Context-dependent effects of ketamine on emotional evidence integration
Miruna Rascu, Jan Grohn, Sara Costi, Caroline Zangani, Samuel Agyapong, Katharine A. Smith, Philip J. Cowen, Laurence Tudor Hunt, Miriam C. Klein-Flügge, Lilian Weber
bioRxiv (Cold Spring Harbor Laboratory) November 4, 2026 preprint DOI: 10.64898/2026.10.30.762604 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Behavioral experiments plus a double-blind, placebo-controlled, within-subject ketamine study |
|---|---|
| Sample size | 121 |
| Population | Online cohort (n=92) and in-person cohort (n=29) of participants performing an emotional evidence integration task |
| Intervention | Ketamine |
| Duration | Emotion integration probed approximately 1.5 hours after the infusion (post-acute period) |
| Topics | Esketamine Ketamine |
| Key findings | Participants integrated emotional information over longer timescales in stable environments and relied more on recent evidence under volatility, consistent with perceptual decision-making principles. Ketamine modulated the temporal weighting of emotional evidence, shifting the balance between recent and past information depending on environmental volatility. |
Abstract
Understanding others' emotions requires continuously integrating noisy affective information as emotional states change over time. Research on emotion processing, however, has thus far focused on static environments or discrete events. Here, we developed a continuous emotional evidence integration task in which participants had to track the average emotional state in a rapidly changing sequence of faces under different levels of environmental volatility. This allowed us to examine emotion integration in changing environments. In online (n=92) and in-person (n=29) cohorts, participants integrated emotional information over longer timescales in stable environments while relying more strongly on recent evidence under volatility, consistent with principles established in perceptual decision-making. We further examined whether this process was modulated by ketamine, an NMDA receptor antagonist associated with evidence integration in the perceptual domain. We conducted a double-blind, placebo-controlled, within-subject study and probed emotion integration during the post-acute period, approximately 1.5 hours after the infusion. Ketamine modulated the temporal weighting of emotional evidence, shifting the balance between recent and past information depending on environmental volatility. Together, these findings show that emotional evidence integration dynamically adapts to the statistical structure of the environment and that ketamine can further modulate this process, which may have relevance for affective disorders.
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 25
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- The Predictive Coding Account of Psychosis. Biological Psychiatry May 25, 2018
- A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders JAMA Psychiatry March 1, 2017
and 20 more in the library