Clinical Anatomy of Motor Systems II

Lecture 7

What will we learn in this lecture ?

We will learn how movement is modified, via. 2 structures you can find in brain, the Cerebellum and the Basal Ganglia

Connectivity of the cerebellar cortex ?

The circuit you will find in cerebellum

Structures in the cerebellum ?

Cerebellar nuclei, cerebellar peduncles.

Cerebellum dysfunction

what happens when the cerebellum is damaged

Where is the cerebellum ? Latin word ?

Back part of the brain, looks like tree. Latin word for little brain. Located below cortex and occipital lobe. Behind brainstem.

What are the 4 functions of the cerebellum ?

1. Maintenance of balance and posture (most important)

2. Coordination of voluntary movements (e.g. when we want to grab coffee/tea)

3. Motor learning (learn how to ride bike, play piano, drive car)

4. Cognitive functions (previously they deleted proteins in the cerebellum which are associated with autism. It caused social impairment in mice. Cerebellum has involvement in the formation of social behaviour. It also helps in regulation of language + regulation of working memory performance.

What is important ?

It is important to know where cerebellum + brainstem as if a stroke occurs in the cerebellum, the bleed could spread into the brainstem (has important neurons which regulate heart frequency + respiration rates). Therefor stroke in cerebellum is not a good prognosis, often lethal.

Cerebellum superior view: Looks like ? Divisions ? Appearance ?

Looks similar to cerebral cortex. Hast Left + Right hemisphere. Divided by a structure (looks like a bridge) called vermis (latin word for warm. If this area is damaged patients have inability to stand upwards.

When you go down, there is a deep groove called vallecula (left behind this groove - you find 4th ventricle of the brain)

Cerebellum inferior view: Where are you looking ? Components ? and their functions ?

Looks at bottom of cerebellum.

Nodule - important structure involved in control of balance and posture.

On each side of nodule, we have flocculus - very important for control of eye movements for patients who have damage (no ability/impairements in the eye movement)

Tonsils: folding ridges you can see on left + right hemisphere. Often compressed when there is a high pressure in the brain due to stroke. Leads to impairement in balance + posture.

Anatomical structures and divisions: Architecture

White matter of cerebellum (looks like a tree, they extend into cortex of cerebellum) called arbor vitae (tree of living in Latin)

Cerebellum has same architecture you can find in the cortex (outer layer is brown - contains cell nuclei), white matter tracts appear white as they are surrounded in myelin sheath. Cerebellum consists of two hemispheres.

Anatomical lobes of the cerebellum ?

3 lobes:

1. Posterior lobe (biggest lobe)

2. Anterior lobe

3. Flocculonodular lobe (small lobe) - important for the control of balance + control of eye movement.

Three major functional subdivisions of the cerebellum ?

Cerebellum hidden below cortex.

1. Spinocerebellum - located on top. Control of muscle tone / coordination regulates body and limb movements.

2. Vestibulocerebllum (inner ear) - partially covered by cortex. Balance, Postural adjustements, Coordintation of eye movements.

3. Cerebrocerebellum / POntocerebellum (sits directly on the pons) - Planning + timing of movement, evaluating sensory information, cognitive function of cerebellum (involved in control of social behaviour, language production, control of speech).

Microscopic anatomy + connectivity of the cerebellar cortex ?

1. Molecular layer (outer layer)

• Stellate cells (appearance of stars) - inhibitory

• Basket cells (inhibitory interneurons)

2. Purkinje layer (very small layer0

• purkinje cells (large dendritic trees) extend into moelecular + granular layer

• Purkinje cells also receive input from the inferior olivary nucleus via. climbing fibres

3. Granular layer: extend into other regions

• granule cells (receive excitatory input from mossy fibers)

• Unilateral brush cells

• Golgi cells (inhibitory (star like appearance)

• All of these cells are connected to each other + form circuit

Cerebellum: input / output ?

Cerebellum receives input + gives output to other brain regions.

Input comes from the mossy fibers + climbing fibers (these are excitatory. So they are glutamatergic). They project to granular cell layer + purkinje cell layer.

From the purkinje cell, we have neurons going out to the cerebellar deep nuclei (output of cerebellum to other brain regions). This is the output region of cerebellum.

This is a general overview of how these neurons are connected.

Cerebellar nuclei ? Functions ?

4 different nuclei

1. Fastigial nucelus

2. Glubose nucelus

3. Emboliform nucleus

4. Dendate nucleus

Functions of these nuclei: To give motor output to other regions of the brain as well as the spinal cord.

