Theme 2 Flashcards
What is motor control
A dynamically changing mix of conscious and unconscious regulation of muscle force, informed by continuous and complex sensory feedback operating in a framework sculpted by evolutionary pressures
What are the different types of motor control?
- Voluntary (running, talking)
- Goal-directed (conscious, explicit, controlled)
- Habit (unconscious, implicit, automatic)
- Involuntary (eye movements, cardiac, intercostals)
Describe briefly how we escape pain?
- Pain
- Spinal cord
- Escape
- Motor, autonomic, endocrine defense related ouput
Describe briefly how we avoid looming threat?
- Loom
- Sensorimotor midbrain
- Avoidance
- Motor, autonomic, endocrine defense related ouput
Describe briefly how we avoid a learned threat?
- Threat
- Cortex and limbic system
- Avoidance / Solution
- Motor, autonomic, endocrine defense related ouput
What does more complex, sophisticated threat detection and avoidance require?
Additional or more complex neural processing
What is the overview of the basal ganglia and cerebellum
- Basal ganglia (WHAT to do)
- Cerebellum (HOW to do it)
Where do upper motor neurons have their cell bodies?
Higher centres (cortex and brain stem), project down to lower motor neurons
Where do lower motor neuron have their cell bodies?
Brainstem or grey matter of spinal cord, projecting to muscle
Describe the descending control system
- Association cortex
- Motor cortex
- Brainstem circuits
- Spinal circuits
- Motor units
- Affect on the world
Feedback on all levels
How do individual muscle fibres act
All or none, contracted or not
So control relays on how lower motor neurons activate different fibres
What are the three types of muscle
- Skeletal
- Smooth
- Cardiac
How do we achieve a wide range of movements with all or none muscle contractility?
- Antagonistic arrangement
- Recruitment of a range of muscle fibres (fast / slow twitch, small and large motor units)
What is antagonistic arrangement?
Combined co-ordinated action between opposing muscles
How does training affect muscle fibres
Number of muscle fibres remains unchanged
They change type (fast / slow twitch), and diameter
Describe the structure of muscle fibres in skeletal muscle
- Attached to bone by tendon
- Muscle fasciculi (groups of muscle fibres)
- Muscle fibres (groups of muscle cells)
- Made of myofibrils (actin and myosin)
- When depolarised, actin and myosin slide against each other - contraction
Describe the cellular mechanism of muscle movement
- ACh causes cascade resulting in release of calcium from inside muscle cell
- Myosin head changes shape and binds with actin
- ATP required to break bond between actin and myosin
(rigor mortis, no more ATP, stiff muscles)
What is a motor unit?
Single alpha motor neuron + all the muscle fibres it innervates
How does motor unit size affect movement
Fewer fibres per neuron means greater movement resolution (eg, fingers and tongue)
What is the size principle?
Motor units are recruited in order of size (smallest first)
Fine control typically required at lower forces
What are slow muscle fibres for?
Type 1
Stuff you can do all day eg. maintaining posture
What are fast fatigue resistant muscle fibres for?
Type 2a
Bursts of force, they will fatigue but not for a while (running, swimming)
What are fast fatigueable muscles?
Type 2b
Very quick and powerful contractions, but tire easily
Where do all the alpha motor neurons from the motor units go to?
The motor pool for each muscle in the spinal cord (ventral horn)
How are motor pools arranged in spinal cord?
Proximal muscles medially
Distal muscles laterally
What can activate cell bodies in the ventral horn / motor pools?
- Sensory information from muscle
- Descending information from brain
(inter-neurons between dorsal column and ventral column for communication)
What does the CNS need to know to control movement?
- Muscle tension (golgi tendon organ)
- Stretch of muscle (muscle spindles)
What does the golgi tendon organ do?
Send ascending sensory information to the brain about how much force is in the muscle
Critical for proprioception
Can inhibit muscle fibres via spinal cord circuit to prevent damage
What does the muscle spindle do?
Sense the length of muscles, ie amount of stretch
Describe the basic reflex circuit of muscle spindles
- Muscle spindle detects stretch change
- Sends signal into spinal cord
- Activates alpha motor neurons
- Affects muscle and returns it to original position
- Important for maintaining steady state
What is the role of intrafusal muscle fibres
Detect changes in muscle length
Why are intrafusal muscle fibres supplied by a different motor neuron than extrafusal?
If it was the same, when the muscle was slack or taught the system would not be sensitive to slight changes
What innervates intrafusal muscle fibres?
Gamma motor neurons
What coils around the intrafusal fibres of muscle spindles?
Sensory fibres
Describe the withdrawal reflex
- Painful stimulus
- Signal sent to spinal cord by cutaneous afferent fiber from nociceptor
- Interneuron relays signal to motor neuron (from dorsal column to ventral)
- Signal travels down alpha motor neuron - muscle withdrawn
Describe the vestibular righting reflex?
