Motor Control and Parkinson's Disease

Question 1

Describe how a movement occurs and the integration of motor control

Answer 1

1 - The idea/decision to move arises in the cortical association areas
2 - The premotor area plans the sequence of muscle contractions
3 - Primary motor cortex generates the neural impulse
4 - LMN in spinal cord or brainstem transmit impulse to voluntary muscles
5 - The cerebellum receives proprioceptive and kinaesthetic info from periphery to evaluate movements, checking adjusting movements as neccessary
6 - Basal ganglia and cerebellum modulate and perfect the movement. Basal ganglia unblocks the cortex and blocks unwanted movements

Question 2

Describe the function and organisation of the pyramidal tract

Answer 2

It is the main pathway carrying commands from the motor cortex to muscles. The upper motor neurons are pyramidal cells in motor cortex layer 5, descending fibres cross in the medula, synapsing with LMN in ventral horn (corticospinal tract) or brain stem (corticobulbar tract). 85-90% of corticospinal fibres cross in medulla (forming the lateral tract for limb control), the other 10-15% form the anterior tract (postural adjustments following limb movements)

Question 3

Describe the stages in the pyramidal tract

Answer 3

1 - Impulse for movement starts in PMC
2 - Internal capsule - white matter tract connecting cortex with underlying structures
3 - Decussation
4 - Corticospinal tract through lateral funiculus of spinal cord and terminate in ventral horn
5 - UMN synapse with LMN that have soma in ventral horn (cranial nerve nuclei in corticobulbar tract). LMN exit spinal cord as spinal nerves and innervate muscles

Question 4

How do contractions and relaxations lead to movement?

Answer 4

Movement rarely involves a single muscle, it’s a series of contractions and relaxations, and adjustments of postural muscles. PMC receives inputs from premotor area, which coordinates complex sequences. Also, somatosensory, proprioceptive, and visual stimuli to guide movement

Question 5

Describe the extrapyramidal tracts

Answer 5

They are UMN tracts from motor control centres in brainstem specialising in certain functions. The two main extrapyramidal control centres fine tune movement - basal ganglia and cerebellum.

Question 6

What is the function of the vestibulospinal tract?

Answer 6

Helps maintain balance, controlling postural adjustments mostly via neck and trunk muscles

Question 7

What is the function of the rubrospinal tract?

Answer 7

Facilitates flexor movements in the upper limbs

Question 8

What is the function of the reticulospinal tract?

Answer 8

Controls orientation of the body towards or away from sitmuli

Question 9

What is the function of the tectospinal tract?

Answer 9

Controls neck musculature in response to visual stimuli, orientates head during eye movement

Question 10

What are the functions of the basal ganglia?

Answer 10

They ensure that movements are planned and executes precisely, they encode the decision to move, direction of movement, amplitude of movement, motor expression of emotions.

Question 11

What are the basal ganglia?

Answer 11

The basal ganglia are large grey matter masses deep in the cerebral hemispheres. They include the caudate, putamen, and globus pallidus, that lie to lateral to the thalamus. Substantia nigra in the rostral midbrain, and subthalamic nucleus inferior to the thalamus. Putamen + GP = Lenticular nucleus
Caudate + Lenticular Nucleus = Striatum

Question 12

What is the function of the striatum?

Answer 12

They are the input nuclei to the basal ganglia, they receive mostly excitatory input mainly from the cortex and thalamus

Question 13

What is the function of the GP?

Answer 13

Has lateral (external) and medial (internal) parts that have different functions and connections within the basal ganglia. It is an output nucleus with inhibitory projections to the thalamus

Question 14

What is the function of the subthalamic nucleus?

Answer 14

It receives afferent neurons from the cortex and other basal ganglia. It’s output is excitatory glutaminergic projections to globus and nigra. Central in basal ganglia connectivity - AKA basal ganglia clock

Question 15

What is the function of the substantia nigra?

