The effect of ketamine on affective modulation of the startle reflex and its resting-state brain correlates
Zümrüt Duygu Sen, Tara Chand, Lena Vera Danyeli, Vinod Kumar, Lejla Colic, Meng Li, Merve Yemisken, Nooshin Javaheripour, Alexander Refisch, Nils Opel, Tamar Macharadze, Moritz Kretzschmar, Esra Akyüz Özkan, Matthias Deliano, Martin Walter
Scientific Reports August 16, 2023 DOI: 10.1038/s41598-023-40099-4 (opens in new tab)
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Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blind, placebo-controlled, cross-over study Peer reviewed |
|---|---|
| Sample size | 32 |
| Population | Healthy male participants |
| Interventions | S-ketamine placebo |
| Duration | Assessments at baseline and 24 hours after each infusion |
| Measures | affect-modulated startle reflex paradigm (AMSR), resting-state functional magnetic resonance imaging at 7 T |
| Topics | Esketamine Ketamine |
| Key points | Ketamine did not alter startle potentiation to unpleasant stimuli but diminished startle attenuation to pleasant stimuli one day after infusion, a change that correlated with end-of-infusion plasma ketamine and norketamine levels. Ketamine also reduced resting-state functional connectivity in the modulatory startle pathway. The authors suggest ketamine may attenuate the motivational significance of pleasant stimuli in healthy participants. |
Abstract
Ketamine is a rapid-acting antidepressant that also influences neural reactivity to affective stimuli. However, the effect of ketamine on behavioral affective reactivity is yet to be elucidated. The affect-modulated startle reflex paradigm (AMSR) allows examining the valence-specific aspects of behavioral affective reactivity. We hypothesized that ketamine alters the modulation of the startle reflex during processing of unpleasant and pleasant stimuli and weakens the resting-state functional connectivity (rsFC) within the modulatory pathway, namely between the centromedial nucleus of the amygdala and nucleus reticularis pontis caudalis. In a randomized, double-blind, placebo-controlled, cross-over study, thirty-two healthy male participants underwent ultra-high field resting-state functional magnetic resonance imaging at 7 T before and 24 h after placebo and S-ketamine infusions. Participants completed the AMSR task at baseline and one day after each infusion. In contrast to our hypothesis, ketamine infusion did not impact startle potentiation during processing of unpleasant stimuli but resulted in diminished startle attenuation during processing of pleasant stimuli. This diminishment significantly correlated with end-of-infusion plasma levels of ketamine and norketamine. Furthermore, ketamine induced a decrease in rsFC within the modulatory startle reflex pathway. The results of this first study on the effect of ketamine on the AMSR suggest that ketamine might attenuate the motivational significance of pleasant stimuli in healthy participants one day after infusion.
Comparable studies
Other randomized controlled trials on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community | 1994 | Randomized controlled trial | n = 19 |
| Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode | 2013 | Randomized controlled trial | n = 73 |
| Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery | 2005 | Randomized controlled trial | n = 75 |
| Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures | 2014 | Randomized controlled trial | n = 41 |
| Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers | 2000 | Single-blind placebo-controlled study | n = 20 |
Citations in the library
Cites 10
- Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder JAMA Psychiatry April 16, 2014
- Adjunctive Ketamine With Relapse Prevention–Based Psychological Therapy in the Treatment of Alcohol Use Disorder American Journal of Psychiatry January 11, 2022
- Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression: a meta-analysis of randomized clinical trials Pharmacological Reports April 16, 2020
- Regulation of neural responses to emotion perception by ketamine in individuals with treatment-resistant major depressive disorder Translational Psychiatry February 17, 2015
- The NMDA antagonist ketamine and the 5-HT agonist psilocybin produce dissociable effects on structural encoding of emotional face expressions Psychopharmacology July 26, 2012
and 5 more in the library