The authors investigated the use of slow-frequency repetitive transcranial magnetic stimulation (rTMS) to the unaffected hemisphere to decrease interhemispheric inhibition of the lesioned hemisphere and improve motor function in patients within 12 months of a stroke. Patients showed a significant decrease in simple and choice reaction time and improved performance of the Purdue Pegboard test with their affected hand after rTMS of the motor cortex in the intact hemisphere as compared with sham rTMS.

We examined the dynamic involvement of different brain regions in implicit and explicit motor sequence learning using PET. In a serial reaction time task, subjects pressed each of four buttons with a different finger of the right hand in response to a visually presented number. Test sessions consisted of 10 cycles of the same 10-item sequence. The effects of explicit and implicit learning were assessed separately using a different behavioural parameter for each type of learning: correct recall of the test sequence for explicit learning and improvement of reaction time before the successful recall of any component of the test sequence for implicit learning. Regional cerebral blood flow was measured repeatedly during the task, and a parametric analysis was performed to identify brain regions in which activity was significantly correlated with subjects' performances: i.e. with correct recall of the test sequence or with reaction time. Explicit learning, shown as a positive correlation with the correct recall of the sequence, was associated with increased activity in the posterior parietal cortex, precuneus and premotor cortex bilaterally, also in the supplementary motor area (SMA) predominantly in the left anterior part, left thalamus, and right dorsolateral prefrontal cortex. In contrast, the reaction time showed a different pattern of correlation during different learning phases. During the implicit learning phase, when the subjects were not aware of the sequence, improvement of the reaction time was associated with increased activity in the contralateral primary sensorimotor cortex (SM1). During the explicit learning phase, the reaction time was significantly correlated with activity in a part of the frontoparietal network. During the post-learning phase, when the subjects achieved all components of the sequence explicitly, the reaction time was correlated with the activity in the ipsilateral SM1 and posterior part of the SMA. These results show that different sets of cortical regions are dynamically involved in implicit and explicit motor sequence learning.

We studied the facilitation of the motor evoked potential (MEP) elicited with transcranial magnetic stimulation by increasing the stimulus intensity and the degree of voluntary activation of the target muscle in patients with Parkinson's disease (PD) and in normal volunteers. The threshold intensity for eliciting MEPs with the muscle at rest did not differ in PD patients and normal subjects. At rest, stimuli of similar intensity, related to the individual's threshold, elicited MEPs with amplitudes consistently larger in patients than in normal subjects, although when we compared the averaged MEP amplitude across all stimulus intensities, the differences reached only borderline statistical significance. Voluntary muscle activation elicited a smaller increase in the MEP area in PD patients than in normal subjects. Increasing the degree of voluntary muscle activation at fixed stimulus intensities elicited a smaller increase of MEP amplitude, duration, and area in PD patients than in normal subjects. These results suggest that control of the excitability of the motor system is abnormal in PD patients, with enhancement of excitability at rest and weak energization during voluntary muscle activation.

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Reorganization of corticospinal pathways after spinal cord injury and amputations leads to increased excitability of motor pathways targeting muscles proximal to the level of interruption of efferents from the CNS. To study the timing of these changes, we have recorded motor evoked potentials (MEPs) in the arm muscles of three normal subjects before, during, and after anesthetic block of the forearm and hand. The amplitudes of MEPs from biceps, which was the muscle immediately proximal to the block, gradually increased with anesthesia and then returned to preanesthesia levels within approximately 20 minutes after anesthesia was ended. MEPs from the contralateral arm were unaffected. Such rapid changes strongly suggest unmasking of preexisting synaptic connections, due to disinhibition at cortical or subcortical levels, as the mechanism underlying acute modulation of motor outputs.

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We studied the effects of transcranial motor cortex stimulation on the electromyographic characteristics of tremor in 9 patients with familial essential tremor and in 12 patients with postural tremor associated with Parkinson's disease. Transcranial magnetic stimulation reset both types of tremor equally. The resetting depended on the stimulus intensity, but was most closely correlated with the duration of the electromyographic silent period that followed the stimulus-induced motor evoked potential. Tremor resetting was present bilaterally even after focal, unilateral stimulation. Transcranial electrical stimulation failed to reset the tremor in either patient group. These results emphasize the role of central, intracortical structures in the generation of essential tremor and postural tremor in Parkinson's disease.

To determine if linguistic processing could be selectively disrupted with repetitive transcranial magnetic stimulation (rTMS), rTMS was performed during a picture-word verification task. Seven right-handed subjects were trained in two conditions: picture-word verification, which required the subject to verify whether the picture of an object matched the subtitle name on the same page, and frame verification, which required subjects to verify whether there was a rectangular frame around the combined object picture and subtitle. Half of the trials were performed during rTMS. The effects of rTMS on performance were evaluated at the following four scalp positions: left anterior (the area where rTMS produced speech arrest), a mirror site on the right, and two positions in the left and right parietal region. Stimulation over the left deltoid muscle served as a control. Subjects had less difficulty in making picture-word matching decisions during unstimulated compared with stimulated trials at the left anterior and posterior positions. No significant difference in accuracy was detected in the frame verification condition, but response times in the frame verification condition were longer with stimulation at the left anterior position. Because rTMS of the dominant hemisphere affected linguistic processing independent of speech motor output, we confirm that rTMS may be used to investigate language and other cognitive functions.