title: Transcranial Magnetic Stimulation of Left Dorsolateral Prefrontal Cortex Induces Brain Morphological Changes in Regions Associated with a Treatment Resistant Major Depressive Episode: An Exploratory Analysis.
abstract: Repetitive transcranial magnetic stimulation (TMS) is an FDA-approved antidepressant treatment but little is known of its mechanism of action. Specifically, downstream effects of TMS remain to be elucidated.
  
  
  
  This study aims to identify brain structural changes from TMS treatment of a treatment resistant depressive episode through an exploratory analysis.
  
  
  
  Twenty-seven subjects in a DSM-IV current major depressive episode and on a stable medication regimen had a 3T magnetic resonance T1 structural scan before and after five weeks of standard TMS treatment to the left dorsolateral prefrontal cortex. Twenty-seven healthy volunteer (HVs) subjects had the same brain MRI acquisition. Voxel-based morphometry was performed using high dimensional non-linear diffusomorphic anatomical registration (DARTEL).
  
  
  
  Six clusters of gray matter volume (GMV) that were lower in pre-treatment MRIs of depressed subjects than in HVs. GMV in four of these regions increased in MDD after TMS treatment by 3.5-11.2%. The four brain regions that changed with treatment were centered in the left anterior cingulate cortex, the left insula, the left superior temporal gyrus and the right angular gyrus. Increases in the anterior cingulate GMV with TMS correlated with improvement in depression severity.
  
  
  
  To our knowledge, this is the first study of brain structural changes during TMS treatment of depression. The affected brain areas are involved in cognitive appraisal, decision-making and subjective experience of emotion. These effects may have potential relevance for the antidepressant action of TMS.
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA; Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, USA. Electronic address: mjl2159@cumc.columbia.edu.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Lan
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA; Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, USA.
authors.forename: Binod Thapa
authors.initials: BT
authors.lastname: Chhetry
authors.affiliation: Department of Psychiatry, Weill Cornell Medical College, USA; Fell Family Brain and Mind Research Institute, Weill Cornell Medical College, USA.
authors.forename: Conor
authors.initials: C
authors.lastname: Liston
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA; Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, USA.
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
authors.affiliation: Department of Psychiatry, Weill Cornell Medical College, USA; Fell Family Brain and Mind Research Institute, Weill Cornell Medical College, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Dubin
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology*; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000628:therapy*; D061218:Depressive Disorder, Treatment-Resistant / Q000000981:diagnostic imaging / Q000628:therapy*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D050781:Transcranial Magnetic Stimulation / Q000379:methods*
keywords: Anterior cingulate cortex; Antidepressive agents; Depressive disorder; Gray matter; Magnetic resonance imaging; Transcranial magnetic stimulation