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.

Trial registration: ClinicalTrials.gov NCT00024635.

Keywords: Connectivity; Depression; Independent components analysis (ICA); Ketamine; Magnetoencephalography (MEG); Resting state.

Conflict of interest statement

Dr. Zarate is listed as a co-inventor on a patent application for the use of ketamine and its metabolites in major depression; he has assigned his rights in the patent to the US Government but will share a percentage of any royalties that may be received by the Government. The remaining authors declare no competing financial interests.

Published by Elsevier Ireland Ltd.

Figures

Figure 1

(A) Mean beta weight within right and left amygdala regions of interest (ROIs) as a measure of connectivity with left lateralized insulo-temporal independent component (IC) at baseline in participants with major depressive disorder (MDD) and healthy controls, and post-ketamine in participants with MDD. (B) Voxel-wise map of significant differences in connectivity between healthy controls and patients with MDD at baseline. BL: baseline; KET: ketamine; HC: healthy controls.

Figure 2

(A) Mean beta weight within right and left amygdala regions of interest (ROIs) as a measure of connectivity with right lateralized insulo-temporal independent component (IC) at baseline in participants with major depressive disorder (MDD) and healthy controls, and post-ketamine in participants with MDD. BL: baseline; KET: ketamine; HC: healthy controls.

Figure 3

(A) Mean beta weight within the subgenual anterior cingulate cortex (sgACC) region of interest (ROI) as a measure of connectivity with the bilateral precentral independent component (IC) at baseline in participants with major depressive disorder (MDD) and healthy controls, and post-ketamine in participants with MDD. (B) Voxel-wise map of significant differences in connectivity between patients with MDD at baseline and post-ketamine infusion. BL: baseline; KET: ketamine; HC: healthy controls.

Figure 4

(A) Bilateral parahippocampal gyrus/subgenual anterior cingulate cortex (sgACC) independent component (IC). (B) Voxel-wise map of significant differences in connectivity between patients with major depressive disorder (MDD) at baseline and post-ketamine infusion.

Figure 5

Scatter plot illustrating subgenual anterior cingulate cortex (sgACC) connectivity with the bilateral precentral independent component (IC) shown in Figure 3A, plotted vs. glucose metabolism in the same sgACC region of interest (ROI). Panels from top to bottom depict absolute sgACC rMRGlu at baseline, post-ketamine, and the difference between post-ketamine and baseline sessions, plotted against connectivity at the same time points. Data from eight subjects with both magnetoencephalography (MEG) and positron emission tomography (PET) data are shown.