title: Identification of reproducible individualized targets for treatment of depression with TMS based on intrinsic connectivity.
abstract: Transcranial magnetic stimulation (TMS) to the left dorsolateral prefrontal cortex (DLPFC) is used clinically for the treatment of depression however outcomes vary greatly between patients. We have shown that average clinical efficacy of different left DLPFC TMS sites is related to intrinsic functional connectivity with remote regions including the subgenual cingulate and suggested that functional connectivity with these remote regions might be used to identify optimized left DLPFC targets for TMS. However it remains unclear if and how this connectivity-based targeting approach should be applied at the single-subject level to potentially individualize therapy to specific patients. In this article we show that individual differences in DLPFC connectivity are large, reproducible across sessions, and can be used to generate individualized DLPFC TMS targets that may prove clinically superior to those selected on the basis of group-average connectivity. Factors likely to improve individualized targeting including the use of seed maps and the focality of stimulation are investigated and discussed. The techniques presented here may be applicable to individualized targeting of focal brain stimulation across a range of diseases and stimulation modalities and can be experimentally tested in clinical trials.
authors.affiliation: Partners Neurology, Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School, Boston, MA, USA. Electronic address: foxmdphd@gmail.com.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Fox
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School, Boston, MA, USA.
authors.forename: Hesheng
authors.initials: H
authors.lastname: Liu
authors.affiliation: Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA; Institut Guttmann, Hospital de Neurorehabilitació, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pascual-Leone
mesh_terms: D000328:Adult; D001931:Brain Mapping; D003863:Depression / Q000628:therapy*; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008297:Male; D008875:Middle Aged; D057285:Precision Medicine; D017397:Prefrontal Cortex / Q000502:physiology*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D055815:Young Adult
keywords: Depression; Dorsolateral prefrontal cortex; Individual differences; Intrinsic connectivity; MRI; Resting state functional connectivity; Seed map; Subgenual; TMS; Transcranial magnetic stimulation; Variability