RAPID COMMUNICATION Dose-Dependent Reduction of Cerebral Blood Flow During Rapid-Rate Transcranial Magnetic Stimulation of the Human Sensorimotor Cortex

Paus, Tomáš, Robert Jech, Christopher J. Thompson, Roch stimulating coil that varied as a function of the amount of Comeau, Terry Peters, and Alan C. Evans. Dose-dependent restimulation. duction of cerebral blood flow during rapid-rate transcranial magnetic stimulation of the human sensorimotor cortex. J. NeurophysM E T H O D S iol. 79: 1102–1107, 1998. Rapid-rate transcranial magnetic stimulation (rTMS) was used to stimulate the primary sensorimotor Experimental design cortex in six healthy volunteers while regional changes in cerebral blood flow (CBF) were simultaneously measured by means of In six healthy volunteers, a figure-eight TMS coil was positioned positron emission tomography. A figure-eight TMS coil (Cadwell over either the left primary sensorimotor cortex (M1/S1) or the Corticoil) was positioned, using frameless stereotaxy, over the left frontal eye-field (FEF); the FEF findings have been reported probabilistic location of the left primary sensorimotor cortex, and elsewhere (Paus et al. 1997). For each condition, CBF was meaa series of brief 10-Hz trains of TMS was delivered at subthreshold sured in six 60-s O-H2O scans acquired with the CTI/Siemens HR/tomograph. During the scan the subjects kept their eyes closed intensity during each of six 60-s scans. The scans differed in the and white noise (80-dB SPL) was played through insert earphones number of trains delivered, namely 5, 10, 15, 20, 25, and 30 trains/ to mask the coil-generated clicks. The subjects were instructed to scan, respectively. In the left primary sensorimotor cortex, CBF relax and not to move during the scan. The EMG was recorded covaried significantly and negatively with the number of stimulus with surface electrodes placed over muscles of the right anterior trains. These CBF decreases may reflect TMS–induced activation forearm (flexor carpi radialis and palmaris longus) , posterior foreof local inhibitory mechanisms known to play a role in TMS– arm (extensor carpi radialis and brachioradialis) , and the thenar related phenomena, such as the electromyographic silent period. (flexor pollicis brevis and abductor pollicis brevis) . To allow for a correlational analysis of CBF data, a different number of TMS pulse-trains was delivered in the six scans, namely 5, 10, 15, 20, I N T R O D U C T I O N 25, and 30 pulse-trains per scan. The order of scans was randomized within each condition, and the order of conditions (M1/S1 A focal single-pulse transcranial magnetic stimulation and FEF) was counterbalanced across subjects. (TMS) of the human motor cortex typically increases electromyographic (EMG) activity in relaxed muscles (Barker Subjects et al. 1985; Cracco et al. 1993; Hallett and Cohen 1989). During voluntary contraction, however, the same TMS stimFour female and two male subjects volunteered for the study ulus produces a prolonged postexcitatory inhibition of musafter giving written informed consent [average age 28 { 6.5 (SD) cle activity, i.e. a silent period (Amassian et al. 1990; Triggs yr] . All subjects, but one, were right-handed. Following the safety guidelines for the use of a rapid-rate TMS in normal volunteers et al. 1992). Similarly, when a suprathreshold test pulse is (Pascual-Leone et al. 1993), the subjects were screened for a hispreceded by a subthreshold one, the EMG response to the tory of neurological disorders, in particular personal and family test stimulus is reduced (Kujirai et al. 1993; Wassermann history of epilepsy. The study was approved by the Research and et al. 1996a). It is believed that intracortical inhibitory mechEthics Committee of the Montreal Neurological Institute and Hosanisms underlie, at least in part, such TMS–induced supprespital. sion of EMG activity. The involvement of the intracortical rather than spinal mechanisms has been inferred from studies Transcranial magnetic stimulation comparing the effects of central and peripheral stimulation on EMG activity and spinal reflexes (Brasil-Neto et al. 1995; The Cadwell high-speed magnetic stimulator and the Cadwell Sabatino et al. 1995) as well as from pharmacological (Ziefigure-eight coil (Corticoil, 2 tear-shaped coils of Ç5-cm diam each) were used to produce a focal stimulation of the cerebral mann et al. 1996) and lesion (Schnitzler and Benecke 1994; cortex through the skull. The duration of a single TMS pulse was von Giesen et al. 1994) studies. 200 ms; the pulses were delivered in five pulse-trains of 400-ms In this report we provide evidence for TMS–induced reduration each (between-pulse interval of 100 ms; i.e., a stimulation duction in cerebral blood flow (CBF) and, by inference, frequency of 10 Hz). A different number of pulse-trains was delivsynaptic activity in the human sensorimotor cortex. By using ered in six 60-s scans, namely 5, 10, 15, 20, 25, and 30 pulse-trains. positron emission tomography (PET), changes in CBF were The shortest between-train interval was 1,600 ms. The intensity of measured during brief trains of subthreshold rapid-rate TMS stimulation was set at 70% of the maximum output of the stimulaapplied over the left primary sensorimotor cortex. We found tor. For the figure-eight coil used in this study, the estimated volume of stimulated tissue was 20 1 20 1 10 mm, with the point significant decreases in CBF in the brain tissue under the