Movement: Cortex, cerebellum, Basal ganglia

Question 1

what is motor equivalence?

Answer 1

A property of the motor system where same motor tasks can be performed in various ways depending on the context.

Question 2

How are voluntary movements executed?

Answer 2

by the output of motor commands which specify the correct temporal sequence of muscle activation. The planning of voluntary movements and the elaboration of motor commands for their execution is done by the motor cortex which has its outputs via the lateral motor pathways.

Question 3

What is used to fine-tune a movement’s execution so that the performance matches the desired goal?

Answer 3

Sensory feedback during a movement, for example from proprioceptors such as muscle spindles and the visual system

Question 4

There are two lateral pathways for descending control of voluntary movement. Where do they originate from?

Answer 4

Both originate in the motor cortex which lies on the frontal lobe just anterior to the central sulcus.

Question 5

What does the corticospinal tract consist of?

Answer 5

The corticospinal tract consists of the axons of about one million pyramidal cells in layer V of the cortex. Over half come from the primary motor cortex (M1, Brodmann area 4) or secondary motor area (MII, Brodmann area 6). About 40% of cortico- spinal tract axons come from the somatosensory cortex (Brodmann areas 1, 2, and 3) or other regions of parietal cortex (Brodmann areas 5 and 7)

Question 6

Where does the corticospinal tract project to?

Answer 6

These axons project to the ventral horns of the spinal cord to alter the activity of a and g motor neurons. Axons from the parietal cortex terminate in the dorsal horns of the spinal cord and regulate sensory input.

Question 7

What are the properties of the axons/ cells in the corticospinal tract?

Answer 7

It consists of fine myelinated and unmyelinated axons with conduction velocities between 1 and 25 ms-1. However, there are about 30 000 extremely large (20–80 μm diameter) pyramidal cells in area 4, called Betz cells, with big myelinated axons that conduct with velocities of 60–120 ms-1.

Question 8

What is the path that axons of the corticospinal tract take to the brainstem?

Answer 8

They pack tightly to pass through the internal capsule which lies between the thalamus and the lentiform nucleus and descend into the brainstem.

Question 9

What happens to most of the medial fibers of the corticospinal tract in the brainstem?

Answer 9

most medial fibers peel off and cross the midline to go to nuclei (trigeminal (V), facial (VII), hypoglossal (XII), and accessory (XI)) of the cranial nerves. These are corticonuclear (corticobulbar) fibers and are motor to the face, tongue, pharynx, larynx, and sternomastoid and trapezius muscles.

Question 10

Why is the corticospinal tract also called the pyramidal tract?

Answer 10

The fibers that do not peel off in the brainstem descend through the medulla causing a swelling on its ventral surface, the pyramid.

Question 11

What happens to the corticospinal tract at the caudal medulla?

Answer 11

85% of fibers cross the midline as the pyramidal decussation, giving rise to the lateral corticospinal tract. The remaining ipsilateral axons form the anterior corticospinal tract, which crosses over at spinal cord level.

Question 12

What neurotransmitter does corticospinal neurons use?

Answer 12

Glutamate and they are excitatory.

Question 13

Where do corticospinal tracts synapse?

Answer 13

They either synapse directly with a motor neurons supplying distal limb muscles in Rexed lamina IX, or synapse with interneurons in laminae VII and VIII which make polysynaptic connections with a motor neurons of proximal limb muscles and axial muscles.

Question 14

Why must Fusimotor (g-efferent) neurons be coactivated with a motor neurons ? How are they excited?

Answer 14

to override the stretch reflex during voluntary movement - they are excited polysynaptically.

Question 15

How does the corticospinal tracts effects on extensors vs flexors differ?

Answer 15

Stimulation of the corticospinal tract is predominantly excitatory to flexors but inhibitory to extensors. The corticospinal tract inhibits motor neurons disynaptically via Ia inhibitory interneurons.

Question 16

Where do the corticospinal tract axons arising from the somatosensory cortex project to and what is their effect?

Answer 16

cranial nerve sensory nuclei and dorsal horns and produce presynaptic inhibition on primary afferent terminals except for 1a spindle afferents.

Question 17

Other than the corticospinal tract where do the pyramidal cells in layer V of the cortex send their axons to?

Answer 17

They send their axons in the corticorubral tract to the red nucleus in the midbrain, which also receives collaterals from the corticospinal tract.

Question 18

What does the red nucleus give rise to?

Answer 18

the rubrospinal tract, the second of the lateral motor pathways.

Question 19

Where do the axons of the rubrospinal tract go to?

Answer 19

Some of its axons go to cranial nerve nuclei in the pons and medulla. In
humans the rubrospinal axons descend as part of the corticospinal tract.

Question 20

What three areas is the motor cortex divided into?

Answer 20

MI, MII, which contains the supplementary motor area (SMA), and premotor area (PM). These are reciprocally connected with each other

Question 21

Where are all the three areas of the motor cortex connected to?

Answer 21

They are connected with subcortical structures which send inputs back to the
motor cortex via the thalamus forming closed motor loops. Reciprocal back projections from the motor cortex to the thalamus also exist

Question 22

The supplementary motor area is part of a motor loop with which structures?

Answer 22

with the basal ganglia. It sends output to the striatum which projects back to the SMA via the globus pallidus and ventrolateral (VLO) thalamus

Question 23

In which brainstem structure does many corticospinal tract axons from M1 either terminate or give off collaterals?

Answer 23

The pons. These make synapses with pontine neurons which project to the cerebellum.

Question 24

Outputs from the cerebellum to the thalamus project back to where to form other motor loops?

Answer 24

M1 and PM motor areas

Question 25

Which motor loops are required for the initiation of specific motor patterns
and their coordination?

Answer 25

The ones with the basal ganglia and the cerebellum.