- Vestibular system detects that body is not upright, as well as any acceleration due to gravity
- Information from vestibular system combined with visual somatosensory and proprioceptive sensory input
- Motor plan specified by this input to restore uprightness
- Cerebellum compares intended motor plan with the actual situation (critical for computing the desired activity)
Why is it hard to build moving robots?
Control of gross movement patterns can be devolved to simple spinal circuity
BUT
Constant modulation based on feedback is required - higher CNS centres constantly adjust ongoing activity to resolve conflicting demands on the motor system
How does the brainstem control movement?
Balance and postural control - integrating eye muscles to vestibular system
What is the role of the motor cortex?
exerts direct, top down control over muscle activity (with as few as one synapse in the spine between a cortical neuron and innervation of muscles)
Describe the pathway of the motor cortex
- Motor command originates in pyramidal cells (layer 5-6 grey matter)
- These are the upper motor neurons
- Pyramidal cell axons project directly or indirectly (eg. via brainstem) to spinal cord
- Synapse with lower motor neurons
What do axons of upper motor neurons descending to lower motor neurons form?
The pyramidal tract
What is the issue with the homunculus?
Reasonable representation, but oversimplified
In reality, overlap and plasticity make it more complex
Few motor commands require isolated activation of a single motor unit
Where does the dorsolateral path travel?
(lateral corticospinal tract)
- Direct pathway is from motor cortex
- Decussate in medulla
- Down dorsolateral tract to contralteral distant limbs
Indirect via red nucleus
Where does the ventromedial path travel?
(anterior corticospinal tract)
- From motor cortex
- Down to spinal cord
- Down ventromedial tract to both sides proximal limbs and trunk
Indirect route via tectum, vestibular nuclei, reticular formation and cranial nerve nuclei
Similarities between dorsolateral and ventromedial tracts
- Both have direct corticospinal route
- Both contain an indirect route via brainstem nuclei
Differences between dorsolateral and ventromedial tracts
- Lateral innervates contralteral side of one segment of spinal cord
- Lateral sometimes projects directly to alpha motor neuron
- Medial has diffuse innervation projecting to both sides and multiple segments of spinal cord
What is the basal ganglia?
Group of nuclei lying deep within cerebral hemispheres
How does the basal ganglia modulate motor control, briefly?
- Receives excitatory input from many areas of cortex
- Output goes back to cortex via the thalamus (GABA)
Why is the basal ganglia important
Acting to ensure you are not doing more than 1 thing at 1 time, balancing our behaviour to get control of the motor system
Reducing interference
What is the cerebellum?
Large brain structure that acts as a parallel processor, enabling smooth, co-ordinated movements
Also involved in a range of cognitive, emotional, and reward processes
What % of CNS neurons are found in the cerebellum?
Around 50%
What are the inputs of the cerebellum?
- Cortical - motor plan (copy of commands)
- Spinal - proprioceptive information about movement from muscle spindles, golgi tendon organs and mechanoreceptors
- Vestibular - rotational and acceleratory head movement from semicircular canals
What is the role of the cerebellum?
Knows current motor command
Knows body position and movement
Projects back to cortex
So computes motor error and adjusts commands accordingly
What are the other roles of the cerebellum?
- Motor learning too, in collaboration with basal ganglia and cortical circuits
- fMRI has shown it is implicated in a wide variety of non motor tasks
How could we use brain computer interface for movement?
Given that the motor plan is in the cortex, we could bypass a damaged spinal cord to activate LMNs
Decode signals from cortex, learn to control avatar in VR, gradually increase number of movement parameters controlled
Specify desired movement
Moves
Decoding is hard - no feedback
What is the vestibulo-ocular reflex?
When the head rotates, the eyes move in the opposite direction
Keeps the visual world stable
Why is the vestibulo-ocular reflex important?
- If the eye moves relative to the world, the image moves across the retina
- This blurs vision - information is irretrievably lost
- Fail to detect prey / predator - very early evolutionary
When do we use the vestibulo-ocular reflex?
When we walk
When we turn our heads
What is the optokinetic reflex?
Response to movement of whole retinal image
Motion of retinal image adjusts the speed of eyes
How can we measure the optokinetic reflex?
Move either the actual surroundings or a projected image
What are the purposes of stability reflexes (VOR and OKR)?
Avoid image drift
What are saccades?
Very fast flicks of the eye
During saccades, vision is suppressed
So you can’t see your own but you can see other people
How many saccades do we make?
While awake around 3 per second
Why do we do saccadic eye movements?
When we want to focus on something, we are shifting the fovea to look at it
What is the solution to not being able to have high acuity vision everywhere?
