title: Increases in frontostriatal connectivity are associated with response to dorsomedial repetitive transcranial magnetic stimulation in refractory binge/purge behaviors.
abstract: BACKGROUND
  Conventional treatments for eating disorders are associated with poor response rates and frequent relapse. Novel treatments are needed, in combination with markers to characterize and predict treatment response. Here, resting-state functional magnetic resonance imaging (rs-fMRI) was used to identify predictors and correlates of response to repetitive transcranial magnetic stimulation (rTMS) of the dorsomedial prefrontal cortex (dmPFC) at 10 Hz for eating disorders with refractory binge/purge symptomatology.
  
  
  METHODS
  28 subjects with anorexia nervosa, binge-purge subtype or bulimia nervosa underwent 20-30 sessions of 10 Hz dmPFC rTMS. rs-fMRI data were collected before and after rTMS. Subjects were stratified into responder and nonresponder groups using a criterion of ≥50% reduction in weekly binge/purge frequency. Neural predictors and correlates of response were identified using seed-based functional connectivity (FC), using the dmPFC and adjacent dorsal anterior cingulate cortex (dACC) as regions of interest.
  
  
  RESULTS
  16 of 28 subjects met response criteria. Treatment responders had lower baseline FC from dmPFC to lateral orbitofrontal cortex and right posterior insula, and from dACC to right posterior insula and hippocampus. Responders had low baseline FC from the dACC to the ventral striatum and anterior insula; this connectivity increased over treatment. However, in nonresponders, frontostriatal FC was high at baseline, and dmPFC-rTMS suppressed FC in association with symptomatic worsening.
  
  
  CONCLUSIONS
  Enhanced frontostriatal connectivity was associated with responders to dmPFC-rTMS for binge/purge behavior. rTMS caused paradoxical suppression of frontostriatal connectivity in nonresponders. rs-fMRI could prove critical for optimizing stimulation parameters in a future sham-controlled trial of rTMS in disordered eating.
authors.affiliation: Institute of Medical Sciences, University of Toronto, Toronto, Canada ; MRI-Guided rTMS Clinic, University Health Network, Toronto, Canada.
authors.forename: Katharine
authors.initials: K
authors.lastname: Dunlop
authors.affiliation: Institute of Medical Sciences, University of Toronto, Toronto, Canada ; Department of Psychiatry, University Health Network, Toronto, Canada ; Department of Psychiatry, University of Toronto, Toronto, Canada ; Eating Disorders Program, University Health Network, Toronto, Canada.
authors.forename: Blake
authors.initials: B
authors.lastname: Woodside
authors.affiliation: Eating Disorders Program, University Health Network, Toronto, Canada.
authors.forename: Eileen
authors.initials: E
authors.lastname: Lam
authors.affiliation: Department of Psychiatry, University Health Network, Toronto, Canada ; Department of Psychiatry, University of Toronto, Toronto, Canada ; Eating Disorders Program, University Health Network, Toronto, Canada.
authors.forename: Marion
authors.initials: M
authors.lastname: Olmsted
authors.affiliation: Department of Psychiatry, University Health Network, Toronto, Canada ; Department of Psychiatry, University of Toronto, Toronto, Canada.
authors.forename: Patricia
authors.initials: P
authors.lastname: Colton
authors.affiliation: MRI-Guided rTMS Clinic, University Health Network, Toronto, Canada ; Department of Psychiatry, University Health Network, Toronto, Canada ; Department of Psychiatry, University of Toronto, Toronto, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Giacobbe
authors.affiliation: Institute of Medical Sciences, University of Toronto, Toronto, Canada ; MRI-Guided rTMS Clinic, University Health Network, Toronto, Canada ; Department of Psychiatry, University Health Network, Toronto, Canada ; Toronto Western Research Institute, University Health Network, Toronto, Canada ; Department of Psychiatry, University of Toronto, Toronto, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Downar
mesh_terms: D000328:Adult; D000856:Anorexia Nervosa / Q000503:physiopathology / Q000628:therapy; D056912:Binge-Eating Disorder / Q000503:physiopathology / Q000628:therapy; D052018:Bulimia Nervosa / Q000503:physiopathology / Q000628:therapy; D001068:Feeding and Eating Disorders / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods*; D017397:Prefrontal Cortex / Q000503:physiopathology*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D066328:Ventral Striatum / Q000503:physiopathology*; D055815:Young Adult