Week 8

Question 1

Motor Units

Answer 1

• Motor Unit - smallest unit of
control – motor neuron and
skeletal fibres it innervates
• Neuromuscular Junction –
synapse between neuron
and muscle fibre -
acetylcholine release
activates the motor end
plate (post-synaptic) causing
the muscle fibre to contract
• Each motor neuron can innervate multiple muscle fibres, but
each fibre innervated by only 1 motor neuron
• Number of fibres innervated reflects fineness of control – 5 for an
eye muscle (22,000 fibres) and 1,800 for a large leg muscle (1
million fibres) (can range widely within a single muscle)
• Motor pool –the collection of motor neurons that supply a single
muscle
• Typical muscle controlled by a pool of a few hundred motor
neurons
• 3 properties of motor units - contraction speed, maximal force,
fatiguability

Question 2

Lower Motor Neurons

Answer 2

• Motor neurons of the
spinal cord and brain
stem that directly
innervate muscle
• Inputs from brain, muscle
spindles, spinal
interneurons (excitatory
or inhibitory)
• Located in ventral horn
and project out via
ventral root

Question 3

Spinal Motor Circuits

Answer 3

Motor circuits of spinal cord
show considerable complexity
Reflexes
Recurrent collateral inhibition
Reciprocal innervation
Locomotion

Question 4

Reflexes

Answer 4

• stretch (e.g. patellar – muscle
spindle afferent synapses
directly onto lower motor
neurons - monosynaptic)
• withdrawal – multisynaptic –
simultaneous excite/inhibit
flexor/extensor

Question 5

Recurrent collateral inhibition

Answer 5

• motor neuron axon branches
onto inhibitory interneuron that
projects back to itself
• each time it fires, briefly inhibits
itself (for a break) and shifts
responsibility to some other
member of the muscle’s motor
pool

Question 6

Reciprocal innervation

Answer 6

• constant contraction of
most muscles
• smooth, precise movement
requires adjustments –
antagonistic muscles must
be reciprocally adjusted

Question 7

Locomotion

Answer 7

• cats with severed spinal
cord walk on a treadmill
• with appropriate
sensory feedback, spinal
walking circuits activate
• basic motor pattern for
stepping in spinal cord
but initiation and fine
control requires range
of brain inputs

Question 8

Descending Motor Pathways

Answer 8

• Lower motor neuron has
many inputs
• Major inputs from the
brain
• Can synapse directly
• Most synapse indirectly via
a spinal interneuron
From the primary motor cortex, signals descend to the muscles
through 4 pathways - 2 in dorsolateral regions in the spinal cord
and 2 in the ventromedial region in the spinal cord
2 Dorsolateral tracts – one direct and one indirect
• terminate in contralateral half of one spinal cord segment, and
sometimes directly on a motor neuron
• limbs - especially independent movement of limbs
2 Ventromedial tracts – one direct and one indirect
• more diffuse, with axons innervating interneurons in several
segments of spinal cord
• body - control of posture and whole-body movements, and they
control the limbs movements involved in these activities

Question 9

Dorsolateral Tracts

Answer 9

Contralateral
Single spinal segment
Limbs
Dorsolateral
Corticorubrospinal
Tract
INDIRECT
Dorsolateral
Corticospinal
Tract
DIRECT

Question 10

Ventromedial Tracts

Answer 10

Ipsilateral/Bilateral
Diffuse
Trunk and girdles
Ventromedial
Cortico-brainstem-spinal
Tract
INDIRECT
Ventromedial
Corticospinal
Tract
DIRECT

Question 11

Dorsolateral Tracts

Answer 11

• Corticospinal (direct)
• Descend contralaterally
• Synapse on small interneurons of spinal grey which
synapse on lower motor neurons that innervate distal
muscles – wrist, hands, fingers, toes
• Animals that can move digits independently have
some that synapse directly onto the motor neuron
• Corticorubrospinal (indirect)
• Descend contralaterally
• Ultimately control distal muscles of arms and legs

