Biology subjects

Brody, C.

Publications and source records attributed to Brody, C..

16 recordsLinked to original sources

bioRxiv2026

The geometry of knowledge in the hippocampal-prefrontal system

Decision making is associated with frontal brain circuits and spatial navigation with the hippocampus. In addition, recent work in spatial decision making tasks found single neurons in both areas encoding space conjunctively with other task-relevant variables. However, circuit function is not determined by tuning alone, but also by representational geometry, i.e. the representation of task-relevant variables in neural state space. Here, using Neuropixel recordings in a complex spatial decision making task combined with nonlinear dimensionality reduction, we show an intrinsically low-dimensional neural manifold in medial prefrontal cortex (mPFC) on which key task variables were represented as smooth gradients. This geometry resembled the hippocampal (HPC) map. The mPFC and HPC manifolds from one mouse can predict the behavior across other mice and brain areas. A non-linear representational map between the mPFC and HPC manifolds demonstrates alignment in time. Our work suggests that the representational geometry in HPC and mPFC is distributed and time-aligned using low-dimensional neural codes.

neuroscience↗

bioRxiv2026

Hippocampal engrams configure prefrontal context representations to guide flexible decisions

Flexible behavior requires using past experiences to configure cortical computations to suit current task demands. A central question in neuroscience is how memory representations control such reconfigurations. Although hippocampal (HPC) engrams can drive learned behaviors, prior studies have been largely limited to a fixed stimulus-response computation. Thus, whether engrams can drive retrieval of a set of stimulus-response mappings, rather than a specific response itself, remains unresolved. Moreover, how engrams affect cortical task representations and dynamics so as to produce engram-consistent behavior remains unstudied. Here, we address both questions by combining tagging and reactivation of HPC engrams with simultaneous large-scale recordings in medial prefrontal cortex (mPFC) during a context-dependent task-switching paradigm in mice. We report that HPC engram reactivation caused mice to apply engram-consistent decision-rules rather than a specific motor output. Simultaneous mPFC recordings revealed that reactivating the HPC engram for a given context reinstated the representation of that context in mPFC within hundreds of milliseconds, indicating that it was mediated by rapid network effects, leading to choice behavior consistent with the reactivated HPC engram. Other aspects of endogenous dynamics in mPFC were left remarkably intact. Together, our findings provide direct causal evidence that HPC engrams can configure task-relevant population states of downstream cortical circuits in real time, establishing a neural mechanism by which memory traces control flexible behavior.

neuroscience↗

bioRxiv2026

Single-Cell Perturbations Reveal Selective Modulation of Causal Connectivity During Decision-Making

How does cortical connectivity support decision-making? Behavioral tasks often involve multiple sequential phases that implement different computations. For perceptual decision-making during navigation these can include evidence accumulation, decision commitment, and motor program read out. How are these different phases implemented in circuits with fixed anatomical synaptic connectivity? One potential contribution is that the connectivity of neurons is modulated in the different phases, but this has never been tested. Here we used an all-optical method to probe the causal connectivity of excitatory neurons in layer 2/3 of mouse retrosplenial cortex during different behavioral epochs of a navigation-based decision-making task, as well as in the absence of the task. In-task connectivity was different from no-task connectivity: furthermore, these differences were selective to the cue / decision phase, tapering off in later stages of the task. We propose that fast modulation of connectivity is a prevalent mechanism in neural circuit function.

neuroscience↗

bioRxiv2025

A Multi-Region Brain Model to Elucidate the Role of Hippocampus in Spatially Embedded Decision-Making