Question 26

Several somatotopic maps exist in the motor cortex, but are distorted. Where is the most cortical space devoted to?

Answer 26

the face, tongue, and hands than other regions, allowing great variety and precision of
movements.

Question 27

M1 neurons are wired to be responsive to the sensory
consequences of their actions, how is this possible?

Answer 27

M1 receives a substantial input from the somatosensory cortex and many M1 neurons have sensory receptive fields. These are located where activity of the neuron
is likely to cause movement.

Question 28

How do we know that the somatotopic mapping of the motor cortex is not one-to-one mapping to individual muscles or movements?

Answer 28

● Output from single cortical neurons diverging to several motor neuron pools
● Converging outputs from quite a wide area of M1 onto the motor neuron pools for
muscles moving a specific body part
● A given muscle being subserved by a region in the motor cortex which overlaps with regions controlling neighboring muscles

Question 29

During execution of a movement, what does the set of neurons activated in the region depend on?

Answer 29

the nature of the movement; for example, its direction and force.

Question 30

How do we know that M1 cells do not exclusively encode a single movement parameter?

Answer 30

that M1 cell firing can correlate with force, rate of change of force, velocity, acceleration, direction of movement, or joint position. None of these parameters is mapped in an orderly way in the cortex. Firing of an M1 cell during a task is usually related to two or three of these variables.

Question 31

How is the direction of movement encoded?

Answer 31

It is very precisely coded by the average firing of a few hundred cells. This is an example of population coding. The population of cells encoding the direction
of a given movement are quite widely distributed across the cortex.

Question 32

The secondary motor cortex contains neurons that fire in a way that correlates with which variables of movement?

Answer 32

Direction and force of movement

Question 33

How does the SMA control the proximal limb muscles?

Answer 33

directly via its output to the corticospinal tract

Question 34

How do the premotor area neurons control axial and proximal limb muscles?

Answer 34

They synapse with
brainstem reticular neurons that go to axial and proximal limb muscles.

Question 35

How does the SMA and premotor area neurons control distal limb muscles?

Answer 35

via M1

Question 36

What is the crucial function of the SMA and which motor loop does it use to achieve this?

Answer 36

The SMA has bilateral representations of the body and is crucial for movements involving both sides of the body, particularly those that have been learnt. For this, the motor loop involving the basal ganglia is important.

Question 37

What is the premotor area implicated in? How does it achieve this?

Answer 37

implicated in movements in response to sensory (mostly visual) cues. The premotor area gets a large input from the posterior parietal cortex (Brodmann areas 5 and 7) association cortex which receives visual, somatosensory, and vestibular sensory input.

Question 38

The posterior parietal cortex provides sensory input for targeted movements. Some posterior parietal neurons are context specific, what does this mean?

Answer 38

They fire only during goal-directed behavior (e.g., reaching for food) but remain silent if the limb moves in the same way in the absence of the goal.

Question 39

What proves that a key role in the secondary motor cortex is in planning movements?

Answer 39

firstly, by the fact that neurons here fire a long time (possibly up to 800 ms) before a voluntary movement begins. Secondly, a simple movement involves increased cbf in MI only, a more complex task is accompanied by increased cbf in secondary motorvcortex as well; but mentally rehearsing a complex task results in an increase in cbf was seen restricted to the secondary motor cortex.

Question 40

What are the similarities between the red nucleus and the corticospinal tract neurons?

Answer 40

The red nucleus has a somatotopic map. Its activity precedes intentional movements and correlates with parameters such as force, velocity, and direction. rubrospinal axons have the same distribution to proximal and distal limb motor neurons as the corticospinal tract and their activity moves individual digits.

Question 41

What type of movements is the rubrospinal tract involved in?

Answer 41

gross limb movements, but not fine ones

Question 42

What is the difference between the rubrospinal and corticospinal tracts?

Answer 42

While the rubrospinal tract is active when previously learnt automated movements are executed, the corticospinal tract is required when novel movements are being learnt.

Question 43

What does the pathway that acts to switch activity between the two motor systems involve?

Answer 43

the inferior olive, one function of which is to detect and correct errors in motor performance.

Question 44

How does each lateral motor system compensate for the loss of the other?

Answer 44

As a new movement is successfully learnt its execution is switched from the corticospinal tract to rubrospinal tract control. The switch operates in the opposite direction if an automatic movement needs to be adapted.

Question 45

Why do corticospinal tract lesions have a more severe and protracted effect than rubrospinal tract lesions?

Answer 45

new movements cannot be executed and only the old rubrospinal tract repertoire can be called upon.

Question 46

transection of the corticospinal tract below the pyramidal decussation causes what?

Answer 46

an ipsilateral motor deficit below the level of the section.

Question 47

Transection of the corticospinal tract above the pyramidal causes what?

Answer 47

a contralateral deficit.

Question 48

What is the deficit seen with a pure corticospinal lesion?

Answer 48

loss of the ability to make fine movements with distal muscles. Almost complete recovery is eventually seen

Question 49

Is recovery seen if both lateral motor pathways are cut?

Answer 49

No, results in permanent deficits.

Question 50

What does transection of the vestibulospinal and reticulospinal tracts which control output to proximal limb and axial muscles produce?

Answer 50

much more extensive
deficits in posture and walking, but leaves fine control of distal muscles intact.

Question 51

What is the classic pattern of motor and sensory deficits seen when spinal cord is severed on one side (Brown–Sequard syndrome)?

Answer 51

On the side of the lesion there is a motor paralysis and loss of all sensation transmitted through the dorsal columns (touch and
proprioception). On the contralateral side there is loss of nociceptor and thermoreceptor sensation from a few spinal segments below the lesion. This is due to the interruption of the anterolateral columns which contain spinothalamic axons

Question 52

Which patients show an increase in extensor tone called decerebrate rigidity?

Answer 52

Patients in whom brain trauma or a tumor produces functional disconnection of the brainstem from the rest of the brain at the level between the red nucleus and the vestibular nuclei

Question 53

what is the mechanism of decerebrate rigidity?

Answer 53

It is caused by tonic activity in the vestibulospinal and reticulospinal neurons that is no longer opposed by the powerful facilitation of flexor motor neurons by the rubrospinal tract. The overall effect of the vestibulospinal activity is the activation of extensors. Reticulospinal inhibition and excitation of extensor motor neurons tend to cancel, but reticulospinal inhibition of interneurons mediating flexor reflexes results in net extensor activity. The high firing rates of both a and g motor neurons facilitated by vestibulospinal and reticulospinal inputs requires on-going sensory input from muscle spindles.

Question 54

Where do lower motor neuron lesions occur?

Answer 54

brainstem and spinal cord neurons innervating skeletal muscle

Question 55

Where do upper motor neuron lesions occur?

Answer 55

refers not only to the corticospinal and corticobulbar neurons of the
pyramidal tract, but also to cortical cells that drive reticulospinal (medial pathway) neurons. (Strokes are the most common cause)

Question 56

What is the commonest cerebrovascular accident (CVA, stroke)?

Answer 56

caused by a thromboembolism affecting the branch of the middle cerebral artery that supplies the internal capsule.

Question 57

Why doesnt Infarction of the internal capsule produce a syndrome which resembles experimental lesions of the lateral motor pathways?

Answer 57

because the internal capsule also contains corticoreticular axons which drive lateral and medial reticulospinal tracts.

Question 58

After an initial period of flaccid paralysis and lack of reflexes on the side opposite the lesion, what are the two major deficits seen after infarction of the internal capsule?

Answer 58

hemiparesis and spasticity

Question 59

What is the usual pattern of hemiparesis?

Answer 59

Muscle weakness on one side that is greatest in arm extensors and leg flexors, because arm flexors are stronger than extensors and in the legs the reverse is true. If the corticobulbar fibers are affected, voluntary facial movements are compromised.

Question 60

What is hemiplegia?

Answer 60

When the weakness of hemiparesis is so severe that paralysis results

Question 61

Why does the muscle weakness occur in a hemiparesis?

Answer 61

because the loss of descending excitation means fewer motor units are recruited.

Question 62

What is spasticity?

Answer 62

An increase in muscle tone is seen in the stronger (antigravity) limb muscles.

Question 63

What is spasticity caused by?

Answer 63

by enhanced excitability of the stretch reflex, particularly the phasic component, since attempts at rapid muscle stretch are met with much greater resistance than slow stretch. Forceful attempts to stretch a muscle are met with great resistance (caused by the stretch reflex), which fails suddenly (the clasp knife response) due to firing of high threshold muscle (non-spindle) afferents.

Question 64

Spasticity in part results from the loss of presynaptic inhibition on Ia terminals. How is this presynaptic inhibition normally brought about?

Answer 64

It is inhibition is brought about by the action of the reticulospinal tracts on GABA-ergic Ia presynaptic inhibitory interneurons. GABA released from these interneurons acts on GABAB and GABAA receptors on the Ia terminals. GABAB receptors are metabotropic
receptors and when stimulated act via G proteins to increase the K+ conductance. The resulting hyperpolarization reduces Ca2+ influx into the primary afferent terminal, so
curtailing the release of glutamate onto the motor neurons.

Question 65

What happens to the presynaptic inhibition of 1a afferents in spastcity?

Answer 65

this descending
reticulospinal input is lost. This leads to failure of presynaptic inhibition and so
hyperexcitability of the stretch reflex.

Question 66

Which medications can be used to treat spasticity?

Answer 66

Baclofen is an agonist at GABAB receptors and is used orally and intrathecally. Benzodiazepines (e.g., diazepam) are agonists at the GABAA receptors involved in presynaptic inhibition.

Question 67

What are the three lobes of the cerebellum?

Answer 67

the anterior lobe and posterior lobe, separated by the primary fissure, and
the flocculonodular lobe, separated from the posterior lobe by the posterolateral fissure

Question 68

What are the longitudinal sections of the cerebellum?

Answer 68

a central vermis and
two lateral hemispheres.

Question 69

What are the cerebellum lobes further divided into?

Answer 69

lobules

Question 70

What lies over the surface of the cerebellum?

Answer 70

the cerebellar cortex which is folded into coronal
strips called folia (singular; folium).

Question 71

What provides the output of the cerebellum?

Answer 71

deep (intracerebellar) nuclei contained in the cerebellum’s internal core of white matter and vestibular nuclei

Question 72

What do the afferent and efferent connections of the cerebellum go via?

Answer 72

three pairs of cerebellar peduncles.

Question 73

What is the input to the cerebellum?

Answer 73

● Skin, proprioceptor, and vestibular input from brainstem and spinal cord
● Cognitive, motor, and sensory signals from the cerebral cortex via pontine nuclei in thehuge corticopontinecerebellar tract
● Motor information from the inferior olivary nucleus

Question 74

Where does output from the cerebellum go?

Answer 74

● The ventrobasal thalamus which projects to the motor cortex, to modify corticospinal tract outflow
● The red nucleus, to modify the rubrospinal tract output
● Vestibular and reticular nuclei to modulate the activity of medial motor pathways

Question 75

What is used by the cerebellum to guide motor performance?

Answer 75

Proprioceptor information coming from muscle spindles, Golgi tendon organs, and receptors in joints which provides for conscious awareness of body position and movement.

Question 76

What is the origin of the
cuneocerebellar tract that supplies upper body proprioceptor input to the cerebellum?`

Answer 76

accessory cuneate (external arcuate) nucleus, receives axon collaterals from the dorsal columns. Proprioceptor input from
the neck, arms, and upper trunk is relayed in the dorsal columns to the cuneate nucleus, from where it follows exactly the same path as touch sensation from the same areas.

Question 77

What is the proprioceptor pathway which serves the lower trunk and legs?

Answer 77

Proprioceptor affer-
ents from the lower body enter the nucleus dorsalis (Clark’s column), located in lamina VII between spinal segments C8 to L3. Axons of Clarke’s column neurons ascend on the same side as the dorsal spinocerebellar tract (DST) to the cerebellum.

Question 78

What provides the input for conscious lower body proprioception?

Answer 78

Collaterals of the DST synapse with neurons in nucleus Z which project to the medial lemniscus

Question 79

Where does the ventral spinocerebellar tract arise from and what does it arise from ?

Answer 79

from the ventral horn and transmits signals reflecting the current state of spinal cord central pattern generators involved in
locomotion.

Question 80

What lobe does the functional subdivision of the vestibulocerebellum correspond to?

Answer 80

Flocculonodular lobe

Question 81

what constitutes the spinocerebellum?

Answer 81

The anterior and posterior lobes are organized into three parallel sagittal zones in humans. The medial zone occupies the vermis, Together the medial and intermediate zones constitute the spinocerebellum.

Question 82

What is the output of the medial and intermediate zones of the cerebellum?

Answer 82

The medial zone sends its output to the fastigial nucleus. The intermediate zone projects to the interpositus nucleus (separate emboliform and globose nuclei in humans).

Question 83

What does the cerebrocerebellum correspond to?

Answer 83

The lateral zone of the posterior lobe

Question 84

Where does the cerebrocerebellum send its output to?

Answer 84

Dentate nucleus

Question 85

what is the input and output of the vestibulocerebellum?

Answer 85

input from the ipsilateral vestibular labyrinth via the vestibulocochlear (VIII) nerve, and projects directly to the vestibular nuclei.

Question 86

What is the function of the vestibulocerebellum?

Answer 86

its connections bring about postural adjustments via the lateral and medial vestibulospinal tracts.

Question 87

What do lesions of the vestibulocerebellum cause?

Answer 87

swaying and truncal ataxia (staggering gait). If the lesion is unilateral the head is tilted to the side of the injury and nystagmus is seen.

Question 88

What are the connections of the medial zone of the spinocerebellum?

Answer 88

It receives sensory input from vestibular, proprioceptor, and cutaneous somatosensory input from the trunk, together with visual and auditory input. The output
goes by way of the fastigial nucleus to the vestibular nuclei.

Question 89

What is the function of the medial zone of the spinocerebellum?

Answer 89

It controls postural adjustments in response to sensory input by signaling to axial muscles via the medial motor systems. In primates, inactivation of the fastigial nucleus causes animals to fall towards the side of the lesion.

Question 90

What is the input to the intermediate zone of the spinocerebellum ?

Answer 90

the cuneocerebellar and dorsal spinocerebellar tracts and from the ventral spinocerebellar tract which imparts information about the activity of spinal motor circuits. In addition, it receives inputs from the somatosensory and motor
cortex via axon collaterals of the corticospinal tract that synapse with nuclei in the pons.

Question 91

The corticopontinecerebel-
lar pathway, containing 20 million axons, is one of the largest tracts in the CNS, What is this pathway?

Answer 91

pontine nuclei give rise to fibers that cross the midline to enter the contralateral
cerebellar cortex by way of the middle cerebellar peduncle. It goes to the intermediate zone of the spinocerebellum and the cerebrocerebellum.

Question 92

What is the output of the intermediate zone of the spinocerebellum?

Answer 92

via the interpositus nucleus which projects to the ventrolateral thalamus and the red nucleus. By this route the spinocerebellum controls the lateral motor pathways to the limbs.

Question 93

What is an intention tremor and what is it caused by?

Answer 93

a large amplitude tremor of the limbs when one attempts to reach for an object resulting from inactivation of the interpositus nuclei

Question 94

Where does the cerebrocerebellum get its input from?

Answer 94

frontal, parietal, and occipital cerebral cortex relaying sensory, motor, and visual information by way of the corticopontinecerebellar tract. it also gets input from prefrontal cortex concerned with cognitive not motor functions.

Question 95

What is the output of the cerebrocerebellum?

Answer 95

outflow via the dentate nucleus goes to the ventrolateral thalamus which in turn projects to frontal cortex motor and prefrontal
areas. the dentate nucleus has reciprocal connections with the red nucleus.

Question 96

What do lesions of the cerebrocerebellar cortex or dentate nucleus cause?

Answer 96

slight delays and modest overshooting of movements involving single joints (dysmetria). However, for multijointed movements the deficits are much more severe, so patients have difficulty using their fingers-dysdiachokinesia. Cognitive, including language, deficits
are also seen

Question 97

What is the basic circuitry of the cerebellum?

Answer 97

The cerebellar cortex has three layers and contains five cell types that are organized into a simple circuit repeated millions of times

Question 98

Which cell type is the major input to the cerebellum?

Answer 98

mossy fibers (mf), axons of second-order neurons from the spinal cord and brainstem conveying proprioceptor input, or the pontinecerebellar relay from the cerebral cortex conveying sensory and motor signals. These are glutamatergic and excitatory.

Question 99

Where do mossy fibers terminate?

Answer 99

in a discrete patch of cortex. after giving off an axon collateral which goes to the appropriate deep cerebellar (or vestibular) nucleus, they synapse with granule cells in synaptic complexes called glomeruli

Question 100

What does a cerebellar glomerulus consist of ?

Answer 100

Each glomerulus consists of the swollen terminal of a single mossy fiber which forms 15–20 synapses with the surrounding dendrites of four to five granule cells. Mossy fibers branch, so each one can excite about 30 granule cells. Every granule cell is contacted by five to eight mossy fibers. Glomeruli also contain axodendritic synapses between Golgi cells and granule cells.