Question 12

Ventromedial Tracts

Answer 12

• Corticospinal (direct)
• Descend ipsilaterally, branch diffusely and innervate
interneurons on both sides at several levels
• Cortico-brainstem-spinal (indirect)
• Upper motor feed complex network of brainstem
structures (tectum, vestibular, motor programs in
reticular formation)
• Outputs descend bilaterally (each side carrying info
from both hemispheres)
• Each neuron synapses on interneurons over several
segments – innervate proximal muscles of trunk and
limbs (e.g. should/hip)

Question 13

Descending Motor Pathways

Answer 13

Lawrence & Kuypers (1968) transected descending motor
pathways in monkeys
• Dorsolateral (corticospinal)
• After surgery, monkeys could stand, walk and climb
• But could not use limbs for other activities (e.g. reaching for
things; and could not move fingers independently)
• Ventromedial tracts
• Monkeys had postural abnormalities
• Impaired walking and sitting
From the primary motor cortex, signals descend to the muscles
through 4 pathways - 2 in dorsolateral regions in the spinal cord
and 2 in the ventromedial region in the spinal cord
2 Dorsolateral tracts – one direct and one indirect
• terminate in contralateral half of one spinal cord segment, and
sometimes directly on a motor neuron
• limbs - especially independent movement of limbs
2 Ventromedial tracts – one direct and one indirect
• more diffuse, with axons innervating interneurons in several
segments of spinal cord
• body - control of posture and whole-body movements, and they
control the limbs movements involved in these activities

Question 14

Motor Neuron Disease

Answer 14

• Group of diseases characterised by degenerative loss of motor neurons (upper, lower,
both)
• Amyotrophic lateral sclerosis (ALS) most common (many variations and classifications)
• Progressive muscle weakness and wasting - no cognitive impairment
• Pattern of weakness, rate and pattern of progression, survival time all vary
• No cure or treatment - survival 2-5 years from onset
• Cause uncertain – environment, lifestyle, subtle genetic (5 - 10% have family history)
• Inclusion bodies – cytoplasmic protein aggregates
• Early signs subtle – hard to diagnose (10-18 months) – sometimes confusion between
MND and myasthenia gravis

Question 15

Motor Cortex

Answer 15

• Voluntary movement – purposeful interaction with environment
• Differ from reflex and basic locomotor patterns
• Intentional – internal decision to act
• Organised to achieve some goal in the near or distant future
• Context dependent associations with sensory input
• Improve with experience
• Learn new skills

Question 16

Primary Motor Cortex (M1)

Answer 16

• Major outgoing point from cortex
(NOT the only) – descending motor
pathways
• Major point of convergence of
sensorimotor signals - inputs from
PMC, SMA, frontal, basal ganglia,
cerebellum
• Penfield – electrical stimulation led
to activation of contralateral muscle
and simple movement – motor
homunculus – somatotopic and
cortical magnification
• 2 subdivisions
• Old rostral and new caudal
(primates)
• Caudal are the ones that
synapse directly onto lower
motor neurons for upper limbs
– dexterity – dorsolateral
corticospinal (i.e. direct) tracts
• Each neuron in M1 previously thought to encode
direction of movement of a muscle
• Recently – stimulate with long bursts similar to duration
of motor response – elicit complex species typical
natural response sequences (eg feeding response)
• Natural activity - particular neuron firing related to end
point of movement rather than direction – e.g. 90deg
bend in elbow – different responses depending on initial
configuration – say straight (180) or bent (45)
• Lesions – hemiplegia
• Very large may disrupt movement of particular body part
independently of others (e.g. finger)
• Reduce movement speed, accuracy, force
• Not eliminate voluntary movement entirely – descending
from secondary motor areas and subcortical
• Distal extremities much more affected than proximal limb
and truck

Question 17

Secondary Motor Cortex

Answer 17

• Input from association
cortex (posterior parietal
and dlPFC)
• Output to primary motor
cortex
• Initially – PMC and SMA;
now at least 8 in each
hemisphere
• SMA, pre-SMA,
supplementary eye fields
• Dorsal and ventral PMC
• 3 small cingulate motor areas
(at least 2 in humans)
• Become active just before initiation of voluntary
movement and remain active during movement
• Electrical stimulation results in complex movements,
typically bilateral
• Programming of specific patterns of movement, with
input from the dorsolateral prefrontal cortex
• PMC/SMA functional distinction – externally or
internally guided action
• PMC – strong reciprocal connections with posterior
parietal cortex – sensory guided actions (catch a ball)
• SMA – strong connections with medial frontal cortex –
internally guided goals (playing piano)

