Mechanisms of deep brain stimulation and future technical developments.

Possible mechanisms underlying the therapeutic effect of deep brain stimulation (DBS) are reviewed, particularly the notion that DBS is inhibitory. Computer simulations are described that model the effect of different frequencies and regularity of neuronal activity (target neuron), either spontaneous or stimulated, on information transfer between two other neurons. Most simulations resulted in a loss of information. These were the least with high frequency and regular activity or stimulation of the target neuron with regularity having the least deleterious effect on information transfer. The simulations suggest that irregular activity in neurons converging with other neurons can result in a loss of information transfer. This may explain why increased irregularity in globus pallidus activity associated with Parkinson's disease, dystonia and hemiballismus may result in symptoms. Further, the therapeutic effect of DBS may be due to driving neurons at higher and perhaps more importantly, regular frequencies. There were simulations in which information transfer was augmented suggesting the presence of stochastic resonance. This most often occurred with low frequency activity in the target neuron. It is hypothesized that low frequency activity, either spontaneous or stimulated, could account for involuntary movements, including tremor. Future directions and challenges to DBS are also discussed.