Week 8 Flashcards
What is the Spinal Motor Circuits?
The descending motor circuits and feedback circuits to the muscles, association cortex, secondary motor cortex, primary motor cortex and brain stem motor nuclei
what are the 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 Pathways in the brain
primary motor cortex to the brain stem motor nuclei
Descending Motor Pathways
• Lower motor neuron has many inputs • Major inputs from the brain • Can synapse directly • Most synapse indirectly via a spinal interneuron
Descending Motor Pathways- tracts
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
Dorsolateral to Corticorubrospinal is INDIRECT
Dorsolateral
Corticospinal
Ventromedial Tracts
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- monkey experiment
• 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
Descending Motor Pathways
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, or 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%
of cases 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- in the brain
Secondary motor cortex and primary motor cortex
Primary Motor Cortex (M1)- Part 1
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
Primary Motor Cortex (M1)- Part 2
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
Primary Motor Cortex (M1)- Part 3
• 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)
Primary Motor Cortex (M1)- Part 4
• 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- brain diagram
• 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)
Secondary Motor Cortex- explaination
• 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
Purpose of the Action
• 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
• 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)
Mirror Neurons in Humans- ballet example
• Viewing ballet steps recruits premotor and parietal mirror areas more strongly in expert ballet dancers than in nondancers or in martial-art teachers • Recruitment of motor areas with mirror properties strongly correlates with motor rather than visual expertise • People can improve their ability to judge the goal of an unusual action simply by practising that action themselves; this improvement occurs even when they practise while 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 • 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 but 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 our own body
parts are doing
• Intrinsic coding is essential when a body part is
obscured from vision at some stage in the movement
planning and execution
• PJ: 50yo F; head injury when 43yo, 30min 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 nonmotor functions)
• Caudate and putamen (striatum), globus pallidus, subthalamic nucleus, substantia nigra
• Inputs from all over 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- brain diagram
Direct – enhances thalamic output Indirect – inhibits thalamic output But – indirect slightly delayed so brief enhancement then balance SN input – turns up DIRECT and turns down INDIRECT To Enhances overall process
Basal Ganglia
• This circuit model is speculative – details are way
more complicated
• Other inputs, outputs, connections, and
complexities not mentioned here
• Output (discharge rates) likely not the only
important factor
• Neuronal firing patterns likely important
• Synchrony of higher level activity likely important
• Complex 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- part 1
• 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
Parkinson’s Disease- part 2
• Reduction in spontaneous movement (hypokinesia)
• Slow initiation of movement (akinesia);
• Progressive slowing or freezing during a movement and
reduced range and scale of movement
• Micrographia
• Slow gait, often with freezing and small steps
• Poor arm swing
• 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
Parkinson’s Disease
Direct – enhances thalamic output Indirect – inhibits thalamic output Enhancement of direct versus indirect reduced Decreased thalamic output
Huntington’s Disease- diagram
Direct – enhances thalamic output Indirect – inhibits thalamic output Thalamic inhibition reduced – increased thalamic excitation of motor cortex
Huntington’s Disease
• First signs usually affective: depression, anxiety, irritability,
impulsivity, aggression
• Followed by: restlessness, clumsiness, poor coordination,
forgetfulness and 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 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- part 1
• 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 ….
Motor Acts, Volition, and Free Will- part 2
• 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
Motor Acts, Volition, and Free Will- part3
• 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”
Motor Acts, Volition, and Free Will- part 4
• 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
Key Learnings- part 1
• Hierarchical, functional segregation, parallel, feedback
• Simple spinal circuits control some movement
• 4 descending pathways dorsolateral for fine control of
limbs, ventromedial for axial muscles/ whole body
movement (direct and indirect for each)
• MND – neurodegeneration of upper and/or lower
motor neurons
• Motor cortex – primary (M1) and several secondary
• Stimulate M1 – complex unilateral movement – motor
homunculus
Key Learnings- part 2
• Stimulate secondary – complex bilateral movements
• Secondary – functional distinction – internally or
externally guided action
• Mirror neurons – goal directed actions
• Association cortex – functional distinction - spatial
information and decide/initiate
• Basal ganglia – selection and initiation of action – PD
and HD
• Cerebellum – fine tuning and learning – cerebellar
ataxia
• ‘Voluntary’ action
