LIFESCI 3K03 ALL

What are the three stages + areas of control of movement and what do they do?

1. Determines what needs to be done (Ready) - Prefrontal Cortex

   1. Identifies the goal of the movement and best strategy to accomplish this goal

2. Plans the specific movement (Set) - Motor Cortex

   1. Specific sequences of muscle activations and patterns required to do the movement

3. Execute the plan (Go) - Spinal Cord

   1. Activation of the motor neurons to do the movement and make minor adjustments

What is the range of complexity in the 3 stages of control of movement?

What does the Prefrontal Cortex do?

• Highest in the chain of command and greatest complexity

• Identifies a goal and determines what needs to be done to accomplish this

  • “What you need to do”

• Highly connected with sensory cortex

• Executive Function (EF)

  • Higher cognitive processes for planning, organizing, and controlling thoughts, speech, and behaviors

  • Involves a wide-range of skills

What are the two components of Executive Function and Movement?

1. Goal-directed actions

• Organizing

  • What is the goal and how does this relate to the current sensory state?

• Planning

  • What will need to be done to accomplish the goal?

• Directing

  • Sending this information to the next processing station (i.e., motor cortex)

2. Attention

• Multitasking

  • Allocating attention among tasks performed simultaneously

• Response inhibition

  • Respond effectively with distractions/irrelevant information

  • Similar to a second level of “sensory gating” (i.e., thalamus filtering)

How is EF and aging related?

Executive function declines with age

• Lesions in white matter

• Loss of gray matter

• Loss of dendritic branching

Changes are highly variable

• Decline can be minimal in healthy aging

• Influenced by things like lifestyle, education, genetics, etc.

What are the age related declines related to EF?

Aging related declines in:

• Overall processing speed

• Problem solving ability

  • Organizing, planning, directing (Goal-directed actions)

• Controlling attentional resources

  • Multitasking and response inhibition (Attention)

Declines are not to a level of dysfunction in healthy aging

What are the changes in gait parameters with age?

In general, with aging we see:

• Decrease in gait speed

• Decrease in step length

• Increase in step time

• Increase in variability in these parameters

However, healthy older adults may have little to no change

Reduced EF may be an important driver of these changes

What is Gait in relation to executive function?

• Gait is a complex motor task that uses executive function

  • Not fully managed by CPGs (especially in humans)

  • EF needed to plan, organize, and direct of movements

  • Often must also divide attention to other tasks

• EF allows effective division of attention between gait and other tasks

  • Dual-task or Multi-tasking (e.g., Walk and talk/text)

What are the important parts of the motor cortex in relation to control of movement?

• Motor cortex is involved after you have decided what you need to do, in order to decide how you will do it

  • Supplementary Motor Area (SMA)

  • Premotor Area (PMA)

  • Primary Motor Cortex (M1)

How are the PMA & SMA involved in the planning of movement?

• Created movement plans and holds them until ready to execute

  • Active just BEFORE movement occurs

  • Up to 1s before voluntary movement

• Plans must be highly integrated with sensory information

• Details of coding taking place remains unclear

Premotor Area (PMA)

• Selection of best motor plans based on current sensory information (e.g. picking up an object)

Supplementary Motor Area (SMA)

• More complex motor sequences often with bilateral connections

• May be more internally driven (remembered sequences) (e.g. performing a dance)

How was the planning of movement tested?

Through experiment with monkeys

• Measuring the planning of movement

  • Instruction stimulus

    • Red light where movement will need to be

    • PMA neuron begins firing

  • Trigger stimulus

    • Blue light tell it to act

    • PMA neuron stops firing soon after the action is made

  • Specific to the side required for movement

What is active when planning (or even watching) movement?

“Mirror neurons” exist in the PMA

• Respond when movement is imagined or watched

• May be part of an extensive brain system for understanding actions and intentions of others

Monkey’s motor neurons didn’t activate when seeing the peanut being picked up by a tool instead of the monkey hand or human hand

What does the primary motor cortex (M1) do in relation to movement?

