Neural correlates of ketamine-induced dilation of temporal expectation

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.