Question 101

Granule cells in the granule cell layer are small (5–8 μm diameter) and one of the most numerous neurons types in the brain. Where do they ascend to?

Answer 101

They ascend to the most superficial layer of the cerebellar cortex, the molecular layer, where they bifurcate into parallel fibers that in primates extend for 6 mm or so in each direction along the long axis of a folium.

Question 102

What do parallel fibers synapse with?

Answer 102

They intersect with the perpendicularly oriented planar dendritic trees of Purkinje neurons. Because of this arrangement every parallel fiber excites a longitudinal beam of 2000–3000 Purkinje cells, making just a single synapse with each one. Every Purkinje cell is contacted by about 200000 parallel fibers.

Question 103

What is the background firing rate of mossy fibers and the granule cells that are driven by them?

Answer 103

They have high background firing rates (50–100 Hz) that is changed by sensory input and during movements.

Question 104

What is the effect of parallel fiber activity?

Answer 104

It is to cause the Purkinje cell to fire simple spikes repetitively. Purkinje cells fire at back- ground rates between 20 and 50 Hz and even weak mossy fiber input produces increased Purkinje cell firing. Moreover, since Purkinje cells can fire in excess of 400 Hz they can follow a wide range in firing of mossy fiber inputs.

Question 105

Where is the second input to the cerebellum, climbing fibers, from?

Answer 105

come exclusively from the inferior olivary nucleus (ION) via the olivocerebellar tract.

Question 106

Where do climbing fibers synapse?

Answer 106

Each climbing fiber (about 15 million) establishes contact with around 10 Purkinje cells;
each Purkinje cell getting input from just one climbing fiber that winds its way round the soma and dendrites making about 300 powerful glutamatergic, excitatory synapses.

Question 106

Where do climbing fibers synapse?

Answer 106

Each climbing fiber (about 15 million) establishes contact with around 10 Purkinje cells;
each Purkinje cell getting input from just one climbing fiber that winds its way round the soma and dendrites making about 300 powerful glutamatergic, excitatory synapses.

Question 107

How do climbing fibers fire?

Answer 107

with a frequency of 1–10 Hz, each time causing the Purkinje cell to discharge a complex spike

Question 108

other than climbing and mossy fibers, what is the third diffuse set of input?

Answer 108

from monoaminergic cells in the brainstem. They establish sparse connections with deep cerebellar nuclei and cortex to produce modulating effects.

Question 109

Via which cells is the sole output of the cerebellar cortex?

Answer 109

Purkinje cells, which have their large cell bodies (50 μm diameter) in the Purkinje cell layer of the cortex.

Question 110

What is the structure/ pathway of the purkinje cell dendrites?

Answer 110

Their extensive dendrites
are aligned into a flat plane and are all oriented in the same direction, at right angles to the long axis of the folium in which they are located.

Question 111

What is the pathway of the axons of the purkinje cells?

Answer 111

They cells go to the deep cerebellar nuclei. Purkinje cells use GABA as a neurotransmitter so the entire output of the cerebellar cortex is inhibitory.

Question 112

What are the three types of GABAergic inhibitory interneuron in the cerebellar cortex?

Answer 112

Basket, stellate and golgi cells.

Question 113

What is the input and output of Basket cells and stellate cells in the molecular layer of the cerebellum?

Answer 113

receive input from parallel fibers and send axons
at right angles to them to synapse with proximal or distal dendrites, respectively, of neighboring Purkinje cells.

Question 114

What is the surround antagonism that produces spatial focusing of cerebellar cortex output?

Answer 114

Activation of a mossy fiber excites a cluster of granule cells and hence stimulates linear arrays of on-beam Purkinje cells via the parallel fibers. However, the basket and stellate cells inhibit surrounding off-beam Purkinje cells.

Question 115

How Golgi cells bring about temporal focusing so that the net effect of mossy fiber input is brief firing of Purkinje cells?

Answer 115

Golgi cells get input from parallel fibers and synapse with granule cells to produce feedback inhibition.

Question 116

What is the overall function of the inhibitory interneurons in the cerebellum?

Answer 116

constrain Purkinje cell output both in space and time.

Question 117

The cerebellar cortex has several maps which exhibit fractured somatotopy and encode visual and auditory input from the tectum and somatosensory input. What are the three maps in register that make up these representations?

Answer 117

One is formed by mossy fiber input, a second is corticopontine input
and the third is an output map that preserves a
somatotopic projection of movements.

Question 118

the cerebrocerebellum can initiate movements,
particularly in response to visual and auditory stimulation, what is the order of activation of these movements?

Answer 118

dentate nucleus–motor cortex–interpositus nucleus–
muscle.

Question 119

What are the major functions of the cerebellum?

Answer 119

coordinates precise timing of movements initiated from the motor cortex, can initiate movements itself, and learn new motor tasks. The cerebellum is important for complicated multijoint movements.

Question 120

What anatomical configuration supports the findings that the cerebellum is important for multijoint movements?

Answer 120

parallel fibers average 6 mm in length and so affect a comparable length array of Purkinje cells (PCs) that lie across the cerebellum. This is sufficiently long to span an entire deep cerebellar nucleus or bridge adjacent nuclei. PC arrays coupling both fastigial nuclei, for example, would ensure coordination of postural muscles across the midline, which is important in gait. The PC arrays influenced by a given set of parallel fibers span muscles over several joints.

Question 121

What are the two modes that the cerebellum operates in?

Answer 121

feedback or feedforward

Question 122

During the execution of well-rehearsed movements that are not too fast, how does the cerebellum act as a feedback device?

Answer 122

compares motor intentions with motor performance, and
works to reduce any mismatch between them.

Question 123

What connections with the spinocerebellum enable it to operate in feedback mode?

