Neural correlates of ketamine-induced dilation of temporal expectation
- 1Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University; Department of Neuroscience, University of Pittsburgh
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.
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BibTeX
@misc{waters2026neural,
title = {{Neural correlates of ketamine-induced dilation of temporal expectation}},
author = {J. R. Waters and B. Madeira and M. N. Shadlen and S. Shushruth},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.12.758574},
url = {https://www.biorxiv.org/content/10.64898/2026.10.12.758574v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Neural correlates of ketamine-induced dilation of temporal expectation
AU - J. R. Waters
AU - B. Madeira
AU - M. N. Shadlen
AU - S. Shushruth
PY - 2026
DA - 2026/10/12
PB - bioRxiv
DO - 10.64898/2026.10.12.758574
UR - https://www.biorxiv.org/content/10.64898/2026.10.12.758574v1
AB - 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.
ER -