Iterative Strategies to Refine and Optimize Deep Brain Stimulation for Depression
MetadataShow full item record
It is now more than twelve years since the first study of Deep Brain Stimulation (DBS) for treatment resistant depression (TRD). While multiple centers, testing this and other targets, have replicated these initial positive findings, pivotal industry clinical trials have proven unsuccessful. Strategies to understand these contradictory outcomes are now a priority in the field, particularly with continued interest in development of more advanced invasive neurotechnologies for depression and other treatment refractory neuropsychiatric disorders. Given emerging evidence of sustained long-term positive outcomes despite short term failed trials, a systematic assessment of variables contributing to the observed response heterogeneity are critically needed. To this end, the refinement of DBS of the subcallosal cingulate (SCC) for TRD is illustrative. Until recently, surgical implantation of DBS electrodes relied on high resolution structural images to localize the SCC grey matter-white matter border followed by trial-and-error behavioral testing of chronic stimulation at individual contacts. Clinical response however, may be optimized by more precise targeting along specific white matter tracts, as evidenced by recent diffusion tensor imaging and tractography analyses of DBS responders and non-responders. Based on these retrospective findings, standardization of the surgical procedure has now been improved by use of individualized maps to prospectively guide electrode targeting. The use of close clinical monitoring and systematic long-term follow-up using small experimental cohorts outside of industry-sponsored trials has further provided new perspectives on the time course, trajectory and sustainability of DBS-mediated effects. Next-generation devices additional allow ongoing recordings of local field potentials during acute and chronic stimulation enabling real-time electrophysiological measurements of the time course, trajectory and sustainability of DBS-mediated antidepressant effects. This strategic integration of combined multimodal neuroimaging, behavioral and neural recordings offers a unique opportunity to link first person experiences to changes in measurable physiological biomarkers.