Cerebellar nuclei: Input vs Output ?

Input:

Purkinje cells (inhibitory - GABAergic)

Mossy and climbing fibers (excitatory - Glutamatergic)

Output:

All outputs from the cerebellum originate from the cerebellar deeo nuclei

Cerebellar peduncles: What are they ? How can you find them ? Functions ?

Three Fibre bundles carry the sensory input and motor output (into the spinal cord + brain) of the cerebellum.

How can you find them ? they are based on the brainstem. You would have to remove cerebellum.

Function:

• Inferior cerebellar peduncle

» sensory input / motor output to the cerebellum

• Middle cerebellar peduncle

» Sensory input to the cerebellum

• Superior cerebellar peduncle: (when this is destroyed no motor info can go out of cerebellum to other brain areas)

» motor output of the cerebellum

Input and output teo the cerebellum: Functions ? Input ? Output ?

Function of cerebellum: Function is to fine tune movements. Does not generate movement by its own, but it adjusts the movement what we plan to do. Does this by receiving input from other regions as well as from the muscles in the periphery. THis info is processed in cerebellum, then goes out to muscles + motor cortex + spinal cord.

Input to the cerebellum: Major input from cerebral cortex.

Sensory input from:

INferior olive

» Learning and memory

Spinal cord (dorsal nucleus of Clarke)

» monitor position and motion

Vestibular nucelus

» posture + position of head, neck, eyes.

Outputs to the cerebellum: cerebellar cortex - deep cerebellar nuclei - ventral complex (thalamus) - primary motor + premotor cortex (as well as to muscles in the periphery. Cerebellum can fine tune the movement, does not initiate the movement)

Function - eye movement, stance and gait, limb coordination

Cerebellar dysfunction: causes (4), what ?, General features (8), what do you examine in clinic ?

causes:

• Vascular / stroke

• physical trauma - TBI

• Tumors (growing in cerebellum)

• chronic alcoholic excess

what ?

Cerebellar dysfunction - conditions affecting the cerebellum disrupt motor coordination and timing, loss of muscle tone (complete loss)

General features:

• Ataxia (slow/awkward movement). Most general features. walk is fragmented, not right posture.

• Dysmetria (distorted rannge/force) (not able to grab object for eg. overshooting)

• Decomposition of movement: jerky and segmented

• Cerebellar damage leads to intentional limb movements. With a coarse tremor at right angles to the direction of movement. The tremor dissapears when muscles are ay risk.

• Ataxic dysarthria (speech disorder): anamolous force, timing and amplitude of movement. Ataxic respiratory muscles create uncontrolled changes in breath pressure at the vocal cords, causing irregular, sometimes explosive changes in vocal pitch / loudness (patients with stroke. speech is slow + unclear, slurred, dont have regular rhythm)

• Speech has hypernasality

Eye movements, you normally examine when they come into clinic - often not able to make eye movements.=

Melloblastoma /Lesion in Vermis: What is it ? Associated with what ? Cause ? Symptoms ? What is it ? Disruption ?

• Severe form of cancer, which grows on the cerebellum on the vermis. ONe of the first symptoms is that they cannot stand upright anymore.

• Associated with cerebellum

• Vermis: back part of the cerebellum

Cause: medulloblastomas / lesion in vermis (common in children)

Symptoms:

• Headache (due to increase in intracranial pressure as tumor grows) problems with balance + coordination

• Vomiting

• DRowsiness

• Truncal Ataxia: INability to stand upright

• Nystagmus: INnacurate visual tracking of finger due to vermis lesion, poor control of gaze centres.

» disrupts pathway from vermis to nucelus of vestibular nerve

» Malfunction of lateral vestibulospinal tract

Pontocerebellum lesions: What are they ? Symptoms ?

Pontocerebellum lesions: incoordination of voluntary movements

Symptoms:

• Affects upper limb (in hand movement)

• INtention tremor when grasping

• Overshoot

• DEcomposition of movement (looks fragmented)

• Dysdia-do-cho-kinesia: irregular rapid alternating movements “finger-to-nose” and “heel to kneel” tests

• Impaired phonation

• Slurred articulation

Anterior lobe lesions or degeneration; where ? Disease of what ? Common in what ? Loss of what ? Reversible ?

Anterior lobe of cerebellum

Disease of anterior lobe common in chronic alcoholics, cerebellar degeneration.

