Biology subjects

Prasad, D.

Publications and source records attributed to Prasad, D..

11 recordsLinked to original sources

bioRxiv2026

Multiple forms of sensory reinstatement in category-selective cortex

Visual recall is classically thought to depend on reinstatement: areas engaged when encoding a visual input are similarly reactivated when remembering it. Here we investigated if reinstatement might be differently implemented across the diverse category-selective systems of visual cortex. Using fMRI in 25 participants, we assessed possible reinstatement organizations across scene-, face-, and body-selective cortex. We asked whether memory reactivates the same category-selective areas engaged during perception, whether it engages same or distinct vertices, and whether perceptual-mnemonic distinctions were topographically organized. All regions were selectively engaged during both perception and memory, though memory activity was weaker overall. At the vertex-level, most regions--including body-selective LOS, ITG, MTG; face-selective FFA1, FFA2; and scene-selective PPA--showed classic reinstatement, with memory enriched in the most perceptually selective vertices. In contrast, OFA and OPA showed separable perception-and memory-biased vertices. Critically, only scene-selective areas showed topographic distinction: in both PPA and OPA, mnemonic activity was located consistently anterior to perceptual activity, whereas no face-or body-selective areas showed such a distinction. Thus, while all category-selective areas are reactivated during memory, scene-selective cortex topographically separates memory from perception, suggesting different sensory reinstatement implementations across high-level visual cortex, possibly reflecting the distinct computational demands.

neuroscience↗

bioRxiv2026

A Low-Cost, Modular Hardware and Software Platform for Head-Fixed Mouse Decision-Making Tasks

Head-fixed behavior in rodents is a foundational technique in systems neuroscience which enables use of sophisticated imaging techniques in combination with animal behavior. However, accessibility of head-fixed behavior techniques is limited. Animal training consumes a large amount of experimenter labor and commercial setups, when available, are largely inflexible and financially burdensome. Here, we present a low-cost, modular, and open-source hardware and software implementation for head-fixed rodent decision-making tasks. Our design lowers experimenter labor and enables large teams of researchers to participate in animal training with minimal experimenter error using a simple touchscreen GUI and automated training progression. We demonstrate the efficacy of the platform by training a cohort of animals in a two-choice probabilistic rapid-reversal task in which mice continuously update action choices based on recent reward history. The presented design lowers the barrier to entry for laboratories seeking to conduct head-fixed rodent behavior and provides modular solutions for developing custom rigs based on experimental demands. Significance StatementHead-fixation in behaving rodents is a common neuroscience procedure that enables the use of electrical or optical techniques for neural circuit interrogation. While commercial head-fixed behavior platforms are available, their high cost and inflexibility make them unsuitable for modification or high-throughput training. This study presents a novel open-source hardware and software system for mouse head-fixed behavior. The modular design and use of low-cost components enable broad adaptability across behavioral tasks, compatibility with practical research demands, and significantly lowers the barrier to entry to head-fixed behavioral research.

neuroscience↗

bioRxiv2025

The renin angiotensin system in cognitive flexibility: Effects of single-dose losartan on task-switching in healthy volunteers

IntroductionCognitive flexibility, defined as the ability to shift mental strategies when environmental demands change, may influence psychological well-being and psychiatric treatment outcomes. Emerging research increasingly implicates the renin angiotensin system (RAS) in cognition, yet its role in cognitive flexibility is inadequately understood. MethodsWe conducted a double-masked trial with N=60 healthy adults aged 18-50. Participants were randomly assigned to receive a single 50 mg dose of losartan, an angiotensin II receptor blocker, or placebo. Following a waiting period, participants completed a task-switching paradigm as a measure of cognitive flexibility, which required dynamically categorizing arrows based on location or direction. Statistical analyses were conducted to determine group (losartan vs. placebo), task (location vs. direction), and switch (switching vs. repeating a task) effects on reaction time (RT) and accuracy independently. A composite bin score was also computed, integrating both RT and accuracy data. ResultsAll participants displayed the expected switch costs. While participants on losartan exhibited numerically superior RTs and accuracy, losartan did not significantly improve task-switching performance relative to placebo. This was confirmed by the bin score analysis, which indicated no benefit of losartan when RT and accuracy were considered together. An exploratory probe suggested that losartan improved accuracy on direction switch trials, indicating a potential drug effect under specific cognitive conditions. ConclusionOverall, we found no significant benefits of losartan on task-switching in healthy adults. Our results may be explained by ceiling effects in our sample, which could have hindered the detection of group differences, or possibly reflect a negligible role for the RAS in cognitive flexibility.

