Neural correlates of ketamine-induced dilation of temporal expectation
Jack R. Waters, Brian Madeira, Michael Neil Shadlen, S. Shushruth
bioRxiv (Cold Spring Harbor Laboratory) October 19, 2026 preprint DOI: 10.64898/2026.10.12.758574 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational animal study with pharmacological manipulation |
|---|---|
| Sample size | 2 |
| Population | Two male macaques performing a time-anticipation task |
| Intervention | Ketamine |
| Dose | subanesthetic doses |
| Topics | Esketamine Ketamine |
| Key findings | Subanesthetic ketamine caused a dose-dependent dilation of time estimation in macaques, so they responded as though less time had elapsed than had actually passed. In parietal area LIP, ketamine flattened single-neuron anticipatory ramping and rotated population delay-period activity in neural state space away from the pre-ketamine configuration, paralleling the behavioral change. |
Abstract
Time estimation is critical to many cognitive operations, including decision-making, working memory, and action planning. Neural correlates of interval timing have been described across multiple cortical and subcortical networks, both at a single-neuron level (as ramping activity) and population level (as dynamical motifs). Low-dose ketamine, a dissociative anesthetic and potent antidepressant, is known to distort time perception, but how it affects these neural correlates is unknown. In two male macaques performing a time-anticipation task, we administered subanesthetic doses of ketamine under a pharmacokinetically guided intravenous infusion protocol. We recorded neural activity from the parietal area LIP, a region associated with interval timing. Behaviorally, ketamine caused monkeys to respond as though less time had elapsed than had actually passed under objective clock time, a dose-dependent dilation of time estimation. This behavioral change was accompanied by parallel effects on the neural representation of elapsed time. At the single-neuron level, ketamine flattened anticipatory ramping activity. At the population level, it induced a rotation of delay-period activity in neural state space, away from the pre-ketamine configuration. By linking a graded pharmacological manipulation to concurrent shifts in behavior and cortical neural activity, we show that ketamine dilates perceived time while reshaping LIP population dynamics. These findings offer a route to probe how cortical activity supports time estimation and point to a network mechanism that could contribute to ketamine's dissociative and antidepressant effects.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| 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 Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |