Motor and Planning Flashcards
What do we use muscle contractions for?
Moving limbs Moving the external world Moving yourself around Communication - speech/gesture/writing To move visual and somatosensory sensors
Define apraxia
Movements poorly prepared or planned
Inability to carry out purposeful sequences of action. Perhaps struggle to hold goal in mind while performing individual actions. Have functioning motor equipment
Define noise
Random variation in signals, both motor and sensory, which renders them imprecise
Define redundancy
There are many possible ways to achieve a goal - the ‘motor equivalence’ problem: which do you pick?
Describe biological delays
- Conduction of AP delays signals
- Muscle contracts slowly
- Eye muscles 20ms to full force, limb muscles 30-50ms
- Must specify when force reaches its peak to produce accurate movement
Define nonlinearity
Mixing individual motor commands doesn’t produce predictable results - force depends on length, load and velocity of shortening in a more complex way
Define non-stationarity
The behaviour of motor systems can change over time; muscle contraction depends on history e.g. thixotropy (gels becoming fluid when disturbed)
How many synapses does a motorneuron receive?
30K
How big is the EPSP of an excitatory synapse?
0.1mV
What is the spike threshold for a muscle?
> 10mV depolarisation (e.g -55mV)
What are the stages of simple shifts of position?
Acceleration (agonist)
Deceleration (antagonist)
Final position holding force (agonist)
What are the sensors of the outside environment?
Auditory Visual Somatosensory Proprioceptors Vestibular receptors
Define negative feedback
System that acts as a regulator to maintain a given parameter at a set point. Deviation from the set point is detected by sensors and a correction generated to nullify the deviation
Define closed-loop feedback
A negative feedback system that can shift state when the set point changes
What are the major problems with negative feedback loops?
Time delays in the feedback loop (sensory transduction, conduction to and from brain)Leads to instability and oscillation
How do cerebellar lesions affect feedback systems?
Damage ability to anticipate motor commands (feedforward), so only leave negative feedback?
Define feedforward/open-loop feedback
Sensory information is used to generate a prediction of what is needed in the future
Define internal model system
Simulator in the brain that represents the mechanics of the body and the behaviour of the outside world Can learn (with experience) to predict which motor commands would be useful in a given situation
Define inverse model
A representation of transformation from motoneuron activity to movement in reverse so that from the desired outcome, motor demands to generate it can be estimated
What are the problems with inverse models?
Small errors in the initial stages of the calculation lead to massive errors in the final stages
Define forward model
Predicts consequences of motor commands before the slow muscle movement is complete, using information on what the motor commands were via efference copy/internal feedback. This is used to predict the movement that will follow, so the predictions can be set to the desired result and follow up corrections can thus be set up for errors as they are in the process of occurring.
What is the main centres for feedforward control?
Cerebellum and motor areas of cerebral cortex
Where in the spinal cord are the alpha-motoneurons?
Ventral horn
Define motoneuron pool
The 200-500 motoneurons that innervate a given muscle
What is the organisation of motoneurons within the ventral horn?
Proximal medial, distal lateral
Flexor posterior, extensor anterior
Somatotopic organisation
What is a motor unit?
The muscle fibres that one motoneuron innervates
How many motor units are in a muscle?
Several hundred
What are the three categories of motor unit?
- Slow
- Fast fatigue resistant
- Fast fatiguable
Describe the anatomy, biochemistry, and physiology of slow fibres?
Red
Anatomy: small fibres, few fibres/unit, highly vascular
Biochemistry: oxidative, lots of myoglobin (red)
Physiology: slow twitch, low tension, fatigue resistant, slow axons
Used in endurance training
Describe the anatomy, biochemistry, and physiology of fast, fatigue resistant fibres?
Anatomy: intermediate fibres, intermediate fibres/unit, intermediate vascularity
Biochemistry: intermediate oxidative and glycolytic, intermediate levels myoglobin
Physiology: intermediate twitch, intermediate tension, intermediate fatiguability, intermediate speed axons
Describe the anatomy, biochemistry, and physiology of fast, fatiguable fibres?
Pale
Anatomy: many fibres/unit, few capillaries
Biochemistry: glycolytic, little myoglobin
Physiology: fast twitch, high tension, fatiguable, fast axons
Used in sprint training
What is the benefit of having motor units with different properties?
Slow units can use for continuous generation of small forces (finely graded, low force contractions)
Fast fatigueable units can produce high forces over a short period (strength needed)
How is motor unit utilisation controlled?
- Rate coding: vary motoneuron firing rate. Fuse into tetanus at quite low freq though
- Motoneuron recruitment: recruit more motor units as more force is required
What is the size principle?
That motor units are recruited in an orderly sequence from lowest force to highest force units as force increases. Means that force always increments by finest available motor unit, and so is as smooth as possible.
How does the size principle work?
Developmental plasticity
Motoneurons with low firing threshold innervate few muscle fibres and induce them to become slow twitch/low force/fatigue resistant. Motoneuons with the highest firing thresholds recruited last innervate many muscle fibres and induce them to become fast twitch.
Reduces work of the motor system.
What are the 3 sources of synaptic input to motoneurons?
- Afferent fibres from muscle spindles
- Descending fibres: direct from brainstem or cerebral cortical structures, relatively rare but with an exception
- Spinal interneurons: most numerous connection, most cases receive input from sensory pathways and descending pathways
What are the two types of reflex?
