Week 8 Flashcards
Motor Units
• 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
Lower Motor Neurons
• 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
Spinal Motor Circuits
Motor circuits of spinal cord show considerable complexity Reflexes Recurrent collateral inhibition Reciprocal innervation Locomotion
Reflexes
• stretch (e.g. patellar – muscle spindle afferent synapses directly onto lower motor neurons - monosynaptic) • withdrawal – multisynaptic – simultaneous excite/inhibit flexor/extensor
Recurrent collateral inhibition
• 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
Reciprocal innervation
• constant contraction of most muscles • smooth, precise movement requires adjustments – antagonistic muscles must be reciprocally adjusted
Locomotion
• 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
Descending Motor Pathways
• 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
Dorsolateral Tracts
Contralateral Single spinal segment Limbs Dorsolateral Corticorubrospinal Tract INDIRECT Dorsolateral Corticospinal Tract DIRECT
Ventromedial Tracts
Ipsilateral/Bilateral Diffuse Trunk and girdles Ventromedial Cortico-brainstem-spinal Tract INDIRECT Ventromedial Corticospinal Tract DIRECT
Dorsolateral Tracts
• 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
Ventromedial Tracts
• 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)
Descending Motor Pathways
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
Motor Neuron Disease
• 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
Motor Cortex
- 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
Primary Motor Cortex (M1)
• 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
Secondary Motor Cortex
• 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)
Mirror Neurons
• 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
Goal Directed Action
• 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
Understanding Action
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
Mirror Neurons examples
• Social cognition: knowledge of perception, ideas, intentions of others • Action understanding: cooperation, teaching/learning • Language • Emotional understanding - empathy
Mirror Neurons in Humans
• 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
Association Cortex
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
Posterior Parietal Cortex
• 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
Posterior Parietal Cortex
• Outputs to secondary motor areas, FEF, and dlPFC • Subregions associated with eye, hand, or arm movements • Damage – apraxia and contralateral neglect
PPC Damage - Apraxia
• 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
PPC Damage – Contralateral Neglect
• 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
PPC Damage – Body Representation
• 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
Dorsolateral Prefrontal Cortex
• Input from PPC • Outputs to M1, secondary motor, FEF • Evaluate external stimuli and decide to act – goals based • Decisions to initiate voluntary movement
Basal Ganglia
• 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
Basal Ganglia- excitatory
Turn up increases
output of target
Turn down decreases
output of target
Basal Ganglia- inhibitory
Turn up decreases
output of target
Turn down increases
output of target
Basal Ganglia- process
Direct – enhances thalamic output Indirect – inhibits thalamic output But – indirect slightly delayed so brief enhancement then balance
Basal Ganglia- process with SN
Direct – enhances thalamic output Indirect – inhibits thalamic output SN input – turns up DIRECT and turns down INDIRECT To Enhances overall process
Basal Ganglia cont.
- 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
Basal Ganglia - Disorders
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
Parkinson’s Disease
• 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
Parkinson’s Disease Treatment
• 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?
Huntington’s Disease
• 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
Cerebellum
• 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
Cerebellar Dysfunction - Ataxia
• 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
Motor Acts, Volition, and Free Will
• 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