Answer 123

the motor intentions are the signals relayed by the corticopontinecerebellar tract. Motor performance is
monitored by proprioceptor (and other sensory) input, and by the ventral spinocerebellar signals reporting on the activity of spinal cord and brainstem motor circuits.

Question 124

How does the cerebrocerebellum produce error signals that reflect a discrepancy between motor
planning and motor commands?

Answer 124

compares inputs from the supplementary motor cortex and the primary motor cortex to produce error signals that reflect this discrepancy

Question 125

What part of the cerebellum is involved in correcting errors in limb movements such as when a limb is perturbed by unexpected force, what is the order in which various neural elements fire?

Answer 125

intermediate spinocerebellum. muscle afferents–interpositus nucleus–motor
cortex–dentate nucleus.

Question 126

An error means that the actual position of a limb is not the intended one. What does this produce?

Answer 126

This produces unpredicted muscle stretch because the appropriate coactivation of a and g efferents to the muscle spindle has not happened. Precisely the same thing happens if an unexpected force is applied to a limb.
In either case the muscle stretch will excite Ia and Ib afferents in the loaded muscles.

Question 127

What is the pathway of the error signal?

Answer 127

These proprioceptor signals are relayed to the cerebellum by mossy fibers. The stimu-
lated mossy fibers deliver tonic excitation to the intracerebellar (interpositus) nucleus via axon collaterals and stimulate a group of granule cells. The granule cell parallel fibers activate several arrays of on-beam Purkinje cells which strongly inhibit their target neurons in the interpositus nucleus.

Question 128

Normally, when mossy fibers are firing at background rates, what is the effect on the interpositus nucleus?

Answer 128

their tonic facilitation of the interpositus dominates the inhibition by Purkinje cells. Consequently, interpositus neurons maintain excitation of the red nucleus and the ventrolateral thalamus.

Question 129

what is the mechanism of the pattern of activation
of the deep cerebellar interpositus nucleus being a negative image of the input activation?

Answer 129

When the mossy fibers are activated during a movement Purkinje cell inhibition disfacilitates the interpositus neurons and this inhibition is transmitted downstream to the red nucleus and thalamus. In contrast, neighboring off-beam PC arrays, inhibited by the GABAergic interneurons in the cortex allow their interpositus cells to fire at higher than background rates.

Question 130

The overall effect of feedback error correction is to correct the movement error by activating spinal reflexes that defend the correct limb position and
dampen those that do not. How is this done?

Answer 130

Mediated by the rubrospinal and corticospinal tracts, this is probably done by adjusting the firing of g efferents to
muscle spindles.

Question 131

How is the action of purkinje cells different for the reciprocal vs co contraction of agonist/ antagonist muscles?

Answer 131

During reciprocal activation of agonist and antagonist muscles, Purkinje cells responsible for controlling these muscles fire alternately, driving interpositus neurons to do the same. During co-contraction, however, the Purkinje cells are silent.

Question 132

What is the action tremor following lesions to the interpositus nucleus or intermediate cerebellar cortex due to?

Answer 132

derangement in the timing of agonist contraction.

Question 133

What is the normal sequence of muscle action during a rapid wrist movement?

Answer 133

involves an initial burst of activity in the agonist, followed by a burst in the antagonist to produce braking, and finally a second agonist burst to stabilize the joint at the desired
end point

Question 134

What sets up the cerebellar tremor in terms of antagonist and agonist movement?

Answer 134

the start of the movement is normal but the second agonist burst is late. Consequently the antagonist burst moves the wrist beyond the end point.

Question 135

For what movements is the feedforward operation mode required?

Answer 135

For the execution of well-practiced, very rapid (ballistic) movements (insufficient time for feedback correction errors

Question 136

What is feedforward operation mode?

Answer 136

it runs a program that predicts the motor consequences of its own action. Unexpected perturbations that occur when the cerebellum is in this mode cannot be corrected for in time and so performance will be degraded.

Question 137

What is motor learning? (probably important in acquiring skill in all voluntary motor tasks, including learning to walk)

Answer 137

Process by which the predictions inherent to feedforward operation must be learnt during numerous trials attempting to perform the task.

Question 138

In the cerebellar feedback-error-learning model) the cerebellum acquires a program called an inverse model of the motor task, what is this?

Answer 138

the transformation from the desired trajectory to the motor commands needed to bring about the movement. In this model movement errors are initially represented as sensory errors

Question 139

In the inverse model programme, how does the cerebellum receive the sensory errors?

Answer 139

Sensory errors are converted into a neural firing pattern that specifies errors in motor performance, an operation of the inferior olivary nucleus (inferior olive). The inferior olive sends these motor error signals to the cerebellum via the olivocerebellar tract climbing fibers

Question 140

In the inverse model, what is the effect of error signals carried by climbing fibers?

Answer 140

causes concurrent mossy fiber input to become less effective in activating Purkinje cells. Whenever the same pattern of mossy fiber input occurs subsequently, the Purkinje cells fire fewer simple spikes and cause less inhibition on downstream motor pathways. This corrects the motor output. The cellular mechanism that alters the responsiveness of the Purkinje cells is long term depression.

Question 141

What is the classical role of the basal ganglia?

Answer 141

selecting appropriate learned motor sequences during voluntary movement, and in stimulus–reward learning to form novel motor strategies.

Question 142

Where are most inputs to the basal ganglia from and where do they enter?

Answer 142

from the cerebral cortex and enter the striatum

Question 143

What is the output of the basal ganglia?

Answer 143

emerges from the pars interna (internal part) of the globus pallidus, and the substantia nigra pars reticulata, to go to the thalamus. The thalamus projects back to the cortex thus closing a loop. The thalamocortical axons return to the same region of cortex which gave rise to the striatal inputs.

Question 144

What makes up the the dorsal striatum (neostriatum)?