- Targeted at specific small groups of muscles to regulate their force e.g. stretch reflex, associated reciprocal and recurrent inhibition
- Complex reflexes that generate functional movements that involve multiple muscles e.g. nociceptive withdrawal reflex
Define a withdrawal reflex
Coordinated pattern of muscle contraction to move the stimulated part of the body away from the stimulus
Describe ‘local sign’ of the foot.
Different reflexes are evoked from different locations. Stim of plantar (bottom) surface of foot evokes leg flexion, stim of foot dorsum evokes leg (top) extension.
Where do nociceptive afferents terminate?
Substantia gelatinosa of the dorsal horn
What are proprioceptors?
Sensory fibres from muscles and joints that provide information on the musculoskeletal system. 1/5 of mechanoreceptors.
3 major groups:
1. Muscle spindle afferents = stretch receptors/length
2. Golgi tendon organ afferents = muscle tension receptors/force
3. Joint receptors = signal joint position and movement especially at the extremes
What are exteroceptors?
The receptors on the surface of the body, e.g. cutaneous receptors. Especially ruffini endings are involved in movement
What are teloceptors?
Receptors that sense the environment at a distance e.g. eyes, ears, nose
Define proprioception
The sense of position and movement of the body
Takes information from proprioceptors, exteroceptors, vision and vestibular systems
Describe muscle spindles
Proprioceptors: activated by stretch of the central regions of the intrafusal fibres
Spindle-shaped structures embedded in muscles whose afferents signal muscle length and change in muscle length
Comprises an encapsulated bundle of small specialised intrafusal muscle fibres
Striated at the ends of their fibres - contractions change the sensitivity of the sensory nerve endings
How many spindles in a muscle?
20-100
What is the difference between extra and intrafusal muscle fibres?
Intrafusal aren’t contractile, smaller than extrafusal which are contractile
What are the two types of muscle spindles?
Bag fibres: swollen centre and contain many nuclei, contractile ends. 2 forms
Chain fibres: uniform diameter, uniformly contractile along length.
What are the sensory receptors that attach to intrafusal muscle fibres?
Primary/1a spindle afferents: very large and fast conducting axons with terminal branches that end in coils/annulospiral endings around the central region of the intrafusal muscle fibre
Secondary/II spindle afferents: end adjacent to the central region of the intrafusal muscle fibre.
Both activated by stretch
What are the motorneurons that attach to intrafusal muscle fibres?
Gamma motoneurons
Innervate the ends of the intrafusal fibres
(In some mammalian fibres, beta innervation)
Different gamma neurons innervate bag and chain fibres
What is beta innervation?
In amphibian/reptile muscle, where alpha motoneurons innervate the intrafusal (as well as extrafusal) muscle fibres
What is the difference between what bag fibres sense and what chain fibres sense?
Chain fibres = uniform mechanical properties along length, so sensory endings esp II afferents, signal static muscle length linearly
Bag fibres = esp 1a afferents, dynamic sensitivity to changes in stretch. Because central region isn’t contractile, but elastic, so rapid stretches rapidly elongate it (rapid strong activation of afferents at stretch onset), which is subsequently relieved as the viscoelastic contractile ends of the fibres elongate - rapid adaptation.
What is the function of gamma innervation?
Innervate the ends of the intrafusal fibres
Shorten
Stretch central region of fibres where the receptors are located
Increases both firing and sensitivity of receptors
Lets the muscle signal length changes from different starting muscle lengths (a form of adaptation)
Define adaptation
Adjusting the receptor sensitivity to extend the range over which the sense organ operates
How come the brain isn’t confused by both gamma motoneurons or muscle contractions being able to signal the same thing from muscle spindles?
Brain receives efference copies of the commands sent to gamma motoneurons
Describe Golgi tendon organs
Activated by active tension in the tendon
Passive stretches of relaxed muscle doesn’t increase tension in the tendon, but muscle contractions do.
Signal strongly proportional to the load on the muscle
What is the stretch reflex?
Muscles respond to being stretched by contracting, e.g. knee jerk: tap patellar tendon, stretches muscle spindles, reflex contraction of quadriceps, close synergists, and excite interneurons that inhibit antagonist muscles
Which muscles do not have a stretch reflex?
Eye, tongue
What is reciprocal inhibition?
A spinal reflex. In stretch reflexes, agonist contracts, but also (via interneurone) reflexive relaxation of antagonist
What was Merton’s proposal?
That movement was driven by gamma motoneurons altering set points such that the spinal cord itself determines the appropriate force required via negative feedback
What were the problems with Merton’s proposal?
- For this to work the stretch reflex would need a gain of one (it’s actually less)
- Delay which would lead to oscillation
What is clonus?
Oscillation following a muscle stretch in pathological situations following damage to descending corticospinal pathway systems such that the stretch reflex is exaggerated
What are the roles of proprioceptors?
- Spinal reflex action
- Kinesthesia (sense of position, movement and effort)
- Information for supraspinal motor systems involved in predictive feedforward control
What do proprioceptors contribute to supraspinal control?
Information on current state of play at outset of movement to model predictions on
Assessment of the outcome after the movement, critical for learning in the model system to ensure they are accurate
What was the Nashner experiment?
