We investigated interhemispheric interactions between the human hand motor areas using transcranial cortical magnetic and electrical stimulation. A magnetic test stimulus was applied over the motor cortex contralateral to the recorded muscle (test motor cortex), and an electrical or magnetic conditioning stimulus was applied over the ipsilateral hemisphere (conditioning motor cortex). We investigated the effects of the conditioning stimulus on responses to the test stimulus. Two effects were elicited at different interstimulus intervals (ISIs): early facilitation (ISI = 4–5 ms) and late inhibition (ISI ≥ 11 ms). The early facilitation was evoked by a magnetic or anodal electrical conditioning stimulus over the motor point in the conditioning hemisphere, which suggests that the conditioning stimulus for early facilitation directly activates corticospinal neurones. The ISIs for early facilitation taken together with the time required for activation of corticospinal neurones by I3‐waves in the test hemisphere are compatible with the interhemispheric conduction time through the corpus callosum. Early facilitation was observed in responses to I3‐waves, but not in responses to D‐waves nor to I1‐waves. Based on these results, we conclude that early facilitation is mediated through the corpus callosum. If the magnetic conditioning stimulus induced posteriorly directed currents, or if an anodal electrical conditioning stimulus was applied over a point 2 cm anterior to the motor point, then we observed late inhibition with no early facilitation. Late inhibition was evoked in responses to both I1‐ and I3‐waves, but was not evoked in responses to D‐waves. The stronger the conditioning stimulus was, the greater was the amount of inhibition. These results are compatible with surround inhibition at the motor cortex.

Paired-pulse magnetic stimulation techniques have been used to study the intracortical circuitry of the motor cortex in humans. There are several paired stimulation methods. Two of them have been used for studying inhibitory and facilitatory connections in the motor cortex at short interstimulus intervals (ISIs). When the first stimulus (S1) is subthreshold and the second (S2) suprathreshold, electromyographic (EMG) responses to both stimuli are smaller than the responses to S2 alone at short ISIs (1-5 ms; intracortical inhibition) and larger at longer ISIs (Kujirai et al. 1993). In contrast, when S1 is suprathreshold and S2 subthreshold, EMG responses to both stimuli can be larger than the control responses at ISIs of 1.3, 2.6 and 4.0 ms (Tokimura et al. 1996; Nakamura et al. 1997b; Ziemann et al. 1998;Rothwell, 1999). These two effects were not observed when S2 was a low intensity anodal electrical stimulus, which tends to evoke D-waves (direct waves: descending volleys produced by direct activation of pyramidal tract neurones), but were very clear when S2 was a magnetic stimulus that elicited I-waves (indirect waves: descending volleys produced by indirect activation of pyramidal tract neurones via presynaptic neurones). Based on these results, both effects were considered to be produced at the motor cortex. The latter effect has been termed 'intracortical I-wave facilitation ' (Ziemann et al. 1998).Several studies have shown that later I-waves are more affected by intracortical inhibition than early I-waves (Nakamura et al. 1997a; Hanajima et al. 1998; Di Lazzaro et al. 1998). I3-waves appear to be particularly susceptible to intracortical inhibition, whereas I1-waves are little affected (Hanajima et al. 1998). However, it remains to be determined whether there are differences in intracortical I-wave facilitation among different I-waves. In this paper, in order to clarify details of this effect, we studied intracortical I-wave facilitation of I1-and I3-waves using both single motor unit and surface EMG recordings. METHODS SubjectsTen healthy volunteers (8 men and 2 women; 28-46 years old; height, 143-180 cm; weight, 45-95 kg) were studied. Written informed consent was obtained from all the subjects. Surface EMG recordings were done in all subjects. Single motor unit studies were performed in nine subjects, one subject (a In order to elucidate the mechanisms underlying intracortical I-wave facilitation elicited by pairedpulse magnetic stimulation, we compared intracortical facilitation of I1-waves with that of I3-waves using single motor unit and surface electromyographic (EMG) recordings from the first dorsal interosseous muscle (FDI). We used a suprathreshold first stimulus (S1) and a subthreshold second stimulus (S2). In most experiments, both stimuli induced currents in the same direction. In others, S1 induced posteriorly directed currents and S2 induced anteriorly directed currents. When both stimuli induced anteriorly directed currents (I1-wave effects), an interstimulus interval (ISI) of 1.5 ms res...

A characteristic diphasic pattern of SSEPs reaffirmed the electrophysiological endorsement of this target. Tremors, both proximal and distal, were remarkably improved in all patients. The rate of improvement, as indicated by the total tremor score, was a mean of 81%. Axial tremors in the legs and head were also improved. Most of the contacts associated with remarkable improvement were located in the posterior part of the subthalamic white matter (the zona incerta and prelemniscal radiation). Neither major complications nor neurological deterioration was observed. The authors concluded that DBS of the posterior part of the subthalamic white matter together with SSEP recording is a safe and effective method to ameliorate severe intractable tremors.

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Unilateral ZI/PRL stimulation is a reliable and long-term therapeutic modality and can be considered another surgical target for the treatment of tremor-dominant Parkinson's disease.