A wide field of view that signals items of interest
Combine with fast eye movement system to direct fovea to items of interest
What are smooth pursuit movements?
For following slow moving targets, ie keeping them on the fovea
How can we see smooth pursuit movements?
Following movement of a pendulum
What is vergence?
Eye movement where the eyes move in different directions, to look at targets moving towards or away from you
What is the speed of vergence?
Can be fast like saccades or slow like smooth pursuit
What are the two eye movements to stabilise retinal image?
- Vestibulo-oculo reflex
- Optokinetic reflex
What are the three eye movements to acquire and follow targets?
- Saccades
- Smooth pursuit
- Vergence
How does the vestibulo-ocular reflex work and through what pathways?
- Head rotations sensed by semicircular canals in the labyrinth
- Axons (primary vestibular afferents with cell bodies in Scarpa’s ganglion)
- Synapse with the medial vestibular nucleus (interneurons)
- Project to nuclei containing the neurons that control eye muscles (CN3 and 6)
What is the input and output to the VOR?
Input: Head movement
Output: Eye movement
Feedforward control, no feedback
How does the optokinetic reflex work and through what pathways?
- Retina and pretectum detect image velocity
- Signals to brainstem vestibular and oculomotor nuclei
- Eye movement command to eye muscles
The output (eye movement) affects retinal slip - so it is feedback control
Why do we have two stabilising reflexes?
OKR on its own inadequate - does not work for rapidly changing movements
What is the OKR good / bad at?
Delay in feedback loop - retinal processing of image slip takes time (50-100ms)
Can get runaway instability at higher frequencies
Solution - low gain at higher frequencys
What is the VOR good / bad at?
High frequency head movements, eg. walking or running with a very fast response time (~14ms)
Poor for low frequency constant movements due to semicircular canal mechanics
Why do we need OKR and VOR?
They compliment each other
How does the VOR know how big an eye movement command to send to the eye muscles?
We need the firing rate for muscles to keep working as our bodies grow / change, so we need to learn
Eye movement command sent to cerebellum, uses retinal slip to keep reflex accurate, adds input to brainstem
How can we test VOR learning?
Put glasses on a monkey and watch the system gradually adapt so VOR can get bigger or smaller
What is the structure of the cerebellum
3 layers
Very uniform structure across the whole cerebellum (unlike entire cerebral cortex areas)
What are the inputs to the cerebellum?
Mossy fibre inputs from many different regions of brain and spinal cord (including current motor commands and state of body)
Synapse to granule cells in granular layer
How many more granule cells are there?
Outnumber mossy fibres by at least 50:1
What do granule cells do?
Somehow recode mossy-fibre input to make it more suitable for learning (unclear of exact mechanism)
Where do granule cells project to?
Send their axons to the top layer where they split into two parallel fibres that synapse with Purkinje cells
What are the Purkinje cells of the cerebellar cortex?
Output cells
Largest cell in cortex
Describe the input to the Purkinje cells?
Around 150,000 parallel fibre synapses
Input from a single climbing fibre (axon from base of brainstem)
Climbing fibre wraps itself around Purkinje cell dendritic tree, forming 1000s of synapses with same input single
What do Purkinje cells do?
Sum the weighted input from parallel fibre, and this is the cerebellar output signal that tries to make movement accurate
What do climbing fibre signals do?
Adjust weights of synapses between parallel fibres and Purkinje cells, altering cerebellar output
These signals contain information about movement accuracy (error signal)
What does cerebellar damage / impairment result in?
Makes movements inaccurate, slow and uncoordinated
What is the key idea of the Marr-Albus model?
To learn to make accurate movements, you must have information about what you did wrong - an error signal
Climbing fibres convey that error signal
What is the suggested learning rule for the cerebellum?
A synaptic weight between parallel fibres and Purkinje cell is changed according to the correlation between the parallel fibre signal and the error signal from the climbing fibre
If positive correlation, reduce weight
If negative correlation, increase weight
When does learning stop in the cerebellum?
When there is no longer correlation between any parallel fibre signal and the climbing fibre signal
Decorrelation learning rule
What happens if you inhibit the flocculus?
You cannot have VOR adaptation
How does the flocculus interact with VOR?
Located on side path to reflex
- Mossy fibre inputs contain copy of eye movement commands
- Climbing fibre inputs convey image about retinal image movements
- If gaze holding fails - retinal slip
How is the correlation between motor command and retinal slip an important source about accuracy of motor commands
If there is no correlation between motor commands and the error, then no causation - external slip
If there is correlation between motor command and retinal slip error, the motor commands are incorrect
Summarise cerebellar input like paul
Input: mossy fibres . These synapse onto granule cells, whose axons (parallel-fibres) synapse onto Purkinje cells. Purkinje cells provide the output of cerebellar cortex. Purkinje cells also receive climbing-fibre inputs, which behave in a very unusual way.