Question 18

Mirror Neurons

Answer 18

• Rizzolatti et al. (90’s) studying monkey premotor cortex
using single cell recordings
• Interested in neurons that respond to complex hand
(and mouth) actions – reaching for a toy or reaching
for food
• Found neurons that fired preferentially when reaching
for one type of object but not for different object
• Then found that some of these neurons responded
identically when reaching for the object and when
observing human performing the same action
• Mirror Neurons – fire when perform a particular goal
directed hand movement or when observing the same

Question 19

Goal Directed Action

Answer 19

• Response to goal directed
actions – no response to same
action if mimed and no object
• Respond to the goal of an action
such as the grasping of a piece of
food even when this action is
performed with different tools
(such as normal or reverse pliers)
requiring opposite sequences of
movements (closing or opening
of the fingers)
• Transform complex visual input
into high level understanding of
observed action

Question 20

Understanding Action

Answer 20

Don’t need to see the key
action if enough clues to
create a mental representation
• Screen to block and monkey
must imagine what is going on
• But if first show monkey that
no object behind the screen –
no response
• Some mirror neurons in
inferior PPC respond to
purpose of action rather than
the action itself
• Fire when food grasped if it
was clear it was to be eaten
• If repeatedly grasp food to put in bowl – little firing

Question 21

Mirror Neurons examples

Answer 21

• Social cognition: knowledge of
perception, ideas, intentions
of others
• Action understanding: cooperation, teaching/learning
• Language
• Emotional understanding -
empathy

Question 22

Mirror Neurons in Humans

Answer 22

• Confirmation in humans not
as strong (single cell
recording) but similar mirror
networks (large scale)
suggested by fMRI and EEG
• Motor imagery – imagine
doing an action – PMC, PPC,
M1 all become active
(imagine observing – weak
motor activation – mainly
visual)
• Viewing ballet recruits
premotor and parietal mirror
areas more strongly in expert
ballet dancers than nondancers or martial-art teachers
• Recruitment of motor areas
with mirror properties strongly
correlates with motor rather
than visual expertise
• Can improve ability to judge
the goal of an unusual action
by practising the action;
improvement occurs even
when practise blindfolded

Question 23

Association Cortex

Answer 23

To move …
• Need to know where things are – objects in the
environment and parts of the body
• Need to make a decision to initiate voluntary movement
• Posterior parietal cortex (PPC) - spatial information
• Dorsolateral prefrontal cortex (dlPC) - decide and initiate

Question 24

Posterior Parietal Cortex

Answer 24

• Input from multiple
sensory systems (visual,
auditory,
somatosensory)
• Localisation of the body
and external objects in
space - integrates
• Recall PPC in MSI and
dorsal pathways
• Directs attention

Question 25

Posterior Parietal Cortex

Answer 25

• Outputs to secondary
motor areas, FEF, and
dlPFC
• Subregions associated
with eye, hand, or
arm movements
• Damage – apraxia and
contralateral neglect

Question 26

PPC Damage - Apraxia

Answer 26

• Disorder of voluntary movement - not a simple motor
deficit
• Difficulty making movements on request, but can make the
same movement under natural conditions when not
thinking about it
• Eg – can hammer a nail but cant demonstrate hammering
when asked
• Bilateral symptoms but damage usually unilateral – left PPC
• Conscious planning of complex coordinated action

Question 27

PPC Damage – Contralateral Neglect

Answer 27

• Disturbance of ability to respond to stimuli on side
opposite lesion
• Usually right lesions and neglect left space
• Patients fail to appreciate that they have a problem
• Egocentric left – left of body – head tilt doesn’t change
(tilt) field of neglect
• Also neglect left side of body