Answer 144

caudate nucleus and putamen (functionally a single unit) but are split anatomically by the internal capsule.

Question 145

What system is ventral striatum (nucleus accumbens) part of?

Answer 145

Limbic

Question 146

Via what pathway does the striatum receive excitatory input from the cortex, and where does it terminate?

Answer 146

glutamatergic corticostriate pathway. The input is organized topographically so that somatotopy is preserved in the projections from the somatosensory cortex and motor cortex. Corticostriate axons terminate on the major neuron type in the striatum, the medium spiny neuron

Question 147

Medium spiny neurons make up 95% of striatal neurons, use GABA as their transmitter, what are the two types?

Answer 147

One type has substance P (SP) and dynorphin (DYN) as co-transmitters, expresses dopamine D1 receptors, and projects to the globus pallidus pars interna (GPi) and substantia nigra pars reticulata (SNpr). The second uses enkephalin (ENK) as a co-transmitter, expresses D2 dopamine receptors, and projects to the globus pallidus pars externa (GPe).

Question 148

The medium spiny neurons receive projections via the nigrostriatal pathway from the substantia nigra pars compacta (SNpc), how are the two types of MSN modulated differently by dopamine input from this pathway?

Answer 148

At the GABA/SP/DYN cells, dopamine acting on D1 receptors enhances the effect of excitatory cortical input. In contrast, the action of dopamine on D2 receptors on GABA/ENK cells is to reduce the effect of cortical excitation

Question 149

Medium spiny neurons also have input from aspiny interneurons, what are the properties of these?

Answer 149

constitute about 2% of striatal neurons. These cells use ACh as a transmitter, are excitatory, and driven by cortical inputs.

Question 150

What structure of the striatum is revealed after staining it with acetylcholinesterase?

Answer 150

shows it to be compartmented into a heavily stained matrix and a lightly stained three-dimensional labyrinth, the striosomes, that are about 10–20% of the striatal bulk.

Question 151

How does the connectivity between the two compartments of the striatum differ?

Answer 151

The matrix gets inputs from throughout the cerebral cortex and sends outputs to the entire globus pallidus and SNpr, whereas the striosomes get restricted input from the prefrontal cortex and project to the SNpc.

Question 152

What is the difference in function between the two compartments of the striatum?

Answer 152

matrix is concerned with sensorimotor function, while striosomes are associated with the limbic system, and may control the dopaminergic pathway from SNpc to striatum.

Question 153

Both the globus pallidus and substantia nigra are divided into two parts. Which parts of each of these have similar structures and functions?

Answer 153

globus pallidus pars interna (GPi) and the substantia nigra pars reticulata (SNpr).

Question 154

What are the connections and functions of the GPi and SNpr?

Answer 154

Both get inhibitory connections from the GABA/SP/DYN population of striatal neurons and excitatory inputs from the subthalamic nucleus, and both send GABAergic inhibitory outputs to the thalamus. The thalamus in turn projects to specific locations in the cerebral cortex. The GPi and SNpr make connections with several thalamic nuclei that project to motor cortex, providing basal ganglia output for limb and facial movements. Part of the SNpr is concerned with eye movements.

Question 155

What are the connections of the globus pallidus pars externa?

Answer 155

It receives its striatal connections from the GABA/ ENK medium spiny neurons. The GPe neurons are GABAergic and project mostly to the subthalamic nucleus.

Question 156

The subthalamic nucleus (STN) lies at the junction between midbrain and diencephalon, what are its connections?

Answer 156

gets excitatory input from the motor cortex and GABAergic input from the GPe. The STN neurons use glutamate as a transmitter, are excitatory, and send their axons principally to the GPi and SNpr.

Question 157

Which is the only basal ganglia structure that does not have somatotropic representation?

Answer 157

substantia nigra pars compacta

Question 158

How does the connectivity of basal ganglia circuits allow highly specific and well-focused behavioral outcomes?

Answer 158

The output of the basal ganglia to the thalamus establishes somatotopic maps there. The somatotopic maps in the thalamus produced by the basal ganglia are separate from those produced by the cerebellum.

Question 159

What are the basic connections of the 5 parallel basal ganglia-thalamocortical circuits?

Answer 159

each gets corticostriatal inputs from an area of frontal cortex and projects back to the same area by way of specific basal ganglia regions and thalamic nuclei.

Question 160

What are the functions of the basal ganglia-thalamocortical circuits?

Answer 160

Apart from the motor circuit there are circuits associated with eye movement, executive functions (problem solving, working memory), the limbic system, and lateral orbitofrontal cortex.

Question 161

How does the limbic basal ganglia-thalamocortical circuits differ from the other ones?

Answer 161

goes by way of the ventral striatum (nucleus accumbens), which is part of the dopamine motivation system, rather than the caudate or putamen.

Question 162

The limbic circuit contains the medial orbitofrontal cortex. What is the orbitofrontal cortex implicated in?

Answer 162

seems to be implicated in rapid stimulus-reinforcement learning and its reversal, with the medial OFC being more concerned with positive reinforcers and the lateral OFC with negative reinforcers. In one model the OFC is the brain structure responsible for measuring the hedonic quality of stimuli which is crucial for goal-directed behaviors such as eating and drinking. Both the limbic and lateral orbitofrontal circuits are important in emotion.

Question 163

What do the the different outcomes of the operation of each of the basal ganglia circuits depend on?

Answer 163

cortical regions they are connected to, and the contexts in which they are activated.

Question 164

There are two routes through the basal ganglia circuitry with opposite effects on firing of thalamic, and hence cortical, neurons, what is the effect of direct pathway?

Answer 164

uses the GABA/SP/DYN medium spiny striatal neurons which inhibits GABAergic outflow of the GPi and SNpr to the thalamus. Cortical activation of this pathway increases the firing of thalamic neurons (since inhibiting an inhibition is excitation).