Summarise cerebellar circuits like paul
Theory: climbing fibres convey an error signal about movement inaccuracy. This adjusts the weights of the synapses between parallel fibres and Purkinje cells, thus altering Purkinje cell output an a way that makes movements more accurate
What evidence do we have for this structure of cerebellar circuitry?
Practice: evidence from adaptation of the VOR consistent with theory. It also works for VOR adaptation in robots
What is the anatomy of the basal ganglia
Caudate nucleus top middle
Putamen
Globus Pallidus externus
Globus Pallidus internus
Sub thalamic nucleus
Substantia nigra pars compacta
Substantia nigra pars reticulara
What is the striatum?
The caudate nucleus and putamen
What is the main nucleus of the basal ganglia?
Striatum
What is a principle feature of the striatum?
85-90% are GABAergic projection neurons
What are the two types of GABAergic projection neurons in the basal ganglia?
D1 dopamine receptors
D2 dopamine receptors
Where do D1 dopamine receptors project to?
Primarily to globus pallidas internus and substantia nigra
Where do D2 dopamine receptors project to?
Globus pallidus externus
What is the GO pathway of the basal ganglia?
- Cortex fires
- Striatum D1 activity increases
- GPi/SNr activity decreases
- Thalamus activity increases
- Cortical activity increases
What is the STOP pathway of the basal ganglia?
- Cortex fires
- Striatum D2 and STN activity increases
(2.5 - STN gets excited directly by cortex, and is released by D2 inhibiting the GPe) - GPi/SNR activity increases
- Thalamus activity decreases
- Cortical activity decreased
How does optogenetics work?
Use viral vector to insert light sensitive protein into membranes of receiving neurons
Can get it into different cells, eg. D1 or D2 depending on associated promoter region
What is another possible role of the basal ganglia?
Central switch in the vertebrate brain, that enables action selection from a whole possibility of actions (Redgrave et al. 1999)
What are the predisposing conditions for action selection?
- Sensory input
- Cognitive state
- Homeostasis
- External conditions
What is action selection?
Picking the action that will get access to limited motor resources
What are the possible models for the action selection competition model?
- Each action communicates with each other, full connectivity - but enormous amount of redundant wiring and energy required
- Central switch ?basal ganglia that they all talk to individually - striatum is like arena where they fight it out for expression - winner takes all
What is the first evidence for action selection hypothesis?
Disorders where basal ganglia is damaged cause disorders of too few or too much movement
Parkinson’s - Bradykinesia, cogwheel rigidity, resting tremor
Huntington’s - Chorea
Aside from Parkinson’s and Huntington’s disease, what other pathology is BG implicated in?
- Dystonia - abnormal fixed posture
- Tourette’s Syndrome
- If the action selection hypothesis is true, what must the BG receive?
Input from a wide variety of brain areas
Putative “command” centres for action requests
Should be cortical and subcortical
Where does the striatum receive input from?
All over the brain:
1. Cerebral cortex
2. Subcortical nuclei such as superior colliculus (via thalamus)
- If the action selection hypothesis is true, what must the BG be able to do?
Switch on selected resources
How can the BG switch on selected resources?
Disinhibition gating hypothesis
Locks and unlocks the thalamus
- If the action selection hypothesis is true, how must the BG be able to communicate?
Flow of information between command centres, basal ganglia and associated motor centres
How does the BG communicate in loops?
Cortex -> BG -> Thalamus -> Cortex
Structures that feed into BG also send copy to motor area that they are going to use for motor output
BG says “yes” allowing behaviour to be expressed
What loops through the BG have been identified?
- Motor
- Oculomotor
- Prefrontal 1
- Prefrontal 2
- Limbic
Basal ganglia may have influence on selection of actions and emotion, as well as movement
How are different body parts represented in BG?
Different areas of body are different areas in BG
Discrete channels - could be very specific
What subcortical structures talk into basal ganglia?
- Superior colliculi
- Pedunculopontine tegmental nucleus (PPN)
- Periaqueductal grey
Lots of subsystems gain connection
- If the action selection hypothesis is true, how must the BG be able to weigh up requests?
Extract the salience or urgency of each request
How is saliency communicated to the basal ganglia?
Encoded into request - the one that is “shouting the loudest”
Intrinsic connectivity of striatum
- If the action selection hypothesis is true, what must their be evidence of in the BG?
Neuronal selection mechanisms
How would a selection mechanism work in the BG?
- Up-down states of spiny projection neurons (striatum can filter)
- Local inhibition in striatum - excitation in one area inhibits areas around it
- Subthalamic clamp on actions we do not want to do - STOP pathway holds back all the actions we don’t want to go (diffuse), GO pathway acts specifically (focused)