Brains excel at robust decision-making and data-efficient learning. Understanding the architectures and dynamics underlying these capabilities can inform inductive biases for deep learning. We present a multi-region brain model that explores the normative role of structured memory circuits in a spatially embedded binary decision-making task from neuroscience. We counterfactually compare the learning performance and neural representations of reinforcement learning (RL) agents with brain models of different interaction architectures between grid and place cells in the entorhinal cortex and hippocampus, coupled with an action-selection cortical recurrent neural network. We demonstrate that a specific architecture- where grid cells receive and jointly encode self-movement velocity signals and decision evidence increments-optimizes learning efficiency while best reproducing experimental observations relative to alternative architectures. Our findings thus suggest brain-inspired structured architectures for efficient RL. Importantly, the models make novel, testable predictions about organization and information flow within the entorhinal-hippocampal-neocortical circuit: we predict that grid cells must conjunctively encode position and evidence for effective spatial decision-making, directly motivating new neurophysiological experiments.*

neuroscience↗

bioRxiv2023

Deep Phenotyping of Sleep in Drosophila

Animal behavior depends on internal state. While subtle movements can signify significant changes in internal state, computational methods for analyzing these "microbehaviors" are lacking. Here, we present FlyVISTA, a machine-learning platform to characterize microbehaviors in freely-moving flies, which we use to perform deep phenotyping of sleep. This platform comprises a high-resolution closed-loop video imaging system, coupled with a deep-learning network to annotate 35 body parts, and a computational pipeline to extract behaviors from high-dimensional data. FlyVISTA reveals the distinct spatiotemporal dynamics of sleep-associated microbehaviors in flies. We further show that stimulation of dorsal fan-shaped body neurons induces micromovements, not sleep, whereas activating R5 ring neurons triggers rhythmic proboscis extension followed by persistent sleep. Importantly, we identify a novel microbehavior ("haltere switch") exclusively seen during quiescence that indicates a deeper sleep stage. These findings enable the rigorous analysis of sleep in Drosophila and set the stage for computational analyses of microbehaviors.

neuroscience↗

bioRxiv2023

Non-canonical attractor dynamics underlie perceptual decision-making

Perceptual decision-making is the process by which an animal uses sensory stimuli to choose an action or mental proposition. This process is thought to be mediated by neurons organized as attractor networks1,2. However, whether attractor dynamics underlie decision behavior and the complex neuronal responses remains unclear. Here we use simultaneous recordings from hundreds of neurons, together with an unsupervised, deep learning-based method, to discover decision-related neural dynamics in frontal cortex and striatum of rats while the subjects accumulate pulsatile auditory evidence. We found that trajectories evolved along two sequential regimes, the first dominated by sensory inputs, and the second dominated by the autonomous dynamics, with flow in a direction (i.e., "neural mode") largely orthogonal to that in the first regime. We propose that the transition to the second regime corresponds to the moment of decision commitment. We developed a simplified model that approximates the coupled transition in dynamics and neural mode and allows precise inference, from each trials large-scale neural population activity, of a putative neurally-inferred time of commitment ("nTc") on that trial. The simplified model captures diverse and complex single-neuron temporal profiles, such as ramping and stepping3-5, as well as trial-averaged curved trajectories6-8, and reveals distinctions between brain regions. The estimated nTc times were not time-locked to stimulus onset or offset, or to response onset, but were instead broadly distributed across trials. If nTc marks the moment of decision commitment, sensory evidence before nTc should affect the decision, while evidence afterward should not. Behavioral analysis of trials aligned to their estimated nTc times confirmed this prediction. Our results show that the formation of a perceptual choice involves a rapid, coordinated transition in both the dynamical regime and the neural mode of the decision process that corresponds to commitment to a decision, and suggest this moment as a useful entry point for dissecting mechanisms underlying rapid changes in internal state.

neuroscience↗

bioRxiv2023

Magnetic voluntary head-fixation in transgenic rats enables lifetime imaging of hippocampal neurons

The precise neural mechanisms within the brain that contribute to the remarkable lifetime persistence of memory remain unknown. Existing techniques to record neurons in animals are either unsuitable for longitudinal recording from the same cells or make it difficult for animals to express their full naturalistic behavioral repertoire. We present a magnetic voluntary head-fixation system that provides stable optical access to the brain during complex behavior. Compared to previous systems that used mechanical restraint, there are no moving parts and animals can engage and disengage entirely at will. This system is failsafe, easy for animals to use and reliable enough to allow long-term experiments to be routinely performed. Together with a novel two-photon fluorescence collection scheme that increases two-photon signal and a transgenic rat line that stably expresses the calcium sensor GCaMP6f in dorsal CA1, we are able to track and record activity from the same hippocampal neurons, during behavior, over a large fraction of animals lives.

