Ph.D Thesis

Ph.D StudentLitvak Vladimir
SubjectAnalysis of the Effects of Transcranial Magnetic Stimulation
on Functional States and Connectivity of the Human
Cerebral Cortex Using
DepartmentDepartment of Biomedical Engineering
Supervisors PROFESSOR EMERITUS Hillel Pratt
ASSOCIATE PROF. Menashe Zaaroor


Transcranial magnetic stimulation (TMS) is a noninvasive method for stimulating the human brain based on the principle of electromagnetic induction.

The present research aimed at developing new methods for characterization of the immediate and long-term effects of TMS on the brain and for developing more precise stimulation protocols that would allow purposeful modification of the brain’s functional state and connectivity. Electroencephalography (EEG) was chosen as the neuroimaging method due to its high temporal resolution and the possibility to combine it with TMS.

Three studies were carried out. The first was aimed at characterizing EEG responses to TMS applied to the left and right primary motor cortex. For this purpose it was necessary to solve the problem of TMS artifacts hampering the analysis of several tens of milliseconds immediately following the stimulus. This was achieved by analyzing data recorded with a specially adapted recording system and subtracting the residual artifact in software. Combining these two approaches enabled almost complete removal of the artifact without distorting physiological brain signals. Based on the artifact-free data, a model of the response that revealed remarkable symmetry between the responses to stimulation at the left and right sides of the brain was suggested.

The second study examined the long-term effects of TMS. The specific protocol tested - paired associative stimulation (PAS) is an attempt to mimic natural neural learning mechanisms. PAS consists of pairing an electrical stimulus of the median nerve at the wrist with magnetic stimulation of the primary somatosensory cortex. A long series of such paired stimuli has been found to modify the amplitude of a particular peak in the EEG response to median nerve stimulation. Our aim was to better understand the mechanism of this modification and test whether it affects the perceptual discrimination ability. We showed that PAS affects synapses at superficial layers of cortical area 3b which is responsible for processing tactile information. We also found significant effects of PAS on behavioral performance related to changes in the EEG response.

The third study addressed the variability of muscular responses to TMS pulses delivered under identical conditions. We showed that this variability is, at least partially, related to oscillatory activity in the sensorimotor cortical areas. The finding that increase in the power of the oscillations was associated with a larger muscular response to TMS challenges the accepted view that oscillations appear during an idling state of the motor system.