CNS, Neuromuscular and Musculoskeletal Function Flashcards
What is the function of the cerebellum?
Coordination of planned, voluntary multi-joint movements, balance and muscle tone
Comparator function - detects difference in ‘motor error’ i.e. between intended movement and actual movement. Correction of ongoing movements
Error reduced via projections from cerebellum to upper motor neurones
Motor memory - stores learned movement. Consciousness to unconsciousness, e.g. riding a bicycle, driving a car, professional sportsperson
What is the function of the basal ganglia?
Control of movement - Motor cortex produces commands (excitatory) - basal ganglia exerts inhibitory influence to modulate the initiation and termination of motor commands
Selection and maintenance of voluntary movements
Inhibitory influence on motor systems suppresses inappropriate movements
Modulates movements through complex feedback circuitry
Also involved in non-motor functions, e.g. cognition, working memory, attention
What is the function of both the cerebellum and basal ganglia?
Improve the accuracy of movements by providing feedback loops with motor and sensory areas in cortex
Modify signal of upper motor neurones only - no direct connection to lower motor neurones
What are the effects of damage to the cerebellum?
Disrupts the modulation and coordination of ongoing movements - movements in patients become jerky, imprecise, slow and uncoordinated
Movement errors are always on the same side of the body as the damage to the cerebellum (sensory and motor information are represented ipsilaterally)
What are the effects of damage to the basal ganglia?
Uncontrolled movements at rest, e.g. Parkinson’s, Huntington’s, Hemiballism
Describe the cerebellum.
‘Little brain’
Located in the hindbrain
Dorsal surface is folded - folia (ridges) and divided into lobules, has two hemispheres and lots of lobules
Cerebellum constitutes about one tenth of total volume of brain, but contains approximately 50% of total number of neurones in the CNS (high surface area)
White matter - arbor vitae (interior)
Grey matter - highly convoluted with lots of surface area (exterior)
Deep cerebellar nuclei (deep within)
What are the divisions of the cerebellum?
Based on sources of input
Cerebrocerebullum - Large in humans. Inputs from cerebral cortex. Involved in the regulation of highly skilled movements (complex sequences of movements including speech), two - one on either side (medial)
Spinocerebellum - Direct input from spinal cord. Lateral part involved in movements of distal muscles. Central part (vermis) concerned with movements of proximal muscles
Vestibulocerebellum - |Includes nodules and flocculus. Inputs from vestibular nuclei in brainstem. Involved in movements underlying posture and balance
What are the cerebellar peduncles?
Stalks which attach the cerebellum to the brainstem (pons)
What is the structure of the cerebellar peduncles?
Superior cerebellar peduncle - almost entirely an efferent pathway from cerebellum
Middle cerebellar peduncle - Afferent pathway to the cerebellum via pons (largest)
Inferior cerebellar peduncle - Both afferent and efferent pathways
Main white matter tracts
What are the inputs to the cerebellum?
Motor inputs from cerebral cortex via relay neurones in pons cross over to the opposite cerebellar hemisphere (middle cerebellar peduncle)
Sensory inputs (muscle proprioceptors, vestibular, visual, auditory) on same side convey position and motion information (inferior cerebellar peduncle)
Inferior olive - modulatory inputs - timing, learning, memory
What are the outputs from the cerebellum?
Deep cerebellar nuclei - major output structures
Cerebellar cortex -> deep cerebellar nuclei -> superior cerebellar peduncle -> VL complex (thalamus) -> primary motor and premotor cortex
What are the deep cerebellar nuclei?
Major output structures
Embedded in deep white matter
Relay cortical cerebellar information to motor cortex and brainstem to make corrections in movement
Dentate nucleus, two interposed nuclei, fastigial nucleus (lateral to medial)
What nucleus is each cerebellar division paired with?
Vestibulocerebellum - Fastigial nucleus or direct (vestibular nuclei) (balance and eye movement)
Spinocerebellum - Interposed (+ fastigial) nucleus (motor execution)
Cerebrocerebellum - Dentate nucleus (motor planning)
What are the main cell types of the cerebellar cortex?
Inputs:
- Climbing fibres (from inferior olive)
- Mossy fibres (all other inputs)
Outputs:
- Purkinje fibres
Interneurons:
- Granule
- Stellate
- Golgi
- Basket cells
What are the layers of the cerebellar cortex?
Molecular layer
Purkinje layer (contains purkinje cell bodies)
Granule cell layer
White matter
What is a simplified view of the microcircuitry of the cerebellar cortex?
