Anterior Cingulate Desynchronization and Functional Connectivity with the Amygdala During a Working Memory Task Predict Rapid Antidepressant Response to Ketamine
- 10 March 2010
- journal article
- Published by Springer Nature in Neuropsychopharmacology
- Vol. 35 (7), 1415-1422
- https://doi.org/10.1038/npp.2010.24
Abstract
Pregenual anterior cingulate cortex (pgACC) hyperactivity differentiates treatment responders from non-responders to various pharmacological antidepressant interventions, including ketamine, an N-methyl-D-aspartate receptor antagonist. Evidence of pgACC hyperactivition during non-emotional working memory tasks in patients with major depressive disorder (MDD) highlights the importance of this region for processing both emotionally salient and cognitive stimuli. However, it is unclear whether pgACC activity might serve as a potential biomarker of antidepressant response during working memory tasks as well, in line with previous research with emotionally arousing tasks. This study tested the hypothesis that during the N-back task, a widely used working memory paradigm, low pretreatment pgACC activity, as well as coherence between the pgACC and the amygdala, would be correlated with the clinical improvement after ketamine. Magnetoencephalography (MEG) recordings were obtained from 15 drug-free patients with MDD during working memory performance 1 to 3 days before receiving a single ketamine infusion. Functional activation patterns were analyzed using advanced MEG source analysis. Source coherence analyses were conducted to quantify the degree of long-range functional connectivity between the pgACC and the amygdala. Patients who showed the least engagement of the pgACC in response to increased working memory load showed the greatest symptomatic improvement within 4 h of ketamine administration (r=0.82, p=0.0002, false discovery rate (FDR) r=−0.73, p=0.0021, FDR <0.05).These data implicate the pgACC and its putative interaction with the amygdala in predicting antidepressant response to ketamine in a working memory task context.Keywords
This publication has 42 references indexed in Scilit:
- Cognitive fitness of cost-efficient brain functional networksProceedings of the National Academy of Sciences, 2009
- Effects of Intravenous Ketamine on Explicit and Implicit Measures of Suicidality in Treatment-Resistant DepressionBiological Psychiatry, 2009
- Targeted electrode-based modulation of neural circuits for depressionJCI Insight, 2009
- Family History of Alcohol Dependence and Initial Antidepressant Response to an N-methyl-D-aspartate AntagonistBiological Psychiatry, 2008
- Increased Anterior Cingulate Cortical Activity in Response to Fearful Faces: A Neurophysiological Biomarker that Predicts Rapid Antidepressant Response to KetamineBiological Psychiatry, 2008
- Cognitive therapy versus medication for depression: treatment outcomes and neural mechanismsNature Reviews Neuroscience, 2008
- Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depressionBrain Structure and Function, 2008
- Frontal and Limbic Activation During Inhibitory Control Predicts Treatment Response in Major Depressive DisorderBiological Psychiatry, 2007
- Limbic over-activity in depression during preserved performance on the n-back taskNeuroImage, 2005
- A New Depression Scale Designed to be Sensitive to ChangeThe British Journal of Psychiatry, 1979