Mechanisms of action of deep brain stimulation (DBS)

Deep brain stimulation (DBS) is remarkably effective for a range of neurological and psychiatric disorders that have failed pharmacological and cell transplant therapies. Clinical investigations are underway for a variety of other conditions. Yet, the therapeutic mechanisms of action are unknown. In addition, DBS research demonstrates the need to re-consider many hypotheses regarding basal ganglia physiology and pathophysiology such as the notion that increased activity in the globus pallidus internal segment is causal to Parkinson's disease symptoms. Studies reveal a variety of apparently discrepant results. At the least, it is unclear which DBS effects are therapeutically effective. This systematic review attempts to organize current DBS research into a series of unifying themes or issues such as whether the therapeutic effects are local or systems-wide or whether the effects are related to inhibition or excitation. A number of alternative hypotheses are offered for consideration including suppression of abnormal activity, striping basal ganglia output of misinformation, reduction of abnormal stochastic resonance effects due to increased noise in the disease state, and reinforcement of dynamic modulation of neuronal activity by resonance effects.