neuroscience↗

bioRxiv2023

Trial-history biases in evidence accumulation can give rise to apparent lapses

Trial history biases and lapses are two of the most common suboptimalities observed during perceptual decision-making. These suboptimalities are routinely assumed to arise from distinct processes. However, several hints in the literature suggest that they covary in their prevalence and that their proposed neural substrates overlap - what could underlie these links? Here we demonstrate that history biases and apparent lapses can both arise from a common cognitive process that is normative under misbeliefs about non-stationarity in the world. This corresponds to an accumulation- to-bound model with history-dependent updates to the initial state of the accumulator. We test our models predictions about the relative prevalence of history biases and lapses, and show that they are robustly borne out in two distinct rat decision-making datasets, including data from a novel reaction time task. Our model improves the ability to precisely predict decision-making dynamics within and across trials, by positing a process through which agents can generate quasi-stochastic choices.

animal behavior and cognition↗

bioRxiv2022

Chronic brain functional ultrasound imaging in freely moving rodents performing cognitive tasks

Functional ultrasound imaging (fUS) is an emerging imaging technique that indirectly measures neural activity via changes in blood volume. To date it has not been used to image chronically during cognitive tasks in freely moving animals. Performing those experiments faces a number of exceptional challenges: performing large durable craniotomies with chronic implants, designing behavioural experiments matching the hemodynamic timescale, stabilizing the ultrasound probe during freely moving behavior, accurately assessing motion artifacts and validating that the animal can perform cognitive tasks at high performance while tethered. In this study, we provide validated solutions for those technical challenges. In addition, we present standardized step-by-step repro-ducible protocols, procedures and data processing pipelines that open up the opportunity to perform fUS in freely moving rodents performing complex cognitive tasks. Moreover, we present proof-of-concept analysis of brain dynamics during a decision making task. We obtain stable recordings from which we can robustly decode task variables from fUS data over multiple months. Moreover, we find that brain wide imaging through hemodynamic response is nonlinearly related to cognitive variables, such as task difficulty, as compared to sensory responses previously explored.

neuroscience↗

bioRxiv2021

Neural population dynamics underlying evidence accumulation in multiple rat brain regions

Accumulating evidence to make decisions is a core cognitive function. Previous studies have tended to estimate accumulation using either neural or behavioral data alone. Here we develop a unified framework for modeling stimulus-driven behavior and multi-neuron activity simultaneously. We applied our method to choices and neural recordings from three rat brain regions -- the posterior parietal cortex (PPC), the frontal orienting fields (FOF), and the anterior-dorsal striatum (ADS) -- while subjects performed a pulse-based accumulation task. Each region was best described by a distinct accumulation model, which all differed from the model that best described the animals choices. FOF activity was consistent with an accumulator where early evidence was favored while the ADS reflected near perfect accumulation. Neural responses within an accumulation framework unveiled a distinct association between each brain region and choice. Choices were better predicted from all regions using a comprehensive, accumulation-based framework and different brain regions were found to differentially reflect choice-related accumulation signals: FOF and ADS both reflected choice but ADS showed more instances of decision vacillation. Previous studies relating neural data to behaviorally-inferred accumulation dynamics have implicitly assumed that individual brain regions reflect the whole-animal level accumulator. Our results suggest that different brain regions represent accumulated evidence in dramatically different ways and that accumulation at the whole-animal level may be constructed from a variety of neural-level accumulators. Impact StatementA computational framework for combining neural and behavioral data to infer latent dynamics underlying decision-making reveals distinct accumulation dynamics in different brain regions in the rat.

