Assessing Brain Hyperexcitability with Transcranial Magnetic Stimulation and Electroencephalography

Take an epilepsy patient with an electroencephalography, or EEG, cap to record brain activity.

The patient’s pre-recorded brain scan reveals a deep-seated structural abnormality that is functionally connected to a target superficial cortical region.

Attach electrodes to the contralateral hand to capture muscle contractions.

Secure an infrared detector to track and nullify head movement and use neuronavigation to align the head position with the brain scan.

Position the magnetic coil over the cortical region responsible for hand movement. Apply the lowest-intensity pulse that elicits hand muscle contraction, confirming cortical neuron stimulation.

Deliver suprathreshold pulses to stimulate the target cortical region, inducing neural activity that propagates to the abnormal brain area and other functionally connected regions in the epileptic network.

Record the brain activity to identify abnormal EEG responses indicative of neuronal hyperexcitability in the epileptic brain.

Map the origin of the abnormal EEG peaks to locate the seizure-onset zone.

Prior to testing, determine the two TMS target regions by superimposing each subject's functional connectivity map onto each subject's structural image. To begin the experimental session, bring the subject into the testing room and have them sit-in a chair. Measure the subject's head and select an electroencephalography, or EEG, cap of appropriate size to enable low electrode impedances.

Next, thoroughly clean the skin underneath each electrode using a cotton tip applicator and alcohol. Add conductive gel to each electrode and press down on the electrode to ensure good contact between the scalp, gel and electrode. To minimize charging artifacts, ensure that the gel does not spread outside of the electrode holder.

Place the reference and ground electrodes on the forehead and as far from the stimulation coil as possible, to minimize the possibility of a TMS-induced electrode artifact contaminating the entire recording. Place these electrodes within a few centimeters of each other to minimize common mode noise. Then press the measure impedances button on the EEG system.

Check electrode impedances by plugging the EEG output cables into the impedance jack of the EEG recording system. Ensure that the electrode impedance is not greater than 5 kilo ohms. Next, prepare the electromyography electrodes on the contralateral hand. Give the subject earplugs to minimize risk of hearing loss and tinnitus. Then, place the infrared detectors on the subject's head, ensuring that the detectors are placed in a way to minimize risk of movement during the experimental session.

Co-register the subject's head with the MRI images by identifying the location of the preselected external anatomic fiducial markers on the subject using the pointer that is included with the neuronavigation equipment. Familiarize the subject with stimulation by applying a pulse elsewhere or by applying a low intensity stimulation pulse to the scalp.

Determine the resting motor threshold by locating the subject's motor cortex on the hemisphere ipsilateral to the functional connectivity based targets. Angle the coil perpendicular to the gyrus with the handle pointing occipitally, and begin stimulation at an intensity that is expected to be subthreshold. Then increase stimulation intensity in steps of 5% max stimulator output until TMS consistently evokes motor-evoked potentials with amplitudes greater than 50 microvolts in each trial.

Decrease stimulation intensity in steps of 1% max stimulator output until less than 5 positive responses out of 10 are recorded. Finally, set the TMS intensity to the desired value. Apply single pulses of TMS to each of the target regions using the neuronavigation software, with variable intervals between pulses to minimize cortical plasticity and subject expectancy effects.