• Transforms the motor plan into specific movement patterns

• Motor map masks the deeper complexity

  • Complex and overlapping neurons work together to control specific movements

  • Coding related to direction and force of movement

How does the coding of movement in the primary motor cortex work?

Movement direction is encoded by the collective activity of neurons

• Many neurons are active for every movement

• Activity of each cell represents a single “vote”

• Direction of movement is based on a tally (and averaging) of votes

A single cell’s vote = Direction Vector

Tally of all cell votes = Population Vector

So…A population vector is based on MANY individual direction vectors

What is a direction vector?

Recordings from a single cell in M1 create a direction vector

• Each cell has a “preferred” direction where firing rate is highest

• Firing rate reduces as movement direction changes

Direction of the arrow stays the same for a given cell, but the length changes based on the direction of movement

How do you make a population vector from 2 direction vectors?

• Based on testing we know cell 1 and cell 2’s preferred directions

• Measure the firing rate in cell 1 & cell 2 in response to a particular motion

• Create a population vector that represents the actual movement

Population vectors are created from many cells

What forces in relation to population vectors?

Population vectors generated in the direction in which force is needed

Population vectors based on normal movement

Population vectors based on moving against a resistive force (pushing in a specific direction)

Neural decoding in M1

• We have a greater understanding of signals in M1

  • compared to prefrontal, SMA, and PMA

• Still, decoding these overlapping signals remains extremely complex:

  • Requires interpreting inputs from potentially thousands of neurons

  • Relating to multiple muscle movements

What is the basal ganglia?

Group of subcortical nuclei which supports the selection and initiation of willed movements, while preventing unwanted movements

What are the 2 motor pathways of the basal ganglia?

Direct Pathway

• Facilitates movement

• Helps to select motor plans

Indirect Pathway

• Inhibits movement

• Help to suppress competing or inappropriate motor plans

Need a healthy balance between the two

What is the direct pathway of the basal ganglia?

What is the indirect pathway of the basal ganglia?

What is the direct and indirect balance of the basal ganglia?

Direct = facilitates appropriate movements (Releasing the brake)

Indirect: Inhibits inappropriate movements (Riding the brake)

What is Parkinson’s Disease?

A disorder of the direct pathway

• Difficulty stimulating wanted movement

  • Reduced direct pathway release of thalamus inhibition

  • Arises from a loss of dopaminergic neurons acting on the striatum in the direct pathway

What are hypokinetic disorders?

Reduced voluntary motor activity due to a disorder of the direct pathway

• Bradykinesia - slowness of movement

• Akinesia - lack of movement (e.g., freezing of gait)

How does a direct pathway disorder work?

• Loss of dopaminergic neurons from Cerebral Cortex to Striatum (and from the substantia nigra to the striatum)

• Levodopa supplements help maintain the pathway

What is Huntington’s disease?

A Disorder of the indirect pathway

• Difficulty suppressing unwanted movements

  • Reduced indirect pathway = reduction in thalamus inhibition

  • Arises from a loss of striatum neurons acting on the globus pallidus external in the indirect pathway

  • Rare genetic disorder (<0.01% of people)

  • Symptoms arise in 30s or 40s

  • Neuron loss will also occur in other areas of the cerebral cortex, leading to:

    • Dementia

    • Personality changes

    • Death (~20 years after diagnosis)

What are hyperkinetic disorders?

Disorders of the indirect pathway that involve excessive involuntary motor activity

• Chorea - spontaneous and uncontrollable movements

How does an indirect pathway disorder work?

Loss of neurons from striatum to GPe

• Final overall inhibition cannot occur

What is the cortico-cerebellar loop and what are the 3 parts?

Proper execution of planned, voluntary, multi-joint movements

• Necessary to fine tune the sequences (i.e., timing) of muscle contractions

3 parts:

• Cortex to cerebellum

• Within cerebellum

• Cerebellum to cortex

What is the cortico-ponto-cerebellar pathway of the cortico-cerebellar loop?

