cognitive content if title contains:
• spatial, mental, emotion*, affective, reasoning, language, linguistic, planning, fluency, cognit*, memory, attention*, executive, nonmotor, or neuropsych*
– Cognitive/Motor content if title contains:• timing, learning, conditioning, or speech
– Motor content if title contains• motor, sensorimotor, oculomotor, movement*, postur*,
balance, gait, gaze,saccad*, nystag*, locomot*, or walking
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Human Animal
Desmond, J.E. (2010) Behav Neurol 23, 1-2.
Brain Development
• The nervous system develops from ectoderm(outer layer) of the embryo which forms a plate (~day 18)– The edges of the plate curl and eventually fuse
together forming a neural tube
– By ~day 28, the rostral end of the neural tube has formed the ventricles and the tissue that surrounds these hollow chambers has formed three major divisions of the brain
• Forebrain, midbrain, and hindbrain
BrainDevelopment~ 4 weeks ~ 5-6 weeks
Brain Development
Brain Development Neuroanatomy: Orientation
Planes of Sectioning
Coronal
Sagittal
Axial
axial
coronal
Superior/Dorsal
Inferior/Ventral
Ant
erio
r/R
ostr
al
Pos
teri
or/C
auda
l
Superior View
Inferior View
Posterior ViewAnterior View
Sagittal Section
Cerebellum has 3 lobes
• Anterior lobe
• Posterior lobe– The latter are divided by the primary
fissure
• Flocculonodular lobe– (most primitive, appears in fish)
3 Lobes of the Cerebellum
Superior View of Cerebellum Flocculonodular lobe
Flocculus
Nodulus
Longitudinally, there are Three Regions
• Vermis (midline)
• Intermediate zone
• Lateral zone
Longitudinal Zones
Vermis = “Worm” Note many parallelConvolutions, ie.,“folia” 10 Lobules
• There are 10 vermian and hemispheric “lobules”
• The naming of the lobules has been variable across investigators and species studied
Cerebellar Lobule Naming
Brodal, A. (1981) Neurological Anatomy in Relation to Clinical Medicine, Third edn, Oxford University Press, New York.
Human Animal
Examples
Human:Posterior Quadrangular LobuleAnimal: Simplex LobuleSchmahmann name:Hemispheric lobule VI
Human: Superior Semi-Lunar LobuleAnimal: Crus ISchmahmann name:Crus I
Vermis Nomenclatures
Schmahmann et al (1999) NeuroImage. 10, 233-60.
10 Lobules
• Lobules are separated by fissures
Schmahmann et alAtlas Nomenclature
Schmahmann et al (1999) NeuroImage. 10, 233-60.
Cerebellar Fissures
Schmahmann et al (1999) NeuroImage. 10, 233-60.
Anterior View
Superior View
Cerebellar FissuresPosterior View
Inferior View
Left Lateral View
Best view of the hemisphere lobules is on coronal sections
Best view of vermis lobules is on sagittal section
Cerebellar Deep Nuclei
• Medial: Fastigial nuclei
• Intermediate: Interposed nuclei– In humans: Emboliform and Globose nuc
• Lateral: Dentate nuclei
Deep NucleiDeep Nuclei Visibility
Y= -52
Cryo section (coronal)
MRI
MRI
T1-weighted
T2-weighted
Schmahmann et al (1999) NeuroImage. 10, 233-60.
Deep Nuclei – Childrenvs Adults
29 years old 12 years old
Raw functional images from two subjects
Courtesy of Dr. Dominic Cheng
Deep Nuclei Visibility
Y= -52
Nissl stain
Myelin stainSchmahmann et al (1999) NeuroImage. 10, 233-60.
