Combined Peripheral Nerve Stimulation and Controllable Pulse Parameter Transcranial Magnetic Stimulation to Probe Sensorimotor Control and Learning

This technique provides insight into how sensory information is integrated into motor planning and execution. The implementation of controllable pulse parameter TMS enables us to identify specific sensory-to-motor pathways and how these pathways may be disrupted in neurological disorders. Motor skill acquisition and performance requires a fine balance between the conscious declaratives and subconscious procedural process.

Short latency afferent inhibition is a potential marker of how cognition may shape different procedural sensory motor circuits in the motor cortex of healthy and clinical populations. Afferent inhibition quantifies the impact of afferent inputs on motor cortical output as elicited by transcranial magnetic stimulation. As a measure of sensory motor integration, it compliments functional magnetic resonance imaging and electroencephalography by probing the contributions of specific neuronal populations on a global hemodynamic and electrical responses elicited by skilled motor behavior.

The lock parameters of magnetic stimuli generated by traditional transcranial magnetic stimulators recruit a mixture of sensory motor circuits. On the other hand, controllable pulse parameter transcranial magnetic stimulators unlock several stimulus parameters enhancing the specificity of sensory motor circuits probed by afferent inhibition during skilled behavior. Assessing sensory motor innervation during performance is critical to establishing markers of skilled and unskilled motor execution.

Reliable and valid markers are an important step in developing enhanced models of motor control that will enhance or boost best practices in healthy populations as well as minimize the impact of movement disorders through effective clinical interventions. Enhanced modeling of sensory motor circuits and the factors that influence their function can help provide objective markers of function and dysfunction that will inform best practices for motor performance, skill acquisition, and rehabilitation in both healthy and neurological populations. Continued definition of psychomotor and pharmacological influences over sensory motor circuits converging a motor cortex is critical.

Combining afferent inhibition with electroencephalography provides an exciting opportunity to quantify afferent inhibition in non-motor areas as a marker of movement disorders and neuropsychiatric disorders. To begin, screen the participant for any contraindications to transcranial magnetic stimulation, or TMS. Inform the participant about the study objectives and procedures.

Review the risks outlined in the institution's Ethics Review Board-approved consent document, answer any questions about the potential risks, and obtain written informed consent before beginning any study procedures. To begin, instruct the participant to sit in the experimental chair with their elbows resting on the arms of the chair and bent to allow the wrist or hand to rest comfortably on the desk workplace. Adjust the height of the chair and desk workplace as needed.

Clean the skin over the abductor pollicis brevis, or APB, first dorsal interosseous, or FDI, and the ulnar styloid process using a mildly abrasive cream placed on a round cotton pad. Wipe away any residue using an alcohol prep pad. For each muscle, place one disposable silver/silver chloride adhesive electrode over the muscle belly.

Place a second electrode on a nearby bony landmark as a reference. Finally, place one additional silver/silver chloride adhesive electrode on the ulnar styloid process to serve as a ground. Connect each pair of electrodes and the ground to the electromyography, or EMG, amplifier and data acquisition system.

Use channel one for the first dorsal interosseous and channel two for the abductor pollicis brevis. To begin, use a mildly abrasive cream to clean the skin inside the forearm. Start from the wrist flexion crease and extend to six centimeters proximal approximately.

Extend cleaning to the area from the wrist midline to the radial side of the forearm. Wipe away any residue using an alcohol prep pad. Next, apply the conducting gel to a reusable stimulating bar electrode.

Use enough gel to cover the metal discs of the anodal and cathodal contact points. Place the stimulating electrode on the palmar side of the wrist with the cathode proximal to the anode. Place the cathode slightly medial and proximal to the radial styloid process.

On the peripheral stimulator set the stimulus type selector to monophasic, stimulus duration to 200 microseconds, and select an appropriate voltage and amperage, double-checking any multiplication factors. While holding the stimulating electrode, deliver a single electrical stimulus by depressing the trigger switch on the constant current stimulator. Then visually inspect the abductor pollicis brevis or APB, muscle and the electromyography, or EMG, display for evidence of a muscle contraction.

The muscle contraction, also known as the M-wave, is elicited by direct activation of the motor axon by the electrical stimulus and should occur between six and nine milliseconds after the peripheral electrical stimulus artifact. If there is no evidence of a muscle contraction, then ask the participant if they felt a tingling sensation radiating toward the fingers or immediately underneath the electrode. If the participant reports no sensation or is restricted to the skin immediately below the electrode, then increase the amperage in increments of 0.05 until the participant reports a tingling sensation radiating up to the fingers or thumb.