• Sensory and motor cortex axons form massive projection on pons

• Pontine nuclei relay information to cerebellar cortex

What is ‘within the cerebellar cortex’ of the cortico-cerebellar loop?

Granule cells

• Most numerous cells in the cerebellum

• Excitatory/inhibitory output on Purkinje cells

Purkinje cells

• Largest cells in cerebellum

• Received thousands of synaptic inputs

• Excitatory/Inhibitory output to deep cerebellar nuclei

Deep cerebellar nuclei

• Excitatory or inhibitory output to thalamus

What is the ‘cerebello-thalamo-cortical pathway’ in the cortico-cerebellar loop?

• Deep cerebellar nuclei relay to thalamus (VL)

• VL relays information back to M1

  • Basal Ganglia was area 6 (premotor)

  • Here, M1 (area 4) signifies last chance tuning (timing, direction, force)

What results from cerebellar lesions?

Ataxia: uncoordinated and inaccurate movements

Summary of Brain Control

What are the two major groups of pathways in descending spinal tracts?

• Lateral motor pathways

  • Commands for voluntary movements

• Ventromedial motor pathways

  • Posture and reflex movements

What is the corticospinal tract (CST)?

Primary pathway for voluntary motor control

• Neck to feet

• One of the largest and longest pathways

Pyramidal cells arising from the motor cortex

• M1, but also premotor and other areas

Can be further divided into:

• Lateral (limbs) vs. anterior (trunk, neck, shoulders)

Lateral vs. Anterior CST

Lateral CST

• 90% of CST axons

• Decussate in medullary pyramids

• Control proximal/distal muscles (i.e., limbs)

Anterior CST

• 10% of CST axons

• Decussate within spinal cord

• Control axial muscles

Check slides for all diagrams

What is the lateral vs. anterior corticospinal tract pathway? (Draw it out)

How are the three different pathways impacted in Brown-Sequard Syndrome (Draw)?

What are the types of motor neurons?

Upper motor neurons

• Cerebral cortex and brainstem

• Can only connect to muscle through lower motor neurons

Lower motor neurons

• Ventral horn of spinal cord

• Direct connection to muscle

What do lower motor neurons involve?

Axons exit in ventral root

Can receive input from:

• Upper motor neuron

• Interneurons in spinal cord

• Sensory input

Exist ventrally and join sensory fibers in spinal nerve

• 31 pairs classified in 4 segments (C-T-L-S-c)

*Mixed spinal nerve: both sensory and motor info coming in

What is the distribution of motor neurons in the spinal cord?

Not an even distribution

• Cervical enlargement (C3-T1)

• Lumbar enlargement (L1-S3)

These areas contain most of the motor neurons for distal and proximal muscles

Distribution of motor neurons in spinal cord?

Organized at each level by area and function of the muscle they innervate

• Axial muscles more medial than distal muscles

• Flexors (decrease angle between bones) more posterior to extensors (increase angle between bones)

Flexors vs Extensors

Flexors: decrease the angle between bones

• motor neuron will be more dorsal in the spinal cord

• E.g. Hamstring (in-between distal and medial)

Extensors: muscles that increase the angle between our bons

• motor neuron is most likely in the ventral area (3-4) of the spinal cord

• E.g. Glutes (distal)

What are the two primary types of lower motor neurons?

• Alpha motor neurons

  • Directly trigger the contraction of muscles for movement

• Gamma motor neurons

  • Regulate muscle tone and control sensitivity of muscle spindles

Motor unit vs. Motor neuron pool?

Motor unit

• Motor neuron and all the muscle fibers it innervates

Motor neuron pool

• All the alpha motor neurons that innervate a single muscle

What are the steps of excitation-contraction coupling?

(electrical activity to mechanical contraction)

• (A) Alpha motor neurons release ACh

• (B) ACh produces large EPSP in muscle fiber

• (C) EPSP evokes muscle action potential

• (D) Action potential triggers Calcium ion release from Sarcoplasmic reticulum

• (E) Fiber contracts (sliding filament model)

• (F) Calcium ion reuptake

• (G) Fiber relaxes

What is the sliding filament model of contraction?

