Hierarchy of Motor Control - Basal Ganglia

Question 1

What is the role of the basal ganglia and what shall this lecture focus on?

Answer 1

This lecture will only focus on motor effects of the basal ganglia and basal ganglia damage in relation to this.

Basal ganglia also associated with disordered emotions, cognition and eye movements

Question 2

What are the two main parts of the basal ganglia?

Answer 2

Striatum and the Globus Pallidus (pallidum)

Question 3

What does the basal ganglia do in relation to motor control?

Answer 3

The striatum receives a copy of the “readiness potential,” which is then processed by the striatum and palladium then relayed via the thalamus back to the motor cortex and premotor cortex

Basal ganglia are involved in processing the readiness potential so that INITIATION of voluntary movement can occur

Basal ganglia make important connections with 2 midbrain nuclei, the substantial nigra and the sub thalamic nucleus

Question 4

How do diseases of the basal ganglia manifest?

Answer 4

Difficulties in starting voluntary movements or in stopping unwanted movements

Question 5

What are the two extremes that basal ganglia disorders will vary between?

Answer 5

Parkinson’s disease

Hyperkinetic Disorders:

• Huntington’s Chorea (Disease)
• Athetosis
• Ballism

Question 6

At its basis Parkinson’s Disease is characterised by akinesia.
Explain Akinesia along with its symptoms and signs

Answer 6

Extreme difficulty in starting voluntary movements: i.e. initiation
Patients “feel frozen”

Even simple movements, require immense efforts of concentration and will

There is also loss of “association movements” e.g. swinging arms when you walk
Patients have a very characteristic shuffling gait with stooped posture
Loss of facial expression = dead-pan face, reptilian stare.

So all of these contribute to “poverty of movement” = hypo kinetic features

Question 7

Akinesia is the major feature of Parkinson’s.

What features are superimposed on this?

Answer 7

Hyperkinetic features

a) resting tremor of limbs and sometimes head and neck, all shake when at REST, low frequency 5-8Hz

Tremor disappears when movement is in progress

b) Rigidity: “lead-pipe rigidity” Increased muscle tone which affects both flexors and extensors
(opposite to spastic rigidity, which mainly affects extensors)

Question 8

What is Huntington’s Chorea?

Answer 8

Jerky spasmodic movements at “rest” and incorporated into “normal” voluntary movements

(as if unwanted movements have been released)

Question 9

What is Athetosis?

Answer 9

Slow writhing movements which affect the extremities.

When trunk and limb muscles affected get torsion spasm and the adoption of grotesque postures.

(as if unwanted movements have been released)

Question 10

What is Ballism?

Answer 10

Violent flailing movements of the limbs

as if unwanted movements have been released

Question 11

When does the basal ganglion fire in relation to when voluntary movements occur?

Answer 11

BEFORE

BG is a prerequisite for a role in movement initiation

Question 12

What is the key to understanding the basal ganglion?

Answer 12

CELLS OF THE PALLIDUM HAVE A HIGH LEVEL OF SPONTANEOUS ACTIVITY.

Therefore CONTROL of movement relates to VOLUNTARY REGULATION of this SPONTANEOUS ACTIVITY

Question 13

How does the striatum control the spontaneous activity of the pallidum?

Answer 13

Exerts a profound inhibitory effect on the pallidum, via the neurotransmitter GABA (gamma amino butyric acid)

This is called the striato-paladal potential

Question 14

How is voluntary movement prevented or allowed to occur in the basal ganglia?

Answer 14

Organising cortical input arrives via the striatum.
At rest, when no voluntary movements are in progress, excitation of this pathway inhibits pallidal activity and the body is still.

When a voluntary movement is to be initiated, patterned inhibition in the form of the readiness potential, allows organised excitation to be transferred to the motor cortex

Question 15

How does the substantia nigra play into control of the striatum of the basal ganglia?

Answer 15

The inhibitory pathway from the striatum to the pallidum is kept in check by the substantia nigra which ensures the pallidum doesn’t get too much inhibition.

This nigrostriatal pathway uses DOPAMINE

Question 16

What happens to the basal ganglia during Huntington’s Chorea?

