Emerging Outlook on Personalized Neuromodulation for Depression: Insights from Tractography-Based Targeting.

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Abstract

Deep brain stimulation (DBS) has shown individual promise in treating treatment resistant depression (TRD), but larger-scale trials have been less successful. Here, we create the largest meta-analysis with individual patient data (IPD) to date to explore if the use of tractography enhances the efficacy of DBS for TRD.We systematically reviewed 1823 articles, selecting 32 that contributed data from 366 patients. We stratified the IPD based on stimulation target and use of tractography. Utilizing two-way type III Analysis of Variance (ANOVA), Welch Two Sample t-tests, and mixed-effects linear regression models, we evaluated changes in depression severity 9-15 months post-surgery (1-Y) and at last follow-up (LFU) (4 weeks - 8 years) as assessed by depression scales.Tractography was used for medial forebrain bundle (MFB, n=17/32), subcallosal cingulate (SCC, n=39/241), and ventral capsule/ventral striatum (VC/VS, n=3/41) targets; and not used for bed nucleus of stria terminalis (n=11), lateral habenula (n=10), and inferior thalamic peduncle (n=1). Across all patients, tractography significantly improved mean depression scores at 1-Y (p<0.001) and LFU (p=0.009). Within the target cohorts, tractography improved depression scores at 1-Y for both MFB and SCC, though significance was only met at the alpha = 0.1 level (SCC: ß=15.8%, p=0.09; MFB: ß=52.4%, p=0.10). Within the tractography cohort, MFB with tractography patients showed greater improvement than those with SCC with tractography (72.42±7.17% versus 54.78±4.08%) at 1-Y (p=0.044).Our findings underscore the promise of tractography in DBS for TRD as a methodology for personalization of therapy, supporting its inclusion in future trials.

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