• Calcium ions binding to troponin allows myosin heads to bind to actin-myosin heads then pivot, causing filaments to slide

What is the force-length relationship?

A fundamental property of contractions

• Describes the relationship of isometric muscle fiber forces with its length

• Goldilocks zone for maximum number of cross-bridges (not too short, not too long)

• Force output changes based on the speed it shortens (or lengthens)

What about power output in relation to force and velocity?

Power = force x velocity

• If velocity = 0, then power = 0

• In an isometric contraction, you have a lot of force, but the velocity on the x-axis 0, therefore there is no power

What is Titin?

“Spring” on the end of myosin filaments (connects the end of the thick filaments)

• Provides elastic component in muscle fibers

  • Main source of passive force in a single fiber

  • Minimal source of passive force in complete muscle

What is residual force enhancement?

“When an active muscle is stretched, its isometric, steady-state force following the stretch is greater than the corresponding (same length, same activation) purely isometric contraction.”

What is residual force enhancement in relation to titin?

• Titin appears to be an “adjustable” spring which plays an important role in residual force enhancement

• Muscle activation can lead to a change in the stiffness and length of this spring

So… titin can help to increase force (+efficiency) in movements that involve activated/stretching muscles…

What is Electromyography (EMG)?

• The quantification of a muscle(s) electrical activity (sum of action potentials)

• Bipolar electrode configuration to record the difference in electrical activity

  • e.g., V1 - V2

  • …above the scope here

What are the applications of EMG?

• Linear relationship to muscle force in isometric contractions

• Provides amplitude of muscle activation (level of recruitment)

• Provides timing of activation (activation patterns)

• Fatigue and advance analyses

What are the differences in developmental changes with gait seen through EMG?

• Considerable co-contraction of agonists and antagonists can be observed in in the infant

• Brief periods of well-defined EMG activity can be seen in the adult

• Muscle co-contraction returns in some older adults as a stabilizing feature

What are the limitations of EMG?

• Not a direct relationship to muscle force (especially during motion)

• Sensitive to differences in placement/processing

• Surface EMG: Cross-talk between muscles, recording through skin/adipose

• Fine-wire EMG - more accurate and gets intramuscular data

What can group 1 sensory neurons be divided into?

Ia axons & Ib axons

What are Ia axons?

• Largest and fastest group I sensory neurons

• Excitatory synapses with spinal interneurons and directly on alpha motor neurons

• Muscle spindles (amount of stretch)

What are Ib axons?

• Slightly smaller/slower group I sensory neurons

• Inhibitory synapses with spinal interneurons

• Golgi tendon organ (amount of force)

What are muscle spindles?

Sensory receptor

• First thought to be a “muscle bud”

Sits within a muscle to measure the change in length

• Small intrafusal muscle fibers

• Parallel to primary muscle fibers (extrafusal)

• Wrapped with a sensory neuron (Ia)

What is the stretch reflex (myotatic reflex)?

When a muscle is pulled (stretched), it pulls back (contracts)

• Resists changes in muscle length

• Important for maintaining limb position or posture

Monosynaptic stretch reflex

• Primary sensory neuron (Ia - muscle spindle)

• Primary motor neuron (alpha motor neuron)

What are the steps of the stretch reflex (myotatic reflex)?

1. Muscle is stretched (extrafusal & intrafusal)

2. Ia depolarizes from stretch

3. Action potential propagates along axon through dorsal root

4. Synapses with alpha motor neuron

5. Alpha motor neuron sends action potential to contract muscle

How do muscle spindles stay responsive to stretch?

• Intrafusal fibers need the ability to contract, just like extrafusal fibers

• Gamma motor neurons receive input from brain to keep intrafusal fiber taut

How does fine tuning muscle length with the gamma loop occur?

1. Descending command from brain sets first estimate

• Coactivation of both alpha and gamma motor neurons (tuning for the initial guess)

2. Muscle spindle detects muscle is too long

3. Ia axons send signal to alpha motor neuron

4. Alpha motor neuron activate extrafusal fibers to shorten muscle

What is Gama bias?