Question 28

PPC Damage – Body Representation

Answer 28

• Intrinsic spatial coding: knowing what own body parts are
doing
• Intrinsic coding essential when body part is obscured from
vision during planning and/or execution
• PJ: 50yo F; head injury at 43yo, loss of consciousness
• Jerking of the right arm at 48years, focal seizures, presented
for assessment
• No visual neglect or extinction, no other visual deficits
• Perceives her right arm and leg to drift
and fade unless she is able to see them
• In bed, loss of knowledge in limb
position
• In public transport, other passengers
tripping over her leg, which had drifted
into the aisle
• MR: cyst encroaching on the cortex and
subcortical white matter of left superior
parietal lobe

Question 29

Dorsolateral Prefrontal Cortex

Answer 29

• Input from PPC
• Outputs to M1,
secondary motor, FEF
• Evaluate external
stimuli and decide to
act – goals based
• Decisions to initiate
voluntary movement

Question 30

Basal Ganglia

Answer 30

• Complex heterogenous collection of interconnected nuclei
• Modulatory function – loops receiving cortical input then back
to cortex via thalamus (other non-motor functions)
• Caudate and putamen (striatum), globus pallidus, subthalamic
nucleus, substantia nigra
• Inputs from cortex (sensory, motor, association) to striatum;
output from GP and SN to motor and frontal cortex via
thalamus
• Critical role in selection and initiation of action
• Complex, heterogenous
interconnected nuclei
• Connections excitatory or
inhibitory
• Initiate selected movement

Question 31

Basal Ganglia- excitatory

Answer 31

Turn up increases
output of target
Turn down decreases
output of target

Question 32

Basal Ganglia- inhibitory

Answer 32

Turn up decreases
output of target
Turn down increases
output of target

Question 33

Basal Ganglia- process

Answer 33

Direct – enhances thalamic
output
Indirect – inhibits thalamic
output
But – indirect slightly
delayed so brief
enhancement then balance

Question 34

Basal Ganglia- process with SN

Answer 34

Direct – enhances thalamic
output
Indirect – inhibits thalamic
output
SN input – turns up DIRECT
and turns down INDIRECT
To Enhances overall process

Question 35

Basal Ganglia cont.

Answer 35

• This circuit model is speculative – details way more complicated
• Other inputs, outputs, connections, and complexities not mentioned
• Output (discharge rates) not the only important factor
• Neuronal firing patterns likely important
• Synchrony of higher level activity likely important
• Coordinated activity of multiple interconnected nuclei – fine balance
• Basics of function from disorders

Question 36

Basal Ganglia - Disorders

Answer 36

Disorders of motor control:
• Parkinson’s Disease – loss of modulatory dopaminergic
neurons in the substantia nigra
• Huntington’s Disease – loss of inhibitory GABAergic
neurons in the striatum
Note – these disorders have broader effects than just
motor and involve neurodegeneration in multiple regions

Question 37

Parkinson’s Disease

Answer 37

• Loss of dopaminergic neurons in the substantia nigra
• Increase indirect and decrease direct – decrease thalamic output
• Latest – changes in neuronal firing patterns and synchrony rather
than reduced discharge rate
• Primarily affect indirect pathway
• Ultimately - decreased cortical activity
• Cardinal features – akinesia (slowed initiation), bradykinesia (slowed
movement), muscle rigidity, tremor
Direct – enhances thalamic
output
Indirect – inhibits thalamic
output
Enhancement of direct
versus indirect reduced
To Decreased thalamic output no SN
• Reduction in spontaneous movement (hypokinesia)
• Slow initiation of movement (akinesia); Slow gait, often with freezing
and small steps, poor arm swing
• Progressive slowing or freezing during a movement and reduced
range and scale of movement
• Postural instability = many falls
• Dull, weak voice without inflections (hypophonia) and slow speech
• Mask-like, unemotional expression

Question 38

Parkinson’s Disease Treatment

Answer 38

• Dopamine agonist: L-Dopa (precursor)
• Increase dopamine generally
• Efficacy drops with usage
• Numerous side effects
• Chronic high frequency deep brain stimulation (DBS)
• Implanted device to stimulate STN (usually)
• High frequency disrupts activity
• Not sure how/why it works
• Reduce inhibition of thalamus?
• Replace irregular BG output to cortex with a regular, better
tolerated pattern?
• Disrupt abnormal frequencies?

