Lecture 13: Principles of Neurostimulation

Question 1

List the underlying objectives of patterned electrical stimulation applied to motor or sensory pathways in the CNS or PNS

Answer 1

 alleviate chronic pain (e.g., gate control theory)
 replace lost sensory modalities (hearing, vision, touch)
 reanimate paralyzed muscles that remain innervated,
 augment voluntary use of partially paralyzed limbs,
 restore voluntary use of completely paralyzed limbs,
 augment sensory-motor integration (reflex pathways)
 modulate activity levels in central pathways (neuromodulation)
 assist voluntary control of prosthetic limbs in amputees

Question 2

What are the underlying objectives to delivering patterned electrical stimulation to the CNS or PNS

Answer 2

alleviate chronic pain (e.g., gate control theory)
 replace lost sensory modalities (hearing, vision, touch)
 reanimate paralyzed muscles that remain innervated,
 augment voluntary use of partially paralyzed limbs,
 restore voluntary use of completely paralyzed limbs,
 augment sensory-motor integration (reflex pathways)
 modulate activity levels in central pathways (neuromodulation)
 assist voluntary control of prosthetic limbs in amputees

Question 3

What are 2 physiological Mechanisms that Control Muscle Force Production

Answer 3

1. Orderly Recruitment of Motoneurons/Motor Units (small, oxidative, type 1 (slow) are first to be recruited; size principle)
2. Motor Unit Firing Rate Modulation (slow to higher frequency of firing to develop force)

Question 4

Why do small diameter motor neurons fire first?

Answer 4

If the same current enters both neurons, the generated voltage is higher in smaller motor neurons as it has higher resistance. Thus, will reaches action potential firing threshold

Question 5

What happens when you increase current in a motoneuron that is already above its threshold for recruitment?

Answer 5

firing frequency increases (rate modulation)

Question 6

Describe type 1 motor units

Answer 6

recruited first! ^^ - low action potential threshold due to high resistance
oxidative
slow axonal conduction velocity (small axon)
slow muscle contraction time

smaller soma size
higher soma input resistance
larger EPSP size

Question 7

Describe type 2 motor units

Answer 7

glycolytic
fast axonal conduction velocity (large axon)
fast muscle contraction time

Question 8

Type FR motor units

Answer 8

fast twitch, fatigue resistance

aka MHC2a

Question 9

FF

Answer 9

fast twitch and fast fatiguing
MHC2B

Question 10

What determines the different types of motor units?

Answer 10

Myosin heavy chain isoforms

Question 11

What are the 4 motor unit types

Answer 11

slow twitch

fast twitch, fatigue resistance

fast twitch, fatigue intermediate

fast twitch, fatigable

Question 12

how can we externally induce an action potential?
* describe cathodal and anodal nerve stimulation

Answer 12

briefly depolarize membrane by adding negative charges outside the target axons using cathodes

Anions (-) flow from the cathode,
into the tissue, and back to the
anode. Negative charges will accumulate extracellularly, depolarizing the axon membrane

Anodal Nerve Stimulation
Cations (+) flow from the anode, into
the tissue, and back to the cathode.
Positive charges will accumulate extracellularly; the axon
membrane is hyperpolarized

Question 13

What is the nerve fibre’s response to extracellular stimulation?

What axons are more easily depolarized with electrical stimulation?

Answer 13

electrical stimulation of axons usually causes bidirectional generation of action potentials

large diameter axons are more easily depolarized with electrical stimulation than small axons (Ohm’s Law)

Question 14

What happens when you bring anode close to nerve fibre?

Answer 14

inverted transmembrane potential observed

transient hyperpolarization can result in anodal break excitation (membrane depolaration and action potential generation not right next to anode but some distance away and in both directions)

Question 15

In paralyzed muscle, what do all motor units convert to?

How does electrical stimulation therapy help with this?

Answer 15

fast type, fast fatiguing (MHC-2B);

electrical stimulation rebuilds muscle force capacity, and converts it back to slower types. increasing its resistance to fatigue.

Question 16

List the 4 Controllable Electrical Stimulation Parameters

Answer 16

• Stimulation Pulse Amplitude (in V or better, in mA); better to measure in mA (current); voltage depends on resistance
• Stimulation Pulse Duration (in μS or mS)
• Stimulation Pulse Polarity (-/+)
• Inter-pulse Interval (Stimulation Frequency). If stimulation frequency is too high, you may catch a neuron during an absolute refractory period thus it won’t be excitable.

