Biology subjects

Shushruth, S.

Publications and source records attributed to Shushruth, S..

7 recordsLinked to original sources

bioRxiv2026

Neural correlates of ketamine-induced dilation of temporal expectation

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.

neuroscience↗

bioRxiv2026

Decoupling Choice from Motor Response Reduces Choice-History Effects

Perception and action form a loop as an organism interacts with its environment. Here, we probe the interdependence between the two in the context of choice-history effects, the tendency of past choices and their outcomes to bias current choices. We investigated if the modulation by previous choices depended on the coupling between perceptual choices and the motor responses reporting these choices. We analyzed data from non-human primates (Macaca mulatta; three females and five males) performing two different perceptual decision-making tasks. Each task had a "coupled" variant with a fixed mapping between perceptual choices and motor plans used to report the choice, and an "uncoupled" variant, in which this mapping varied randomly across trials. We found that, in both tasks, the animals in the coupled variant had larger choice-history effects compared to the animals in the uncoupled variant. Decoupling choices from motor responses was further associated with an inability by the animals to learn experimentally induced stimulus sequence regularities. Together, these findings identify choice-response coupling as a factor shaping animals ability to use recent history to guide behavior and highlight the tight link between cognitive and motor processes.

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bioRxiv2025

A canonical gated neural circuit model for flexible perceptual decisions

Flexible perceptual decision-making requires rapid, context-dependent adjustments, yet the neural circuit mechanisms underlying its parsimonious representations remain unclear. Here, we propose a minimal mean-field neural circuit model that integrates sensory evidence and selects actions via distributed neuronal encoding, guided by data from a task that dissociates perceptual choice from motor response - abstract perceptual decision-making. The models nonlinear gating of action selective (AS) neurons replicates parietal cortical activity observed during task performance. Critically, recurrent excitation within the evidence integration (EI) population supports sensory evidence accumulation, working memory for sequential sampling, and reward rate optimisation. Moreover, the dynamics of EI and AS neuronal activities in the same model respectively mirror parietal neuronal activities related to sensory evidence encoding and ramping-to-threshold firing in a separate reaction-time task, while suggesting that decision readout engages both neuronal populations. The model also predicts decision interference in a novel two-stage decision version of the task, accounting for choice accuracy decrements observed in other experiments while predicting slower decisions. Together, these findings propose a minimal mean-field circuit-level mechanism unifying perceptual, memory-based, and abstract decision-making.

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bioRxiv2025

Sequential sampling from memory underlies perceptual decisions unyoked from actions

Perceptual decision-making refers to the class of decisions in which sensory evidence is used to categorize percepts and guide actions. Conventionally, categorical decisions are thought to precede motor actions. However, recent studies in nonhuman primates challenge this assumption -- when perceptual decisions were uncoupled from the actions they bear upon, animals postponed the decisions until relevant response options were revealed. To determine whether this postponement stems from cognitive limitations unique to nonhuman primates, we conducted a similar experiment with human subjects. Naive subjects viewed a random-dot motion (RDM) stimulus that was difficult to categorize. After a delay period following the RDM, two choice targets were presented and subjects decided which target lay closer to the perceived motion direction. Decision accuracy varied across subjects, reflecting individual differences in ability to integrate motion evidence. Notably, subjects with higher decision accuracy showed prolonged deliberation after choice-target presentation. Furthermore, the time they took to report their decisions depended on the strength of the motion evidence. This pattern of accuracy and decision reporting time could be accounted for by a bounded diffusion model in which subjects sequentially sample stored sensory information from memory during the target selection phase. When the RDM was challenging to categorize, the subsequent appearance of the targets provided a framework to interrogate stored evidence and render a decision. Our results reveal a strategic feature of working memory of retaining information based on its future utility. This observation opens new avenues for investigating how memory and decision-making interact.

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bioRxiv2021

Deficits in decision-making induced by parietal cortex inactivation are compensated at two time scales

Perceptual decisions arise through the transformation of samples of evidence into a commitment to a proposition or plan of action. Such transformation is thought to involve cortical circuits capable of computation over time scales associated with working memory, attention, and planning. Neurons in the lateral intraparietal area (LIP) are thought to play a role in all of these functions, and much of what is known about the neurobiology of decision making has been influenced by studies of LIP and its network of cortical and subcortical connections. However a causal role of neurons in LIP remains controversial. We used pharmacological and chemogenetic methods to inactivate LIP in one hemisphere of four rhesus monkeys. Inactivation produced clear biases in decisions, but the effects dissipated despite the persistence of neural inactivation, implying compensation by other unaffected areas. Compensation occurs on a rapid times scale, within an experimental session, and more gradually, across sessions. The findings resolve disparate studies and inform interpretation of focal perturbations of brain function.

neuroscience↗

bioRxiv2021

Sequential sampling from memory underlies action selection during abstract decision making

The study of perceptual decision making in monkeys has provided insights into the process by which sensory evidence is integrated towards a decision. When monkeys make decisions with the knowledge of the motor actions the decisions bear upon, the process of evidence integration is instantiated by neurons involved in the selection of said actions. It is less clear how monkeys make decisions when unaware of the actions required to communicate their choice--what we refer to as abstract decisions. We investigated this by training monkeys to associate the direction of motion of a noisy random-dot display with the color of two targets. Crucially, the targets were displayed at unpredictable locations after the motion stimulus was extinguished. We found that monkeys postponed decision formation until the targets were revealed. Neurons in the parietal association area LIP represented the integration of evidence leading to a choice, but as the stimulus was no longer visible, the samples of evidence must have been retrieved from short-term memory. Our results imply that when decisions are temporally unyoked from the motor actions they bear upon, decision formation is protracted until they can be framed in terms of motor actions.

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bioRxiv2017

Comparison of decision-related signals in sensory and motor preparatory responses of neurons in Area LIP

Neurons in the lateral intraparietal area (LIP) of Macaques exhibit both sensory and oculomotor preparatory responses. During perceptual decision making, the preparatory responses have been shown to track the state of the evolving evidence leading to the decision. The sensory responses are known to reflect categorical properties of visual stimuli, but it is not known if these responses also track evolving evidence. We compared sensory and oculomotor-preparatory responses in the same neurons during a direction discrimination task when either the discriminandum (random dot motion) or an eye movement choice-target was in the neurons response field. Both configurations elicited task related activity, but only the motor preparatory responses reflected evidence accumulation. The results are consistent with the proposal that evolving decision processes are supported by persistent neural activity in the service of actions or intentions, as opposed to high order representations of stimulus properties.\n\nSIGNIFICANCE STATEMENTPerceptual decision making is the process of choosing an appropriate motor action based on perceived sensory information. Association areas of the cortex play an important role in this sensory-motor transformation. The neurons in these areas show both sensory- and motor-related activity. We show here that, in the macaque parietal association area LIP, signatures of the process of evidence accumulation that underlies the decisions are predominantly reflected in the motor-related activity. This finding supports the proposal that perceptual decision making is implemented in the brain as a process of choosing between available motor actions rather than as a process of representing the properties of the sensory stimulus.

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