neuroscience↗

bioRxiv2021

Stable choice coding during changes of mind

How do we choose the best action in a constantly-changing environment? Many natural decisions unfold in dynamic environments where newer observations carry better information about the present state of the world. Recent work has shown that rats can learn to optimally discount old evidence, updating their provisional decision when the environmental state changes. Provisional decisions are thought to be represented in the Frontal Orienting Fields (FOF), but this has only been tested in static environments where the provisional and final decisions are not easily dissociated. Here, we characterize the representation of accumulated evidence in rat FOF during decision-making in a dynamic environment. We find that FOF encodes evidence throughout decision formation with a temporal gain modulation that rises until the period when the animal may need to act. Using a behavioral model to predict the timing of changes of mind revealed that FOF neurons respond rapidly to these events, representing the new provisional decisions in their firing rates. Our results suggest that the FOF represents provisional decisions even in dynamic, uncertain environments, allowing for rapid motor execution when it is time to act.

neuroscience↗

bioRxiv2020

Multiple timescales of sensory-evidence accumulation across the dorsal cortex

Cortical areas seem to form a hierarchy of intrinsic timescales, but whether this is causal to cognitive behavior remains unknown. In particular, decisions requiring the gradual accrual of sensory evidence over time recruit widespread areas across this hierarchy. Here, we causally tested the hypothesis that this recruitment is related to the intrinsic integration timescales of these widespread areas. We trained mice to accumulate evidence over seconds while navigating in virtual reality, and optogenetically silenced the activity of many cortical areas during different brief trial epochs. We found that the inactivation of different areas primarily affected the evidence-accumulation computation per se, rather than other decision-related processes. Specifically, we observed selective changes in the weighting of evidence over time, such that frontal inactivations led to deficits on longer timescales than posterior cortical ones. Likewise, large-scale cortical Ca2+ activity during task performance displayed different temporal integration windows matching the effects of inactivation. Our findings suggest that distributed cortical areas accumulate evidence by leveraging their hierarchy of intrinsic timescales.

neuroscience↗

bioRxiv2019

Sequential and efficient neural-population coding of complex task information

Recent work has highlighted that many types of variables are represented in each neocortical area. How can these many neural representations be organized together without interference, and coherently maintained/updated through time? We recorded from large neural populations in posterior cortices as mice performed a complex, dynamic task involving multiple interrelated variables. The neural encoding implied that correlated task variables were represented by uncorrelated neural-population modes, while pairs of neurons exhibited a variety of signal correlations. This finding relates to principles of efficient coding for task-specific information, with neural-population modes as the encoding unit, and applied across posterior cortical regions and layers 2/3 and 5. Remarkably, this encoding function was multiplexed with sequential neural dynamics as well as reliably followed changes in task-variable correlations through time. We suggest that neural circuits can implement time-dependent encoding in a simple way by using random sequential dynamics as a temporal scaffold.

neuroscience↗

bioRxiv2019

Childhood conditions, pathways to entertainment work and current practices of female entertainment workers in Cambodia Baseline findings from the Mobile Link trial

BackgroundEntertainment venues have been identified as an important location for HIV prevention due to the increasing number of young female entertainment and sex workers at these venues. The purpose of this report is to increase understanding of the childhood conditions, pathways to entertainment work and current practices of female entertainment workers (FEWs) in Cambodia.\n\nMethodsData used for this study were collected in April 2018 as part of the baseline survey of the Mobile Link, a randomized controlled trial to improve sexual and reproductive health of FEWs in Cambodia. We used a stratified random sampling method to recruit 600 FEWs for face-to-face interviews using a structured questionnaire. Descriptive analyses were performed.\n\nResultsMost participants came from childhood homes without electricity (82.0%) or running water (87.0%). Most women moved to the city in the last ten years (80.5%) for economic reasons (43.7%). About a third worked in the garment industry prior to the entertainment industry (36.7%). Participation in transactional sex in the past three months was reported by 36.0%. Women reported low condom use practices with non-paying partners (23.4% used condom with partner at last sex), excessive and forced alcohol use at work (33.1% reported being forced to drink alcohol at work more than once a month), low modern contraception use (31.4% was using modern contraception), and experiences of gender-based violence (23.3% reported verbal threats, physical abuse or forced sex in the past six months).\n\nConclusionsThis information will help to support the development of future individual and structural level interventions for the safety and support of FEWs. In addition, these results may contribute to an evidence base that can inform policy level changes intended to support the realization of full human rights for entertainment works in Cambodia including the rights to health, safety, and respectful employment.

