Session 6

Question 1

Describe basal ganglia anatomy

Answer 1

Substantia nigra pars compacta (SNc, source of dopamine in the midbrain) 

Striatum (receives input from SNc and cortex)

• Caudate nucleus (c-shaped nucleus lining lateral ventricle)
• Putamen 

Globus pallidus

• Internal and external segment 

Caudate + putamen = striatum (functionally related) 

Putamen + globus pallidus = lentiform nucleus (anatomically but not functionally related) 

Subthalamic nucleus (small area sitting beneath the thalamus) 

The basal ganglia communicate with the motor cortex via the thalamus. Increased thalamic activity causes increased cortical activity and vice versa

Question 2

Describe the normal function of the basal ganglia

Answer 2

Unclear 

Probable role in reinforcing appropriate movements and removing inappropriate movements.

Think about a simple behaviour like picking up a cup of tea – you need to facilitate appropriate movements (e.g. elbow flexion) and suppress inappropriate movements (e.g. elbow extension) 

Direct pathways reinforces appropriate movements (excitatory to motor cortex) 

Indirect pathway edits out inappropriate movements (inhibitory to motor cortex) 

Dopamine facilitates movement by exciting the motor cortex (excites direct pathway by stimulating excitatory D1 receptors on striatal neurones taking part in the direct pathway, inhibits indirect pathway by activating inhibitory D2 receptors on striatal neurones taking part in the indirect pathway) 

Basal ganglia regulate ipsilateral motor cortex, hence if SNc is affected unilaterally (rare) there will be contralateral signs due to decussation of the corticospinal tract 

Question 3

Parkinson’s disease

Answer 3

 Caused by degeneration of dopaminergic neurones in SNc 

Therefore have lost the dopamine-driven facilitation of movement via both pathways  Symptoms and signs:

• Tremor (unclear mechanism, but may be related to dysfunction of indirect pathway which would normally suppress unwanted movements)
• Rigidity (unknown mechanism, may be related to lack of co-ordination between agonists and antagonists)
• Bradykinesia (best understood mechanism. Slow movements due to loss of cortical excitation)
• Hypophonia (quiet speech = bradykinesia of larynx and tongue)
• Decreased facial movement / mask-like facies (bradykinesia of face)
• Micrographia (small handwriting = bradykinesia in hands)
• Dementia (possible progression of currently unknown causative agent (e.g. protein aggregates))
• Depression (basal ganglia also have a role in cognition and mood)

Question 4

Huntington’s chorea

Answer 4

 Autosomal dominant, progressive disorder 

Early onset around 30-50 years old 

Early stages associated with loss of inhibitory projections from striatum to GPe

• This leads to hyperkinetic features (increased movement as the brakes have been taken off the thalamus) 

Features

• Chorea (dance-like movements due to increased motor cortex activation)
• Dystonia (uncomfortable contractions of agonists and antagonists simultaneously leading to odd postures caused by over activity in agonist/antagonist muscle circuits and loss of co-ordination between these)
• Loss of co-ordination (similar to above presumably)
• Cognitive decline and behavioural disturbances (related to role of basal ganglia in higher metal functions)

Question 5

Hemiballismus

Answer 5

 Rare disorder 

Can be caused by damage to subthalamic nucleus which normally inhibits the thalamus via GPi 

Can be caused by sub-cortical stroke (lacunar infarct)  Causes unilateral explosive (‘ballistic’) movements

Question 6

Describe the anatomy of the cerebellum

Answer 6

 Midline vermis and two laterally placed hemispheres 

Vermis deals with trunk, hemispheres with the ipsilateral side of the body 

Communicates with the rest of the CNS via the cerebellar peduncles (different to the cerebral peduncles!)

• Superior cerebellar peduncle connects to midbrain
• Middle cerebellar peduncle connects to pons
• Inferior cerebellar peduncle connects to medulla 

Sits above the fourth venricle

• Cerebellar lesions (e.g. tumours) can cause hydrocephalus

Question 7

Normal functions of the cerebellum?

Answer 7

 Obscure! 

However, has a clear role in the sequencing and co-ordination of movements 

Uses sensory information to decide upon the most appropriate sequence of movements to perform an action 

Works with basal ganglia which decide most appropriate movements. Cerebellum then sequences these movements. So, to develop the picking up a cup of tea example: basal ganglia say that elbow flexion, shoulder flexion, finger flexion and wrist flexion are most appropriate.

Cerebellum then puts these in most appropriate sequence based upon current position of limb (maybe finger flexion followed by wrist extension followed by elbow then shoulder depending upon position). 

Hence, cerebellum has profuse sensory inputs from proprioceptive neurones and the sensory cortices 

Cerebellum receives sensory input from ipsilateral spinal cord and contralateral sensory cortices. Its outputs are to the contralateral motor cortex. Hence, ipsilateral signs of cerebellar damage due to decussation of corticospinal pathway

Question 8

What are the signs of cerebellar disease?

Answer 8

 Dysdiadochokinesia

• Difficulty with rapidly alternating movements (presumably as a result of a problem with sequencing pronationsupination-pronation-supination…) 

Ataxia

• Unsteady gait as a result of difficulty sequencing lower limb muscle contractions as well as loss of unconscious proprioception from lower limbs 

Nystagmus

• Flickering eye movements due to malcoordination of extraocular muscles 

Intention tremor

• A tremor that worsens as a target is approached 

Slurred speech (dysarthria)

• Caused by malcoordination of laryngeal and tongue musculature 

Hypotonia

• Unclear mechanism