Longitudinal Zones Project toDifferent Deep Nuclei
• Vermis Fastigial Nuclei
• Intermediate Interposed Nuclei
• Lateral Dentate Nuclei
Deep Cerebellar NucleiHave Somatotopic Maps
Inputs and Outputs: Big PictureThalamus projects to neocortex
Pontine Mossy fiberinputs via middlecerebellar peduncle
Outputs from deepcerebellar nucleivia the superiorcerebellar peduncle
Climbing fiberinputs via inferiorcerebellar peduncle
Spinal Mossy fiberinputs via inferiorcerebellar peduncle
Inputs to Cerebellum
• Mossy fibers– Come from (contralateral) pontine nuclei and
spinal cord– Pontine fibers project through the middle
cerebellar peduncle (aka: brachium pontis)– Spinal cord fibers project through inferior
cerebellar peduncle (aka: restiform body)• Climbing fibers
– Come from the (contralateral) inferior olivary nucleus
– Project through the inferior cerebellar peduncle
Cerebellar PedunclesAnterior View from 4th ventricle
Mossy fiber inputsClimbing fiber inputs
Cerebellar Peduncles
Superior
Inferior
Posterior View – Cerebellum Removed
Functional divisions• Vestibulocerebellum = flocculonodular lobe
– Eye movements, vestibulo-ocular reflexes, gait, balance– Inputs from vestibular organs– Projects to vestibular nuclei– Evolution: oldest part (archicerebellum)
• Spinocerebellum = vermis & intermed zone– Somatosensory inputs from spinal cord and trigeminal nerve, as well
as auditory, visual and vestibular inputs– Projects to fastigial and interposed nuclei– Influences descending motor systems– Evolution: Newer (paleocerebellum)
• Cerebrocerebellum = lateral zone– Inputs from cerebral cortex via the pons– Outputs to dentate nuc– Evolution: Newest (neocerebellum)
Mossy FiberInputs to
Functional Divisions
Cerebrocerebellum
Spinocerebellum
Vestibulocerebellum
Cortico-Ponto-Cerebellar Circuitry
Kandel, E.R. et al, eds. Principles of Neural Science, 3rd Ed. New York: Elsevier, 1991
• Note that cerebellar damage has ipsilateral motor effects, due to double decussation of inputs and outputs– E.g., left cerebellar damage causes
problems in left limbs
– In contrast left motor cortex damage causes problems for the right limbs
Decussation frompons to cbl cortex
Decussation fromdentate to thalamus
Decussation=fibers (axons) cross midline
Schmahmann, J. D. Human Brain Mapping 4:174-198 (1996).
Cortico-pontine projections
Ponto-Cerebellar Projections
Brodal, A. (1981) Neurological Anatomy in Relation to Clinical Medicine, Third edn, Oxford University Press, New York.
Anatomical Tracing in Animals
• Old: Silver impregnation methods to view degenerating axons
• Newer: Horseradish peroxidase and autoradiographical methods
• Newest: Transneuronal tracing using viruses, e.g., Herpes, Rabies– Peter Strick & colleagues: Studies
performed in monkeys
Transneuronal transport of virus
Neocortex
Thalamus
Dentate Nuc
PurkinjeCells
First order
Second order
Third order
Neocortex
Rabies: Retrograde Herpes: Anterograde
Pons
GranuleCells
PurkinjeCells
Injection Sites
Kelly, R.M. and Strick, P.L. (2003) J Neurosci 23, 8432-44.
Retrograde transneuronal transport of rabies virus
Dorsal
Ventral
Dorsal Dentate: Primary MotorVentral Dentate: Prefrontal
Very Significant: There is connectivity between cerebellum and cognitive neocortex!
Kelly, R.M. and Strick, P.L. (2003) J Neurosci 23, 8432-44.
M1: Nearly Identical Patterns for Anterograde & Retrograde Tracing
Retrograde Tracing Anterograde Tracing
Kelly, R.M. and Strick, P.L. (2003) J Neurosci 23, 8432-44.
Area 46: Nearly Identical Patterns for Anterograde & Retrograde Tracing
Retrograde Tracing Anterograde Tracing
Kelly, R.M. and Strick, P.L. (2003) J Neurosci 23, 8432-44.
Implication: Closed Cortico-ponto-cerebello-thalamo Loops
Kelly, R.M. and Strick, P.L. (2003) J Neurosci 23, 8432-44.
Lobular Evolution
Pct ofcerebellumoccupiedby the lobule
Balsters et al (2010) Neuroimage 49, 2045-52.