Move a platform backwards with a person on it, pulls feet, measure muscle response in gastrocnemius. The more you do it, the more the early stretch reflex response comes in. Did it again but tilt the platform: caused the same stretch, and get the same strong reflex, which induces a body sway as you expect the previous set of circumstances.
What type of synapse is there between 1a afferents and inhibitory interneurons?
Glycinergic
What is recurrent inhibition?
Renshaw cells
Motoneuron axons have branches called recurrent collaterals within the spinal cord that innervate a type of inhibitory interneuron called Renshaw cells. Renshaw cells seem to regulate the timing of motoneuron firing, preventing synchrony and so jerkiness or tremor
What does it mean that Golgi tendon reflexes are context dependent?
In static positions, activation of tendon organs mainly inhibits the parent muscle
In locomotion, activation of tendon organs mainly leads to excitation, where it supports contraction against a load
What are 3 neonatal reflexes that change with development?
- Grasp reflex
- Babinski’s sign (plantar reflex)
- Reflex stepping
Describe the grasp reflex
In first 6-12 months then disappears
Babies grasp onto things and generate enough force to support the body
Can reappear after brain damaged
Describe Babinski’s reflex
Toes curl up in response to plantar stimulation (in adults they turn down)
Neonatal reflex reappears after brain damage
Describe spasticity
Exaggerated stretch reflexes. Muscles are tense and stiff. Stretch elicits strong reflexes and clonus
Describe the clasp knife reflex
The limbs snap into flexion or extension during movement (not due to tendon organs)
What are central pattern generators?
Biological neural networks that produce rhythmic outputs with the absence of rhythmic inputs. Can function without input from higher brain areas, but are modulated by them. Can also function without sensory inputs, e.g. by cutting dorsal roots of spinal cord.
Made up of spinal interneurons
How much do CPGs generate locomotion in man?
Little
Pattern that greater encephalisation is associated with weaker ability to generate locomotion. Mammals less prone to produce movement after removal of the brain
Where do the two descending motor pathways sit in the spinal cord white matter?
Dorsolateral
Ventromedial
What do the ventromedial pathways control?
Axial and proximal limb muscles
Role in whole body movement (posture/locomotion)
Crossed and uncrossed
What is the ventromedial pathway divided into?
Reticulospinal from reticular formation
Vesibulospinal from vestibular nuclei
Tectospinal from superior colliculus (orientation of your head in space)
What are the dorsolateral systems?
Control goal directed movements of the limbs esp hands, feet, face, lips
What is the dorsolateral system divided into?
Rubrospinal pathway: Red nucleus in midbrain. Probably vestigial in man.
Corticospinal tract: from motor areas of cerebral cortex, largest descending pathway in all mammals, the dominant descending control pathway in man.
Crossed
What and where are the receptors for the vestibular system?
Hair cells in labyrinth of semi-circular canals and otolith organs (saccule and utricle)
Describe the utricle and saccule
Static information
Hair cells project into jelly-like mass that gravity acts on
Hair cells have different directional sensitivities
Specific sets of hair cells activated when the head in different positions
So inform on effective direction that gravity is acting - when immobile = head position
Describe the semicircular canals
Dynamic signal when the head starts or stops to move.
Hair cells embedded in mass that almost closes the canal called the cupula
Cupula neutrally buoyant in the endolymph in the canals so stationary when head is stationary
Head moves –> fluid has inertia so tends to remain stationary but cupula fixed to head so cupula deflected –> activates hair cells.
Why do you feel dizzy when you drink alcohol?
Alcohol equilibrates more quickly into the cupula than endolymph cells, so the cupula becomes buoyant and you feel like you’re constantly rotating
Which is more likely to provide signals for feedforward control: otolith or semicircular canals?
Semicircular canals
How does the vestibular system being activated affect posture?
Activation –> vestibulospinal pathways –> extensor/antigravity muscles
How can the vestibular system get damaged?
Labrynthitis, centrally through brainstem stroke or cerebellar damage
How does the body differentiate between body sway, when it needs to move, and head sway, when it doesn’t
Efference copy from motor systems that move the head: if the predicted vestibular signals match the actual vestibular signals, the vestibular reflexes are cancelled
What is the point of gaze-fixing mechanisms?
Visual system is bad at resolving moving images, so eye needs to be kept fixed relative to the outside world as much as possible.
What are saccades?
Very rapid gaze shifting eye movements
What are the two major gaze fixing mechanisms in mammals?
Vestibuloocular reflex
Optokinetic reflex
Define the vestibuloocular reflex
Moves the eyes equal and opposite to the head
What does the MLF connect?
Medial longitudinal fasciculus
Semicircular canal afferents, vestibular nculei, motoneurons of oculomotor nuclei
Which bit of the cerebellum controls vestibuloocular reflexes?
Flocculus
Calibrates what oculomotor movement is needed to be done by the cerebellum
How many synapses are thee between the semicircular canals and the eyes moving?
4:
1 canal –> nerve
2 nerve to second nerve in vestibular nucleus
3. second nerve to third nerve in oculomotor nucleus
4. third nerve to eye muscle
What is the function of the optokinetic system?
Moves the eyes to follow slow movements of the visual field
What drives the optokinetic system?
Visual cortex
How does the optokinetic system work?
When eye deviates from it axis within the orbit, saccades reset the eye to the centre: nystagmus.
Define nystagmus
Drift and saccade eye sequence resulting in a ‘sawtooth’ motion of the eye
Can occur physiologically due to optokinetic or vestibular stimuli, or pathologically after cerebellar or vestibular damage.