Answer 15

It has dopaminergic neurons projecting to the putamen and caudate. Melanin is a byproduct of dopamine synthesis

Question 16

How do the basal ganglia regulate cortical activity?

Answer 16

They receive info from widespread cortical areas, which is funnelled through the circuitry, and results in regulation of the thalamus, which regulates cortical activity.

Question 17

What does the direct pathway regulate?

Answer 17

Facilitates target oriented and efficient behaviour

Question 18

Describe the direct pathway

Answer 18

1 - The cortex provides glutamate to the striatum
2 - This increases the GABA output from striatum to GP and substantia nigra
3 - This decreases GABA output to thalamus
4 - This increases glutamate to the cortex, which results in movement
The substantia nigra is tonically stimulated by the subthalamic nuclei. Dopamine from nigra activate D1 dopaminergic neurons, enhancing cortex excitatory input

Question 19

Describe the indirect pathway

Answer 19

1 - Cortex stimulates striatum
2 - Striatum releases GABA onto GPe
3 - GPe releases less GABA onto subthalamic nucleus
4 - Increased glutamate to GPi
5 - Increased GABA to thalamus
6 - Reduced glutamate to cortex (increased tonic inhibition via different thalamic neurons)
The nigra inhibits the subthalamic nucleus, which stimulates the nigra - controls the basal ganglia input. The nigra releases dopamine to the striatum which inhibits excitatory D2 expressing cholinergic interneurons

Question 20

What are the two functions of the indirect pathway?

Answer 20

The indirect pathway decreases thalamic output -> less excitation of cortex and less movement. Puts the brakes on direct pathway, but also inhibits unwanted movements movements so that it only allows intentional movement facilitated by direct pathway

Question 21

What is the general role of the substantia nigra?

Answer 21

It reinforces the effects of the direct pathway, and opposes the effects of the indirect pathway

Question 22

What is the role of the cerebellum in motor control?

Answer 22

It is the coordinator and predictor of movement and mediates muscle control for skilled manipulation. It receives info from periphery ie. proprioception and muscle tone. It compares and integrates this info with the plans for movement received from the cortex. Cerebellum can predict consequences of movement through feed forward mechanisms and modulate on-going movement patterns eg. optimising balance, head-eye movements and hand-eye coordination

Question 23

How does LMN damage clinically manifest?

Answer 23

Paresis (weakness) or paralysis (loss of movement), loss of reflexes (efferent limb of somatosensory reflexes is lost), loss of muscle tone (lcontrolled by tonic activation of LMN by muscle spindles). Muscle atrophy eventually occurs

Question 24

Which tracts comprise the upper motor system?

Answer 24

Pyramidal and extrapyramidal tracts. Disorders involving each tract show different clinical signs

Question 25

What happens as a result of the corticospinal tract damage?

Answer 25

Paralysis on one side of the body below the lesion. Damage to the cotricospinal tract anywhere from cortex to lower spinal cord, it leads to pyramidal motor disease. Can include spinal cord injury, cerebral palsy, MS, acquired brain injury including stroke

Question 26

What are extra pyramidal disorders?

Answer 26

They are movement disorders resulting from basal ganglia lesions. They can be characterised by negative (hypokinetic) or positive (hyperkinetic) signs, depending on the structure involved

Question 27

What are negative signs (hypokinetic) in extra pyramidal disorders?

Answer 27

Postural disturbances (parts of body held in a fixed position), bradykinesia (slowness or loss of voluntary movement). Bradykinesia is a feature of Parkinson's which can include reduced facial expression, blinking, and postural adjustments. Postural disturbances are also seen with limbs and trunk

Question 28

What are positive (hyperkinetic) signs in extrapyramidal disorders?

Answer 28

Involuntary movements - tremor, chorea (irregular, repetitive, jerky eg. in Huntington's), athetosis (irregular, repetitive, writhing), dystonia (slow, sustained abnormal), or ballismus (violent flinging movements)

Question 29

How do cerebellar disorders manifest?