Climbing Fiber Inputs:Inferior Olivary Nucleus
Inferior Olive: Cross Section Inf. Olive and Pontine Nuc.
https://www.msu.edu/~brains/brains/human/brainstem/select_cell.html
Pontine Nuclei
Inferior Olivary Nuclei
Superior cbl peduncle
Sup. And Inf. Cerebellar Peduncles
Superior cbl peduncle
Inferior cbl peduncle
https://msu.edu/~brains/brains/human/sagittal/0272_cell.jpg
Middle Cerebellar Peduncle
Middle cbl peduncle
https://msu.edu/~brains/brains/human/sagittal/0392_cell.jpg
Inf. Olivary Subdivisions
• Three main subdivisions:
• Principal olive (PO)
• Dorsal accessory olive (DAO)
• Medial accessory olive (MAO)
Inf. Olivary Subdivisions
• lPO (purple)=lamina of principal olive– Can be preceded by l
(lateral), m (medial), d (dorsal), v (ventral)
• DAO (red)=dorsal accessory olive
• MAO (blue)=medial accessory olive
• yellow: dc = subnuclei of MAO, vlo = ventrolat. outgrowth (of MAO)
transverse sections showing left side only,numbers caudal to rostral. Top is dorsal.
Inferior Olivary Inputs
• Somatosensory input from spinal cord, trigeminal nuclei, dorsal column nuclei– Mostly in cMAO and DAO
• Vestibular and optokinetic input– dc, vlo
• Visual information– cMAO
• Cerebral Cortex via Red Nucleus– PO, rMAO
• Direct projections from Deep Cerebellar Nuclei
Cortico-rubro-olivary projections
The neocortex can influence climbinginputs to the cerebellum through thisprojection, in addition to influencing themossy fiber inputs in the pons via cortico-pontine projections.
Outputs of Inf. Olive =“Climbing Fiber” Inputs to
Cerebellum
• Climbing Fibers project to:– Cerebellar Cortex
– Cerebellar Deep Nuclei
Outputs from Cerebellum
• Come from the deep cerebellar nuclei
• Project through the superior cerebellar peduncle (aka: brachium conjunctivum)– Most fibers cross the midline
(decussation)
Cerebellar Peduncles
Cerebellar Outputs Outputs of Functional Divisions
+ more
+ more
• Flocculonodular lobe receives vestibular input and projects directly to vestibular nuclei
• Vermis receives input from neck, trunk, vestibular, retina and extraocular muscles. Output focuses on ventromedial descending motor systems (reticulospinal, vestibulospinal, and medial corticospinal)
Vestibulocerebellarand Medial
Spinocerebellar Outputs• Intermediate zone of
spinocerebellum receives sensory input from limbs and influences dorsolateral descending motor systems (rubrospinal and corticospinal) acting on ipsilateral limbs– Note: magnocellular RN involved
• Cerebrocerebellum receives input from many cortical areas via the pontine nuclei and influences those areas via dentato-thalamo-cortical projections. There is also dentate -red nucleus – inferior olive loop– Note: parvocellular RN involved
Lateral Spinocerebellar and Cerebrocerebellar
Outputs
distal parts of limbs
Zones of cerebellar cortex, deep nuclei and inferior olive
Microzones &Microcomplex
~5000 microcomplexes in human cerebellumMicrocomplex = microzone + related deep nucleus+nuclear target+olivary region
Sometimes referred to byits latin name, Nucleus RuberRuber = “red”
from red nuc.
Overall Picture: Cerebellar Loops
Cerebral Cortex
Thalamus
RedNucleus
Cerebellar Cortex
Deep Nuclei
InferiorOlive
Sensory Input
Motor Execution
Pontine Nuclei
mossy fibers
clim
bing
fib
ers
Cortico-ponto-cerebello-thalamo loop
Cerebral Cortex
Thalamus
RedNucleus
Cerebellar Cortex
Deep Nuclei
InferiorOlive
Sensory Input
Motor Execution
Pontine Nuclei
mossy fibers
clim
bing
fib
ers
clim
bing
fib
ers
Local Inferior Olive Loop
Cerebral Cortex
Thalamus
RedNucleus
Cerebellar Cortex
Deep Nuclei
InferiorOlive
Sensory Input
Motor Execution
Pontine Nuclei
mossy fibers