• Base level of firing for the intrafusal fibers to keep sensory “online”

• Constant activity to keep the intrafusal fiber taut

• Firing rate simply increases or decreases to compensate for changes in extrafusal fiber length

What is fusimotor gain?

• Ability of the nervous system to adjust/fine tune the sensitivity to small changes

• Ramping up/fine tuning the sensitivity of this loop to identify small changes

• E.g. postural control

  • When a muscle stretches as you lean to one side, there is a stretch reflex to contract to get you back straight

How can we improve our fusimotor gain?

Balance training and plyometric training can help increase sensitivity (we can quickly/easily react to small changes)

What is the Gamma (motor) loop?

• The loop between the muscle spindle (sensory fiber + gamma motor neuron) and muscle (alpha motor neuron)

What is the difference between static and dynamic response?

Static response:

• Intrafusal fibers: Nuclear chain and static nuclear bag

• Static gamma motor neurons

• Type (group) II sensory fibers

Dynamic response:

• Intrafusal fibers: Dynamic nuclear bag

• Dynamic gamma motor neurons

• Type (group) Ia sensory fibers

Why do we care about the static vs dynamic distinction?

Static response:

• Primarily related to changes that are constant/predictable

• Example: Static stretch (20-30s)

• Inhibitory

Dynamic response:

• Primarily related to changes that are quick/unpredictable

• Example: Stretch reflex

• Excitatory

Light green: static gamma motor neuron

Red: static (II sensory fiber), static, inhibitory

Dark green: Ia sensory fiber, dynamic, excitatory

Purple: Dynamic gamma motor neuron

Blue: Alpha motor neuron to extrafusal fibers

Static vs. Dynamic stretching?

Static stretch:

• Likely to reduce muscle performance (if immediately prior to exercise)

• Improves flexibility (may be required for specific taks)

  • activating type II sensory fibers (static response)

Dynamic stretching:

• May increase muscle performance and sport specific performance

  • Activating type Ia sensory fibers (dynamic response)

  • Ramping up fusimotor gain → improving response to quick/unpredictable muscle length changes

However, if static stretching is integrated into a full warmup (aerobic, SS, DS, sport-specific activities), there is no evidence to say it is detrimental

What are Golgi tendon organs?

• Sensory receptor

  • Sensory neuron (Ib) intertwined within the collagen fibers of tendons

• Allows for the measure of force of contraction (strain of muscle)

• Regulate muscle tension within optimal range

• GTP fibers are in series rather than parallel

  • force must go directly through them

Synapse with inhibitory interneurons

• Primarily helps to regulate muscle force

• Allows for a protection of overload as last resort

What is the stretch-shortening cycle (SSC)?

Involves an eccentric stretching of the muscle, immediately followed by an enhanced concentric contraction

E.g. Vertical jump

• Jump height:

  • Squat jump vs. countermovement jump

Mechanisms of the SSC?

1. Elastic energy

2. Stretch reflex

3. Neural potentiation

4. Active State

5. Mechanical potentiation

What is the elastic energy involved in the SSC?

• Generated from all elastic components, but tendons dominate the storage and release of elastic energy

• >0.5s may negate all effects of elastic energy

• More elastic energy = fast eccentric immediately followed by fast concentric w/ minimal pause

What is the stretch reflex of the SSC?

• Fast lengthening of muscle (eccentric contraction)

• Dynamic nuclear bag convey sensory information of the stretch of the muscle through type Ia sensory neurons

• Firing rate is dependent on the speed/amount of stretch

• Improved fusimotor gain can help to maximize sensitivity of the reflex

What is neural potentiation in relation to the SSC?

• Electromechanical decay

• Picking up the “slack” in the unit

• 30-100ms

What is the active state of the SSC?

• Time for cross-bridges to build up force

• 100ms - 1s

What is mechanical potentiation of the SSC?

• Residual force enhancement

What is involved in a fast SCC?

