MECHANISMS OF DEEP BRAIN STIMULATION.

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Electrical stimulation within the human brain is now an accepted method for the treatment of some types of movement disorders. However the mechanism of action of deep brain stimulation (DBS) is still not well understood. Two current hypotheses are that DBS produces inhibition of the neurons in the vicinity of the electrode by releasing GABA from inhibitory neurons or terminals pr terminals in the region or by causing a depolarization block of the surrounding neurons. Our proposal aims to obtain new information on the possible mechanisms of DBS. A newly developed dual microelectrode recording system will be employed during functional stereotactic surgery for implantation of DBS electrodes in the subthalamic nucleus (STN) and globus pallidus (GP) of Parkinson's disease patients. One of the two electrodes will be used for micro- or in some cases macro-stimulation and the effects of such stimulation assessed on the firing of neurons recorded at distances of 250 mum or more. Additionally, effects of high frequency and of lidocaine and muscimol microinjections into STN will be assessed on tremor, rigidity and bradykinesia. Preliminary studies using these methods have shown that stimulation in the GP very effectively inhibits the firing of most neurons in a manner that strongly suggests release of GABA. However, pilot studies in STN and motor thalamus, suggest that other or additional mechanism(s) might be involved. The findings of these studies focused on STN should provide new insights into the mechanisms underlying DBS and may lead to improvements in electrode design, electrode placement and optimal stimulation parameters thus leading to improvements in the therapeutic efficacy on this technique.