Zhoule Zhu1, Elizabeth Hubbard2, Xinxia Guo1, Daniel A N Barbosa3, Abdul Malik Popal1, Chengwei Cai1, Hongjie Jiang1, Zhe Zheng1, Jingquan Lin1, Wei Gao1, Jianmin Zhang1, Katrina Bartas4, Desiree Macchia2, Pieter Derdeyn4, Casey H Halpern3, Helen S Mayberg5, Kevin T Beier6, Junming Zhu7, Hemmings Wu8. 1. Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310009, China. 2. Department of Physiology and Biophysics, University of California, Irvine, CA, 92697-4560, USA. 3. Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, 94305, USA. 4. Program in Mathematical, Computational, and Systems Biology, University of California, Irvine, CA, 92697-4560, USA. 5. Departments of Neurology and Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. 6. Department of Physiology and Biophysics, University of California, Irvine, CA, 92697-4560, USA; Department of Neurobiology and Behavior, University of California, Irvine, CA, 92697-4560, USA; Department of Biomedical Engineering, University of California, Irvine, CA, 92697-4560, USA; Department of Pharmaceutical Sciences, University of California, Irvine, CA, 92697-4560, USA; Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA, 92697, USA. Electronic address: kbeier@uci.edu. 7. Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310009, China. Electronic address: dr.zhujunming@zju.edu.cn. 8. Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310009, China. Electronic address: hemmings@zju.edu.cn.
Abstract
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.
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.
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