Ketamine administration reduces amygdalo‐hippocampal reactivity to emotional stimulation
Milan Scheidegger, Anke Henning, Martin Walter, Mick Lehmann, Rainer Kraehenmann, Heinz Boeker, Erich Seifritz, Simone Grimm
Human Brain Mapping February 25, 2016 DOI: 10.1002/hbm.23148 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study with fMRI and resting-state fMRI Peer reviewed |
|---|---|
| Sample size | 23 |
| Population | Healthy subjects |
| Intervention | Ketamine |
| Dose | intravenous bolus of 0.12 mg/kg, followed by a continuous infusion of 0.25 mg/kg/h |
| Topics | Ketamine Esketamine |
| Keywords | Amygdala Stimulation Hippocampal formation Anterior cingulate cortex Antidepressant Resting State FMRI Functional imaging Hippocampus Cognition |
| Citations | 78 |
| Key findings | Ketamine reduced neural reactivity in the bilateral amygdalo-hippocampal complex during emotional stimulation, and the intensity of psychedelic alterations of consciousness predicted the reduction in neural responsivity to negative stimuli. |
Abstract
Increased amygdala reactivity might lead to negative bias during emotional processing that can be reversed by antidepressant drug treatment. However, little is known on how N-methyl-d-aspartate (NMDA) receptor antagonism with ketamine as a novel antidepressant drug target might modulate amygdala reactivity to emotional stimulation. Using functional magnetic resonance imaging (fMRI) and resting-state fMRI (rsfMRI), we assessed amygdalo-hippocampal reactivity at baseline and during pharmacological stimulation with ketamine (intravenous bolus of 0.12 mg/kg, followed by a continuous infusion of 0.25 mg/kg/h) in 23 healthy subjects that were presented with stimuli from the International Affective Picture System (IAPS). We found that ketamine reduced neural reactivity in the bilateral amygdalo-hippocampal complex during emotional stimulation. Reduced amygdala reactivity to negative pictures was correlated to resting-state connectivity to the pregenual anterior cingulate cortex. Interestingly, subjects experienced intensity of psychedelic alterations of consciousness during ketamine infusion predicted the reduction in neural responsivity to negative but not to positive or neutral stimuli. Our findings suggest that the pharmacological modulation of glutamate-responsive cerebral circuits, which is associated with a shift in emotional bias and a reduction of amygdalo-hippocampal reactivity to emotional stimuli, represents an early biomechanism to restore parts of the disrupted neurobehavioral homeostasis in MDD patients. Hum Brain Mapp 37:1941-1952, 2016. © 2016 Wiley Periodicals, Inc.
Comparable studies
Other experimental studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine activates psychosis and alters limbic blood flow in schizophrenia Schizophrenic individuals | 1995 | Experimental study | |
| The spectral exponent of the resting EEG indexes the presence of consciousness during unresponsiveness induced by propofol, xenon, and ketamine Healthy participants | 2019 | Controlled experimental study | n = 15 |
| Ketamine Increases Human Motor Cortex Excitability to Transcranial Magnetic Stimulation Normal human subjects | 2003 | Experimental study | n = 7 |
| Evidence that Subanesthetic Doses of Ketamine Cause Sustained Disruptions of NMDA and AMPA-Mediated Frontoparietal Connectivity in Humans Human participants | 2015 | Experimental study | |
| Simultaneous population pharmacokinetic modelling of ketamine and three major metabolites in patients with treatment‐resistant bipolar depression Patients with treatment-resistant bipolar depression | 2012 | Population pharmacokinetic analysis | n = 9 |
Citations in the library
Cited by 35
- Psychedelic-Assisted Psychotherapy: A Paradigm Shift in Psychiatric Research and Development Frontiers in Pharmacology July 5, 2018
- The anterior cingulate cortex as a key locus of ketamine’s antidepressant action Neuroscience & Biobehavioral Reviews May 10, 2021
- Modulation of amygdala reactivity following rapidly acting interventions for major depression. Human Brain Mapping May 1, 2020
- Pharmacological fMRI: Effects of subanesthetic ketamine on resting-state functional connectivity in the default mode network, salience network, dorsal attention network and executive control network NeuroImage: Clinical 2018
- The neurophysiology of ketamine: an integrative review Reviews in the Neurosciences May 5, 2020
and 30 more in the library
Cites 13
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- The Standardized Psychometric Assessment of Altered States of Consciousness (ASCs) in Humans Pharmacopsychiatry July 1, 1998
- Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers Biological Psychiatry April 26, 2014
and 8 more in the library