• Fast eccentric phase, with an explosive concentric phase

• Stiff joint, high activation in eccentric, very little loss of force during amortization

• Contract time <250 ms

• Primary mechanisms:

  • Elastic energy and stretch reflex, as well as mechanical potentiation (i.e., RFE)

What is involved in a slow SSC?

• Slower eccentric phase with less explosive concentric phase

• Less stiff joint, longer contact times, greater neuromuscular activity in the concentric phase

• Contact time >250 ms

• Primary mechanisms:

  • Active state, neural potentiation, and mechanics of contractile component

Slow SSC allows for:

• More work to be done by contractile unit over a greater distance (work = force x distance)

• too fast it may “fall down” the power curve

Spinal interneurons can design simple to highly complex patterns of movement based on input from:

• Primary sensory axons

• Descending axons from brain

• Collaterals of lower motor neuron axons

• Other interneurons

What is reciprocal inhibition?

Reflex arc using spinal interneurons to support simple monosynaptic reflexes (e.g., stretch reflex)

• Contraction of one muscle accompanied by relaxation of its antagonist muscle

What is the withdrawal reflex?

• Reflex arc used to withdraw limb from aversive stimulus

  • Excitatory input for multiple ipsilateral motor units

• What about staying upright?

  • Opposite leg has to take on load

What is the crossed-extensor reflex?

• Reflex arc for extensors and flexors on opposite side

  • Excitatory and inhibitory for ipsilateral and contralateral motor units

What are central pattern generators?

• Circuitry for many rhythmic movements resides in Spinal cord

• Complex network of sensory, motor and interneurons

• Controlled by two “half-centers” of spinal neurons

  • Mutually inhibiting halves that produce alternating bursts of flexor and extensor activity

  • Rhythmic activity will continue as long as input exists

  • Circuitry for walking resides in the lumbar/sacral spinal cord

• Descending control (input from brain) initiates and adapts CPGs

  • can influence both rhythm and pattern generation neural pools

  • Rhythm vs. pattern

• Patterns are continually adjusted from higher and lower inputs

Where do we have evidence of Central pattern generators?

Evidence from animal spinal transections

• Measured bursts of rhythmic and coordinated activity arising for input that was constant

What are the pathways of central pattern generators?

Rhythm Generators

• Setting the timing of patterns to be generated

Pattern Generators

• Sending the required pattern of muscles activations

What is Gait retraining?

Changing the mechanics of how you walk or run

• Easy to override motor patterns or CPGs

• Very difficult to “rewrite” them

CPG evidence in cats

Sensory information may also influence BOTH rhythm and pattern

• Stepping in cats

  • Proception

    • Amount of stretching can regulate the stance phase

    • Cats can match speed of treadmill, through CPG alone (after training / stimulation)

  • Sensory information from the skin

    • Stimulus to dorsal side of paw causes pattern with increased flexion to avoid a tripping hazard

What is fictive movement?

• Primary source of evidence for CPGs

• “Resemble” locomotion, but are not true locomotion…

Reflex theory in CPGs

Reflexes are still present

• We said the reflexed can “influence” the rhythm and pattern of the CPG, but…

  • What if the reflexes themselves are doing all the work

  • Simulations suggest this is possible (in theory)

Evidence vs Evidence against for CPGs

Lots of evidence for:

• Animal models

• Stepping reflexes in infants as foundation for adult locomotion

• Spontaneous or evoked activation patterns SCI patients

• Effective circuitry for controlling robotic locomotion

Evidence against…

• No direction locomotion example in humans (vs. cats)

• Most is “fictive”

• Could simply be reflex-based

So…do humans really use CPGs in walking?

• “Our interpretation is that, taken together, these facts underpin the view that CPGs do exist in the human spinal cord.”

• Perhaps a better question for future research is to what extent do CPGs control our locomotion?

What are Spinal Cord Injuries (SCI)?

Produce sensory, motor, and/or autonomic disfunction

• Complete vs. incomplete

• Paraplegia vs. tetraplegia (quadriplegia)

• Can be from direct trauma or vascular insufficiency