Motor Control and Disease 1 & 2

Question 1

all movements produced by skeletal musculature are initiated by …

Answer 1

lower motor neurons
spinal cord contains central pattern generators that can generate complex behaviour without input from brain
but several subsystems in braininfluence these behaviours

Question 2

stimulation of motor cortex elicits muscle movement

Answer 2

shown on dog that electrical stimulation of part of the cortex elicits contraction f contralateral body muscles
region became known as (primary) motor cortex
neurons found in brain that control motor function are called upper motor neurons

Question 3

motor cortex is also somatotopically mapped

Answer 3

correlated site of stimulation with location of muscle contraction and made topographic map
not identical to somatosensory map
but lower body is still medially represented and upper body - laterally

Question 4

somatic motor system basics

Answer 4

control of lower motor neruons in ventral horn of spinal cord which innverate straited muscle to control movement
speficially:
axial muscles - trunk movement
proximal muscles - shoulder, elbow, pelvis, knee movement
distal muscles - hands, feet, digit movement
innveration via specialised synapse = NMJ

Question 5

lower motor neurons

Answer 5

each muscle fibre receives input from a single lower alpha motor neuron
each lower motor neuron innverates the fibres of one muscle

Question 6

motor unit

Answer 6

motor neuron and all muscle fibres it innverates

Question 7

motor neuron pool

Answer 7

all the motor neurons that innverate a single muscle

Question 8

motor pools are spatially organised in spinal cord

Answer 8

motor pools are grouped in rod shaped clusters within spinal cord extending over several vertebral segments:
we know from experiments in animals where tracers were injected into specific muscles, which were then transported back along the motor axons to the cell bodies in spinal cord
- injection in gastrocnemius, labels a different set of motor neuron cell bodies to injection of soleus

Question 9

motor pool organisation is somatotopic

Answer 9

the medio laterl position of a motor pool reflects whether its motor neurons innverate a proximal or distal muscle
therefore motor pools are organised somatotopically both medio-laterally and rostro-caudally
i.e. there is a 3D map of the bodys musculature within the spinal cord

Question 10

somatotopy in motor cortex ….

Answer 10

reflects location of upper motor neurons that innverate lower motor neurons in spinal cord
lower motor neurons receive inputs from local souces in spinal cord, but also directly from upper motor neurons
upper motor neurons project axons to lower motor neurons via descending tracts of spinal cord
corticospinal tract is key for control of voluntary movement, one of the lateral pathways of spinal cord
axons of certicospinal tract originate in layer 5 of motor cortex

Question 11

pyramidal cells of motor cortex project axons in CST

Answer 11

90% of cortex, including motor cortex, is a 6 layered structure
main inputs are to stellate cells in layer 4
main outputs are from layers 3, 5 and 6
axons of CST derive from large pyramidal cells (Betz cells) in layer 5

Question 12

different sets of upper motor neurons control different functions

Answer 12

CST outputs to upper body originate from lateral motor cortex and outputs to lower body = medial motor cortex
axons of CST then cross midline in pyramidal decussation in medulla, they project laterally in spinal cord, synapse on laterally located lower motor neuron circuits that control distal muscles (especially at limb levels)
the CST is one of lateral pathways

Question 13

upper motor neurons in brainstem

Answer 13

they project to medial motor pools primarily concerned with postural movement
axons from brainstem project ipsilaterally in several tracts e.g. vestibulospinal and reticulospinal
project medially in spinal cord
synapse on medially locatde lower motor neuron circuits that control axial muscles
these are the ventromedial pathways

Question 14

motor cortex upper motor neurons ….

Answer 14

primarly concerned with fine voluntary control of distal structures

Question 15

ventromedial pathways control …

Answer 15

posture
vestibulospinal tract - head balance and turning (inputs from vestibular system)
tectospinal tract - orienting response (inputs from visual system via superior colliculus)
reticulospinal tracts - control antigravity reflexes
project mainly ipsilaterally and medially

Question 16

upper motor neuron control recap:

motor cortex

Answer 16

initiate complex voluntary movements
project mainly contra laterally via CST, primarily to muscles involved in precise limb movements - particularly hands in humans, lateral pathway of spinal cord
also project via corticobulbar tract to hypoglossal nucleus in brainstem - controls tongue movement

Question 17

upper motor neuron control recap:

brainstem

Answer 17

maintenace and balance
in several nuclei including
- reticular formation
- vestibular nucleus
- superior colliculus 
project ipsilaterally to lower motor neurons controlling axial muscles concerned with maintiang posture - the ventromedial pathways of spinal cord

Question 18

upper motor neurons always ….

Answer 18

synapse on lower motor neurons, or their interneuron circuitry

Question 19

lower motor neurons always ….

Answer 19

synapse directly in muscle fibres

Question 20

integration of postural control with voluntary movement

Answer 20

volunteer lifts lever in response to audio tone
recording from different muscles reveals the first to contract are in leg
= anticipatory ‘feedforward’ mechanism, pre adjusts body posture to compensate for forces that will be generated when lever is lifted

Question 21

indirect cortical control of lower motor neurons

Answer 21

feedforward mechanism makes sense when you realise that upper motor neurons in cortex influence spinal cord circuits by 2 routes:
area 6
area 4

Question 22

area 6 control

Answer 22

movement anticipation starts in premotor area (PMA)

activates an indirect projection to axial muscles via reticular formation

Question 23

area 4

Answer 23

movement initiation then happens in primary motor cortex (M1)
activation of voluntary movement direct to spinal cord via corticospinal tract

activity in PMA preceeds activity in M1 and coincides with movement planning/anticipation

