Biology subjects

Shadlen, M. N.

Publications and source records attributed to Shadlen, M. N..

At least 19 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

Behavioral demands organize a decision process into distinct yet coordinated neural representations in parietal cortex

Perceptual decisions are widely modeled as the accumulation of evidence to a bound. In the lateral intraparietal area (LIP), this computation is thought to be implemented in a low-dimensional population representation organized around the single action used to report the choice, consistent with an intentional framework. The intentional framework, however, implies that changing the behavioral demands on the report should change the representation itself, raising a question about the generality of the low-dimensional decision representation described in LIP: is it a special case of decisions reported through a single action, or does it reflect a more general computational architecture that can support multiple behavioral outputs? We tested this by training monkeys to report the \textit{termination} of a motion-discrimination decision with a saccade to a choice-neutral target, and its \textit{content} only later, with a saccade to one of two choice targets. Even though the two reports were behaviorally separable, the timing of termination remained systematically linked to the accumulation of sensory evidence supporting the eventual choice in both monkeys, indicating that both reports continued to draw on a common underlying computation. Using high-density Neuropixels recordings from LIP, however, we found that decision termination and decision content were represented along orthogonal population coding directions supported by largely non-overlapping groups of neurons. Yet the two representations were not independent: trial-by-trial fluctuations in the population encoding content predicted subsequent fluctuations in the population encoding termination, with their coupling strengthening as the decision evolved. These results suggest that a single decision computation can be flexibly reformatted into distinct, action-specific representations, coordinated by selective transfer of information between neural populations.

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.

neuroscience↗

bioRxiv2026

Behavioral Signatures of Post-Decisional Attention in Preferential Choice

Attention plays a key role in decision-making by directing limited cognitive resources to relevant information. It has been proposed that attention also biases the decision process, due to a multiplicative interaction between attention and subjective value (e.g., Krajbich et al., 2010). We tested two predictions of models that posit a causal multiplicative effect of attention on decision formation: (i) the last fixation should be more informative about the choice when the overall value of the alternatives is high, and (ii) more attention should be directed to the chosen option when choices conflict with stated preferences than when they do not. Reanalyzing several datasets from a food-choice task, we found no evidence supporting these predictions. An alternative model where attention reflects choices after the decision has completed, explains key observations, including the last-fixation bias, the gaze-cascade effect and the effect of the overall value of the alternatives on response times. However, this model does not fully account for the association between dwell time and choice. We conclude that gaze behavior prior to the choice report likely reflects both decisional and post-decisional processes.

animal behavior and cognition↗

bioRxiv2025

Transfer of graded information through gated receptivity to widely broadcast signals

Making accurate decisions requires the brain to maintain evolving representations of the evidence supporting different possible choices. The population of neurons that maintains this evolving representation may change over the course of the decision-making process. Such changes may result from a switch in the set of neurons representing the relevant behavioral output or a switch in the set of neurons receiving task-relevant information. Recent work has shown how intervening actions like eye movements or navigation to a new location can shift the set of neurons that encode subsequent inputs and outputs. Here, we present a computational model of how analog-valued information that supports an evolving decision can be flexibly transferred between populations of neurons without changing the synaptic connectivity of the underlying network. This is accomplished through a dynamic gating mechanism in which information is widely broadcast throughout a network, but only those neurons receiving a gating signal are receptive to this information. Using this framework, we provide a mechanistic explanation for recent experimental results in which information supporting an evolving decision was shown to be transferred between different populations of parietal cortex neurons during intervening smooth pursuit and saccadic eye movements. This mechanism enables organisms to maintain a continuous decision process despite changing frames of reference, offering a potentially general framework for cognitive continuity in dynamic environments.

neuroscience↗

bioRxiv2025

ALM enables contextual decision-making via dynamic reconfiguration of local circuits

Cognitive operations often require flexible implementation of stimulus-response contingencies, depending on context. We developed an olfactory task in which mice learned to associate a test odor with a directional lick response, conditional on a preceding context odor drawn from a different odor set. Two-photon imaging revealed that anterior lateral motor cortex (ALM) contains distinct populations encoding context, test odors, and choice. Optogenetic silencing during the context and delay periods impaired performance, suggesting that ALM contributes to configuring the appropriate contingency. Although context odors that instructed the same mapping were represented by separate populations, their influence converged at the level of choice-selective neurons. A subpopulation of these neurons exhibited dual selectivity for context and choice, forming what we term "contingency neurons." These findings suggest that ALM supports flexible behavior not by abstracting over context cues, but by dynamically reconfiguring local circuits to route sensory input to the appropriate motor output.