Question 165

What is the indirect basal ganglia pathway and what is its effect?

Answer 165

starts with the GABA/ENK medium spiny neuron output to the GPe, inhibitory neurons from which go to the STN. The STN excites inhibitory neurons in the GPi and SNpr that go to the thalamus. Corticostriate activation of the indirect pathway results in decreased firing of thalamic neurons.

Question 166

What does dual circuitry of the basal ganglia allow?

Answer 166

the possibility that given movement sequences may be triggered or suppressed by differential activation of direct or indirect pathways respectively.

Question 167

What do the dopaminergic neurons of the substantia nigra pars compacta (SNpc) alter their firing pattern in response to?

Answer 167

to stimuli that reward a movement.

Question 168

Dopaminergic neurons to the SNpc modulate the response of the medium spony neurons to the corticostriate inputs, what are their effects on the 2 populations?

Answer 168

While the GABA/SP/DYN neurons are made more excitable, the GABA/ENK cells become less excitable in the face of SNpc inputs. In summary, the direct pathway is enhanced by, and the indirect pathway suppressed by, the nigrostriatal tract from the SNpc.

Question 169

One function of the basal ganglia is to enable the execution of motor sequences. what are these sequences represented by?

Answer 169

by an array of cells, a micro-loop, within the basal ganglia-thalamocortical motor or oculomotor circuit. While some sequences are stereotyped movements, the circuitry for which is genetically specified, many sequences are learnt; that is, many micro-loops are entrained by experience.

Question 170

What is the firing rate at rest of the medium striatal neurons?

Answer 170

Low frequencies- 0.1- 1Hz

Question 171

What is the background firing rate of GPi and
SNpr neurons?

Answer 171

About 100 Hz

Question 172

What is the effects of the indirect pathway at rest?

Answer 172

Tonic inhibitory output of the GPi and SNpr at rest, which is increased about 50 ms before a movement by excitatory drive from the subthalamus, results in widespread, and complete, suppression of unwanted movement sequences.

Question 173

What basal ganglia pathway is required to ensure a movement is made?

Answer 173

requires that the direct striatopallidal pathway to the
GPi/SNpr cells that enable the movement (those belonging to the correct micro-loop) become activated. These GPi/SNpr cells reduce their firing, releasing their corresponding
thalamocortical cells from inhibition. The nigrostriatal dopamine system acts to raise the likelihood that a movement sequence is actually made.

Question 174

What is the essential operating principle of the basal ganglia?

Answer 174

is to select the most appropriate behavior from among the repertoire of possibilities on the basis of the relative salience (importance) of prevailing inputs, each of which generates a phasic dopamine signal that corresponds to its salience.

Question 175

What is the role of dopamine in basal ganglia choosing the most appropriate actions?

Answer 175

promote reselection of behaviors and context that immediately precede unpredicted sensory events/rewards. In this way, over a series of trials, the basal ganglia learns an association between an event and the behavioral and contextual elements that elicited it, generating new memories.

Question 176

The basal ganglia-thalamocortical circuits can switch between a top-down mode, and a bottom- up mode, what are these?

Answer 176

top-down mode-behavior is triggered from the appropriate cortical region
a bottom-up sensory input mode -driven by attention and by unpredictable events. The switch is provided by excitatory input from the intralaminar nuclei of the thalamus to the striatum.

Question 177

What is the subcortical- basal ganglia loop?

Answer 177

The basal ganglia make extensive connections with subcortical structures involved in sensorimotor function and motivation (e.g., superior colliculus, periaqueductal gray, parabrachial nucleus) forming circuits in which the thalamus sends input into the striatum rather than being on the output side of the basal ganglia. It is possible that these form extensions to the basal ganglia-thalamocortical circuits.

Question 178

What is choreoathetosis?

Answer 178

consists of frequent, random, twitch-like or writhing movements, resembling fragments of normal movements.

Question 179

What is tardive dyskinesia?

Answer 179

an unwanted effect of the treatment of Parkinson’s disease with l-DOPA, or infarcts of the subthalamic nucleus.

Question 180

Huntington’s disease (HD) is a progressive neurodegenerative disorder in which motor and cognitive symptoms begin between 40 and 50 years of age. What is the pathophysiology of it?

Answer 180

It is an autosomal dominant disease caused by an excessive number (> 36) of CAG repeats in the coding region of the gene for huntingtin (Htt) which consequently has a long string of glutamine residues near its N terminus. This affects the GABA/ ENK medium spiny neurons of the striatum. Their death causes excessive inhibition of the subthalamic nucleus, so increased and inappropriate firing of thalamocortical neurons. In summary, the chorea is a failure of the indirect pathway to block unwanted movement sequences.

Question 181

The prototypical hypokinetic disorder is Parkinson’s disease, what is it characterized by?

Answer 181

rigidity, bradykinesia, and tremor.

Question 182

What is the primary lesion of Parkinson’s disease?

Answer 182

massive loss of dopaminergic cells in the SNpc.

Question 183

How does loss of the nigrostriatal pathway cause the symptoms of PD?

Answer 183

Since the normal situation is that dopamine tonically activates the direct pathway via D1 receptors but inhibits the indirect pathway via D2 receptors, the loss of the nigrostriatal pathway leads to an increase in the activity of GABAergic striatal neurons in the indirect pathway and a decrease in the GABAergic striatal neurons in the direct pathway. The overall effect is increased inhibition on the thalamocortical connections that are required for movement.

Question 184

What is the possible cause of OCD?

Answer 184

Brain imaging shows a reduction in cerebral blood flow in the orbitofrontal cortex that correlates with the severity of the disorder in patients. Lesions of the orbitofrontal cortex in primates causes perseveration. This suggests that the cause of OCD may lie with dysfunction of the lateral orbitofrontal basal ganglia-thalamocortical circuit.