title: Preliminary differences in resting state MEG functional connectivity pre- and post-ketamine in major depressive disorder.
abstract: Functional neuroimaging techniques including magnetoencephalography (MEG) have demonstrated that the brain is organized into networks displaying correlated activity. Group connectivity differences between healthy controls and participants with major depressive disorder (MDD) can be detected using temporal independent components analysis (ICA) on beta-bandpass filtered Hilbert envelope MEG data. However, the response of these networks to treatment is unknown. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, exerts rapid antidepressant effects. We obtained MEG recordings before and after open-label infusion of 0.5mg/kg ketamine in MDD subjects (N=13) and examined networks previously shown to differ between healthy individuals and those with MDD. Connectivity between the amygdala and an insulo-temporal component decreased post-ketamine in MDD subjects towards that observed in control subjects at baseline. Decreased baseline connectivity of the subgenual anterior cingulate cortex (sgACC) with a bilateral precentral network had previously been observed in MDD compared to healthy controls, and the change in connectivity post-ketamine was proportional to the change in sgACC glucose metabolism in a subset (N=8) of subjects receiving [11F]FDG-PET imaging. Ketamine appeared to reduce connectivity, regardless of whether connectivity was abnormally high or low compared to controls at baseline. These preliminary findings suggest that sgACC connectivity may be directly related to glutamate levels.
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. Electronic address: nugenta@mail.nih.gov.
authors.forename: Allison C
authors.initials: AC
authors.lastname: Nugent
authors.affiliation: NIMH Magnetoencephalography Core Facility, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Robinson
authors.affiliation: NIMH Magnetoencephalography Core Facility, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Coppola
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Zarate
mesh_terms: D000328:Adult; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D059907:Functional Neuroimaging / Q000379:methods*; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology*; D015225:Magnetoencephalography / Q000379:methods*; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D049268:Positron-Emission Tomography
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine
keywords: Connectivity; Depression; Independent components analysis (ICA); Ketamine; Magnetoencephalography (MEG); Resting state