neuroscience↗

bioRxiv2025

Motor cortex flexibly deploys a high-dimensional repertoire of subskills

Skilled movement often requires flexibly combining multiple subskills, each requiring dedicated control strategies and underlying computations. How the motor system achieves such versatility remains unclear. Using high-density Neuropixels recordings from primary motor cortex (M1) in macaques performing a challenging force-tracking task, we reveal that M1 activity is much higher-dimensional, and far more flexible, than traditionally assumed. Although our task employed only a single external degree of freedom, neural dynamics reflected transitions amongst many dimensions and multiple distinct computations. Different behavioral control strategies were associated with distinct neural locations and dimensions, sometimes used compositionally. Groups of population-level factors became active when a particular form of dynamics was needed, and remained silent otherwise. Neural activity was thus dominated by the engaged subskill, and could be very different even for matched motor output. These findings challenge prevailing views of M1, and reveal an unexpectedly flexible and high-dimensional neural system underlying skilled motor behavior.

neuroscience↗

bioRxiv2024

Population Representation of the Confidence in a Decision in the Lateral Intraparietal Area of the Macaque

Confidence in a decision is the belief, prior to feedback, that ones choice is correct. In the brain, many decisions are implemented as a race between competing evidence-accumulation processes. We ask whether the neurons that represent evidence accumulation also carry information about whether the choice is correct (i.e., confidence). Monkeys performed a reaction time version of the random dot motion task. Neuropixels probes were used to record from neurons in the lateral intraparietal (LIP) area. LIP neurons with response fields that overlap the choice-target contralateral to the recording site (Tin neurons) represent the accumulation of evidence in favor of contralateral target selection. We demonstrate that shortly before a contralateral choice is reported, the population of Tin neurons contains information about the accuracy of the choice (i.e., whether the choice is correct or incorrect). This finding is unexpected because, on average, Tin neurons exhibit a level of activity before the report that is independent of reaction time and evidence strength--both strong predictors of accuracy. This apparent contradiction is resolved by examining the variability in neuronal responses across the population of Tin neurons. While on average, Tin neurons exhibit a stereotyped level of activity before a contralateral choice, many neurons depart from this average in a consistent manner. From these neurons, the accuracy of the choice can be predicted using a simple logistic decoder. The accuracy of the choice predicted from neural activity reproduces the hallmarks of confidence identified in human behavioral experiments. Therefore, neurons that represent evidence accumulation can also inform the monkeys confidence.

neuroscience↗

bioRxiv2024

Incorporation of a cost of deliberation time in perceptual decision making

Many decisions benefit from the accumulation of evidence obtained sequentially over time. In such circumstances, the decision maker must balance speed against accuracy, and the nature of this tradeoff mediates competing desiderata and costs, especially those associated with the passage of time. A neural mechanism to achieve this balance is to accumulate evidence in suitable units and to terminate the deliberation when enough evidence has accrued. To accommodate time costs, it has been hypothesized that the criterion to terminate a decision may become lax as a function of time. Here we tested this hypothesis by manipulating the cost of time in a perceptual choice-reaction time task. Participants discriminated the direction of motion in a dynamic random-dot display, which varied in difficulty across trials. After each trial, they received feedback in the form of points based on whether they made a correct or erroneous choice. They were instructed to maximize their points per unit of time. Unbeknownst to the participants, halfway through the experiment, we increased the time pressure by canceling a small fraction of trials if they had not made a decision by a provisional deadline. Although the manipulation canceled less than 5% of trials, it induced the participants to make faster decisions while lowering their decision accuracy. The pattern of choices and reaction times were explained by bounded drift-diffusion. In all phases of the experiment, stopping bounds were found to decline as a function of time, consistent with the optimal solution, and this decline was exaggerated in response to the time-cost manipulation.

neuroscience↗

bioRxiv2024

Value construction through sequential sampling explains serial dependencies in decision making