Mossy fibres (input from cerebral cortex, spinal cord, vestibular system) synapse with granule cell in granule layer Granule cell leads into molecular layer and branches into a parallel fibre which purkinje cell dendrites synapse with Purkinje cell body in purkinje layer and then output down axon through granule layer Climbing fibres surround purkinje cells (input from inferior olive) and synapse
What are climbing fibres?
Carry error signals when movement has failed to meet target/expectations
Make corrections by alternating effectiveness of the parallel inputs to Purkinje cell
Inputs from inferior olive and twist around dendrites of Purkinje cells
Each Purkinje cell receives input from only one inferior olive neurone, BUT input is very strong (generated large depolarisation in Purkinje cell)
What are Purkinje cells?
Purkinje axons synapse onto neurones in deep cerebellar nuclei
Use neurotransmitter GABA (inhibitory)
Although a Purkinje cell receives only one synapse from each passing parallel fibre it does so from ~100000 parallel fibres
What are granule cells?
Receive input from mossy fibres
Numerous, small, tightly packed. Half the total number of neurones in the brain
Outputs branch like a ‘T’ in molecular layer. Each branch is called a parallel fibre
What arteries supply the cerebellum?
Superior portion including deep nuclei - superior cerebellar artery
- Damage would result in postural and gait ataxia, upper limb ataxia and dysarthria
Inferior portion - posterior inferior cerebellar artery
- Damage would result in trunk ataxia, oculomotor problems
What is the outcome of damage to the vestibulocerebellum?
Disturbances of balance and eye movements
What is the outcome of damage to the spinocerebellum?
Impaired gait, e.g. wide-based gait with small shuffling movements (no sensory feedback to produce smooth actions)
What is the outcome of damage to the cerebrocerebellum?
Impairments in highly skilled sequences of learned movements
What is cerebellar ataxia?
Movements become jerky, imprecise and uncoordinated
What is dyssynergia?
Loss (decomposition) of synergistic multi-joint movement. Patient touching nose with finger will first move shoulder joint, then elbow and then wrist - loss of simultaneous movement of all three
What is dysmetria?
Inability to judge distance - end up at the wrong location, e.g. finger shoots past nose or is short of nose
What is dysdiadochokinesia?
Inability to perform rapid, alternating movements
What is intention tremor?
Tremor when trying to move
What is ataxic dysarthria?
Slurred speech
What damage can alcohol do to the cerebellum?
Degeneration of anterior cerebellum after chronic alcohol misuse
Damage specifically affects movement of lower limbs (represented in anterior spinocerebellum)
Wide and staggering gait but little impairment of arm or hand movements
Why can’t you tickle yourself?
When primary motor cortex sends command to move, cerebellum acts as a ‘gate’, alerting somatosensory cortex about planned movement, in order to dampen any sensations that accompany the movement
What makes up the basal ganglia?
Collection of functionally distinct nuclei:
Caudate nucleus
Putamen
Globus pallidus
Can also add:
Substantia nigra
Sub-thalamic nucleus
DOES NOT INCLUDE THE AMYGDALA
What are the input and the output zones of the basal ganglia?
Caudate nucleus + putamen (striatum) = input zone
Globus pallidus + substantia nigra (pars reticulata) = output zone
What are the input and the output zones of the basal ganglia?
Caudate nucleus + putamen (striatum) = input zone
Globus pallidus + substantia nigra (pars reticulata) = output zone
What are the inputs to the basal ganglia?
Corticostriatal pathway - glutamate (excitatory)
Inputs from cerebral cortex to striatum (caudate and putamen)
- From all parts of cortex, but especially frontal lobes (e.g. motor cortex) and parietal lobes (e.g. sensory association areas)
- Functionally organised - different body parts represented in different parts of striatum
Nigrostriatal pathway - dopamine (modulatory)
Inputs from substantia nigra pars compacta to striatum
What are medium spiny neurones?
Neurones in the striatum that receive inputs
What are the outputs of the basal ganglia?
Eye movements
Striatum (caudate and putamen) -> substantia nigra pars reticulata -> superior colliculus
Limb and trunk movements (direct pathway)
Striatum -> globus pallidus internal -> ventral anterior/ventral lateral complex (thalamus) -> motor cortex
What are the pathways of the basal ganglia?
