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

Sina Sadeghzadeh; Akshay Swaminathan; Priya Bhanot; Samantha Steeman; Audrey Xu; Vaibhavi Shah; David A Purger; Vivek P Buch

doi:10.1016/j.bpsc.2024.04.007

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

Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 Apr 26:S2451-9022(24)00109-5. doi: 10.1016/j.bpsc.2024.04.007. Online ahead of print.

Authors

Sina Sadeghzadeh¹, Akshay Swaminathan², Priya Bhanot³, Samantha Steeman⁴, Audrey Xu⁵, Vaibhavi Shah⁶, David A Purger⁷, Vivek P Buch⁸

Affiliations

¹ Stanford University School of Medicine, Stanford, CA. Electronic address: sinas@stanford.edu.
² Stanford University School of Medicine, Stanford, CA. Electronic address: akshay325@gmail.com.
³ Icahn School of Medicine at Mount Sinai, New York City, NY. Electronic address: priya.bhanot@icahn.mssm.edu.
⁴ Stanford University School of Medicine, Stanford, CA. Electronic address: steeman@stanford.edu.
⁵ Department of Biology, Stanford University, Stanford, CA. Electronic address: yixu2@stanford.edu.
⁶ Stanford University School of Medicine, Stanford, CA. Electronic address: vaibhavi@stanford.edu.
⁷ Department of Neurosurgery, Stanford University, Stanford, CA. Electronic address: dpurger@stanford.edu.
⁸ Department of Neurosurgery, Stanford University, Stanford, CA. Electronic address: vpbuch@stanford.edu.

PMID: 38679323
DOI: 10.1016/j.bpsc.2024.04.007

Abstract

Background: 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.

Methods: 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.

Results: 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: β=15.8%, p=0.09; MFB: β=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).

Conclusions: Our findings underscore the promise of tractography in DBS for TRD as a methodology for personalization of therapy, supporting its inclusion in future trials.

Keywords: Deep brain stimulation (DBS); Diffusion Tensor Imaging (DTI); Neurosurgery; depression; major depressive disorder (MDD); tractography; treatment-resistant depression (TRD); white matter tracts.