Many decisions are expressed as a preference for one item over another. When these items are familiar, it is often assumed that the decision maker assigns a value to each of the items and chooses the item with the highest value. These values may be imperfectly recalled, but are assumed to be stable over the course of an interview or psychological experiment. Choices that are inconsistent with a stated valuation are thought to occur because of unspecified noise that corrupts the neural representation of value. Assuming that the noise is uncorrelated over time, the pattern of choices and response times in value-based decisions are modeled within the framework of Bounded Evidence Accumulation (BEA), similar to that used in perceptual decision-making. In BEA, noisy evidence samples accumulate over time until the accumulated evidence for one of the options reaches a threshold. Here, we argue that the assumption of temporally uncorrelated noise, while reasonable for perceptual decisions, is not reasonable for value-based decisions. Subjective values depend on the internal state of the decision maker, including their desires, needs, priorities, attentional state, and goals. These internal states may change over time, or undergo revaluation, as will the subjective values. We reasoned that these hypothetical value changes should be detectable in the pattern of choices made over a sequence of decisions. We reanalyzed data from a well-studied task in which participants were presented with pairs of snacks and asked to choose the one they preferred. Using a novel algorithm (Reval), we show that the subjective value of the items changes significantly during a short experimental session (about 1 hour). Values derived with Reval explain choice and response time better than explicitly stated values. They also better explain the BOLD signal in the ventromedial prefrontal cortex, known to represent the value of decision alternatives. Revaluation is also observed in a BEA model in which successive evidence samples are not assumed to be independent. We argue that revaluation is a consequence of the process by which values are constructed during deliberation to resolve preference choices.

neuroscience↗

bioRxiv2023

DREDge: robust motion correction for high-density extracellular recordings across species

High-density microelectrode arrays (MEAs) have opened new possibilities for systems neuroscience in human and non-human animals, but brain tissue motion relative to the array poses a challenge for downstream analyses, particularly in human recordings. We introduce DREDge (Decentralized Registration of Electrophysiology Data), a robust algorithm which is well suited for the registration of noisy, nonstationary extracellular electrophysiology recordings. In addition to estimating motion from spikes in the action potential (AP) frequency band, DREDge enables automated tracking of motion at high temporal resolution in the local field potential (LFP) frequency band. In human intraoperative recordings, which often feature fast (period <1s) motion, DREDge correction in the LFP band enabled reliable recovery of evoked potentials, and significantly reduced single-unit spike shape variability and spike sorting error. Applying DREDge to recordings made during deep probe insertions in nonhuman primates demonstrated the possibility of tracking probe motion of centimeters across several brain regions while simultaneously mapping single unit electrophysiological features. DREDge reliably delivered improved motion correction in acute mouse recordings, especially in those made with an recent ultra-high density probe. We also implemented a procedure for applying DREDge to recordings made across tens of days in chronic implantations in mice, reliably yielding stable motion tracking despite changes in neural activity across experimental sessions. Together, these advances enable automated, scalable registration of electrophysiological data across multiple species, probe types, and drift cases, providing a stable foundation for downstream scientific analyses of these rich datasets.

neuroscience↗

bioRxiv2023

Large-scale brain-wide neural recording in nonhuman primates

High-density, integrated silicon electrodes have begun to transform systems neuroscience, by enabling large-scale neural population recordings with single cell resolution. Existing technologies, however, have provided limited functionality in nonhuman primate species such as macaques, which offer close models of human cognition and behavior. Here, we report the design, fabrication, and performance of Neuropixels 1.0-NHP, a high channel count linear electrode array designed to enable large-scale simultaneous recording in superficial and deep structures within the macaque or other large animal brain. These devices were fabricated in two versions: 4416 electrodes along a 45 mm shank, and 2496 along a 25 mm shank. For both versions, users can programmatically select 384 channels, enabling simultaneous multi-area recording with a single probe. We demonstrate recording from over 3000 single neurons within a session, and simultaneous recordings from over 1000 neurons using multiple probes. This technology represents a significant increase in recording access and scalability relative to existing technologies, and enables new classes of experiments involving fine-grained electrophysiological characterization of brain areas, functional connectivity between cells, and simultaneous brain-wide recording at scale.

