Deep brain stimulation: current challenges and future directions

Abstract

The clinical use of deep brain stimulation (DBS) is among the most important advances in the clinical neurosciences in the past two decades. As a surgical tool, DBS can directly measure pathological brain activity and can deliver adjustable stimulation for therapeutic effect in neurological and psychiatric disorders correlated with dysfunctional circuitry. The development of DBS has opened new opportunities to access and interrogate malfunctioning brain circuits and to test the therapeutic potential of regulating the output of these circuits in a broad range of disorders. Despite the success and rapid adoption of DBS, crucial questions remain, including which brain areas should be targeted and in which patients. This Review considers how DBS has facilitated advances in our understanding of how circuit malfunction can lead to brain disorders and outlines the key unmet challenges and future directions in the DBS field. Determining the next steps in DBS science will help to define the future role of this technology in the development of novel therapeutics for the most challenging disorders affecting the human brain.

Fig. 1. Deep brain stimulation mechanisms.

a | Neurotransmitters (inset) are released in response to stimulation, leading to calcium waves and subsequent release of gliotransmitters. This release influences synaptic plasticity, leading to arteriole dilation and increased regional blood flow. b | Deep brain stimulation (DBS)-induced changes in local field potentials within the subthalamic nucleus. Activity in the beta band is rapidly reduced with DBS at 3 V and then resumes with stimulation off.