Hierarchy of Motor Control - Basal Ganglia Flashcards
What is the role of the basal ganglia and what shall this lecture focus on?
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
What are the two main parts of the basal ganglia?
Striatum and the Globus Pallidus (pallidum)
What does the basal ganglia do in relation to motor control?
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
How do diseases of the basal ganglia manifest?
Difficulties in starting voluntary movements or in stopping unwanted movements
What are the two extremes that basal ganglia disorders will vary between?
Parkinson’s disease
Hyperkinetic Disorders:
- Huntington’s Chorea (Disease)
- Athetosis
- Ballism
At its basis Parkinson’s Disease is characterised by akinesia.
Explain Akinesia along with its symptoms and signs
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
Akinesia is the major feature of Parkinson’s.
What features are superimposed on this?
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)
What is Huntington’s Chorea?
Jerky spasmodic movements at “rest” and incorporated into “normal” voluntary movements
(as if unwanted movements have been released)
What is Athetosis?
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)
What is Ballism?
Violent flailing movements of the limbs
as if unwanted movements have been released
When does the basal ganglion fire in relation to when voluntary movements occur?
BEFORE
BG is a prerequisite for a role in movement initiation
What is the key to understanding the basal ganglion?
CELLS OF THE PALLIDUM HAVE A HIGH LEVEL OF SPONTANEOUS ACTIVITY.
Therefore CONTROL of movement relates to VOLUNTARY REGULATION of this SPONTANEOUS ACTIVITY
How does the striatum control the spontaneous activity of the pallidum?
Exerts a profound inhibitory effect on the pallidum, via the neurotransmitter GABA (gamma amino butyric acid)
This is called the striato-paladal potential
How is voluntary movement prevented or allowed to occur in the basal ganglia?
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
How does the substantia nigra play into control of the striatum of the basal ganglia?
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
What happens to the basal ganglia during Huntington’s Chorea?
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
What happens to the basal ganglia during Parkinson’s disease?
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.
How many nigrostriatal fibres have to degenerate before symptoms occur in Parkinson’s disease?
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
What causes tremor and rigidity in Parkinson’s disease?
Poorly understood
Maybe due to disruption of pathways from basal ganglion to the brainstem
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?
Decrease motor activity
What is the treatment strategy in Parkinson’s disease?
Treating symptoms, NOT a cure, there is ongoing progressive degeneration.
Need to compensate for the loss of dopaminergic neurones.
What is the treatment for Parkinson’s disease?
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
What can happen to a patient on L-DOPA for a long term treatment?
Long term treatment with L-DOPA or other DA agonists can produce symptoms of psychosis
How can ACh antagonists be used to treat Parkinson’s?
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
How do you prescribe ACh antagonists in Parkinson’s?
Alone or in combination with L-DOPA
Give some “possible” new treatments in Parkinson’s disease
- Autotransplantation of adrenal medulla (DA is a precursor of Norepinephrine
(Phenylalanine -> Tyrosine -> L-DOPA -> Dopamine -> Norepinephrine -> Epinephrine)
- 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)
How can Deep Brain Stimulation be incorporated into Parkinson’s treatment?
HIGHLY effective at stopping Hyperkinetic movements at the literal flick of a switch.
Medical treatment still required for akinesia
What is ballism?
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
Explain the treatment of Huntington’s Chorea
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
Summarise Parkinson’s and Huntington’s comparing them to scales
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
