Neural Interoceptive Processing is Modulated by Deep Brain Stimulation for Treatment Resistant Depression

Background A critical advance in depression research is to clarify the hypothesized role of interoceptive processing in neural mechanisms of treatment efficacy. This study tests whether cortical interoceptive processing, as indexed by the heartbeat-evoked potential (HEP), is modulated by deep brain stimulation (DBS) to the subcallosal cingulate (SCC) for treatment resistant depression (TRD).Methods Eight patients with TRD were enrolled in a study of SCC DBS safety and efficacy. Electroencephalography (EEG) and symptom severity measures were sampled in a laboratory setting over the course of a six-month treatment protocol. The primary outcome measure was an EEG-derived HEP, which reflects cortical processing of heartbeat sensation. Cluster-based permutation analyses were used to test the effect of stimulation and time in treatment on the HEP. The change in signal magnitude after treatment was correlated with change in depression severity as measured by the 17-item Hamilton Depression Rating Scale.Results HEP amplitude was greater after 24 weeks of treatment ( t (7)=-4.40, p =.003, g= -1.38, 95% Cl [-2.3, -0.42]), and this change was inversely correlated with latency of treatment response (rho = -0.75, 95% Cl [-0.95, -0.11], p= .03). An acute effect of DBS was also observed, but as a decrease in HEP amplitude ( t ([6][1]) =6.66, p <.001, g= 2.19, 95% Cl [0.81, 3.54]). HEP differences were most pronounced over left posterior sensors from 405-425 ms post-stimulus.Conclusion Brain-based evidence substantiates a theorized link between interoception and depression, and suggests an interoceptive contribution to the mechanism of treatment efficacy with deep brain stimulation for severe depression.### Competing Interest StatementDr. Choi is a consultant to Abbott Laboratories. Dr. Mayberg received consulting and IP licensing fees from Abbott Laboratories. Dr. Riva-Posse has received consulting fees Janssen Pharmaceuticals, Abbott Laboratories and LivaNova, Inc. Dr. Rozell is a consultant to Motif Neurotech, Inc. Dr. Figee has received consulting fees from Medtronic. [1]: #ref-6