Neurophysiology

Question 1

What is primary motor cortex?

Answer 1

• a region of the cerebral cortex just anterior to the central sulcus where low intensity electrical stimulation produces reliable muscle contractions
• somatosensory cortex is on other side of central sulcus
• also organized in a homunculus like the somatosensory organization (things over-represented in somatosensory also in motor -> want lots of input for very fine motor control)

Question 2

What does motor cortex do?

Answer 2

• a big debate in the field is whether primary motor cortex control muscles directly or commands movements. Evidence for the latter:
  -> a particular muscle can be activated by stimulating widely dispersed motor cortical sites
  -> single motor cortical neurons make monosynaptic connections with motorneurons innervating several different muscles
  -> motor cortex micro-stimulation can produce purposeful-like movements (bringing food to mouth, reaching, defensive postures, etc.) - elaborate motions

Question 3

Describe electrophysiology of neurons in motor cortex

Answer 3

• discharge before movement onset (proceeds movement)
• discharge preference for movement direction (tuning) -> sensitive to movement in particular direction, may fire more or less in particular directions (some neurons may get deactivated in some directions)
• discharge proportional to force and/or speed of movements

Question 4

Describe the plasticity of the motor cortex

Answer 4

• learning new motor tasks can modify representation of movements in motor cortex (and many other areas)
• injury to motor cortex caused by stroke can lead to changes in adjacent areas of cortex to recover function for affected body part
• same as somatosensory cortex - can change homonculus

Question 5

What is the corticospinal tract?

Answer 5

• only occurs in mammals and show progressive development in higher-order species with greater dexterity
• in humans, ~10% make direct connections on motorneurons
• pyramidal tract (corticospinal projections travel) and the dorsal column medial lemniscal system (from somatosensory system) co-evolved, presumably to support dexterous hand function and tool use

Question 6

Describe motor cortex lesions

Answer 6

• weakness (or paralysis) and spasticity
• caused by increased spinal stretch reflex because of loss of descending inhibition from motor cortex
• effects are most dramatic for distal muscle (ie. hand/ fingers) -> more crude movements, loss of precise control -> can still perform larger tasks (e.g. climbing, running)

Question 7

What are the delays between cortical discharge and movement?

Answer 7

1. conduction time from cortex to spinal cord
2. time for summation of EPSPs to threshold in alpha motorneurons
3. conduction time from spinal cord to neuromuscular junction
4. synaptic delay at NMJ (1 ms)
5. electrical mechanical coupling time -> time from muscle action potential to enough muscle force to overcome the mass/ inertia of the limb
   * dealing w/ delay is very hard computationally (not a good feedback loop) - a lot of motor control out there to correct this -not always through spinal cord?

Question 8

What is the cerebellum?

Answer 8

• latin for “little brain” - based on its similar appearance to cortex
• 10% of the volume of the brain, >50% of the neurons
• highly regular neuronal architecture. Two separate inputs

Question 9

Describe the cerebellar pathways?

Answer 9

• widespread sensory input. none reaches consciousness (does not have access)
• only output is via deep nuclei and Purkinje cells (always inhibitory)
• medial/ lateral division both anatomically and physiologically
• in monkeys and humans, there is increased development of lateral cerebellum, which projects to motor cortex and frontal cortex -> cognitive as well as motor function? - increased precision of motor control and also increases cognitive functions - important for dexterous abilities w/ hands

Question 10

What are the differential effects of medial/ lateral lesions?

Answer 10

1. lateral cerebellum
   -> dysmetric limb movements (not to the appropriate scale - don’t fully make it, or go too far)
   -> intention tremor (when someone wants to make a movement tremor comes on, none when at rest)
   -> arm ataxia (dysfunctional reaching - unstable)
2. Medial cerebellum
   -> dysmetric saccades (rapid, conjugate, eye movement that shifts the center of gaze from one part of the visual field to another)
   -> disorder of smooth pursuit eye movements or disorder of equilibrium and balance
   -> gait ataxia ( poor muscle control that causes clumsy voluntary movements)
   * many of the effects of the cerebellar lesions can be mimicked by alcohol (which may act at GABA ion channels)
   * these disorders occur because of the failure of the cerebellum to “tune-up” the different functions e.g. failure to tune up the generation of saccades (in brainstem reticular formation), limb movements (motor cortex) and balance (vestibular postural reflexes)
   * Ipsilateral -> right side lesion = right side dysfunction

Question 11

What are the functions of the cerebellum?