Question 17

Define: rheobase value/threshold current

Answer 17

the minimal electric current required to excite a tissue (as nerve or muscle) given an indefinitely long time during which the current is applied

Question 18

What are the factors that affect the rheobase value for a motorneuron

Answer 18

• Electrode position on skin
• Skin resistance
• Subcutaneous fat layer
• Edema
• Denervation (will atrophy –> smaller muscle fibre also means more difficult to stimulate; no neuron to stimulate. less easy to stimulate by direct stimulation) /reinnervation (lower threshold for stimulation?)

Question 19

Why are shorter excitation pulses safer?

Answer 19

• less electrode corrosion (less rust) and
• less tissue damage.

Question 20

Explain the difference between physiological vs electrical recruitment

Answer 20

• When the motoneurons in a pool are physiologically recruited, SMALLER neurons tend to be recruited FIRST.
• When external electrical stimulation is applied to a nerve, the LARGEST axons
  tend to be recruited FIRST.
• added current is easier to enter the large axons with lower resistance.

group 1As will be recruited first.

Question 21

What is the strength duration curve?

Answer 21

relates the intensity of a threshold stimulus to its duration. As the duration of a test stimulus increases, the strength of the current required to activate a single fiber action potential decreases

current strength that lies above the curve and along the curve causes stimulation. anything below the curve is subthreshold and won’t cause stimulation

if you make the pulse width longer, you can get away with using a smaller current

Question 22

chronaxie

Answer 22

the minimum time required for excitation of a neuron by a constant electric current of twice the threshold voltage

Question 23

Charge balanced biphasic stimulation. Why is this needed?

Answer 23

negative and positive phases of charge.

“Zero Net Charge” is required to minimize electrode corrosion and tissue damage.

you want the second pulse to fall in the refractory period so it does nothing

Question 24

Describe the charge-duration curve

Answer 24

Demonstrates how charge injected into tissue increases with pulse width (amplitude x pulse width = charge). To minimize charge injection, shorter pulses are recommended.

Also minimzes, electrode corrosion and tissue damage

Question 25

Describe the Threshold Current-Fiber Size Curve

Answer 25

largest fibres have the lowest threshold (first to recruit)

easiest to stimulate are 1a and 1b afferents as they have the largest diameter

Question 26

Describe the current distance curve

Answer 26

Fibers located closer to a stimulating electrode have lower thresholds.

With increases in electrode to axon distance, threshold stimulus must also increase

Question 27

Why does electrical stimulation mostly not cause pain?

Answer 27

doesn’t recruit pain fibres which are very small

Question 28

Define H-reflex

Answer 28

clinically useful reflex to determine if neural pathways involved in monosynaptic reflex works

an indirect muscle response mediated by the monosynaptic stretch reflex pathway.

During electrical stimulation, the current also activates sensory fibers (Ia afferents) within the nerve. These sensory fibers carry information about muscle stretch to the spinal cord, where they synapse with motor neurons. The activated motor neurons then send signals back to the muscle, causing a delayed contraction that is recorded as the H-reflex. The H-reflex essentially mimics the natural stretch reflex elicited by tapping on a tendon.

amplitude of H reflex will increase with increasing stimulation. because you get more spindles. then peaks and declines after some point

This decline occurs due to the simultaneous activation of motor efferent fibers, which produce a direct motor response known as the M-wave. As the stimulation intensity increases, more motor neurons are activated, resulting in a larger M-wave. The electrical signal from the M-wave travels along the motor neurons in the opposite direction (antidromic conduction) to the H-reflex pathway and can collide with or cancel out the orthodromic action potentials of the H-reflex.

Additionally, antidromic conduction (backward traveling action potentials) from the motor axons can collide with and cancel out the orthodromic (forward traveling) action potentials of the H-reflex, causing its amplitude to decrease.

Question 29

What determines the myosin heavy chain (MHC) isoform that is expressed inside any single muscle fiber
1. At birth?
2. In a normal adult?
3. In an athlete specializing in endurance?
4. In an athlete specializing in weightlifting?
5. Weeks after a central neurological lesion above the spinal cord level that supplies the muscle?
6. When the muscle is exercised with electrical stimulation applied to the muscle nerve?