Answer 29

Can be due to stroke, trauma, tumours, neurodegenerative disorders. Manifest in different ways depending on location. Ataxia (loss of coordination and muscle tone), intention tremor (during movement because of poor agonist-antagonist contractions) and typically staggering gait

Question 30

How is Parkinson's disease primarily characterised?

Answer 30

Hand and jaw tremors, hypokinesia, ranging from bradykinesia to akinesia. Also postural disturbances with trunk and limbs. Many patients also suffer cognitive deficits

Question 31

What are the causes of Parkinson's?

Answer 31

Only 5-10% are familial, with specific gene defects, the vast majority is sporadic, but is believed to be due to environmental and genetic factors. The effect on movement is due to degeneration of dopaminergic neurons in the nigra pars compacta.

Question 32

Describe how protein aggregation in Lewy bodies can result in neuronal death in Parkinson's disease

Answer 32

The building (oligomerisation) of proteins. A-synuclein has increased presence in PD patients and due to its insolubility it aggregates and forms Lewy bodies

Question 33

Describe how the disruption of autophagy results in neuronal death in Parkinson's death

Answer 33

In healthy cells, intracellular components are broken down and recycled. If this is disrupted, it results in disease

Question 34

Describe how changes in metabolism results in neuronal death in Parkinson's disease

Answer 34

Mitochondrial function is disrupted, which inhibited energy production, leading to death

Question 35

What happens to dopamine in the synapse?

Answer 35

In the synapse, dopamine is reuptaken, or converted into other substances by enzymes monoamine oxidase B or catechol-O-methyl transferase.

Question 36

How is PD related to dopamine and acetylcholine imbalance?

Answer 36

In striatum, Ach and Dopamine are balanced. When dopaminergic neurons die theres too little dopamine and too much Ach

Question 37

How does the loss of dopaminergic neurons affect the direct pathway?

Answer 37

Loss of excitatory input from nigra (via D1 expressing neurons) to striatum causes amplification of cortical excitatory input to striatum. This leads to less excitatory input from both, so less excitatory output from thalamus to cortex

Question 38

How does the loss of dopaminergic neurons affect the indirect pathway?

Answer 38

The dopaminergic neurons from nigra send inhibitory signals via D2 expressing neurons to excitatory cholinergic interneurons in striatum. Loss of inhibitory dopaminergic neurons leads to reduced inhibiton of excitatory interneurons leads to increased inhibitory signals to GPe, less inhibition to subthalamuc nucleus, more glutamate to GPi, increasing the tonic inhibtion of the thalamus, meaning less excitatory output to cortex. Also, the loss of inhibitory projections from nigra to subthalamic leads to further loss of inhibition of subthalamic nucleus

Question 39

What are the two main approaches to treating Parkinson's disease?

Answer 39

Drug therapy or influencing basal ganglia circuitry via direct stimulation of subthalamic nucleus

Question 40

How does drug therapy work in treating Parkinson's disease?

Answer 40

It can restore dopamine levels in the basal ganglia via administration of Levodopa and many other mechanisms ie inhibiting breakdown, dopamine agonists

Question 41

How do anticholinergic drugs work in treating Parkinson's disease?

Answer 41

Inhibit cholinergic interneurons in striatum which restores the acerylcholine/dopamine balance. Reduces tremor but doesn't work on rigidity and akinesia with limited overall efficacy

Question 42

How does the loss of inhibitory infuence from nigra to subthalamic affect the subthalamic nucleus?

Answer 42

It results in abberant firing pattern in the subthalamic nucleus which leads to excessive output, inhibiting cortical output

Question 43

How does deep brain stimulation work in treating Parkinson's?

Answer 43

Deep brain stimulation of subthalamic nucleus restores the tonic firing pattern, which triggers blood and neurotransmitter flow to restore normal brain function. The electrodes are surgically implanted and a wire pulse generator implanted in the chest that delivers continuous stimulation