Repetitive Transcranial Magnetic Stimulation-Induced Changes in Human Corticomotoneuronal Synapses

Begin with a participant fitted with stimulation electrodes on the tibial nerve to induce peripheral nerve stimulation, and EMG electrodes on the soleus muscle to record muscle contraction.

Electrically stimulate the nerve to deliver PNS, sending sensory signals to the spinal cord and triggering muscle contraction, called the H-reflex.

Stabilize the participant's head on a table. Position the TMS coil over the primary motor cortex.

Apply magnetic stimulation to activate cortical neurons, sending signals down the corticospinal tract and inducing muscle contraction.

Next, position a CMS coil over the cervicomedullary junction.

Apply magnetic stimulation to directly activate corticospinal axons, bypassing the motor cortex.

Pair TMS with PNS and CMS with PNS separately to examine the influence of each stimulation site on the H-reflex.

Apply low-frequency repetitive-TMS to reduce corticospinal excitability.

Repeat TMS with PNS and CMS with PNS to evaluate whether rTMS altered cortical or spinal transmission and affected the H-reflex.

First, perform the calibration procedure for the neuro-navigational system. Use a figure eight coil to stimulate the subject's motor cortical area, contralateral to the placed electrodes.

To find the optimal stimulation spot, first place the coil one centimeter in front of the vertex. Point that handle of the coil backwards to evoke a posterior to anterior flux of induced current in the center of the coil. Identify the position where motor evoked potentials can be evoked with minimum stimulation intensity.

At this point, place the subject's head on the table and use rigid foam to prevent head motion. Use an image guided TMS navigational system for a monitoring coil and head position throughout the experiment. Then, fixate the coil to a stand and the subject's head to the chair and fixate the coil with Velcro strips to the head.

Next, determine the minimum intensity required to evoke motor-evoked potentials with peak to peak EMG amplitudes larger than 50 micro-volts in six out of 10 consecutive trial. This is the subject's resting motor threshold. Also place a double cone magnetic coil at the cervicomedullary junction to excite axons of the corticospinal tract.

Position the coil so that the first derivative of the induced current is cranially directed and that its central position is on or near the enium. To begin, first take care to ensure that the size of the control H-Reflex stays constant throughout the experiment. If a deviation is detected, adjust the stimulation intensity prior to the consecutive trial.

Now, adjust the stimulation intensity of the TMS coil over the motor cortex to between 90% and 100% of the subject's motor threshold. Also set the cervicomedullary stimulation intensity to 100% of the maximum stimulator output. Begin by conditioning the H-Reflex with stimulation over the motor cortex at rest.

Apply TMS and peripheral nerve stimulation by varying the timing between the two stimuli to allow assessment of changes in Corticomotoneuronal transmission. Start with an interstimulus interval of negative five milliseconds, meaning peripheral nerve stimulation is illicited five seconds before TMS, then alter this interval in steps of milliseconds from negative five milli seconds to one millisecond. Depending on the interstimulus interval, the H-Reflex can be shifted forward in relationship to the descending volley where it can be shifted to the right, so that the slower corticospinal pathways can be tested.

Vary the interval randomly from trial to trial, to eliminate bias due to order of stimuli and set the pause between stimulation trials to four seconds. Early facilitation should occur around intervals of negative four to negative two milliseconds. Next, condition the H-Reflex using magnetic stimulation over the cervicomedullary junction.

Use interstimulus intervals between negative nine and negative three milliseconds in steps of one millisecond. Apply these TMS intervals over both locations together in each trial and record the resulting control H-Reflex and motor-evoked potentials. Use the control H-Reflex as a reference for the conditioned H-Reflexes and the control motor-evoked potential to ensure comparable stimulation conditions.

Once pre-measurement is completed, set the stimulation intensity to 1.2 times the subject's motor threshold and apply the slow repetitive TMS intervention. Stimulate over the primary motor cortex at one hertz for 20 minutes to induce long lasting suppression of corticospinal excitability.