What is the pathway that drives gaze-shifting foveation?
Retina –> magnocellular pathway –> superior colliculus –> brainstem reticular formation –> oculomotor nuclei –> saccade
Deep layers of colliculus –> tectospinal tract –> cervical spinal cord –> neck movmeents accompanying eye movements.
Deep layers of colliculus also receive auditory input so can rapidly orientate to sound stimuli too.
Which cortical regions are involved in smooth pursuit?
Visual cortex and medial temporal cortex process visual signals, regions of frontal lobe anterior to motor cortex called frontal eye fields also do
What is smooth pursuit?
Gaze-shifting mechanism: slower eye movements to follow moving objects. Feedforward
Summarise the main gaze-fixing and gaze-shifting mechanisms:
Fixing
VOR
Optokinetic system
Shifting
Foveation
Smooth pursuit
What is the function of the primary motor cortex?
Execution of voluntary movement via the corticospinal or corticobulbar tracts projecting onto motor neurons
What is the effect of unilateral mild stroke in the motor cortex?
Contralateral hemiparesis
Definition hemiparesis
One-sided weakness and partial paralysis
What is the effect of unilateral severe stroke?
Contralateral hemiplegia
Where do: ACA and MCA strokes affect?
ACA = lower limbs, MCA = upper limbs and face
What is the outflow of the motor cortex called?
Internal capsule
What is the pathway of the corticospinal tract?
M1 Forebrain internal capsule Midbrain cerebral peduncle Ventral brainstem Inferior olive of medulla --> corticobulbar fibres Medullary pyramid Pyramidal decussation Lateral corticospinal tract in dorsolateral funiculus of spinal cord (90%) Anterior uncrossed tract (10%)
How do you identify corticospinal tract fibres?
After a stroke that affects a movement, can find which fibres used to supply it by demyelination
What happens to the ventral corticospinal tract fibres?
Either cross or provide control for axial muscles
Don’t control distal ipsilateral muscles: after stroke they are not used for recovery of function
What is an upper motoneuron lesion?
Motor cortex lesions that are complicated by spasticity
What is a lower motoneuron lesion?
Lesion of spinal cord or peripheral nerve which causes flaccid paralysis
What is the function of cortico-motoneuron connections? How do we know?
Direct, monosynaptic, bypass spinal interneurons. Allow for precise, independent movement of extremities (fingers)
Lesions –> permanent deficits most prominent in finger movement and manipulation
Comparative neuroanatomy –> projections to motoneurons appear in species that make independent finger movements but not species without
Development –> evidence these direct projections are developed post-natally at 9months, which is when dexterity begins to develop
Describe the motor homunculus
A simple figure representing the motor cortex organisation
Why is the motor homunculus misleading?
Misleading in that it suggests the motor cortex contains an orderly representation of individual muscles in a fractionated map, and so that lesions in one location will affect a specific muscle or body part, which isn’t the case
What is the representation of the body in M1?
Individual neurons in M1 see sets of synergistic muscles that can be activated together in particular movements
Different groups of motor cortex neurons thus provide ‘alternative libraries’ of muscle synergies e.g. wrist extensors and finger flexors for a power grip
What are the sources of input to the primary motor cortex?
- Motor association areas via direct cortico-cortical connections
- Cerebellum via VL thalamus
- Basal ganglia via VL thalamus
- Sensory afferents via VL thalamus and sensory cortex (tactile and proprioceptive)
- Subcortical areas via VL thalamus
What is the function of the sensory afferents reaching M1?
Rapid feedback correction of ongoing movement
What are the outputs of the motor association areas?
Cortico-cortical to M1
Direct to spinal cord
Connections to cerebellum and basal ganglia, through which they can influence plans and preparation or future movement
What do the motor association areas do?
Plan movement
SMA: Internally generated or self-paced movement, bimanual movement
LPA: Movements that depend on a sensory trigger system
Where are the heaviest projections of the cerebellum and basal ganglia?
Cerebellum –> LPA
Basal ganglia –> SMA
What is the effect of a lateral premotor area lesion?
Inability to appropriately incorporate sensory information into motor actions, particularly grasping
What are mirror neurons?
Neurons that fire in relation to making a movement, but also in relation to seeing another person make the same movement
What is the evidence for the function of the SMA?
- PET Scans
Activity in SMA also occurs during mental rehearsal of imagined movements
Suggests SMA helps predict the sequence of movements needed to achieve a particular end point and in understanding their consequences - SMA more activated when subjects performing a learned sequence of finger movements rather than relying on external cues to signal a novel sequence of finger movements
- Ablation of SMA in monkeys causes i) deficit in bimanual coordination, ii) failure to orient hands and fingers accurately as they approach food, iii) failure to raise hand in the absence of external cues in order to get peanut reward
- Alien hand syndrome: patients with SMA pathology may have their actions divorced from conscious control. Hand responds to outside world but the can’t control it.
What is the function of the prefrontal cortex?
Planning, cognitive and decision making skills
Plans for future strategic goals on which movements are based
What is the prefrontal cortex connected to?
Basal ganglia and cerebellum
Inputs into supplementary motor areas
What are the signs of cerebellar ataxia?
Hypotonia (weakness)
Dysmetria (inappropriate displacement e.g. overreaching)
Dysdiadochokinesis (inability to make rapid alternating movement)
Decomposition of movement (lack of coordination of different joint movements)
How was cerebellar function found?