If the participant reports a radiating sensation in a digit other than the thumb, reposition the electrode by moving it radially until the feeling radiates to the thumb. Once the optimal position of the stimulating electrode is determined, secure the electrode to the wrist using three pieces of tape. Position the first piece over the middle of the electrode, and then use the second and third pieces to secure the top and bottom of the electrode.

After securing the electrode, ask the participant to assume the desired limb orientation to be used during TMS stimulation. Check to make sure a thumb twitch is still elicited. Determine the peripheral stimulus threshold.

The first amperage value where the M-wave exceeds 0.2 millivolts. If the M-wave exceeds the desired 0.2 millivolts target amplitude on three successive stimuli, then decrease the amperage. To determine the optimal coil trajectory for transcranial magnetic stimulation, or TMS, set an initial coil position by placing the coil on the participant's head and recording the coil trajectory.

Ensure that the center surface of the coil is tangential to the scalp. Align the midline of the coil at 45 degrees to the midsagittal plane of the participant's head. On the CTMS stimulator, set the pulse type selector to monophasic positive to induce a PA current in the underlying neural tissue.

Next, set the M ratio to 0.2 and the stimulus intensity to 30%of the maximal stimulator output. Finally, set the pulse width to 120 microseconds. Deliver three to five TMS stimuli while the participant maintains a slight contraction of the first dorsal interosseous, or FDI, muscle.

If no motor-evoked potential, or MEP, elicits, increase the stimulator intensity by 10%and deliver three to five additional TMS stimuli. Increase the stimulator intensity until an MEP of at least 0.2. millivolts is consistently elicited to every stimulus or until the stimulator intensity reaches 60%to 70%of the maximal stimulator output.

If no reliable MEP elicits, keep the stimulation parameters constant and move the TMS stimulator in a circle with an approximately two centimeter diameter around the original stimulation site. Once a reliable MEP elicits, record the coil position, confirm the FDI motor hotspot by keeping the stimulation parameters constant and moving the TMS stimulator two centimeters North, East, South, and West of the current coil location. Record the new coil position and trajectory if a consistently larger MEP elicits at any of the four quadrants.

Use the new coil position and trajectory as the cortical motor hotspot. Attach the coil that will induce the PA current in the brain to the CTMS stimulator. Set the pulse type to monophasic positive, the pulse width to 120 microseconds, and M ratio to 0.2.

Finally, set the stimulus intensity to the one millivolt threshold. After setting the peripheral electrical stimulus intensity, launch the no-task software routine on a personal computer, or PC1. Next, set the interstimulus interval between the peripheral electrical and TMS stimuli to 21 milliseconds.

Position the TMS coil over the first dorsal interosseous, or FDI, motor hotspot and ask the participant to hold a slight contraction of the FDI muscle. Next, run the no task software on PC1 to trigger the peripheral and CTMS stimulators. Repeat the procedure for the AP-30 current configuration using the coil that induces AP current in the brain.

Attach the coil that will induce the PA current in the brain to the CTMS stimulator. Set the pulse type to monophasic positive, the pulse width to 120 microseconds, and M ratio to 0.2. Finally, set the stimulus intensity to the one millivolt threshold.

After setting the peripheral electrical stimulus intensity, launch the sensory motor task software routine on a personal computer, or PC1. Next, set the interstimulus interval between the peripheral electrical and TMS stimuli to 21 milliseconds. Position the TMS coil over the first dorsal interosseous, or FDI, motor hotspot and ask the participant to hold a slight contraction of the FDI muscle.

Keep the desired number of unconditioned and conditioned trials between eight and 24 stimuli per condition. Run the sensory motor task software routine to control the sensory motor task and send the behavior-locked digital triggers to the peripheral and CTMS stimulators. Repeat the procedure for the AP-30 current configuration using the coil that induces AP current in the brain.

The average effect of the peripheral electrical conditioning stimulus is to suppress the corticospinal output elicited by the TMS stimulus as shown by the smaller raw average peak-to-peak MEP amplitudes in the conditioned MEPs compared to the unconditioned MEPs and short-latency afferent inhibition, or SAI, ratios of less than one. The longer MEP onset latency for the AP-30 SAI reflects the longer latency of the input to the corticospinal neuron. In differential effects, the PA-120 SAI was similarly enhanced for an index finger response regardless of whether the participant was queued to the index finger or required to remap their response to the index finger following an invalid queue to a non-index finger.

In contrast, the AP-30 SAI appears to be differentially modulated based on whether the invalid queue required a remap away or toward the index finger.