Deep brain stimulation for movement and other neurologic disorders

Abstract

Deep brain stimulation (DBS) was introduced as a treatment for patients with parkinsonism and other movement disorders in the early 1990s. The technique rapidly became the treatment of choice for these conditions, and is now also being explored for other diseases, including Tourette syndrome, gait disorders, epilepsy, obsessive-compulsive disorder, and depression. Although the mechanism of action of DBS remains unclear, it is recognized that DBS works through focal modulation of functionally specific circuits. The fact that the same DBS parameters and targets can be used in multiple diseases suggests that DBS does not counteract the pathophysiology of any specific disorder, but acts to replace pathologic activities in disease-affected brain circuits with activity that is more easily tolerated. Despite the progress made in the use of DBS, much remains to be done to fully realize the potential of this therapy. We describe some of the most active areas of research in this field, both in terms of exploration of new targets and stimulation parameters, and in terms of new electrode or stimulator designs.

Figure 1

Motor and limbic cortex-basal ganglia-thalamocortical circuits. The targets of current DBS treatments are shown in red, and movement disorders and neuropsychiatric disorders caused by dysfunction of these circuits are listed below the circuit diagrams. Abbreviations: ACA, anterior cingulate area; CMA, cingulate motor area; M1, primary motor cortex; MD, mediodorsal nucleus of thalamus; MOFC, medial orbitofrontal cortex; OCD, obsessive-compulsive disorder; PMC, premotor cortex; SMA, supplementary motor area; TS, Tourette syndrome; VApc, ventral anterior nucleus of thalamus, pars parvocellularis; VAmc, ventral anterior nucleus of thalamus, pars magnocellularis; VLm, ventrolateral nucleus of thalamus, pars medialis; VLo, ventrolateral nucleus of thalamus, pars oralis. See text for other abbreviations. Modified from a figure in ref. [66], used with permission.

Figure 2

Example of the possible use of alternative stimulation regimes [60]. Conventional DBS pulses consist of an initial cathodal stimulation pulse, followed immediately by an anodal (recharge) pulse. This study modeled the impact of introducing a gap between the two pulses, and of reversing the order of cathodal and anodal pulse steps. The two pulse shapes are shown in the top row, where the figure under A. shows the conventional order of stimulation, while the figure under B shows the reversed order. The diagrams on the bottom show the color-coded results of such stimulation. Introduction of a gap within the standard pulse order (A) resulted in a more effective stimulation than conventional stimulation (gap = 0). As shown under (B), reversing the order of stimulation resulted in a similar outcome, although the necessary stimulation strengths were higher than for the conventional order of stimulation pulses. Figure reproduced from figures in [60], used with permission.