Lesion studies of WW1 soldiers
What is the type of synapse between Purkinje cells and deep nuclei?
GABAergic
Concisely define the function of the cerebellum
Construction of movements from appropriately timed, scaled and patterned contractions of specific groups of muscles
Works out the parameters of movement
Describe the organisation of the cerebellum
Superficial molecular layer
Purkinje cell layer
Granular layer
White cell layer (deep nuclei and output)
What are Purkinje cells?
Output of the cerebellar cortex
Dendrites planar
GABA inhibit cerebellar nuclie
What is the largest cerebellar nucleus?
Dentate
Where does the cerebellum project?
Superior cerebellar peduncle
VL thalamus –> basal ganglia, primary motor cortex
VA thalamus –> supplementary motor area
What are the 5 types of cell in the cerebellum?
- Purkinje
- Mossy
- Climbing
- Granule (excitatory)
- Deep nuclear
What is the most numerous cell in the brain?
Granule cells
What is the function of the climbing fibres?
Teach the Purkinje cells which of the parallel fibres carry important information, so cerebellar circuitry could learn which outputs are appropriate to specific inputs
Acts by initiating plasticity
Describe synaptic plasticity in the cerebellum
LTD
Parallel fibre pathways following conjunctive activation of parallel fibres andclimbing fibres
Describe the function of the basal ganglia
Decision making = action selection
Selection of movement patterns and triggering of movements
Define the basal ganglia
Collection of large subcortical forebrain nuclei: largest of these are the putamen and caudate, and globus pallidus
What is the striatum?
Nuclei with stripes of fibres crossing grey matter: putamen, caudate, globus pallidus
What are the 2 midbrain nuclei functionally connected with the basal ganglia nuclei?
Substantia nigra
Subthalamic nucleus
What are the inputs to the basal ganglia?
All lobes of the cerebral corte
What is the main output of the basal ganglia?
Inhibitory to the thalamus –> excitatory to frontal lobes
What are the signs of basal ganglia malfunction?
Excess or paucity of movement
- Hyperkinesia - often of well coordinated movements at inappropriate times
- Dyskinesia - unpredictable movements
- Hypokinesia
What are the types of hyperkinesia?
Chorea (unexpected dancing movement associated with Huntington’s)
Athetosis (writhing movements of hands or face)
Ballismus (flailing ballistic movements)
What are the types of hypokinesia?
- Bradykinesia (slowness associated with Parkinsonism)
2. Rigidity (stiff, fixed position)
What does the terminology pyramidal and extrapyramidal mean?
Pyramidal = stroke Extrapyramidal = basal ganglia disorders. Assumes an alternative descending pathway which is misleading as the main way the basal ganglia affects movements is via motor cortex and pyramidal tract)
What is the direct circuit?
Corticostriate fibres + caudate or putamen - internal globus pallidus - thalamus so + - - stim disinhibition
What is the indirect pathway?
Corticostriate fibres + different caudate or putamen neurons - external globus pallidus - subthalamic nucleus + internal globus pallidus - subthalamic nucleus + internal globus pallidus - thalamus so + – + - net - inhibits movement
What is the physiology of hypokinesia in Parkinsonism?
Loss of dopamine –> imbalances in activity in different pathways as normally dopamine via D1 activates direct pathway, and inhibits via D2 the indirect pathway so loss –> more indirect pathway –> excessive internal globus pallidus activity –> increased inhibition in the thalamus
How do you treat Parkinsonism?
Radical neurosurgery
Controlled lesions of globus pallidus (pallidotomy)
Deep brain stimulation of subthalamic nucleus
L-DOPA, can lead to too much dopamine and hyperkinesia
For the motor circuit
Cortical input and output?
Input: motor, sensory association, output, motor and SMA
For the oculomotor circuit
Cortical input and output?
Prefrontal and visual association
Frontal eye fields
For the association cortex
Cortical input and output?
About cognition
Parietal and temporal association
Prefrontal
For the limbic association cortex
Cortical input and output?
About emotion and motivation
Temporal lobe, cortex and amygdala
Output: cingulate, prefrontal
What are the dorsal and ventral striata?
Dorsal = related to motor function Ventral = related to limbic function
What stops all peripheral stimuli driving saccades?
Superior colliculus tonically inhibited by basal ganglia output (substantia nigra/globus pallidus)
Cerebral cortex can activate appropriate cells in the caudate/putamen to inhibit the output cells, disinhibiting the superior colliculus
BG thus determines whether and when the saccade occurs
What is the normal role of dopamine in the basal ganglia?
Mediates plasticity of the cerebral corticostriate inputs to the caudate and putamen
If an output from the BG is successful, it reinforces the synapses that were active to generate the successful output, so that when those synapses were activated again, the output is generated again
Underlies habit learning
What are the non-motor roles of the basal ganglia?
Nucleus accumbens and ventral striatum project to the prefrontal areas of cortex, which are not usually considered to be overtly motor in function. Concerned with high level executive decisions on strategy, so BG seen to select between strategies or potential behaviours
Also reward processes, DA involved in learning what are good decisions (so can be altered in mental illness)
What are the characteristic signs of patients with prefrontal lesions?
Lack of initiative, poor planning ability and inability to cope in novel situations, poor social skills
Define apraxia. What are the major types?