Question 39

Huntington’s Disease

Answer 39

• Genetic neurodegenerative disease – manifests in
adulthood (35-55); life expectancy 10-25 years post onset
• Autosomal dominant with complete lifetime penetrance,
chromosome 4 – excessive build up of Huntingtin protein
• Destruction of GABAergic neurons in striatum (caudate
and putamen) – primarily affecting indirect pathway
• Progressive striatal atrophy: medial caudate first (small
spiny neurones), then putamen, then tail of caudate
• Reduced (indirect) basal ganglia output
Direct – enhances thalamic
output
Indirect – inhibits thalamic
output
Thalamic inhibition reduced
Increased thalamic
To excitation of motor cortex
no SN to GPe
• First signs affective: depression, anxiety, irritability, impulsivity, aggression
• Then restlessness, clumsiness, forgetfulness, personality changes
• Characteristic - athetosis (writhing movement) and chorea (jerky movement)
• Poor motor dexterity, unsteadiness, reduced speed
• Altered speech and writing, saccadic changes
• They involve multiple joints and thus resemble voluntary action
• They are briefly suppressible, and decrease during sleep
• They increase with stress and with voluntary movements like walking

Question 40

Cerebellum

Answer 40

• Modulatory – fine-tuning and
learning (other non-motor
functions)
• Inputs from cortex (M1 and
secondary motor), descending
motor signals from brain stem
nuclei, somatosensory and
vestibular feedback
• Compare signals with
feedback to correct ongoing
movement that deviates from
intended
• Project to brainstem nuclei directly and cortex (M1 and secondary)
via thalamus
• Role in motor learning especially when sequence timing critical
• Diffuse damage – lose precise control of direction, force, velocity
and amplitude of movement; lose ability to adapt movement to
changing conditions, disturbances in balance, gait, speech, eye
movement
• Cells in cerebellum that project to spinal cord especially sensitive to
effects of alcohol – unsteady gait, disturbance of balance

Question 41

Cerebellar Dysfunction - Ataxia

Answer 41

• Loss of sensory co-ordination of distal limbs disrupting fine
coordination – finger to nose test
• Lack of muscle control or coordination of voluntary movements,
such as walking or picking up objects.
• Speech impacts
• Alcohol abuse, certain medications, stroke, tumour, cerebral palsy,
brain degeneration and multiple sclerosis

Question 42

Motor Acts, Volition, and Free Will

Answer 42

• Described voluntary behaviour as wilful –
intentionally initiated following a decision to act
(including rejection of the alternative of doing
nothing)
• Subjective experience – ownership of action,
agency, conscious control – ‘I’ did something on
purpose
• But ….
• Often act unconsciously or with minimal conscious
control
• Split brain patients – dissociation of action and awareness
• Confabulation – plausible (but incorrect) reasoning about
decisions to act with feeling of agency
• People are subject to other illusions of ownership
• People are subject to other illusions of control
A bilateral slowly increasing negativity (EEG of SMA) (termed the
‘readiness potential’) was shown to precede voluntary action by
Kornhuber and Deeke (1965)
• Libet – have subjects perform a simple motor at random act while
looking at a fast moving ‘clock’ – note the position of the clock
when first aware of the intention to act
• Onset of the readiness potential hundreds of ms before awareness
of intention to act
• “the brain evidently ‘decides’ to initiate or, at the least, prepare to
initiate the act at a time before there is any reportable subjective
awareness that such a decision has taken place”
• Soon et al (2008) – similar approach but using fMRI
• Look at a letter stream – freely press one of two buttons –
recall letter when motor decision was consciously made
• Intentions mostly formed 1000ms before press
• 2 brain regions encoded left vs right decision early –
frontopolar cortex and parietal
• Over 10 seconds before the decision to act (7 seconds on fMRI
signal)
• Timing of decision predicted in preSMA and SMA
• 5 seconds before the decision to act
• Dissociation between outcome of motor decision and timing