The extent of synchronization within and between the nuclei of the basal ganglia is unknown in Parkinson's disease. The question is an important one because synchronization will increase postsynaptic efficacy at subsequent projection targets. We simultaneously recorded local potentials (LPs) from the globus pallidus interna (GPi) and subthalamic nucleus (STN) in four awake patients after neurosurgery for Parkinson's disease. Nuclei from both sides were recorded in two patients so that a total of six ipsilateral GPi-STN LP recordings were made. Without medication, the power within and the coherence between the GPi and STN was dominated by activity with a frequency Ͻ30 Hz. Treatment with the dopamine precursor levodopa reduced the low-frequency activity and resulted in a new peak at ϳ70 Hz. This was evident in the power spectrum from STN and GPi and in the coherence between these nuclei. The phase relationship between the nuclei varied in a complex manner according to frequency band and the presence of exogenous dopaminergic stimulation. Synchronization of activity does occur between pallidum and STN, and its pattern is critically dependent on the level of dopaminergic activity.Key words: globus pallidus interna; subthalamic nucleus; coherence; synchronization; Parkinson's disease; dopamine Studies in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated primates and in patients with Parkinson's disease have found an increase in firing rate and a tendency toward bursting in the neurons of the globus pallidus interna (GPi) and subthalamic nucleus (STN) (Filion and Tremblay, 1991;Bergman et al., 1994;Sterio et al., 1994;Hutchison et al., 1997aHutchison et al., , 1998Merello et al., 1999). These changes are likely to influence the projection targets of the basal ganglia in the thalamus and brainstem, although not as much as if the postsynaptic efficacy of neuronal activity was increased through the synchronization of discharges emanating from these nuclei. There is some evidence for the synchronization of neuronal discharges within the GPi of MPTP-treated primates (Nini et al., 1995), but, to date, there is no evidence for significant synchronization in patients with Parkinson's disease.Here we look for synchronization within and between the human GPi and ipsilateral STN in the presence and relative absence of dopaminergic stimulation, by recording from the basal ganglia in patients undergoing functional neurosurgery for severe Parkinson's disease. Patients were recorded after withdrawal and reinstitution of treatment with the dopamine precursor levodopa, which elevates levels of dopamine and its metabolites in the parkinsonian brain, without significant change in noradrenaline or serotonin (Scatton et al., 1983). To avoid surgery-related time constraints, we recorded local potentials (LPs) postoperatively from the different contacts of macroelectrodes rather than the action potentials of individual neurons using intraoperative microelectrodes. The use of bipolar contacts increased the likelihood that only loca...

1. EMG responses evoked in hand muscles by transcranial stimulation over the motor cortex were conditioned by a single motor threshold electrical stimulus to the median nerve at the wrist in a total of ten healthy subjects and in five patients who had electrodes implanted chronically into the cervical epidural space. 2. The median nerve stimulus suppressed responses evoked by transcranial magnetic stimulation (TMS) in relaxed or active muscle. The minimum interval between the stimuli at which this occurred was 19 ms. A similar effect was seen if electrical stimulation was applied to the digital nerves of the first two fingers. 3. Median or digital nerve stimulation could suppress the responses evoked in active muscle by transcranial electrical stimulation over the motor cortex, but the effect was much less than with magnetic stimulation. 4. During contraction without TMS, both types of conditioning stimuli evoked a cutaneomuscular reflex that began with a short period of inhibition. This started about 5 ms after the inhibition of responses evoked by TMS. 5. Recordings in the patients showed that median nerve stimulation reduced the size and number of descending corticospinal volleys evoked by magnetic stimulation. 6. We conclude that mixed or cutaneous input from the hand can suppress the excitability of the motor cortex at short latency. This suppression may contribute to the initial inhibition of the cutaneomuscular reflex. Reduced spinal excitability in this period could account for the mild inhibition of responses to electrical brain stimulation.

There is a wealth of data suggesting that behavioural events are reflected in the basal ganglia through phasic changes in the discharge of individual neurones. Here we investigate whether events are also reflected in momentary changes in the degree of synchronization between neuronal elements. We simultaneously recorded local potentials (LPs) from the subthalamic nucleus (STN) and/or ipsilateral globus pallidus interna (GPi) or scalp EEG during voluntary movements of a hand-held joystick in six awake patients following neurosurgery for Parkinson's disease. Without medication the power within the STN and the coherence between the STN and the GPi were dominated by activity with a frequency of <30 Hz. This coupling was attenuated by movement. In the presence of exogenous dopaminergic stimulation, power within the STN and coherence between the STN and the GPi was dominated by activity at 70-85 Hz, which increased with movement. The movement-related changes in coherence between the STN and EEG showed a similar pattern of pharmacological dependence, as seen subcortically. Movement-related frequency-specific changes in synchronization occur in the basal ganglia and extend to involve subcortico-cortical motor loops. The dynamic organization of activities in the frequency domain might provide a means for temporal co-ordination within and across different processing streams in the basal ganglia. This organization is critically dependent on the level of dopaminergic activity.

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