clim
bing
fib
ers
Olivary Loops Via Red Nucleus
Cerebral Cortex
Thalamus
RedNucleus
Cerebellar Cortex
Deep Nuclei
InferiorOlive
Sensory Input
Motor Execution
Pontine Nuclei
mossy fibers
CerebellarLoops
DN=Deep NucleiRN=Red NucleusPN=Pontine Nuc
ION=Inferior Olivary NucBG=Basal Ganglia
Cortico-ponto-cerebello-thalamo
loop
DN=Deep NucleiRN=Red NucleusPN=Pontine Nuc
ION=Inferior Olivary NucBG=Basal Ganglia
Olivary Loops Via Red Nucleus
DN=Deep NucleiRN=Red NucleusPN=Pontine Nuc
ION=Inferior Olivary NucBG=Basal Ganglia
Local Inferior Olive Loop
DN=Deep NucleiRN=Red NucleusPN=Pontine Nuc
ION=Inferior Olivary NucBG=Basal Ganglia
Cerebellar Cortex Neuronal Organization
• Five types of neurons– Inhibitory:
• Purkinje
• Golgi
• Basket
• Stellate
– Excitatory• Granule
Cerebellar Cortex Neuronal Organization
• Three Layers of Cerebellar Cortex– Molecular Layer
• Cell bodies of stellate and basket cells• Axons of granule cells, called parallel fibers• Dendrites of Purkinje Cells
– Purkinje Cell Layer• Cell bodies of Purkinje cells
– Granule Cell Layer• Granule cells, which receive inputs from the mossy
fibers (Most numerous neurons in brain, 1010-1011)• Golgi cells, also receive mossy fiber input
Cerebellar Cortical
Cells
Divergence and Convergence
200 million MF inputs diverge onto40 billion granule cellsPF fibers converge onto 15 million PCFurther converge on Deep nuclei
“Fractured somatotopy”One body part represented inMultiple regions due to divergence
Parallel Fibers
Excitatory and Inhibitory
ConnectionsSimple and
Complex Spikes
Recording fromPurkinje Cell
Types of Cerebellar Damage/Disorder
• There are many conditions that can affect the cerebellum
• In most human research studies, patients typically have– Tumor removal (beware of radiation)
– Diffuse cerebellar degeneration (spino-cerebellar ataxias – inherited – multiple forms)
– Stroke involving cerebellar vascular territory
Cerebellar Vascular Supply
SCA
medial branch SCA
lateral SCA
AICA
PICAmedial PICA
lateral PICA
basilar artery
vertebral artery
SCA=superior cerebellararteryAICA=anterior inferiorcerebellar arteryPICA=posterior inferiorcerebellar artery
Brainstem
Superior Cerebellar Arteries SCA Supply Zones
PICA Supply ZonesExample of PICA territory
Infarct
Example SCA Territory InfarctSigns of Cerebellar Damage
Dysmetria
• A lack of accuracy in voluntary movements– Hypermetria = overshoot of target– Hypometria = undershoot
• Delay in initiation of movement is common• Occurs proximally and distally in upper and
lower limbs• Affects both single-joint and multi-joint
movements• Most pronounced in rapid movements• Often followed by corrective movements
Cerebellar damage videos
DWFSG7ambleturn_57_WMV V9.wmv
SPFSG04romb_57-1_WMV V9.wmv
VSFGS02walkturn_57_WMV V9.wmv
Balance/Walking Tests
Abnormal - Finger-to-nose_WMV V9.wmv DWFC09ftnmov_57_WMV V9.wmv
VSFC11ftnmov_57_WMV V9.wmvyoutube.com.Cerebellar ataxia_WMV V9.wmv
Finger-to-nose Test
Abnormal Coordination Exam ; Heel-to-shin_WMV V9.wmv VSFC12heelkshin_57_WMV V9.wmv
Heel-to-shin Test
DWFMSiSpArtic_57_WMV V9.wmv VSFMSiSpArtic_57_WMV V9.wmv
Dysarthria: Impaired Articulation
Ocular Dysmetria
Abnormal - Hand Rapid Alternating Movements_WMV V9.wmvDWFC11prosup_57_WMV V9.wmv
VSFC07suppro_57_WMV V9.wmv youtube.com.Dysdiadochokinesia Song_WMV V9.wmv
Impaired rapid alternating movementDysdiadochokinesia
Dysmetria of Upper Limb: Pointing Movements
Manto, M. (2009) J Neuroeng Rehabil 6, 10.
ComparableAt slow speed
Elbow
Shoulder
Hyperextensionof elbow causesovershoot
Concise elbowmovement
Abnormal EMG in Cerebellar Patients
Manto, M. (2009) J Neuroeng Rehabil 6, 10.
