Phase-amplitude coupling within the anterior thalamic nuclei during seizures.

Cross-frequency phase-amplitude coupling (cfPAC) subserves an integral role in the hierarchical organization of interregional neuronal communication and is also expressed by epileptogenic cortex during seizures. Here, we sought to characterize patterns of cfPAC expression in the anterior thalamic nuclei during seizures by studying extra-operative recordings in patients implanted with deep brain stimulation electrodes for intractable epilepsy. Nine seizures from two patients were analyzed in the peri-ictal period. CfPAC was calculated using the modulation index and interregional functional connectivity was indexed using the phase-locking value. Statistical analysis was performed within subjects on the basis of nonparametric permutation and corrected with Gaussian field theory. Five of the nine analyzed seizures demonstrated significant cfPAC. Significant cfPAC occurred during the pre-ictal and ictal periods in three seizures, as well as the postictal windows in four seizures. The preferred phase at which cfPAC occurred differed 1) in space, between the thalami of the epileptogenic and nonepileptogenic hemispheres; and 2) in time, at seizure termination. The anterior thalamic nucleus of the epileptogenic hemisphere also exhibited altered interregional phase-locking synchrony concurrent with the expression of cfPAC. By analyzing extraoperative recordings from the anterior thalamic nuclei, we show that cfPAC associated with altered interregional phase synchrony is lateralized to the thalamus of the epileptogenic hemisphere during seizures. Electrophysiological differences in cfPAC, including preferred phase of oscillatory interactions may be further investigated as putative targets for individualized neuromodulation paradigms in patients with drug-resistant epilepsy. NEW & NOTEWORTHY The association between fast brain activity and slower oscillations is an integral mechanism for hierarchical neuronal communication, which is also manifested in epileptogenic cortex. Our data suggest that the same phenomenon occurs in the anterior thalamic nuclei during seizures. Further, the preferred phase of modulation shows differences in space, between the epileptogenic and nonepileptogenic hemispheres and time, as seizures terminate. Our data encourage the study of cross-frequency coupling for targeted, individualized closed-loop stimulation paradigms.

L-dopa-induced dyskinesia and stereotactic surgery for Parkinson's disease.

OBJECTIVE: To assess the impact of different surgical targets and techniques, such as ablation and deep brain stimulation, to treat patients with L-dopa-induced dyskinesia (LID), a major therapeutic complication of Parkinson's disease. METHODS: This review analyzes the effects of early surgical procedures to treat hyperkinesia and the current methods and targets used to combat LID in Parkinson's disease, which are mainly thalamotomy, pallidotomy, and deep brain stimulation of the globus pallidus internus and the subthalamic nucleus. RESULTS: Available information indicates that surgery of the globus pallidus internus and thalamus (the pallidal receiving area) and of the subthalamic nucleus has a pronounced antidyskinetic effect. This effect is associated with a concomitant improvement in the parkinsonian ("off"-medication) state. Although it is more profound with pallidal and subthalamic surgery, such an effect can also be observed to some extent with thalamic surgery. The latter is attributable to the fact that surgery of the ventralis intermedius is primarily effective for treating tremor. An integral pallidothalamic pathway is needed for dyskinesia to be expressed. Thus, LID is less frequent after subthalamotomy or deep brain stimulation of the subthalamic nucleus through a functional effect mediated by the physiological normalization of the motor system and by an indirect effect associated with a reduction in the daily dose of L-dopa. CONCLUSION: Surgery is the only treatment available for Parkinson's disease that can predictably improve both the parkinsonian motor syndrome and LID. The exact mechanisms involved in these effects are not well understood. Pallidal and thalamic surgery affecting pallidal relays reduce LID frequency by disrupting the pallidothalamic circuit, probably eliminating the neuronal activity associated with dyskinesia. Alternatively, the antidyskinetic effect of subthalamic nucleus surgery may in part be attributable to a reduction in the L-dopa dose as well as to the stabilization of the basal ganglia circuits after the surgical procedure.