Motor disorder where there is a difficulty performing purposeful or voluntary movements
4 major types: limb, oral, agraphic, constricutional
Define limb apraxia. What causes it?
Problems with arm, hand and finger movements, but general intent or planning of act intact
Bilateral damage to parietal or premotor cortex
Execution and recognition deficits parietal, execution but not recognition premotor (removal and loss of ability to store action plans)
Define oral apraxia. What causes it?
Problems with programming movements of the tongue, lips and throat to produce sequences of speech
Define agraphic apraxia. What causes it
A particular type of writing deficit
Define constructional apraxia. What causes it?.
Inability to copy mental or visual pictures
Right parietal damage
Define ideomotor apraxia
Represent the inability to perform purposeful movements either to command or on imitation
Discuss the Kimura box test
illustrates impairments in learning new sequences of actions. Have to push top button with index finger, pull the handle and then press down on the bar with your thumb. Can’t
Which areas of the brain when damaged are associated with apraxia?
Posterior parietal cortex and frontal premotor areas and the connections between them
Post parietal –> hand and limb apraxias
Ant premotor –> oral
These two are the ideomotor apraxias
What does the posterior parietal cortex do?
Rostral = integration of somatosensory and proprioceptive information relating the relative position of body segments to their movement
Posterior = integration of visual information about events located in the external environment
Mediates reaching into extra-personal space, mediates between spatial perception and the direction of action
What is the evidence that the posterior parietal cortex mediates reaching into extra-personal space?
- Posterior parietal lesions in monkeys impair sequential reaching movements e.g. removing polo mints from a bent wire
- Recordings of the posterior parietal cortex from single units in monkeys demonstrate the existence of neurons within area 7 that
i. Fire when the monkey detects a visual target, increase firing as an arm is projected towards the target and decrease firing when the target is reached (arm projection neurons)
ii. Fire when the target is manipulated (manipulation neurons)
What are the connections from the posterior parietal cortex?
Reciprocally connected to the lateral and medial premotor areas of the frontal lobes
What is the evidence for the function of the lateral premotor area?
- Ablations of PM in monkeys causes i) deficit in performing hand actions based on, or directed by, external cues
- PET studies reveal greater activity in PM when subjects relying on external cues to determine a sequence of finger movements compared to when they are performing a sequence of finger movements from memory
Explain ‘release of reflexes’
Premotor areas (LPA, SMA) inhibit inappropriate actions, especially inappropriate reflexes. Many reflexes present at birth that become inhibited during development re-appear following damage to premotor areas e.g. suckling, rooting, grasping. Think mechanisms reside in the parietal lobe, normally inhibited by the frontal lobes
What is the function of the inferotemporal area of the posterior cortex?
Feature attention
What is the function of the rhinal cortex of the temporal lobe?
Recognition memory - declarative
What is the function of the hippocampus?
Scene/episodic memory - declarative
What is the function of Wernicke’s area?
Speech comprehension
What is the function of Broca’s area?
Speech production
What is the prefrontal cortex connected to?
- Specialised processing modules in posterior cortex (parietal spatial attention and inferotemporal feature attention)
- Declarative memory in temporal lobes (rhinal cortex recognition memory and hippocampus scene/episodic memory)
- Limbic structures involved in emotional processing amygdala and hypothalamus
- Basal ganglia – higher order control of action
- Language processing in post + ant cortex: Wernicke’s and Broca’s
Describe the Winsconsin Card Sort Test
Deficit in inhibitory control seen following damage to the lateral prefrontal cortex. Failure to inhibit previously relevant rules governing behaviour. If patients learn to sort a pack of cards according to colour, they are then unable to switch to sorting according to a different dimension, i.e. shape. Instead persevere with the previously correct dimension.
Describe behavioural inflexibility
monkeys with prefrontal damage, after learning that one object, out of a pair, is associated with reward, cannot switch their responding to the other object when that object becomes rewarded instead
Describe the evidence about spatial and feature detection in the prefrontal cortex.
subjects required to attend to one of three different perceptual features: colour, form or movement (selective attention conditions) or all three (divided attention). Dorsolateral Prefrontal cortex activated spatial, ventrolateral activated most when attending to visual features.
Which brain areas are used in processing spatial info?
Posterior parietal cortex, dorsolateral prefrontal cortex
Which brain areas are used in processing visual info?
Inferotemporal cortex, ventrolateral prefrontal cortex
How does the ventrolateral prefrontal cortex influence the processing of visual information?
Top down control of selective attention
Enhances processing of relevant information by enhancing activity in the sensory cortex involved in processing that information
How does the dorsolateral prefrontal cortex influence the processing of spatial information?
Enhances activity for divided attention linked to spatial attentional mechanisms
Thought dorsolateral region involved in learning and planning of higher-order strategies to achieve the goal
What is the evidence for the prefrontal cortex’s control of short term memory?
- Delayed response tasks: Lesions of regions of prefrontal cortex impair delayed response tasks that require monkeys to remember spatial, object or proprioceptive information over a brief delay. Sample stage where monkey a) shown peanut hidden in one of two locations (spatial), b) shown one of two objects (object), c) or required to press a lever one or five times (proprioceptive). After a few s, choice stage, where monkeys choose the location/object/do the same response. Lesions of pfc do not affect this choice if there is no delay. Implicates the pfc in short term memory
2, Some neurons in lateral regions of pfc in monkeys have been shown to fire during the delay period of the spatial and object versions of the delayed response task
Which region of the prefrontal cortex is involved in emotion?