Answer 16

There is striatal degeneration, so that a the organising cortical input is lost.

Thus the spontaneous activity of the pallidum passes unchecked to the motor cortex without regard to voluntary desire.
Connection between cortex and VOLUNTARY control via cortex is lost.
Motor gibberish -> unwanted movements

Question 17

What happens to the basal ganglia during Parkinson’s disease?

Answer 17

Degeneration of the substantia nigra pathway.

It becomes very difficult to initiate a voluntary movement, have to concentrate really hard to bombard the striatum with inhibition.

Question 18

How many nigrostriatal fibres have to degenerate before symptoms occur in Parkinson’s disease?

Answer 18

Clinical symptoms only appear when >80% of substantia nigra neurones have degenerated.

Always have more neurones than you need for these things. -> this gives delayed symptoms

In post-mortem brains of Parkinson patients, as many as 90% of the nigrostriatal fibres have degenerated

Question 19

What causes tremor and rigidity in Parkinson’s disease?

Answer 19

Poorly understood

Maybe due to disruption of pathways from basal ganglion to the brainstem

Question 20

In addition to everything mentioned there is a cholinergic stratal interneurone.
This excites the striatal-pallidal projection, so what effect will it have on motor activity?

Answer 20

Decrease motor activity

Question 21

What is the treatment strategy in Parkinson’s disease?

Answer 21

Treating symptoms, NOT a cure, there is ongoing progressive degeneration.

Need to compensate for the loss of dopaminergic neurones.

Question 22

What is the treatment for Parkinson’s disease?

Answer 22

Give L-DOPA, the precursor of Dopamine, which itself does not cross the blood brain barrier.
Can be very effective but it is taken up by many tissues in the body so

Question 23

What can happen to a patient on L-DOPA for a long term treatment?

Answer 23

Long term treatment with L-DOPA or other DA agonists can produce symptoms of psychosis

Question 24

How can ACh antagonists be used to treat Parkinson’s?

Answer 24

Both the cortical input and the nigrostriatal inhibition are actually onto stratal cholinergic interneurones.

These are EXITATORY to the striatalpallidal projection neurones, so do not change the story.

Drugs which block ACh can also be effective in increasing the effect of the remaining dopaminergic neurones

Question 25

How do you prescribe ACh antagonists in Parkinson’s?

Answer 25

Alone or in combination with L-DOPA

Question 26

Give some “possible” new treatments in Parkinson’s disease

Answer 26

1. Autotransplantation of adrenal medulla (DA is a precursor of Norepinephrine

(Phenylalanine -> Tyrosine -> L-DOPA -> Dopamine -> Norepinephrine -> Epinephrine)

2. Foetal transplants

NO successful treatment for Parkinson’s disease itself but good treatments now available for dealing with side effects of medication

Surgical lesions and Deep Brain Stimulation (DBS)

Question 27

How can Deep Brain Stimulation be incorporated into Parkinson’s treatment?

Answer 27

HIGHLY effective at stopping Hyperkinetic movements at the literal flick of a switch.

Medical treatment still required for akinesia

Question 28

What is ballism?

Answer 28

A result of stroke

Damage to the sub thalamic nucleus occurs.
This pathway usually inhibits pallidal activity much like the striato-pallidal pathway.
Its damage releases paladin activity

Question 29

Explain the treatment of Huntington’s Chorea

Answer 29

Treatment is aimed at increasing efficacy of remaining stratal interneurones with ACh mimetic and DA blockers

Not very successful
May produce parkinsonism

Huntington’s is inherited as an autosomal dominant
Responds poorly to treatment and is associated with dementia

Question 30

Summarise Parkinson’s and Huntington’s comparing them to scales

Answer 30

Normally Dopamine from Substantia Nigra and ACh from striatum are in balance

Parkinson’s:

• DA is low because of SN degeneration so excess ACh effects
• Treat with L-DOPA or ACh antagonists

Huntington’s:

• Striatal degeneration means not enough ACh and excess DA
• Treat with ACh mimetics or DA antagonists

Very hard to get the balance right during treatment especially in later disease