Answer 29

at birth: genetic programming

normal adult: genetics and activity patterns. Most adult muscle fibers express either MHC I (slow-twitch) or MHC II (fast-twitch) isoforms, depending on the type of muscle activity the fibers typically perform. Muscle use, load, and neural input are key factors that maintain specific MHC isoform expression.

endurance athlete: high demand for fatigue-resistant, oxidative fibers that are more efficient for prolonged, low-intensity activities. Increased mitochondrial density and capillary supply are associated with these changes. leads to MHC I isoforms

weightlifting athlete: requires high power and speed, favor the expression of MHC II isoforms (especially MHC IIx or IIa, which are fast-twitch, glycolytic fibers

SCI: A central neurological lesion disrupts the normal neural input to muscles, leading to muscle atrophy and changes in MHC isoform expression. Muscles may begin to express more MHC IIx isoforms, as they tend to revert to a more default, fast-twitch state due to the loss of slow, tonic neural stimulation

Question 30

What’s better: stimulating with negative current pulses or with positive current pulses? Why?

Answer 30

Negative

Cathodal Stimulation: Applying a negative current pulse using a cathode creates an accumulation of negative charges outside the targeted axons. This depolarizes the axon membrane, making it more likely to reach the threshold for generating an action potential.

Anodal Stimulation: In contrast, using a positive current pulse with an anode leads to an accumulation of positive charges outside the axon, resulting in hyperpolarization of the membrane.This can cause anodal break excitation where an action potential is generated not exactly where anode is placed but distal to it and bidrectionally.

Therefore, negative current pulses (cathodal stimulation) are preferred for neurostimulation because they effectively depolarize the axon membrane and facilitate the generation of action potentials, leading to muscle activation or other desired effects.

However, both negative and positive charges are important which is why we have charge balanced biphasic stimulation

“Zero Net Charge” is required to minimize electrode corrosion and tissue damage which will enhance safety and longevity of treatment.

Question 31

What do you need to avoid when you stimulate a nerve with long trains of negative electrical pulses?

How do you fix this potential problem?

Answer 31

Electrode Corrosion and Tissue Damage: Using only negative pulses for an extended period can lead to a buildup of negative charge in the tissue. This imbalance can cause electrode corrosion and potentially harm the surrounding tissue.

Solution: Employ biphasic stimulation, alternating negative and positive pulses. This approach ensures a “Zero Net Charge”, mitigating electrode corrosion and tissue damage. Different biphasic waveforms exist, such as balanced biphasic and compensated biphasic, each offering specific benefits.

Question 32

What are the easiest nerve fibers to recruit with skin surface electrical stimulation? Why?

Answer 32

Nerve fibres with the largest diameter have the lowest threshold for activation as it has lower axonal resistance and thus a lower threshold to reach action potential (V=I*R where I = stimulation current)

type IIx are recruited first and type I are recruited last

Question 33

Using skin surface electrical stimulation, does it matter where inside a nerve trunk a target nerve fiber is located?

Answer 33

fibers located closer to the surface and closer to the electrodes would be more easily recruited due to higher current density

rheological value is affected by edema, skin resistance, electrode placement, nerve size

Question 34

Define: M-wave

Answer 34

The M-wave represents the direct activation of muscle fibers by electrical stimulation of the motor nerve. When a stimulating electrode is placed over a motor nerve, the electrical current depolarizes the axons of the motor neurons, leading to the generation of action potentials that travel down the nerve and activate the muscle fibers it innervates. This direct activation of the muscle fibers results in a synchronous contraction that is recorded as the M-wave on the EMG.

Question 35

How does the M-wave and H-reflex change in amplitude as the strength of stimulation is increased from zero to maximal M-wave

Answer 35

M-wave: With increasing stimulation strength, more motor axons are recruited, leading to a progressive increase in the number of muscle fibers activated. This results in a gradual increase in the amplitude of the M-wave until it reaches a maximum, representing the activation of all muscle fibers within the stimulated muscle.

H-reflex: The H-reflex exhibits a different pattern. Initially, as stimulation strength increases, the H-reflex amplitude also increases. However, as the stimulation strength continues to rise, the H-reflex amplitude begins to decrease and eventually disappears.

This decline occurs due to the simultaneous activation of motor efferent fibers, which produce a direct motor response known as the M-wave. As the stimulation intensity increases, more motor neurons are activated, resulting in a larger M-wave. The electrical signal from the M-wave travels along the motor neurons in the opposite direction to the H-reflex pathway and can interfere with or inhibit the H-reflex. Additionally, antidromic conduction (backward traveling action potentials) from the motor axons can collide with and cancel out the orthodromic (forward traveling) action potentials of the H-reflex, causing its amplitude to decrease.