Question 24

so anticipation involves …

Answer 24

a circuit from motor cortex to brainstem nuclei

motor cortex innverates both brainstem and spinal cord

Question 25

motor neuron disease

Answer 25

MND/ALS
degenerative disease of motor neurons
characterised by muscle atrophy and sclerosis (hardening or scarring) of lateral spinal cord, which is the mark of degeneration of axons is CST

Question 26

motor neuron disease - neuropathy and etiology

Answer 26

can affect both upper and lower motor neurons
one of several neurodegenerative diseases
what causes neurons to die is not understood
excitoxicity maybe a possibilty - overstimulation, typically by glutamate, leads to neuronal cell death
vicious cycle if glutamate can occur, particularly in hypoxic condition e.g. after cardiac arrest, stoke
only drug to have any effect = blocker of glutamate release (riluzole) but only delays disease by months
10% ahve clear genetic basis
one results from mutation in gene coding for superoxide dismutase, key enzyme that ‘mops up’ free radicals that accumulate in metabolically active cells

Question 27

lower motor neuron disease

Answer 27

characterised by:
muscle paresis/paralysis
loss of muscle tone due to loss of stretch reflexes
leads to severe muscle atrophy (loss of muscle mass)
patients usually die from lung dysfunction - due to atrophy of intercostal muscles

Question 28

upper motor neuron disease

Answer 28

characterised by:
muscle weakness
spasticity due to increased muscle tone (due to failure of modulation of stretch reflex
hyperactive reflexes
loss of fine voluntary movement
patients usually die from loss of input to bulbar muscles - tongue and pharynx - via corticobulbar tract

Question 29

basal galnglia and cerebellum

Answer 29

influence movemnt indirectly by regulating function of upper motor neurons - no direct connection to lower motor neurons

Question 30

basal ganglia and associated structures

Answer 30

key components in initation of movement:
motor cortex (telencephalon)
basal ganglia - forebrain
- caudate
- putamen
- globus pallidus
- subthalmic nucleus
ventral lateral nucleus of thalamus (diencephalon)
substantia nigra - midbrain

Question 31

the motor loop

Answer 31

basal ganglia 
motor cortex connects to the basal ganglia, which in turn feedback to premotor area (area 6) via ventrolateral complex of thalamus to control initiation of movement = motor loop
consists of 2 pathways
- direct
- indirect

Question 32

basal ganglia

direct pathway

Answer 32

with no initaiating cortical input, globlus pallidus internal segment (GPI) tonically inhibits the ventrolateral complex (VLo)
input from many cortical regions converges on stratum
when activated by this input, the straitum inhibits the inhibitory activity of the GPI, releasing the VLo to activate area 6 and initiate movement

Question 33

basal ganglia

indirect pathway

Answer 33

direct pathway is modulated by a complex indirect pathway which involves substantia nigra - SN and globus pallidus external segment - GPE
SN has complex role and acts vis striatum to maintain balance between inhibition and activation of VLo
- excitatory input from SN stimulates VLo by activation, by activating the inhibition of the GPI through the direct pathway
- in indirect pathway, inhibition of GPI by GPE is inhibited by striatum and so VLo is inhibited
- however, inhibitory input from SN decreases striatum inhibition of GPE, which then inhibits the GPI allowing activation of VLo
so SN is balancing/turning the activation of VLo
degeneration of neurons in different parts of this circuit leads to Parkinson’s or huntingtons disease

Question 34

parkinsons disease - incidence and symptoms

Answer 34

2nd most common Neurodegen disorder
sporadic cases = 85-90%
familial cases = 10-15% caused by genetic mutations
caused by loss of dopamine
motor symptoms:
- hyopkinesia - insufficiency of movement
- bradykinesia - very slow movement
- akinesia - no movement
- inc muscle tone - rigidity
- resting tremor
- shuffling gait and flexed posture, impaird balance
- mask-like expression
non motor symptoms = mood disorders, loss of smell

Question 35

dopamine loss

Answer 35

due to loss of dopaminergic neurons in SN
80% of brains dopamine found in basal ganglia, specifically SN
degeneration of these neurons is marked by presenc of lewy bodies - intracell protein aggregates

Question 36

L-DOPA

Answer 36

effective but temporary therapy
provides dramatic but brief relief of symptoms intravenously
later found that oral L-DOPA provides longer and more significant benefits
beneficial effects only last for 5 years:
works by boosting capacity of surviving neurons in SN to make dopamine
but does not stop degeneration of SN neurons
eventually there are insufficient SN neurons left to make dopamine
side effects: increase motor response fluctuations and drug related dyskinesias

Question 37

basal ganglia

effects of loss of dopamine

Answer 37

reduced dopaminergic input from SN to straitum leads to both:
1) increased activity of indirect pathway
and
2) decreased activity of direct pathway
= less inhibition of GPI and so it inhibitory activity is increased
= leads to decreased activity of VLo and so less motor cortex activation
L-DOPA reverses this effect but only as long as DA neurons are present
in severe parkinsons cases, surgical removal of GPI can be effective in reversing effects
but more recently deep brain stimulation is used to inhibit GPI hyperactivity

Question 38

huntingtons disease

Answer 38

rare, hereditary, fatal
symptoms:
early - hyperkinesia or dyskinesia, ‘chorea’ involuntary jerking or twiching movements
late - akinesia and dsytonia (muscle spasms), dementia, psychosis
cause:
autosomal dominant genetic disease
- initally in indirect pathway components of striatum
- subsequently in direct pathway components and in GPE

Question 39

basal ganglia

in huntingtons

Answer 39

early on;
degeneration in striatum reduces the indirect pathway inputs to the GPE
this increases the inhibition of the GPI with the result that VLo is dis-inhibited and there is inappropriate initiation of movement - hyperkinesis, chorea
later:
striatal direct path and GPE neurons also degenerate, releasing GPI to over-inhibit the VLo - akinesis