Motor control 2

Question 1

What are anticipatory feedforward adjustments?

Answer 1

Adjustments that are made before movements begin to stabilise posture - so that we don’t fall over.

Question 2

Where do anticipatory feedforward adjustments come from?

Answer 2

Brainstem reticular formation nuclei.

Question 3

What happens if descending motor pathways are damaged?

Answer 3

Upper motor neuron syndrome.

The site of injury determines symptoms.

Question 4

Describe the symptoms seen in upper motor neuron syndrome.

Answer 4

1) Cortical damage causes immediate flaccidity of contralateral muscles - lift limb and release? Drops passively.
2) Initial hypotonia due to spinal shock as spinal circuits are deprived of cortical input.
3) Days later, spinal circuits regain function - new connections are made which can cause:
- Babinski’s sign
- Spasticity: hypertonia, hyperreflexia, clonus (due to removal of cortical suppressive influences)
- Loss of fine finger movements

Question 5

Where does the major subcortical input to area 6 come from?

Answer 5

Ventral lateral nucleus of the thalamus.

Question 6

What are the input and output regions of the basal ganglia?

Answer 6

Motor cortex and pre-motor cortex provides input to the caudate nucleus and putamen. This then gives information to the output areas which are the globus pallidus and substantia nigra (midbrain).

Question 7

What are the main excitatory and inhibitory neurotransmitters in the brain?

Answer 7

Excitatory is glutamate, inhibitory is GABA.

Question 8

When do the putamen and caudate nucleus fire?

Answer 8

Putamen before limb/trunk movements; caudate before eye movements.

Question 9

What is the function of the basal ganglia?

Answer 9

Involved in initiation and termination of movements - part of the extrapyramidal motor system.

• evidence that BG fire before voluntary movements occur, indicating involvement in initiation.

Question 10

What is the consequence of cortical activation of the putamen?

Answer 10

Cortical excitation:

The direct pathway:

1) excites the putamen which
2) inhibits the inhibitory signal to the globus pallidus which therefore
3) releases cells in VLo from inhibition so
4) activity in VLo boosts SMA activity

–> this acts as a positive feedback loop focussing activation of widespread cortical areas onto cortical SMA

–> the ‘GO’ signal for voluntary movement may occur when the SMA is boosted beyond a threshold level by activity coming through the basal ganglia funnel

Question 11

Describe the chain of neurones arranged in a disinhibitory circuit.

Answer 11

At rest:

• little cortical input so UMN’s in the SMA are not excited

On excitation:

• lots of cortical input to the globus pallidus which is inhibited; thalamus is therefore disinhibited and so excited the UMN’s in the SMA

Question 12

Describe the indirect loop by which cortical input flows through the basal ganglia.

Answer 12

Antagnoises the direct route:

• Striatum inhibits GPe (globus pallidus external) which then inhibits both GPi (globus pallidus internal) and STN (subthalamic nuclei)
• Cortex excites STN which excites GPi and inhibits the thalamus
• This suppresses competing/inappropriate action

Question 13

What is hypokinesia?

Answer 13

Partial or complete loss of muscle movement due to disruption of the basal ganglia.

Slowness, difficulty making voluntary movements, increased muscle tone (rigidity), tremors of hands and jaw.

Question 14

What is hyperkinesia?

Answer 14

Muscle spasms.

• resting tremor of limbs and sometimes head and neck; all shake when at rest
• tremor disappears when movement is in progress

Question 15

What is Huntington’s chorea/disease?

Answer 15

Jerky spasmodic movements at rest and incorporated into normal voluntary movements.

Question 16

Name 3 hyperkinetic disorders.

Answer 16

Huntington’s chorea, athetosis and ballism.

Question 17

What is ballism?

Answer 17

Violent flailing movements of the limbs.

Question 18

What is athetosis?

Answer 18

Slow writhing movements which affect the extremities.

Question 19

How is control of movement regulated?

Answer 19

Cells of the globus pallidus have a high level of spontaneous activity. This needs to be voluntarily regulated to control movement.

Question 20

What happens in the basal ganglia when the body is at rest?

Answer 20

• Caudate nucleus and putamen (striatum) have an INHIBIORY effect on the pallidum via GABA
• At rest, this pathway is excited so that the pallidum is inhibited and the body stays still

Question 21

What happens in the basal ganglia when movement is to be initiated?

Answer 21

Rediness potential inhibits the striatum (so that it cannot inhibit the pallidum) –> exitation can then be transferred to the motor cortex.

This is voluntary control.

Question 22

Describe the pathology of Huntington’s chorea.

Answer 22

Normally, organising cortical inputs go to the striatum to be checked (voluntary control) before they pass to the pallidum then motor cortex via the thalamus.

In HC, there is striatal degeneration. This means that organising cortical inputs are lost, as is voluntary control via striatum –> spontaneous activity of the pallidum is passed to the motor cortex unchecked –> motor gibberish which leads to unwanted movements.

Question 23

Describe the pathology of Parkinson’s disease.

Answer 23

Normally there is a nigrostratial pathway that releases dopamine (DA). This stops the inhibition of the pallidum from the striatum being too strong. When a movement is to be initiated, DA inhibits the GABA pathway which lets the pallidum transmit signals to the motor cortex via the thalamus.

In PD, there is degeneration of the substantia nigra –> no DA pathway to inhibit the striatum –> makes it very difficult to initiate a voluntary movement.

Question 24

Why do patients with PD get tremor and rigidity?

Answer 24

May be due to disruption of pathways from basal ganglia to brainstem, but not fully understood.

Question 25

What effect do cholinergic striatal interneurones have on motor activity?

Answer 25

These excite the striatal pallidal projection and so decrease motor activity by increasing the inhibition by GABA.

Question 26

What is the main treatment for PD?

Answer 26

Need to compensate for the loss of dopaminergic neurons:

1) Give L-DOPA (precursor of DA) - only 0.01% crosses the BBB and reaches the substantia nigra to increase efficacy of remaining neurons
2) Combine with a selective extra-cerebral decarboxylase inhibitor (carbidopa) which reduces peripheral breakdown of L-DOPA to DA
- May also use DA agonists (apomorphine)

Question 27

Why are drugs that block ACh given in PD?

Answer 27

Cholinergic striatal interneurons excite the inhibitory pathway from striatum to pallidum. Blocking these can increase the effect of the remaining domaminergic neurons.

Question 28

Which changes occur in ballism?

Answer 28

There is damage to the subthalamic nucleus which usually sends an inhibitory signal to the pallidum - this means that there’s no inhibitory signal so the same happens as HD.

Question 29

What are the side effects of long-term treatment with L-DOPA or DA agonists?

Answer 29

Psychosis symptoms.

Question 30

Describe possible new treatments for PD.

Answer 30

• Autotransplantation of adrenal medulla as DA is a precursor of NA

Question 31

What is the man treatment for HD?

Answer 31

Aimed at increasing the efficacy of remaining striatal interneurons with ACh mimetics and DA blockers - not very successful and may produce Parkinsonism.