Motor control and disease

Question 1

What are the two types of upper motor neurons? What do they both control?

Answer 1

Motor cortex- fine voluntary control of distal muscles

Brain stem- project to medial motor pools, concerned with postural movement

Question 2

What are upper motor neurons? Where are they found?

Answer 2

Neurons in the brain that control motor function

Primary motor cortex- precentral gyrus

Question 3

How is the motor cortex mapped somatotopically?

Answer 3

Lower body- medial
Upper body- lateral
Proportions reflect density of innervation and behavioral significance (like somatosensory cortex)

Question 4

What do axial muscles control?

Answer 4

Trunk movement

Question 5

What do proximal muscles control?

Answer 5

Shoulder, elbow, pelvis and knee movement

Question 6

What do distal muscles control?

Answer 6

Movement of hands, feet and digits

Question 7

What is a motor unit?

Answer 7

A motor neuron and all the muscle fibres it innervates

Question 8

What is a motor neuron pool?

Answer 8

All the motor neurons that innervate a single muscle

Question 9

What descending tract of the spinal cord controls voluntary movement? What kind of pathway is it?

Answer 9

Corticospinal tract
Lateral- distal muscles
Ventral- axial muscles

Question 10

Where in the brain do axons of the CST originate?

Answer 10

Large pyramidal cells in layer V of the motor cortex

Question 11

What tracts do upper motor neurons of the brain stem project in? What type of pathway are they?

Answer 11

Vestibulospinal and reticulospinal tracts

Ventromedial pathways

Question 12

Where do lateral axons of the CST cross the midline? Where do they synapse onto?

Answer 12

Pyramidal decussation in the medulla

Laterally located motor neuron circuits that control distal muscles

Question 13

Where do axons in the ventromedial pathways synapse onto?

Answer 13

Medially located motor neuron circuits that control axial muscles

Question 14

What do the axons of the vestibulospinal tract control? What other system do they receive inputs from to do this?

Answer 14

Head balance and turning

Vestibular system via the vestibular nucleus

Question 15

What do the axons of the tectospinal tract control? What other system do they receive inputs from to do this?

Answer 15

Orienting response

Visual system via the superior colliculus

Question 16

What do the axons of the reticulospinal tracts control?

Answer 16

Anti-gravity reflexes

Question 17

What directions do the two types of upper motor neurons project in the body?

Answer 17

Motor cortex neurons- contralateral

Brain stem- ipsilateral

Question 18

What is anticipatory ‘feed forward’ mechanism?

Answer 18

Pre-adjustment of body posture to compensate for the forces that will be generated by movement (pulling a lever or stepping on a travelator)
This means there is a link between the upper MNs of the motor cortex and the brain stem

Question 19

How is movement anticipated?

Answer 19

Anticipation starts in the premotor area

activates an indirect projection to axial muscles via the reticular formation

Question 20

After anticipation how is movement initiated?

Answer 20

Initiated in the primary motor cortex

Activation of voluntary movement direct to spinal cord via corticospinal tract

Question 21

What becomes damaged in motor neuron disease?

Answer 21

Sclerosis of lateral spinal cord
Leads to degeneration of axons in the CST
Muscle atrophy

Question 22

What does ALS stand for?

Answer 22

Amyotrophic lateral sclerosis

Question 23

What is lower motor neuron disease characterized by? What do patients usually die from?

Answer 23

Muscle paresis
Loss of muscle tone due to lack of stretch reflexes
Muscle atrophy
Lung dysfunction

Question 24

What is upper motor neuron disease characterised by?

Answer 24

Muscle weakness
Spasticity due to increased muscle tone from failure of modulation of stretch reflexes
Hyperactive reflexes
Loss of fine voluntary movement

Question 25

What are the general consequences of motor neuron degeneration?

Answer 25

Almost always fatal | Intellect is not compromised

Question 26

What role do the basal ganglia and cerebellum play in motor control?

Answer 26

Influence movement indirectly by regulating the function of upper motor neurons

Question 27

What parts of the basal ganglia are involved in the initiation of movement?

Answer 27

Caudate Putamen Globus pallidus Subthalamic nucleus

Question 28

What is the motor loop? What are the two pathways it consists of?