» Loss of granular cells (10%), purkinje cells (20%), and molecular layer (30%) often irreversible

Symptoms:

• Affects lower limbs

• Little impairement of arm or speech

• Failure to heel to toe walk

• Sensory ataxia (inability to sense proprioception)

Basal Ganglia: what is it ? Where can I find ? Grouped ? Consists of what ? And what do these parts do ?

group of subcortical nuclei - can find in structure blow cortex.

Consist of different parts, grouping of these nuclei is related to function rather than anatomy - its components are not part of a single anatomical unit and are spread deep within the brain.

Basal Ganglia consists of 5 pairs of nuclei:

• Caudate nucelus (striatum)

• Putamen (striatum)

• Globus pallidus

• Subthalamic nucleus

• Substantia nigra (very important structure, becomes impaired in parkinsons disease)

Caudate nucleus: movement planning + learning of movement

Putamen: helps control body movements

Globus pallidus: send output signals to stop or adjust movement

Subthalamic nucleus: helps modulate output

Substantia nigra: produces dopamine, critical for movement control.

Basal Ganglia components & function: Generate movement ? Function ?

Do not generate movement.

Function: control movement

• Start movement

• Stop movement

• Smooth out voluntary movements

• Motor learning

Function: control emotions (connected limbic system; hippothalamus, hippocampus, amygdala, control emotions.

• Motivation

• Reward & Pleasure

• Apathy

• Fear & Anxiety

• Habit Formation

Input to the basal ganglia: Receive what ? Exception ? Input zone ? OUtput zone ? Converge ?

• most cortical areas projecting to striatum

• The caudate, putamen, ventral striatum receive cortical projections primarly from the associateion areas of the frontal, parietal and tmeporal lobes

• Exception: are primary visual + auditory cortices in occipital and temporal lobe. Dont project to basal ganglia.

» all of these projections, referred to collectively as the cortciostriatal pathway

» travel through the internal capsule to reach the caudate and putamen directly

Input zone - caudate and putamen

Output zone - globus pallidus and substantia nigra pars reticulata

• Incoming cortical axons: synapse on striatal medium spiny neurons

• Spiny neurons converge on globus pallidus and the substantia nigra pars reticulate, which are the main sources of output from the basal ganglia complex.

Medium spicy neurons: Input ? Divergence ?

• INput onto a medium spiny neuron in putamen and caudate from cortical neurons, DA neurons of the substantia nigrs & local circuit

• Divergence of cortcial input via axon terminal allows a single medium spiny neuron to integrate the influences of thousands of cortical pyramidal cells.

Output from basal ganglia ?

• 1st pathway to frontal lobe motor cortex runs from globus pallidus to motor cortex via ventral anterior (VA) and ventral lateral (VL) nuceli of dorsal thalamus

• 2nd pathway runs from substantia nigra to superior colliculus and synaoses with UMN here, without thalamus relay (eye movements)

• GABAergic output, thus main inhibitory output > disinhibition

Direct + Indirect pathway basal ganglia: Function ? Disturbance ?

Basal Ganglia help to control movement by either, promoting or inhibiting movement.

Direct pathway - helps to start the movement

Indirect pathway - stop + reduce unwanted movement

Often these pathways get out of balance in neurodegenerative diseases, like Parkinsons

Basal Ganglia dysfunction: Damage ? Result ?

• Damage to the basal ganglia will result either involuntary movements or impairemnets to motion

• Overall, a person with basal ganglia dysfunction may difficulty starting, stopping, o sustaining movement.

Basal Ganglia dysfunction: general feature (11) Causes (7)

• Akinesia (lack of movement - difficulty initiating)

• Bradykinesia (slowness of movement) observes in parkinsons

• Shuffling gait (PD)

• Tremor (shaking hands)

• Rigity

• Athetosis (slow, writhing movements of fingers, hands and toes)

• Ballism ( violent, flailing movements)

• Dystonia (distorted) abnormal muscle contraction

• Chorea (abrupt flailing movements of the limbs and facial muscles)

• Speech control, difficulty finding words

• Cognitive, learning via reward + punishment

• Tics: sudden repetotive movements

Causes:

• Drug overdose (heroin)

• Head injury (PD)

• Metabolic (Hypoglycemia) low blood sugar

• Infection (Encephalitis) Brain bacteria / viris

• MItochondrial disorders: Leighs syndrome

• HUntingtons disease

• Parkinsons disase - most important associated with basal ganglia.