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Trains of repetitive transcranial magnetic stimulation (TMS) at 10-30 Hz and intensities of 90-120% motor threshold were delivered through a figure of eight coil over the motor cortex while normal subjects made either rapid, self-terminated (ballistic) wrist movements or maintained the position of their wrist at a fixed angle. Movement kinematics and EMG activity in antagonistic forearm muscles were analysed. In the ballistic task, repetitive TMS had little effect on the velocity or acceleration of the initial segment of the movement, although it induced large terminal oscillations (tremor) around the target position at frequencies between 4.4 and 7.2 Hz. The likelihood that tremor would occur increased with increasing stimulus intensities or frequencies. It was maximal with stimulation over the forearm area, and decreased with stimulation over the leg area, or over parietal sites; there was no tremor during stimulation of cervical nerve roots. The frequency of the induced tremor was independent of the rate of stimulation and did not depend on the presence of excitatory and inhibitory motor responses to the stimulus. Stimulation could also induce tremor of the same frequency in the fixed task, but only during co-contraction of forearm muscles. The amplitude of tremor was proportional to the level of co-contraction. Clinically, the tremor induced by repetitive TMS appeared very similar to cerebellar tremors. In order to confirm this we investigated two cerebellar patients, one with autosomal dominant cerebellar ataxia and the other with multiple sclerosis. Both of them had a terminal tremor of 6-7 Hz in the wrist movement task. In the holding task, the amplitude of their postural tremor increased with the level of co-contraction in forearm muscles. Since the frequency of repetitive TMS-induced tremor was independent of stimulus parameters, we conclude that it represents some intrinsic property of the CNS. We suggest that the tremor is caused by disruption of cortical processes involved in terminating a voluntary movement or maintaining a posture. Similarities to cerebellar patients suggest that repetitive TMS may cause tremor by interfering with adaptive cerebellar afferent inflow to motor cortex. Repetitive TMS-induced tremor, therefore, may represent a model of some forms of cerebellar tremor in man.

A cerebellar-like terminal and postural tremor induced in normal man by transcranial magnetic stimulation