Direct pathway - ‘accelerator’ removes inhibition on thalamus
- D1 receptors in the striatum
- substantia nigra (pars compacta) + dopamine
Indirect pathway - ‘brake’ increases inhibition on thalamus
- D2 receptors in the striatum
- substantia nigra (pars compacta) - dopamine
What is the corticostriatal loop in the direct pathway?
Globus pallidus (internal segment) tonically inhibits thalamus, reducing excitation of motor cortex
Command from cerebral cortex excites striatum
This inhibits globus pallidus (internal segment)
Releases tonic inhibition of thalamus (VA/VL complex)
Allows thalamus to excite motor cortex, initiating movement
Substantia nigra (pars compacta) facilitates the direct pathway via D1 receptors in striatum
What is the corticostriatal loop in the indirect pathway?
Command from cerebral cortex excites striatum
Inhibits external globus pallidus
- Less inhibition on internal globus pallidus - increases tonic inhibition on thalamus
- Less inhibition on sub-thalamic nucleus - increases excitation of sub-thalamic nucleus - increases tonic inhibition on thalamus
Reduces excitation of motor cortex, inhibiting movement
Substantia nigra (pars compacta) inhibits the indirect pathway via D2 receptors in striatum
What is dementia pugilistica?
Brain degeneration caused by multiple concussions (i.e. punched in the head too many times)
What is Parkinson’s?
Hypokinesia disorder - paucity of movement
Epidemiology - ~1 in 500 cases worldwide, peak onset ~60 years old
Cause - Largely idiopathic, but some genetic. Disease is progressive with no cure
Clinical characteristics (TRAP) - Tremor of hands. Rigidity of muscles. Akinesia (absence or poverty of movement). Postural problems.
Neuropathology - Degeneration of neurones in substantia nigra that project to striatum (nigrostriatal pathway). Decrease in dopamine availability. Results in decreased activity of the direct pathway and increased activity of indirect pathway
What is the neuropathology of the substantia nigra in Parkinson’s?
Normal - black substance
Parkinson’s post-mortem - degeneration of pigmented cells (dopamine-utilising neurones) in substantia nigra pars compacta
What is the effect of Parkinson’s on the corticostriatal loops?
Death of cells in the substantia nigra reduces dopaminergic effects on both D1 and D2 receptors
Leads to reduced excitation of the direct pathway (D1)
Also leads to reduced inhibition of the indirect pathway (D2)
Both cause increased inhibition of the thalamus and decrease the effects of motor cortex - reduction of movement
What are the treatments of Parkinson’s disease?
L-DOPA (levodopa)
Precursor of dopamine
Boosts dopamine levels in substantia nigra neurones still alive
But side effects, e.g. drug resistance, involuntary movements (dyskinesia), psychosis
Dopamine agonists
Stimulate postsynaptic dopamine receptors in striatum
But many side effects, e.g. sudden sleepiness
Foetal cell transplants Transplantation of foetal mesencephalic cells (stem cells) into putamen Similar to dopamine replacement therapy Some success Ethics questionable
Deep brain stimulation/surgery
Implanted electrode to inactivate the globus pallidus/STN/thalamus using high frequency stimulation
Remove part of globus pallidus (pallidotomy) or thalamus (thalamotomy)
How may dancing and music help Parkinson’s?
Several studies found that the rhythm of music and dance can help Parkinson’s patients
Enhances audio perception and movement synchronisation
Rhythm in music acts as external cue, replacing internal timing function that is impaired in Parkinson’s disease
Helps compensate for loss of control by the extrapyramidal system
What are some other neuropathologies of the basal ganglia?
Huntingtons
Hemiballismus
What is Huntington’s?
Neuropathology - Genetic disorder (chromosome 4, Huntingtin gene). Loss of output neurones of striatum. Results in cortical motor areas being over-activated
Hyperkinesia disorder - Excessive uncontrollable, jerky movements (chorea)
Treatment - No cure, but drugs can treat symptoms, e.g. tetrabenazine - depletes dopamine
What is hemiballismus?
Rapid, flinging and violent movements of limbs (ballismus) on one side of body (hemi).
Neuropathology - Damage to sub-thalamic nucleus
Treatment - Similar to Huntington’s - deplete dopamine levels
What is the effect of Huntington’s on the corticostriatal loops?
Death of striatal inputs to globus pallidus, external segment (indirect pathway)
Leads to reduced inhibition of sub-thalamic nucleus
Leads to reduced excitation of globus pallidus, internal segment
Leads to less tonic inhibition of thalamus
Causes greater excitation of motor cortex - increase of movement