Intraoperative neural signals predict rapid antidepressant effects of deep brain stimulation

Mohammad S E Sendi,Faical Isbaine,Patricio Riva-Posse,Andrea Crowell,Helen S Mayberg,Ki Sueng Choi,Vineet Tiruvadi,Robert E Gross,Babak Mahmoudi,Allison C Waters,John T Gale

doi:10.1038/s41398-021-01669-0

Abstract

Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) is a promising intervention for treatment-resistant depression (TRD). Despite the failure of a clinical trial, multiple case series have described encouraging results, especially with the introduction of improved surgical protocols. Recent evidence further suggests that tractography targeting and intraoperative exposure to stimulation enhances early antidepressant effects that further evolve with ongoing chronic DBS. Accelerating treatment gains is critical to the care of this at-risk population, and identification of intraoperative electrophysiological biomarkers of early antidepressant effects will help guide future treatment protocols. Eight patients underwent intraoperative electrophysiological recording when bilateral DBS leads were implanted in the SCC using a connectomic approach at the site previously shown to optimize 6-month treatment outcomes. A machine learning classification method was used to discriminate between intracranial local field potentials (LFPs) recorded at baseline (stimulation-naïve) and after the first exposure to SCC DBS during surgical procedures. Spectral inputs (theta, 4–8 Hz; alpha, 9–12 Hz; beta, 13–30 Hz) to the model were then evaluated for importance to classifier success and tested as predictors of the antidepressant response. A decline in depression scores by 45.6% was observed after 1 week and this early antidepressant response correlated with a decrease in SCC LFP beta power, which most contributed to classifier success. Intraoperative exposure to therapeutic stimulation may result in an acute decrease in symptoms of depression following SCC DBS surgery. The correlation of symptom improvement with an intraoperative reduction in SCC beta power suggests this electrophysiological finding as a biomarker for treatment optimization.

Highlights

The long-term efficacy of deep brain stimulation (DBS) to the subcallosal cingulate (SCC) in patients with treatment-resistant depression (TRD) has been repeatedly demonstrated in independent, open-label studies with additional evidence of sustained response and remission over years of ongoing treatment [1,2,3,4,5]
Acute changes in brain electrophysiology following exposure to intraoperative SCC-DBS Logistic regression classifiers with elastic-net regularization discriminated between baseline (PRE) and post-stimulation (POST) local field potentials (LFPs) in the SCC region: area under the curve (AUCmean) = 0.729, SD = 0.034, N = 7. (Data from one patient was excluded from the analysis due to excessive noise in the right hemisphere lead.) The AUC in Fig. 2A represents the average out-of-sample classification performance; repeated iterations used data from six subjects for training the model and the remaining one subject for testing
Intraoperative exposure to stimulation delivered bilaterally in the tractography-defined targets generated electrophysiological changes in LFPs that were successfully discriminated by machine learning classifiers

Summary

Introduction

The long-term efficacy of deep brain stimulation (DBS) to the subcallosal cingulate (SCC) in patients with treatment-resistant depression (TRD) has been repeatedly demonstrated in independent, open-label studies with additional evidence of sustained response and remission over years of ongoing treatment [1,2,3,4,5]. While these accounts have documented a sustained effectiveness of this treatment with chronic stimulation, there are differences in the timeline of recovery across patients.

Methods

Results

Conclusion