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)
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.