Contralateral Negative Bold Responses in the Motor Network during Subthreshold High-Frequency Interleaved Tms-Fmri over the Human Primary Motor Cortex

Abstract

Objective: Transcranial Magnetic Stimulation (TMS) is a noninvasive technique that stimulates a localized brain region underneath a coil. Recently, the application of repetitive Transcranial Magnetic Stimulation (rTMS) to the primary motor cortex (M1) has been used to promote functional recovery in stroke patients with hemiparesis. High-frequency rTMS (5 Hz or greater) was applied over the affected hemisphere to reactivate hypoactive regions. Because of recent advances in MRI technology and, in particular, the gradient coils, high-frequency whole brain rTMS-fMRI is possible. The use of interleaved rTMS-fMRI during stimulation at a frequency of 5 Hz aids in understanding how the brain is modulated during stimulation. Method: We measured BOLD signal changes in whole brain during interleaved rTMS-fMRI (5Hz) using 3T MRI. Image processing and statistical analyses were carried out using the Statistical Parametric Mapping (SPM8) software. Results: Distinct BOLD signal changes extending to the remote motor network during 5 Hz-rTMS over the M1 were successfully demonstrated using interleaved rTMS-fMRI. Negative BOLD responses were observed in the contralateral M1, the dorsal premotor cortex (PMd), and the bilateral supplementary motor cortex (SMA), even though no significant BOLD signal changes were observed in the stimulated M1. The negative BOLD responses gradually became marked during (3 mins 57 sec). Therefore, long-lasting plastic changes may occur within 4 mins. Negative BOLD responses in remote regions away from the directly stimulated M1 suggest that subthreshold high frequency rTMS over the motor cortex induced neuromodulation via neuronal networks. Conclusion: The remarkable negative BOLD responses in the contralateral M1 induced by high-frequency rTMS may be useful for identifying a treatment strategy involving M1 stimulation.