Orbital regions of prefrontal cortex
Describe monkeys with orbitofrontal damage
female monkeys normally submissive and solicitative of the advances of a male, when damaged, replaced either by indifference or aggression. Show indifference towards own offspring.
What is the function of the prefrontal cortex?
Executive function - management and regulation of cognitive processes
Seems like the prefrontal cortex inhibits complex behaviours, is involved in attention, is involved in short term memory, and enables emotions to contribute to complex decision making
What are the different ways that you can divide the prefrontal cortex?
- Type of information that they process
2. Type of cognitive operations that they perform
What is needed to select a goal?
- Hold information in mind
- Filter out irrelevant info (determined by what we have learnt in the past)
- Choose an appropriate goal
- Select appropriate responses to fulfil the goal
- Inhibit inappropriate responses
Are the pyramids dorsal or ventral?
Ventral
Which neurons form the corticospinal tract?
Layer V pyramidal neurons of motor cortex
What histologically distinguishes the primary motor cortex from other areas?
- Layer V contains a population of giant pyramidal neurons only round in M1.
- Motor cortex is thickest area of cortex, but contains few small rounded cells (so sometimes called agranular cortex)
Where does the internal capsule run through?
Between basal ganglia nuclei and thalamus
What is the boundary between medulla and spinal cord?
The motor decussation
What is just deep to the peduncles in the upper midbrain?
The substantia nigra and the red nuclei
Describe the vestibulospinal tracts
Descend in the ventral columns
Arise in vestibular nuclei in the dorsal medulla
Exerts actions mainly on extensor limb muscles and proximal muscles
Involved in maintaining posture and equilibrium
Describe the reticulospinal fibres
Originate from reticular formation of pons and medulla
Several groups of neurons give rise to descending fibres, which are fast conducting and project through the length of the spinal cord
Important for posture and coordinated body movement
Describe the rubrospinal tract
From Red nucleus of midbrain
Large nucleus in man but few fibres that descend to spinal cord
Gets input from cerebellar nuclei and motor areas of the cerebral cortex and output mainly to inferior olivary nucleus (–> climbing fibres)
Thought to function in motor skills learning
What are the folds of the cerebellar cortex called?
Folia
What is the fat middle part of the cerebellum called?
Vermis
What is the flocculus?
Small, semi-detatched part of cerebellum
Concerned with vestibular function
In cerebello-pontine angle
What are the tonsils?
Bilateral small parts of cerebellar cortex that overhang the dorsolateral aspect of the medulla
What is the clinical importance of the tonsil?
In patients with raised intracranial pressure, risk of tonsils collapsing into the foramen magnum if CSF is withdrawn by lumbar puncture. Results in pressure on the brainstem and sudden death due to pressure on vital centres for respiratory and autonomic control: coning.
What are the deep cerebellar nuclei?
Dentate nucleus
Nucleus interpositus
Fastigial nucleus
How does the cerebellum output information?
All via deep nuclei
Except flocculus directly to vestibular nuclei in the medulla
Where do each of the cerebellar peduncles come from?
Superior = deep nuclear output --> thalamus Middle = pons Inferior = medulla
Where and what can you see regarding the superior cerebellar peduncle?
Midbrain dorsally
Can see decussation in low midbrain
Then sends some fibres to the red nucleus
Bridge between the two is the roof of the rostral part of IV ventricle
Where do the ventrolateral and ventroanterior thalamic nuclei project to?
VL –> primary motor cortex
VA –> premotor and supplementary motor
What is the projection through the middle cerebellar peduncle? What does it carry?
Pons to contralateral cerebellum as mossy fibres
Infromation from sensory and sensory association areas
What is the projection through the inferior cerebellar peduncle? What do the fibres carry?
Ascending spinocerebellar mossy fibres (juncrossed)
Somatosensory information (e.g. from Clarke’s nucleus, proprioceptors)
Also fibres form inferior olive climbing fibres - mediate learning
Is the representation in the cerebellum ipsi or contralateral?
Ipsilateral
Do parallel fibres and Purkinje cell fibres run along with the folia or perpendicular to them?
Parallel = parallel Purkinje = perpendicular
How do you stain Purkinje cells?
Silver impregnation (the Golgi method) - selects only some neurons and glia
What can cause upper motoneuron signs? What are they?
Strokes, cerebral palsy, multiple sclerosis
Immediate flaccid paralysis, gradually becomes spastic with hyperreflexia, clonus and + Babinski sign, voluntary movement impaired, reflex contraction remains
What can cause lower motoneuron signs? What are they?
Lesions in spinal cord or peripherally, e.g. poliomyelitis. Muscular weakness, flaccid paralysis, muscle wasting, areflexia
When can ventromedial corticospinal pathways reorganise to allow recovery of function after a stroke?
Prenatally or in early neonatal life
What are AVMs?
Arteriovenous malformations
congenital vascular anomalies consisting of direct fistulas artery –> vein iwhtout an intervening capillary bed
Propensity to bleed/haemorrhage
Treat with surgical resection, focused radiotherapy or endovascular embolisation
What are cavernomas?