Healthy Control Cerebellar Patient
Reduced rise rate
Increased latency
2 bursts not demarcated
Single joint movement, e.g. pull a lever, AGO = agonist muscle (biceps), ANTA = antagonist (triceps)
Normal triphasic pattern
Cerebellar Hypermetria
Wrist flexion movement (MVT)
Normal Subject Cerebellar Patient
Overshoot
Adaptation in Eye-Hand Coordination
A. Special prism glasses bends light sothat you have to look left to see targetdirectly in front
B. When prisms are first put on, throwsdeviate to the left, but there is adaptation.When the glasses are removed there isa rebound effect.
C. Adaptation fails in a patient withunilateral PICA infarction involvinginferior cerebellar peduncle (inferiorolivary climbing fibers!) and inferiorlateral posterior cerebellar cortex
Models of CerebellarFunction
Marr (1969) Model
• Hebb (1949) proposed that synaptic modification based on co-occurrence of pre-and postsynaptic activity might underlie learning
• Marr proposed that parallel fiber synapses onto Purkinje Cells are facilitated (Long Term Potentiation, or LTP) when they are activated together with climbing fiber activation
Marr: Cerebellar Synaptic Plasticity
De Schutter (1997) Prog Brain Res 114, 529-42.
Joint activity from parallelfiber and climbing fiberwas hypothesized tocause synaptic modificationat the parallel fiber synapse
Marr (cont)• Through plasticity
mechanism, cerebellum could learn movement skills from experience
• From divergence of mossy fiber to granule cells, finer representation of sensory information can be achieved
Example
pontine nuclei
finger 1 finger 2
mossy fibers
granule cells
Purkinje cells
finger 1 finger 1and 2 finger 2
Albus (1971)• Suggested that the cerebellum functions
like a perceptron pattern-classification device, with complex spikes (from climbing fibers) as the unconditioned stimulus and mossy fiber input as the conditioned stimulus
Cerebellar Perceptron
Albus, J.S. (1971) Math Biosci 10, 25-61.
Albus (cont)
• Proposed that climbing fiber provides an error signal
• Also proposed that parallel fiber synapse is weakened instead of facilitated– He predicted long term depression (LTD), prior to the
demonstration of its existence by Ito (1982) in cerebellar slices
– Marr’s modified theory is often referred to now as Marr-Albus or Marr-Albus-Ito model
• There is still much debate on whether the cerebellum is the locus of motor learning or if it is more of a control machine
Adaptive Filter Models
• Introduced in 1982 by Fujita
• Influenced by Ito’s suggestion that vestibulo-ocular reflex could be understood in terms of engineering control theory
What is an Adaptive Filter?
• A filter is a hardware or software device that converts an input signal into a different output signal
• E.g., in music a “low pass” filter effectively removes high frequencies of an audio signal
Low Pass Filter Adaptive Filter
• An adaptive filter can learn to attenuate a signal only in the noise frequency band
• E.g., aircraft engine noise
• Requires a second input signal from microphone as an “error” or “teaching” signal
Adaptive Filter
w1 w2 w3
p1(t) p2(t) p3(t)
y(t) = wipi(t)
Signals positively correlated with error signal get weight reducedSignals negatively correlated with error signal get weight increased
error: e(t)
spike inputx(t)
Change insynapticweight
Learningrate constant(typically < 1)
ErrorSignal
Currentoutput
e.g. p3 onset at t=3 coincides with error signal, so w3 is reduced
w1 w2 w3
p1(t) p2(t) p3(t)
y(t) = wipi(t)
Signals positively correlated with error signal get weight reducedSignals negatively correlated with error signal get weight increased
error: e(t)
spike inputx(t)
If =0.1, e(t)=1 for error,otherwise e(t)= -1:w3=(-0.1)(1)(1)= -0.1
t=3
Attractions of Adaptive-Filter Modelof Cerebellum
• Such filters are widely used in signal processing because they are powerful and deliver best (least squares) solution
• There is structural resemblance to cerebellar microcircuit
• Adaptive filters are capable of the kinds of functions associated with the cerebellum– Predicting a movement’s sensory consequences– Refinement of movement so that it is fast and
coordinated
Cerebellar Microcircuit & Adaptive Filters
An explanation of microcircuit features:A large number of inputs (mossy fiber) are needed for an adaptive filterThe teaching signal (climbing fiber) must be capable of affecting everyweight without altering filter output
Predicting Sensory Consequences of Movement:Noise Cancellation
a. (Theoretical) The goal is to teach the adaptive filter to cancel out the noise portion of s(t)+n(t)
b. (Practical) The goal is to attenuate touch signals from whiskers that are generated by the animal’s ownhead movements. Otherwise, everytime whiskers scrape the ground theanimal will interpret it as a possiblefood stimulus.