Answer 11

• contributes to accurate saccades and limb movements
• feedforward, anticipatory, predictive motor control
• motor recalibration, error correction, motor learning
• contributions to cognition

Question 12

Describe the basal ganglia

Answer 12

• fascinating anatomy
• set of nuclei deep in brain
• sits b/w brainstem + cortex
• relevant structures clinically - very well studied (many disorders, Parkinsons)

Question 13

What are the functions of the basal ganglia?

Answer 13

1. Motor -> limb and face movements (PD and HD- huntington’s symptoms)
2. Oculomotor -> fewer and slower saccades
3. Limbic -> emotion (irritability and depression) - lack of control of emotional state - manic
4. Cognitive -> planning, working memory, attention (absent minded, reasoning ability, demetia, tourette’s, OCD) - feel need to do things repeatedly

Question 14

What is the hypothesis about motor function (natural parallels to cognitive function)?

Answer 14

• basal ganglia exerts continuous inhibition which prevents unwanted movements - puts on the breaks
• when a movement is to be made basal ganglia selects the appropriate motor program by releasing them from inhibition - takes off the breaks (once complete, shuts back down quickly)

Question 15

Describe the Parkinson’s disease pathophysiology

Answer 15

• loss of dopaminergic neurons in the substantia nigra (pars compacta). Changes balance of activity in the direct and indirect pathways - balance b/w excitation
  + inhibition
  -> slow movements, rigidity, gait is slow, turn is shuffled very small movements
  -> parkinson’s = more towards inhibition = too much inhibition, breaks are on too hard
• related to basal ganglia

Question 16

What are the features of Parkinson’s disease?

Answer 16

Typically a disease of aging
- rigidity (not spasticity, not velocity dependent)
- resting temor (not intention tremor, pill rolling, stops during movement)
- akinesia (poverty/lack of movement) - don’t move very much, but when do can move fairly normally
- bradykinesia (slowed movement, shuffling gait)
- dementia (via involvement of frontal cortex)
- mask-like face -> lack of expressive faces
* usually discovered from the motor symptoms but often when looked at history see cognitive impairment signs.

Question 17

Mechanism of Parkinson’s disease

Answer 17

• increase in discharge in neurons in GP. This increases inhibition at the thalamus and thus decreased excitation at the motor cortex.q

Question 18

What is the treatment of Parkinson’s disease?

Answer 18

• L-dopa therapy can increase dopamine and rebalance circuit (almost too active in gait, head wobbles potentially)
• high-frequency stimulation (DBS) of internal globus pallidus disrupts the inhibition of thalamus

Question 19

Huntington disease

Answer 19

• degeneration of neurons in caudate and putamen. associated with abnormal repeats of Huntington gene. causes abnormal protein folding and cell death
  -> the first signs of the disorder are subtle: absentmindedness, irritability, and depression, accompanied by fidgeting, clumsiness or falls
  -> uncontrolled movements gradually increase until the pateint is confined to bed or to a wheelchair
  -> speech is slurred at first, then incomprehensible, and finally stops altogether as facial expressions become distorted and grotesque
  -> cognitive functions also deteriorate, and eventually the ability to reason/ think disappears. no treatment is available.
  -> once the disease has begun its course, the pateitn faces years of gradually decreasing capacity, followed by total disability and certain death.
• too much excitation of basal ganglia -> can’t maintain movement, too active, too much motion (kind of opposite of Parkinson’s)

Question 20

What are the features of huntington’s disease?

Answer 20

• heritability
• chorea (decreased from the globus pallidus, motor loop)
• other movement disorders
• dementia (engagement of limbic and cognitive loops)
• no treatment
• death