Answer 28

Motor cortex connects to the basal ganglia Basal ganglia feed back to the premotor area via the ventrolateral complex of the thalamus (VLo) Direct and indirect

Question 29

What happens in the direct pathway when there is no cortical input?

Answer 29

Globus pallidus internal segment (GPi) tonically inhibits the VLo

Question 30

Direct pathway

Answer 30

Input from many cortical regions converge on the striatum Striatum inhibits the inhibitory activity of the GPi This releases VLo to activate area 6 and initiate movement

Question 31

Why is the direct pathway set up like this?

Answer 31

Integration of cortical inputs to trigger a response | Rapidity of response – “engine is running”; inhibition of inhibition releases the “brake”

Question 32

What role does the substantia nigra play in the indirect pathway?

Answer 32

Acts via the striatum to maintain the balance between the inhibition and activation of the VLo

Question 33

Indirect pathway when SN input is excitatory

Answer 33

Excitatory input from the SN stimulates VLo activation by activating the inhibition of the GPi in the direct pathway Inhibition of GPi by GPe is inhibited by the striatum So the VLo is inhibited

Question 34

Indirect pathway when SN input is inhibitory

Answer 34

Inhibitory input by the SN decreases striatum inhibition of GPe This inihibits the GPi Allows activation of the VLo

Question 35

What are the symptoms of Parkinson's disease?

Answer 35

``` Hypokinesia (insufficiency of movement) Bradykinesia (slow movement) Akinesia Increased muscle tone and 'mask like' expression Resting tremor Flexed posture and loss of balance ```

Question 36

What is Parkinson's caused by?

Answer 36

Loss of dopamine due to the loss of dopaminergic neurons in the substantia nigra

Question 37

What are Lewy bodies?

Answer 37

Intracellular protein aggregates | Mark the loss of dopaminergic neurons in Parkinson's

Question 38

How can L-DOPA treat Parkinson's? Why is it only a temporary solution?

Answer 38

Boosts the capacity of existing dopaminergic neurons in the SN to make dopamine Doesn't stop the degeneration of neurons So when there are insufficient neurons left it no longer has any benefits

Question 39

What does reduced dopaminergic output from the SN to the striatum lead to?

Answer 39

Increased activity of indirect pathway Decreased activity of direct pathway Less inhibition of the GPi so it's inhibitory activity is increased Decreased activity of VLo- less motor cortex activation

Question 40

What are the symptoms of Huntington's disease?

Answer 40

Early- hyperkinesia or dyskinesia (involuntary jerking/twitching) Late- akinesia and dystonia, dementia, psychosis/personality disorder

Question 41

What is Huntington's disease caused by?

Answer 41

Autosomal dominant genetic disease causing neuronal degeneration Initially in indirect pathway components of the striatum Later on in direct pathway components + GPe

Question 42

In Huntington's disease, what does degeneration in the striatum lead to? (early stages)

Answer 42

Reduces indirect pathway inputs to the GPe Increases inhibition of Gpi VLo is dis-inhibited as a result Causes inappropriate initiation of movement

Question 43

Compare genetics of PD and HD

Answer 43

Both have a genetic element, but PD is mostly sporadic and HD is mostly genetic

Question 44

What genes presdispose you to developing PD? What are the differences between them?

Answer 44

SNCA is uncommon but has a high penetrance | GBA1 is common but has a low penetrance

Question 45

How can you be genetically predisposed to HD?

Answer 45

Mutations in the HTT gene which encodes the 'Huntington protein'- 100% certainty of getting it but onset varies

Question 46

What do PD genes encode?

Answer 46

Proteins involved in either protein degradation pathways (Parkin, SNCA) which causes the formation of Lewy bodies Or mitochondrial function (PINK1, DJ-1)

Question 47

What is the function of the HTT protein? What does the mutation lead to?

Answer 47

Remains unclear but is involved in intracellular transport Mutant HTT protein contains extended stretches of poly-glutamine (polyQ) which contributes to aggregation of proteins in ‘inclusion bodies’ in affected neurons

Question 48

How is the cerebellum involved in motor control and learning?

Answer 48

Appears to instruct motor cortex neurons with respect to direction, timing and force of movement Uses predictions based on past experiences Compares what is intended and what actually happens- enables motor learning

Question 49

What is cerebellar ataxia?

Answer 49

Lesions to the cerebellum resulting in poorly integrated movement Dyssynergia- inability to coordinate movements