title: Brain connectomics predict response to treatment in social anxiety disorder.
abstract: We asked whether brain connectomics can predict response to treatment for a neuropsychiatric disorder better than conventional clinical measures. Pre-treatment resting-state brain functional connectivity and diffusion-weighted structural connectivity were measured in 38 patients with social anxiety disorder (SAD) to predict subsequent treatment response to cognitive behavioral therapy (CBT). We used a priori bilateral anatomical amygdala seed-driven resting connectivity and probabilistic tractography of the right inferior longitudinal fasciculus together with a data-driven multivoxel pattern analysis of whole-brain resting-state connectivity before treatment to predict improvement in social anxiety after CBT. Each connectomic measure improved the prediction of individuals' treatment outcomes significantly better than a clinical measure of initial severity, and combining the multimodal connectomics yielded a fivefold improvement in predicting treatment response. Generalization of the findings was supported by leave-one-out cross-validation. After dividing patients into better or worse responders, logistic regression of connectomic predictors and initial severity combined with leave-one-out cross-validation yielded a categorical prediction of clinical improvement with 81% accuracy, 84% sensitivity and 78% specificity. Connectomics of the human brain, measured by widely available imaging methods, may provide brain-based biomarkers (neuromarkers) supporting precision medicine that better guide patients with neuropsychiatric diseases to optimal available treatments, and thus translate basic neuroimaging into medical practice.
authors.affiliation: Poitras Center for Affective Disorders Research, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Whitfield-Gabrieli
authors.affiliation: Poitras Center for Affective Disorders Research, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA.|Department of Otology and Laryngoloy, Harvard Medical School, Boston, MA, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Ghosh
authors.affiliation: Poitras Center for Affective Disorders Research, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.|Department of Speech, Language and Hearing Sciences, Boston University, Boston, MA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Nieto-Castanon
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Saygin
authors.affiliation: Poitras Center for Affective Disorders Research, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: O
authors.initials: O
authors.lastname: Doehrmann
authors.affiliation: Poitras Center for Affective Disorders Research, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: X J
authors.initials: XJ
authors.lastname: Chai
authors.affiliation: Poitras Center for Affective Disorders Research, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: G O
authors.initials: GO
authors.lastname: Reynolds
authors.affiliation: Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Hofmann
authors.affiliation: Department of Psychiatry, Rush University Medical Center, Chicago, IL, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Pollack
authors.affiliation: Poitras Center for Affective Disorders Research, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: J D E
authors.initials: JD
authors.lastname: Gabrieli
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000503:physiopathology*; D015928:Cognitive Behavioral Therapy / Q000379:methods; D063132:Connectome; D005260:Female; D006801:Humans; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology; D000072861:Phobia, Social / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy*; D011379:Prognosis; D012146:Rest; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D055815:Young Adult