neuroscience↗

bioRxiv2025

Topography of scene memory and perception activity in posterior cortex - a publicly available resource

Adaptive behavior in complex environments requires integrating visual perception with memory of our spatial environment. Recent work has implicated three brain areas in posterior cerebral cortex -- the place memory areas (PMAs) that are anterior to the three visual scene perception areas (SPAs) - in this function. However, PMAs relationship to the broader cortical hierarchy remains unclear due to limited group-level characterization. Here, we examined the PMA and SPA locations across three fMRI datasets (44 participants, 29 female). SPAs were identified using a standard visual localizer where participants viewed scenes versus faces. PMAs were identified by contrasting activity when participants recalled personally familiar places versus familiar faces (Datasets 1-2) or places versus multiple categories (familiar faces, bodies, and objects, and famous faces; Dataset 3). Across datasets, the PMAs were located anterior to the SPAs on the ventral and lateral cortical surfaces. The anterior displacement between PMAs and SPAs was highly reproducible. Compared to public atlases, the PMAs fell at the boundary between externally-oriented networks (dorsal attention) and internally-oriented networks (default mode). Additionally, while SPAs overlapped with retinotopic maps, the PMAs were consistently located anterior to mapped visual cortex. These results establish the anatomical position of the PMAs at inflection points along the cortical hierarchy between unimodal sensory and transmodal, apical regions, which informs broader theories of how the brain integrates perception and memory for scenes. We have released probabilistic parcels of these regions to facilitate future research into their roles in spatial cognition. Significance statementComplex behavior requires the dynamic interplay between mnemonic and perceptual information. For example, navigation requires representation of the current visual scene and its relationship to the surrounding visuospatial context. We have suggested that the place memory areas, three brain areas located anterior to the scene perception areas in visual cortex, are well-positioned to serve this role. Here, in a large group of participants, we show that the place memory areas are robustly localizable, and that their position at the interface of multiple distributed brain networks is uniquely suited to mnemonic-perceptual integration. We have released probabilistic regions-of-interest and localization procedure so that others can identify these areas in their own participants.

neuroscience↗

bioRxiv2024

The Neural Underpinnings of Aphantasia: A Case Study of Identical Twins

Aphantasia is a condition characterized by reduced voluntary mental imagery. As this lack of mental imagery disrupts visual memory, understanding the nature of this condition can provide important insight into memory, perception, and imagery. Here, we leveraged the power of case studies to better characterize this condition by running a pair of identical twins, one with aphantasia and one without, through mental imagery tasks in an fMRI scanner. We identified objective, neural measures of aphantasia, finding less visual information in their memories which may be due to lower connectivity between frontoparietal and occipitotemporal lobes of the brain. However, despite this difference, we surprisingly found more visual information in the aphantasic twin's memory than anticipated, suggesting that aphantasia is a spectrum rather than a discrete condition.

neuroscience↗

bioRxiv2023

Integrated Protocol of Protein Structure Modeling for Cryo-EM with Deep Learning and Structure Prediction

Structure modeling from maps is an indispensable step for studying proteins and their complexes with cryogenic electron microscopy (cryo-EM). Although the resolution of determined cryo-EM maps has generally improved, there are still many cases where tracing protein main-chains is difficult, even in maps determined at a near atomic resolution. Here, we have developed a protein structure modeling method, called DeepMainmast, which employs deep learning to capture the local map features of amino acids and atoms to assist main-chain tracing. Moreover, since Alphafold2 demonstrates high accuracy in protein structure prediction, we have integrated complementary strengths of de novo density tracing using deep learning with Alphafold2s structure modeling to achieve even higher accuracy than each method alone. Additionally, the protocol is able to accurately assign chain identity to the structure models of homo-multimers.

