The Role of Electrode Location and Stimulation Polarity in Patient Response to Cortical Stimulation for Major Depressive Disorder

Abstract Background Major depressive disorder (MDD) is a neuropsychiatric condition that affects about one-sixth of the US population. Chronic epidural stimulation (EpCS) of the left dorsolateral prefrontal cortex (DLPFC) was recently evaluated as a treatment option for refractory MDD and was found to be effective during the open-label phase. However, two potential sources of variability in the study were differences in electrode position and the range of stimulation modes that were used in each patient. The objective of this study was to examine these factors in an effort to characterize successful EpCS therapy. Methods Data were analyzed from eleven patients who received EpCS via a chronically implanted system. Estimates were generated of response probability as a function of duration of stimulation. The relative effectiveness of different stimulation modes was also evaluated. Lastly, a computational analysis of the pre- and post-operative imaging was performed to assess the effects of electrode location. The primary outcome measure was the change in Hamilton Depression Rating Scale (HDRS-28). Results Significant improvement was observed in mixed mode stimulation (alternating cathodic and anodic) and continuous anodic stimulation (full power). The changes observed in HDRS-28 over time suggest that 20 weeks of stimulation are necessary to approach a 50% response probability. Lastly, stimulation in the lateral and anterior regions of DLPFC was correlated with greatest degree of improvement. Conclusions A persistent problem in neuromodulation studies has been the selection of stimulation parameters and electrode location to provide optimal therapeutic response. The approach used in this paper suggests that insights can be gained by performing a detailed analysis of response while controlling for important details such as electrode location and stimulation settings.