neuroscience↗

bioRxiv2022

Direct observation of the neural computations underlying a single decision

Neurobiological investigations of perceptual decision-making have furnished the first glimpse of a flexible cognitive process at the level of single neurons (Shadlen and Newsome, 1996; Shadlen and Kiani, 2013). Neurons in the parietal and prefrontal cortex (Kim and Shadlen, 1999; Romo et al., 2004; Hernandez et al., 2002; Ding and Gold, 2012) are thought to represent the accumulation of noisy evidence, acquired over time, leading to a decision. Neural recordings averaged over many decisions have provided support for the deterministic rise in activity to a termination bound (Roitman and Shadlen, 2002). Critically, it is the unobserved stochastic component that is thought to confer variability in both choice and decision time (Gold and Shadlen, 2007). Here, we elucidate this drift-diffusion signal on individual decisions. We recorded simultaneously from hundreds of neurons in the lateral intraparietal cortex (LIP) of monkeys while they made decisions about the direction of random dot motion. We show that a single scalar quantity, derived from the weighted sum of the population activity, represents a combination of deterministic drift and stochastic diffusion. Moreover, we provide direct support for the hypothesis that this drift-diffusion signal approximates the quantity responsible for the variability in choice and reaction times. The population-derived signals rely on a small subset of neurons with response fields that overlap the choice targets. These neurons represent the integral of noisy evidence. Another subset of direction-selective neurons with response fields that overlap the motion stimulus appear to represent the integrand. This parsimonious architecture would escape detection by state-space analyses, absent a clear hypothesis.

neuroscience↗

bioRxiv2022

A neural mechanism for terminating decisions

The brain makes decisions by accumulating evidence until there is enough to stop and choose. Neural mechanisms of evidence accumulation are well established in association cortex, but the site and mechanism of termination is unknown. Here, we elucidate a mechanism for termination by neurons in the primate superior colliculus. We recorded simultaneously from neurons in lateral intraparietal cortex (LIP) and the superior colliculus (SC) while monkeys made perceptual decisions, reported by eye-movements. Single-trial analyses revealed distinct dynamics: LIP tracked the accumulation of evidence on each decision, and SC generated one burst at the end of the decision, occasionally preceded by smaller bursts. We hypothesized that the bursts manifest a threshold mechanism applied to LIP activity to terminate the decision. Focal inactivation of SC produced behavioral effects diagnostic of an impaired threshold sensor, requiring a stronger LIP signal to terminate a decision. The results reveal the transformation from deliberation to commitment.

neuroscience↗

bioRxiv2022

Decision formation in parietal cortex transcends a fixed frame of reference

Neurons in the lateral intraparietal cortex (area LIP) represent the formation of a decision when it is linked to a specific action, such as an eye movement to a choice target. However, these neurons should be unable to represent a decision that transpires across actions that would disrupt this linkage. We investigated this limitation by recording simultaneously from many neurons. While intervening actions disrupt the representation by single neurons, the ensemble achieves continuity of the decision process by passing information from currently active neurons to neurons that will become active after the action. In this way, the representation of an evolving decision can be generalized across actions and transcends the frame of reference that specifies the neural response fields. The finding extends previous observations of receptive field remapping, thought to support the stability of perception across eye movements, to the continuity of a thought process, such as a decision.

neuroscience↗

bioRxiv2022

Transient oscillations of neural firing rate associated with routing of evidence in a perceptual decision

To form a perceptual decision the brain must acquire samples of evidence from the environment and incorporate them in computations that mediate choice behavior. While much is known about the neural circuits that process sensory information and those that form decisions, less is known about the mechanisms that establish the functional linkage between them. We trained monkeys to make difficult decisions about the net direction of visual motion under conditions that required trial-by-trial control of functional connectivity. In one condition, the motion appeared at different locations on different trials. In the other, two motion patches appeared, only one of which was informative. Neurons in the parietal cortex produced brief oscillations in their firing rate at the time routing was established: upon onset of the motion display when its location was unpredictable across trials, and upon onset of an attention cue that indicated in which of two locations an informative patch of dots would appear. The oscillation was absent when the stimulus location was fixed across trials. We interpret the oscillation as a manifestation of the mechanism that establishes the source and destination of flexibly routed information, but not the transmission of the information per se.

neuroscience↗

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

Flexible neural control of motor units

Voluntary movement requires communication from cortex to the spinal cord, where a dedicated pool of motor units (MUs) activates each muscle. The canonical description of MU function rests upon two foundational tenets. First, cortex cannot control MUs independently but supplies each pool with a common drive. Second, MUs are recruited in a rigid fashion that largely accords with Hennemans size principle. While this paradigm has considerable empirical support, a direct test requires simultaneous observations of many MUs across diverse force profiles. We developed an isometric task that allowed stable MU recordings even during rapidly changing forces. MU activity patterns were surprisingly behavior-dependent. MU activity could not be accurately described as reflecting common drive, but could be captured by assuming multiple drives. Neuropixels probe recordings revealed that, consistent with the requirements of flexible control, the motor cortex population response displays a great many degrees of freedom. Neighboring cortical sites recruited different MUs. Thus, MU activity is flexibly controlled to meet task demands, and cortex may contribute to this ability.

neuroscience↗