epidemiology↗

bioRxiv2019

Neural Correlates of Cognition in Primary Visual versus Neighboring Posterior Cortices during Visual Evidence-Accumulation-based Navigation

Studies of perceptual decision-making have often assumed that the main role of sensory cortices is to provide sensory input to downstream processes that accumulate and drive behavioral decisions. We performed a systematic comparison of neural activity in primary visual (V1) to secondary visual and retrosplenial cortices, as mice performed a task where they should accumulate pulsatile visual cues through time to inform a navigational decision. Even in V1, only a small fraction of neurons had sensory-like responses to cues. Instead, in all areas neurons were sequentially active, and contained information ranging from sensory to cognitive, including cue timings, evidence, place/time, decision and reward outcome. Per-cue sensory responses were amplitude-modulated by various cognitive quantities, notably accumulated evidence. This inspired a multiplicative feedback-loop circuit hypothesis that proposes a more intricate role of sensory areas in the accumulation process, and furthermore explains a surprising observation that perceptual discrimination deviates from Weber-Fechner Law.\n\nHighlights / eTOC BlurbO_LIMice made navigational decisions based on accumulating pulsatile visual cues\nC_LIO_LIThe bulk of neural activity in visual cortices was sequential and beyond-sensory\nC_LIO_LIAccumulated pulse-counts modulated sensory (cue) responses, suggesting feedback\nC_LIO_LIA feedback-loop neural circuit explains behavioral deviations from Webers Law\nC_LI\n\nIn a task where navigation was informed by accumulated pulsatile visual evidence, neural activity in visual cortices predominantly coded for cognitive variables across multiple timescales, including outside of a visual processing context. Even sensory responses to visual pulses were amplitude-modulated by accumulated pulse counts and other variables, inspiring a multiplicative feedback-loop circuit hypothesis that in turn explained behavioral deviations from Weber-Fechner Law.

neuroscience↗

bioRxiv2017

An accumulation-of-evidence task using visual pulses for mice navigating in virtual reality

The gradual accumulation of sensory evidence is a crucial component of perceptual decision making, but its neural mechanisms are still poorly understood. Given the wide availability of genetic and optical tools for mice, they can be useful model organisms for the study of these phenomena; however, behavioral tools are largely lacking. Here, we describe a new evidence-accumulation task for head-fixed mice navigating in a virtual reality environment. As they navigate down the stem of a virtual T-maze, they see brief pulses of visual evidence on either side, and retrieve a reward on the arm with the highest number of pulses. The pulses occur randomly with Poisson statistics, yielding a diverse yet well-controlled stimulus set, making the data conducive to a variety of computational approaches. A large number of mice of different genotypes were able to learn and consistently perform the task, at levels similar to rats in analogous tasks. They are sensitive to side differences of a single pulse, and their memory of the cues is stable over time. Moreover, using non-parametric as well as modeling approaches, we show that the mice indeed accumulate evidence: they use multiple pulses of evidence from throughout the cue region of the maze to make their decision, albeit with a small overweighting of earlier cues, and their performance is affected by the magnitude but not the duration of evidence. Additionally, analysis of the mice's running patterns revealed that trajectories are fairly stereotyped yet modulated by the amount of sensory evidence, suggesting that the navigational component of this task may provide a continuous readout correlated to the underlying cognitive variables. Our task, which can be readily integrated with state-of-the-art techniques, is thus a valuable tool to study the circuit mechanisms and dynamics underlying perceptual decision making, particularly under more complex behavioral contexts.

neuroscience↗