A connectomic analysis of deep brain stimulation for treatment-resistant depression

Zhoule Zhu, Elizabeth Hubbard, Xinxia Guo, Daniel A.N. Barbosa, Abdul Malik Popal, Chengwei Cai, Hongjie Jiang, Zhe Zheng, Jingquan Lin, Wei Gao, Jianmin Zhang, Katrina Bartas, Desiree Macchia, Pieter Derdeyn, Casey H. Halpern, Helen S. Mayberg, Kevin T. Beier, Junming Zhu, Hemmings Wu

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Objective: Deep brain stimulation (DBS) has been used as a treatment of last resort for treatment-resistant depression (TRD) for more than a decade. Many DBS targets have been proposed and tested clinically, but the underlying circuit mechanisms remain unclear. Uncovering white matter tracts (WMT) activated by DBS targets may provide crucial information about the circuit substrates mediating DBS efficacy in ameliorating TRD. Methods: We performed probabilistic tractography using diffusion magnetic resonance imaging datas from 100 healthy volunteers in Human Connectome Project datasets to analyze the structural connectivity patterns of stimulation targeting currently-used DBS target for TRD. We generated mean and binary fiber distribution maps and calculated the numbers of WMT streamlines in the dataset. Results: Probabilistic tracking results revealed that activation of distinct DBS targets demonstrated modulation of overlapping but considerably distinct pathways. DBS targets were categorized into 4 groups: Cortical, Striatal, Thalamic, and Medial Forebrain Bundle according to their main modulated WMT and brain areas. Our data also revealed that Brodmann area 10 and amygdala are hub structures that are associated with all DBS targets. Conclusions: Our results together suggest that the distinct mechanism of DBS targets implies individualized target selection and formulation in the future of DBS treatment for TRD. The modulation of Brodmann area 10 and amygdala may be critical for the efficacy of DBS-mediated treatment of TRD.

Original languageEnglish
Pages (from-to)1226-1233
Number of pages8
JournalBrain Stimulation
Issue number5
StatePublished - Sep 2021


  • Amygdala
  • Brodmann area 10
  • Deep brain stimulation
  • Tractography
  • Treatment-resistant depression


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