title: Longitudinal Changes in Depressive Circuitry in Response to Neuromodulation Therapy.
abstract: Major depressive disorder (MDD) is a public health problem worldwide. There is increasing interest in using non-invasive therapies such as repetitive transcranial magnetic stimulation (rTMS) to treat MDD. However, the changes induced by rTMS on neural circuits remain poorly characterized. The present study aims to test whether the brain regions previously targeted by deep brain stimulation (DBS) in the treatment of MDD respond to rTMS, and whether functional connectivity (FC) measures can predict clinical response.
  
  
  
  rTMS (20 sessions) was administered to five MDD patients at the left-dorsolateral prefrontal cortex (L-DLPFC) over 4 weeks. Magnetoencephalography (MEG) recordings and Montgomery-Asberg depression rating scale (MADRS) assessments were acquired before, during and after treatment. Our primary measures, obtained with MEG source imaging, were changes in power spectral density (PSD) and changes in FC as measured using coherence.
  
  
  
  Of the five patients, four met the clinical response criterion (40% or greater decrease in MADRS) after 4 weeks of treatment. An increase in gamma power at the L-DLPFC was correlated with improvement in symptoms. We also found that increases in delta band connectivity between L-DLPFC/amygdala and L-DLPFC/pregenual anterior cingulate cortex (pACC), and decreases in gamma band connectivity between L-DLPFC/subgenual anterior cingulate cortex (sACC), were correlated with improvements in depressive symptoms.
  
  
  
  Our results suggest that non-invasive intervention techniques, such as rTMS, modulate the ongoing activity of depressive circuits targeted for DBS, and that MEG can capture these changes. Gamma oscillations may originate from GABA-mediated inhibition, which increases synchronization of large neuronal populations, possibly leading to increased long-range FC. We postulate that responses to rTMS could provide valuable insights into early evaluation of patient candidates for DBS surgery.
authors.affiliation: Department of Biomedical Engineering, Marquette University Milwaukee, WI, USA.
authors.forename: Yagna
authors.initials: Y
authors.lastname: Pathak
authors.affiliation: Department of Psychiatry, Medical College of Wisconsin Milwaukee, WI, USA.
authors.forename: Oludamilola
authors.initials: O
authors.lastname: Salami
authors.affiliation: McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University Montreal, QC, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Baillet
authors.affiliation: Department of Neurology, Medical College of Wisconsin Milwaukee, WI, USA.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Biomedical Engineering, Marquette UniversityMilwaukee, WI, USA; Department of Psychiatry, Medical College of WisconsinMilwaukee, WI, USA; Department of Neurology, Medical College of WisconsinMilwaukee, WI, USA; Department of Bioengineering, Scientific Computing and Imaging (SCI) Institute, University of UtahSalt Lake City, UT, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Butson
mesh_terms: D000328:Adult; D058256:Brain Waves / Q000502:physiology*; D003865:Major Depressive Disorder / Q000503:physiopathology* / Q000628:therapy*; D006801:Humans; D008137:Longitudinal Studies; D015225:Magnetoencephalography; D017063:Outcome Assessment, Health Care / Q000379:methods*; D017397:Prefrontal Cortex / Q000503:physiopathology*; D011569:Psychiatric Status Rating Scales; D050781:Transcranial Magnetic Stimulation / Q000379:methods*
keywords: deep brain stimulation (DBS); depression; dorsolateral prefrontal cortex (DLPFC); functional connectivity; neuromodulation; repetitive transcranial magnetic stimulation (rTMS)