State-dependent responses to intracranial brain stimulation in a patient with depression

Abstract

Deep brain stimulation is a promising treatment for severe depression, but lack of efficacy in randomized trials raises questions regarding anatomical targeting. We implanted multi-site intracranial electrodes in a severely depressed patient and systematically assessed the acute response to focal electrical neuromodulation. We found an elaborate repertoire of distinctive emotional responses that were rapid in onset, reproducible, and context and state dependent. Results provide proof of concept for personalized, circuit-specific medicine in psychiatry.

Fig. 1 |. Mapping mood across the corticolimbic circuit.

a, Examples of the clinical responses to ∼90 s of stimulation. Electrodes that demonstrated a positive or negative mood response to stimulation are enlarged for emphasis and shaded with color of respective region. b, Relationship of patient response to literature. c, Covariance matrix of relationship between depression measures (Methods) (left) and heat map of average Likert scores per stimulation condition (right). Somatic symptoms (side effects) of stimulation are also shown. d, Location of stereoelectroencephalography leads in the VC/VS, SGC and OFC with neighboring fiber tracts defined by diffusion tensor imaging. Left, Anterior thalamic radiations and VC–brainstem tracts (inset); middle, forceps minor, stria terminalis/cingulum bundle and uncinate fasciculus; and right, forceps minor and uncinate fasciculus. AMY, amygdala; HAMD, Hamilton Depression Rating Scale; HPC, hippocampus; VAS, Visual Analog Scale.

Fig. 2 |. Characterization of response properties.

a, Effect of stimulation on arousal dimension of depression across four trials of stimulation in each brain region. b, State dependence for OFC stimulation. The left axis marks the arousal state before stimulation; the right axis shows mood state (Mood_V) measured after stimulation. c, State dependence for SGC and VC/CS stimulation. d, Dose dependence of stimulation for VC/VS on dimensions of both mood and anxiety. Each bar represents response after one trial of stimulation at 1, 2 or 3 mA. e, Response durability for example trials are shown for VC/CS (red), OFC (purple) and SGC (blue) for both arousal (colored line) and Mood_V (gray line). The black bar indicates the duration of stimulation.