Thin dilated vascular channels that don’t have a feeding artery and so don’t appear on angiograms
In brain or spinal cord
Some familial
Risk of bleeding lower than AVM but if multiple haemorrhages, then surgical resection
Which corticobulbar fibres provide bilateral innervation to motor nuclei?
V upper VII XII
Where do you find the cingulated motor areas?
buried medially
What is Clarke’s nucleus?
Part of the spinocerebellar tract (up through inferior cerebellar peduncle)
T1-L3/4
Proprioception related
Spinal interneurons in lamina VII
How do you find the caudate nucleus?
Remove the septum pellucidum on a saggital section, can just about see the caudate inside the lateral ventricle
Follows the course of the lateral ventricles (ant horn, body, inf horn)
Tail of caudate into the temporal lobe
Which part of the brain is the basal ganglia in?
Forebrain
What composes the neostriatum?
Caudate and putamen, separated in development by the internal capsule
Where is the putamen?
Lateral to the internal capsule, medial to the insula
What are the two major divisions of the substantia nigra?
Pars compacta = dopaminergic, innervates the neostriatum
Pars reticulate = non-dopaminergic control of eye movements
What is the shape of the caudate?
Large head anteriorly
Where is the globus pallidus?
More posteriorly, medial to the putamen, inferior to the caudate and internal capsule
Where is the thalamus?
More posteriorly, either side of the third ventricle so medial to the internal capsule
What is the counterpart of the corpus callosum more anteriorly? What else can be seen at this level?
Anterior commissure
Hypothalamus
Caudate, putamen, globus pallidus
How do the basal ganglia structures appear anteriorly to posteriorly?
Caudate (getting smaller), putamen (getting bigger then smaller), then globus pallidus, then thalamus. Most posteriorly thalamus large but putamen and globus pallidus is not present. Internal capsule now ventral and tightly bundled and form cerebral peduncles
Where does the caudate input predominantly originate from?
Prefrontal cortex
Where does the putamen input predominantly originate from?
Sensorimotor cortex
Where do fibres from the internal globus pallidus terminate?
VL VA thalamus, medial nucleus of the thalamus
What does the substantia nigra pars compacta look like in fresh and fixed tissue?
Dark pigmented area in midbrain next to the cerebral peduncles
In a cross section through the brain where myelin has been stained it appears as a lighter area
Where is the subthalamic nucleus?
At the junction of the midbrain and diencephalon
Probably unable to find
Where does the medial dorsal nucleus of the thalamus project to?
Prefrontal cortex, involved in complex executive functions
What does the internal capsule carry?
Corticospinal tract
Other cortical output fibres
Thalamocortical input fibres
What is the clinical significance of the genu?
Where MCA haemorrhage or thrombosis commonly affects the internal capsule
What is the clinical significance of the genu?
Where MCA haemorrhage or thrombosis commonly affects the internal capsule
At the genu there are corticospinal fibres to the the head, neck and part of the upper limb
Give two examples of thalamocortical fibres
LGN –> runs around lateral ventricle –> post –> visual cortex as optic radiation
MGN –> auditory radiation
What is the blood supply of the striatum and internal capsule?
Small arteries originating from the middle and anterior cerebral arteries
End-arteries
Termed striate arteries from the MCA
What is the cause of Hungtington’s chorea?
Partly due to death of cells in the neostriatum
What do lesions of the subthalamic nucleus lead to?
Hemiballismus, violent disorder in which flailing limb movements are produced
What is Wilson’s disease?
Copper deposits in the basal ganglia, kidney, liver, and Kayser-Fleischer rings.
Which deep nuclei are targeted in deep brain stimulation?
Subthalamic nucleus, globus pallidus internal, ventral anterior thalamus, pedunculopontine nucleus
What is ETV?
Endoscopic third ventriculostomy
Surgical procedure involving placing an endoscope through the frontal lobe into the lateral ventricle, then through the foramen of Munro into the third ventricle. There make a hole (ventriculostomy) in the floor of the third ventricle to allow CSF to drain from the ventricle into the subarachnoid space, then onwards to be absorbed. Diverts CSF from any blockage downstream of the third ventricle, e.g. from a tumour obstructing the aqueduct, so preventing hydrocephalus
What is stereotaxy?
coordinate based system used to localise brain regions
Discuss prefrontal damage, and tests for it
Executive function. Inability to inhibit behaviours. Emotional lability.
1. Winsconsin Card Sort Test - perseveration, despite not ‘wanting’ to
2. Sentence suppression task - give someone a sentence with the last word missing out. Ask to complete with a logical word, and can. If you ask to finish with an illogical word, really struggle.
3. Stroop - colour words written in different colours. Told to say what the colour it is printed in is.
Attention - anterior cingulate so dorsomedial and lateral
4. Respond to words with an x - start pressing with non targets after a while.
Working memory - tends to be dorsolateral
5. Delayed matching to sample - Monkeys with two choices, one with food, pause, has to hold on line. Prefrontal firing during delay period sustained.
Emotion - medial and orbital prefrontal
6. Iowa gambling task - risky or non risky gambles. Can manipulate so certain behaviours are optimal. People should be able to resist the big gambles. Medial prefrontal damage struggle with this
Planning - prob lateral (combination of attention, behavioural inhibition etc)
7. Tower of London Task - pegs of different lengths, have to reach a target by moving multiple pegs. Subgoals may be out of keeping with ultimate goals.
Which areas are involved in attention?
Prefrontal and right parietal generally
