title: Deep Brain Stimulation Modulates Gamma Oscillations and Theta-Gamma Coupling in Treatment Resistant Depression.
abstract: BACKGROUND
  Deep brain stimulation (DBS) in the subcallosal cingulate gyrus (SCG) is becoming an effective therapeutic option for treatment resistant depression (TRD).
  
  
  OBJECTIVE
  Identifying the neurophysiological mechanisms altered by DBS may lead to more tailored treatment parameters and enhanced efficacy.
  
  
  METHODS
  Twenty TRD patients with implanted DBS in the SCG were recruited. Patients participated in three EEG recording sessions, one with DBS ON, one with DBS randomized to ON or OFF, and one with DBS OFF. During each session, subjects performed N-back working memory tasks, namely the 0-back and 3-back. Fourteen subjects with valid EEG were included in the analysis. Changes in frontal gamma oscillations (30-50 Hz) and coupling between theta (4-7 Hz) and gamma oscillations as a result of DBS stimulation were quantified and correlated with depressive symptoms.
  
  
  RESULTS
  DBS stimulation resulted in suppression of frontal oscillations in the ON state relative to the OFF state during the N-back tasks. Greatest suppression was demonstrated in beta and gamma oscillations and most pronounced during the 3-back. Suppression of gamma oscillations in the 3-back correlated with a reduction in depressive symptoms. DBS ON relative to OFF in the 3-back also resulted in an increase in theta-gamma coupling that correlated with a reduction in depressive symptoms.
  
  
  CONCLUSIONS
  Suppression of gamma oscillations and increased theta-gamma coupling through DBS is likely mediated by both SCG activation of inhibitory circuits and an enhancement of plasticity in the frontal cortex. Activation of both pathways may explain the therapeutic properties of DBS in TRD.
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, University of Toronto, 1001 Queen Street West, Unit 4-1, Toronto, Ontario M6J 1H4, Canada.
authors.forename: Yinming
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Psychiatry, University Health Network, University of Toronto, Toronto, Ontario M5G 2C4, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Giacobbe
authors.affiliation: Department of Psychiatry, University Health Network, University of Toronto, Toronto, Ontario M5G 2C4, Canada.
authors.forename: Chris W
authors.initials: CW
authors.lastname: Tang
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, University of Toronto, 1001 Queen Street West, Unit 4-1, Toronto, Ontario M6J 1H4, Canada.
authors.forename: Mera S
authors.initials: MS
authors.lastname: Barr
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, University of Toronto, 1001 Queen Street West, Unit 4-1, Toronto, Ontario M6J 1H4, Canada.
authors.forename: Tarek
authors.initials: T
authors.lastname: Rajji
authors.affiliation: Department of Psychiatry, University Health Network, University of Toronto, Toronto, Ontario M5G 2C4, Canada.
authors.forename: Sidney H
authors.initials: SH
authors.lastname: Kennedy
authors.affiliation: Monash Alfred Psychiatry Research Centre, Alfred and Monash University Central Clinical School, Victoria, 3004, Australia.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Fitzgerald
authors.affiliation: Department of Neurosurgery, University Health Network, University of Toronto, Toronto, Ontario M5T 2S8, Canada.
authors.forename: Andres M
authors.initials: AM
authors.lastname: Lozano
authors.affiliation: Department of Electrical and Computer Engineering, University of Toronto, Toronto, Ontario M5S 3G4, Canada.
authors.forename: Willy
authors.initials: W
authors.lastname: Wong
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, University of Toronto, 1001 Queen Street West, Unit 4-1, Toronto, Ontario M6J 1H4, Canada. Electronic address: Jeff.Daskalakis@camh.ca.
authors.forename: Zafiris J
authors.initials: ZJ
authors.lastname: Daskalakis
mesh_terms: D000328:Adult; D046690:Deep Brain Stimulation / Q000379:methods*; D061218:Depressive Disorder, Treatment-Resistant / Q000175:diagnosis* / Q000628:therapy*; D005260:Female; D005625:Frontal Lobe / Q000502:physiology; D065818:Gamma Rhythm / Q000502:physiology*; D006179:Gyrus Cinguli / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D013826:Theta Rhythm / Q000502:physiology*; D016896:Treatment Outcome
keywords: Deep brain stimulation; Electroencephalography; Gamma oscillations; Subcallosal cingulate gyrus; Theta–gamma coupling; Treatment resistant depression