Anterior Cingulate Desynchronization and Functional Connectivity with the Amygdala During a Working Memory Task Predict Rapid Antidepressant Response to Ketamine
Giacomo Salvadore, Brian R Cornwell, Fabio Sambataro, David Latov, Veronica Colon-Rosario, Frederick Carver, Tom Holroyd, Nancy Diazgranados, Rodrigo Machado‐Vieira, Christian Grillon, Wayne C. Drevets, Carlos A. Zarate
Neuropsychopharmacology June 1, 2010 DOI: 10.1038/npp.2010.24 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 15 |
| Population | Drug-free patients with major depressive disorder |
| Intervention | Ketamine |
| Dose | single ketamine infusion |
| Duration | 1 to 3 days before infusion; symptom change assessed within 4 hours of administration |
| Topics | Esketamine Ketamine |
| Keywords | Magnetoencephalography meg N-back Biomarker Beta desynchronization |
| Key findings | Low pre-treatment pgACC engagement during increased working memory load correlated with greater symptomatic improvement within four hours of a single ketamine infusion. |
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) <0.05). Pretreatment functional connectivity between the pgACC and the left amygdala was negatively correlated with antidepressant symptom change ( 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.
Comparable studies
Other observational and cohort studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Taming the Ketamine Tiger Volunteers from a prison population | 2010 | Observational study | n = 20 |
| Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Humans | 2017 | Observational study | |
| Disruption of Frontal–Parietal Communication by Ketamine, Propofol, and Sevoflurane Surgical patients undergoing induction of anesthesia with intravenous ketamine | 2013 | Observational cohort | n = 30 |
| Do the dissociative side effects of ketamine mediate its antidepressant effects? Treatment-resistant inpatients with major depressive disorder or bipolar disorder | 2014 | Observational cohort | n = 108 |
| Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder | 2012 | Observational cohort | n = 30 |
Citations in the library
Cited by 51
- Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression American Journal of Psychiatry October 1, 2015
- Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics Annual Review of Medicine October 23, 2014
- A neurotrophic hypothesis of depression: role of synaptogenesis in the actions of NMDA receptor antagonists Philosophical transactions of the Royal Society of London. Series B, Biological sciences July 23, 2012
- Optogenetic stimulation of infralimbic PFC reproduces ketamine’s rapid and sustained antidepressant actions Proceedings of the National Academy of Sciences June 8, 2015
- The use of ketamine as an antidepressant: a systematic review and meta‐analysis Human Psychopharmacology: Clinical and Experimental April 7, 2015
and 46 more in the library
Cites 5
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Glutamate and the Neural Basis of the Subjective Effects of Ketamine Archives of General Psychiatry February 1, 2008
- Effects of Intravenous Ketamine on Explicit and Implicit Measures of Suicidality in Treatment-Resistant Depression Biological Psychiatry July 9, 2009
- Increased anterior cingulate cortical activity in response to fearful faces: a neurophysiological biomarker that predicts rapid antidepressant response to ketamine. Biological Psychiatry February 15, 2009
- Family History of Alcohol Dependence and Initial Antidepressant Response to an NMDA Antagonist Biological Psychiatry November 8, 2008