Eric M. Wassermann, Timothy A. Kimbrell, Mark S. George, Amy L. Danielson, Peter Herscovitch, Mark Hallett, Robert M. Post
Tuesday April 15 3:00 pm / Exhibit Hall A

OBJECTIVE:
To investigate the effect of focal rTMS on neural activity in local and distant brain areas during 1 Hz stimulation of the primary motor area (M1) using a split 18fluorodeoxyglucose (FDG) PET technique.

BACKGROUND:
Single TMS pulses produce brief facilitation followed by longer-lasting inhibition which is bilateral. Low-frequency rTMS causes persistent decreases in the excitability of M1 and may have therapeutic effects in myoclonus and other disorders with excess cortical activity. It has been suggested that some of the other therapeutic effects of rTMS (e.g. in depression) operate through transsynaptic activation of distant cortical and subcortical areas. This, however, has not been demonstrated.

DESIGN/METHODS:
Six normal subjects were injected with 5 mCi of FDG and then performed a continuous auditory discrimination task requiring a right hand button press in response to a specific tone for 30 min. Following this, they were scanned using a conventional PET technique with sequential arterial sampling. After completion of the first scan, they were injected with another 5 mCi of FDG and performed the discrimination task while receiving 1 Hz rTMS to the right primary motor area (M1) at approximately 1.1 X motor threshold for an additional 30 min. EMG from the left hand was monitored and the stimulation intensity was adjusted continually to maintain muscle responses, but avoid overt movement. Subjects were then rescanned. The unstimulated and stimulated scans were compared by Statistical Parametric Mapping.

RESULTS:
There was no significant absolute global change in cerebral metabolic rate (CMRglu) due to rTMS. Comparison of the normalized scans showed decreased CMRglu in the right M1 directly under the stimulating coil. Additionally, a larger decrease was found in the contralateral (unstimulated) M1 hand area. Subjects reported no side effects of the stimulation.

CONCLUSION:
This study demonstrates that TMS can produce effects in a cortical area distant from the stimulation site. The change in the unstimulated M1 represents a decrease in activity that may have been caused by the activation of a transcallosal inhibitory pathway by the stimulation. The decrease in CMRglu at the stimulation site is consistent with the decrease in cortical excitability found in M1 after treatment with 1 Hz rTMS. However, its relative weakness may have been due the summation of local excitatory and inhibitory effects of the stimulation. These findings strengthen the rationale for treatment of disorders such as myoclonus and epilepsy with low-frequency rTMS.

Sponsored by: NINDS intramural funding.