This article details a protocol for using transcranial magnetic stimulation (TMS) to investigate cortical excitability and inhibition in the human brain. It outlines the setup, methods, and adjustments necessary for effective stimulation and recording of motor-evoked potentials (MEPs).
Begin with a seated participant wearing an electroencephalography cap to record brain activity.
Electromyographic electrodes are placed over the abductor pollicis brevis muscle in the hand.
Position the transcranial magnetic stimulation coil over the primary motor cortex.
Apply low-intensity pulses to depolarize cortical pyramidal neurons.
These neurons transmit signals to spinal motor neurons, triggering muscle contractions, recorded as motor evoked potentials
Identify the cortical site generating the strongest MEPs.
Adjust the TMS intensity to determine the motor threshold--the minimum intensity required to elicit MEPs.
Optimize the intensity to evoke consistent MEPs.
Move the coil to the dorsolateral prefrontal cortex and stimulate using the optimized intensity.
A single pulse depolarizes cortical pyramidal neurons, inducing cortical excitability.
Next, apply a paired-pulse to activate interneurons, triggering inhibitory neurotransmitter release and suppressing pyramidal neuron activity.
The EEG captures this TMS-induced cortical excitation-inhibition balance.
Instruct the participant to rest and remain comfortable with a relaxed back, hands, and legs. Then to find the hotspot, begin by targeting the motor knob as the initial landmark of cortical representation of APB and primary motor cortex, and move the coil until there is corresponding muscle movement.
Use TMS intensities evoking motor-evoked thresholds or MEPs of around 500 microvolts over APB. Optimize the coil orientation by changing its angle and tilt to evoke the largest response over the hotspot. Save this coil positioning in the neuronavigator software and reduce the output intensity in steps of 2-3%. Then give 10 pulses, and if more than five out of 10 MEP responses over 50 microvolts are obtained, continue reducing the intensity.
When less than five out of 10 responses are evoked, start increasing the intensity by steps of 1-2%. Motor threshold is represented as the intensity that produces MEPs larger than 50 microvolts five out of 10 times. The interstimulus interval, ISI, for motor threshold should be longer than one second, usually three to five seconds. Next, adjust intensity starting at 120% of motor threshold to produce MEPs over primary motor cortex from 500 to 1500 microvolts.
Record 10 pulses with this output, increasing or decrease the intensity in steps of 1-2% until reaching an average of one microvolt. The adjustment of the coil intensity is crucial for targeting the neuronal population under investigation, but also for the quality of the signals. At this point, position the coil over dorsolateral prefrontal cortex and stimulate a few times.
If significant artifacts are generated, fine tune the coil placement by moving it slightly away from this location. Now digitize the EEG electrodes so that their position is registered to the brain anatomy. Then replace the earplugs with pneumatic audio earbuds to play white noise audio masking, if desired.
And add headphones over them for hearing protection. At this point, mount the coil on the coil holder and make sure that the coil does not move or press the electrodes under it. Finally, run the experiment including single-pulse TMS as well paired-pulse TMS for short intracortical inhibition, intracortical facilitation, and long intracortical inhibition, in a random order for each participant.
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