…And Speaking of Predicting Sensory
Feedback
Cerebellar Activation Distinguishes Between Self-Produced and Externally-
Produced Tactile Sensation
Blakemore et al (1998) Nat Neurosci 1, 635-40.
Adaptive Filter Model andAccurate Movement
• Vestibulo-ocular reflex (VOR)
• Goal: Keep an image stable on the retina as the head is moved by producing a counteracting eye movement
Cerebellar Adaptive Filter for VOR
1. Output of cancellation module is a motor command to oculomotor system2. The slip of the image off the retina is the error signal3. A copy of motor command feeds back into adaptive filter
Slightly different from noise cancellation module for 3 reasons
Eye muscles
Eye velocity must match head velocityto keep image stableon retina. (When you see “+”and “–” you are hoping the 2signals match).
Cerebellar Adaptive Filter for VOR
(a) Head starts to moveVestibular signals arise
(b) Vestibular signals triggerredEye movements are initiated
(c) Do vestibular signals causeEnough eye movements?
Eye muscles
Cerebellar Adaptive Filter for VOR
(a) Image slipped off retinaError!
(b) Adjust these weights
Cerebellar Adaptive Filter for VOR
(b) Again, image slips off retinaError!
(a) Eye muscles old, weak or damaged.Insufficient movement.
(c) Adjust these weights
Evaluation of the model:Cerebellar flocculus and VOR
• Involvement of flocculus in image stabilization has been established via lesion and inactivation studies
• Main mossy fiber inputs to flocculus carry vestibular info and efference copy of eye movement commands
• Climbing fiber inputs to flocculus carry retinal slip signals
• Plasticity: when VOR gain requirement is altered experimentally, Purkinje cell firing changes
What about the rest of the cerebellum?
• Specific regions of inferior olive project to specific strips of cerebellar cortex in sagittal plane (zones, A-D2)
• Each zone projects to specific deep cerebellar or vestibular nuclei, which project to targets in the rest of the brain, which in turn project back to IO
• Thus there are loops that may be functional subunits
Zones of cerebellar cortex, deep nuclei and inferior olive
Microzones
• Zones can be further subdivided into microzones – 5000 estimated
• This organization suggests a “cerebellar chip”
Cerebellar Chip Challenge for Testing the Model
• In most cases we do not know how a microzone’s output affects behavior
• Thus identifying the error signal of the climbing fiber is challenging
Internal Models State Estimation
• The ability of the brain to control movement is based on its knowledge of the body’s state at any moment
• State can be defined by a set of variables such as velocity and position of different limb segments
• Given accurate knowledge of current state and motor commands the brain ought to be able to estimate the state in the near future and control it
Forward and Inverse models
• Forward model: Given a motor command, what is the predicted new motor state
• Inverse model: Given a desired new motor state, what is the motor command needed to achieve it?
State Estimation ProblemDelay Problem
• Delay in arrival of afferent signals from periphery, along with central processing delays causes out-of-date knowledge of the peripheral system
• So afferent feedback cannot be used for guidance
• Thus, calculation of a state prediction involves not only predicting the state of the limbs, but also predicting the sensory consequences of the new state
Forward modelsTwo Predictions:
• A forward dynamic model is a prediction of limb status, e.g., joint angles and velocities given forces applied
• A forward output model is a prediction of tactile signals, proprioception, vision, audition
Forward models
• What happens if rapid movement has to rely on sensory feedback alone?– Movement would have to be slow or
instabilities/oscillations would occur
– Note: Oscillations are characteristic of cerebellar damage
Forward Model
Forward Model
“catch the ball”Copy of commandGoes to cerebellum
Forward Model
Rapid calc of wherehand will be
Rapid prediction of sensory info with delays accounted for
Forward Model
Another name forthe predicted sensoryconsequences
This is the actual sensory consequences arising from the movement.
Forward Model
Discrepancy of predicted andactual sensory information provides error (teaching) signal for forward dynamic model
Implementing the theoretical model
Cerebellar Patients
With no forward model predictions from the cerebellum, adjustmentsOf the motor command must rely on the relatively slow reafference signals