bioinformatics↗

bioRxiv2023

Tessellation Of Artificial Touch Via Microstimulation Of Human Somatosensory Cortex

When we interact with objects, we rely on signals from the hand that convey information about the object and our interaction with it. A basic feature of these interactions, the locations of contacts between the hand and object, is often only available via the sense of touch. Information about locations of contact between a brain-controlled bionic hand and an object can be signaled via intracortical microstimulation (ICMS) of somatosensory cortex (S1), which evokes touch sensations that are localized to a specific patch of skin. To provide intuitive location information, tactile sensors on the robotic hand drive ICMS through electrodes that evoke sensations at skin locations matching sensor locations. This approach requires that ICMS-evoked sensations be focal, stable, and distributed over the hand. To systematically investigate the localization of ICMS-evoked sensations, we analyzed the projected fields (PFs) of ICMS-evoked sensations - their location and spatial extent - from reports obtained over multiple years from three participants implanted with microelectrode arrays in S1. First, we found that PFs vary widely in their size across electrodes, are highly stable within electrode, are distributed over large swaths of each participants hand, and increase in size as the amplitude or frequency of ICMS increases. Second, while PF locations match the locations of the receptive fields (RFs) of the neurons near the stimulating electrode, PFs tend to be subsumed by the corresponding RFs. Third, multi-channel stimulation gives rise to a PF that reflects the conjunction of the PFs of the component channels. By stimulating through electrodes with largely overlapping PFs, then, we can evoke a sensation that is experienced primarily at the intersection of the component PFs. To assess the functional consequence of this phenomenon, we implemented multi-channel ICMS-based feedback in a bionic hand and demonstrated that the resulting sensations are more localizable than are those evoked via single-channel ICMS.

neuroscience↗

bioRxiv2023

Mobilisation and analyses of publicly available SARS-CoV-2 data for pandemic responses

The COVID-19 pandemic has seen large-scale pathogen genomic sequencing efforts, becoming part of the toolbox for surveillance and epidemic research. This resulted in an unprecedented level of data sharing to open repositories, which has actively supported the identification of SARS-CoV-2 structure, molecular interactions, mutations and variants, and facilitated vaccine development and drug reuse studies and design. The European COVID-19 Data Platform was launched to support this data sharing, and has resulted in the deposition of several million SARS-CoV-2 raw reads. In this paper we describe (1) open data sharing, (2) tools for submission, analysis, visualisation and data claiming (e.g. ORCiD), (3) the systematic analysis of these datasets, at scale via the SARS-CoV-2 Data Hubs as well as (4) lessons learned. As a component of the Platform, the SARS-CoV-2 Data Hubs enabled the extension and set up of infrastructure that we intend to use more widely in the future for pathogen surveillance and pandemic preparedness.

bioinformatics↗

bioRxiv2023

Biomimetic multi-channel microstimulation of somatosensory cortex conveys high resolution force feedback for bionic hands

AO_SCPLOWBSTRACTC_SCPLOWManual interactions with objects are supported by tactile signals from the hand. This tactile feedback can be restored in brain-controlled bionic hands via intracortical microstimulation (ICMS) of somatosensory cortex (S1). In ICMS-based tactile feedback, contact force can be signaled by modulating the stimulation intensity based on the output of force sensors on the bionic hand, which in turn modulates the perceived magnitude of the sensation. In the present study, we gauged the dynamic range and precision of ICMS-based force feedback in three human participants implanted with arrays of microelectrodes in S1. To this end, we measured the increases in sensation magnitude resulting from increases in ICMS amplitude and participants ability to distinguish between different intensity levels. We then assessed whether we could improve the fidelity of this feedback by implementing "biomimetic" ICMS-trains, designed to evoke patterns of neuronal activity that more closely mimic those in natural touch, and by delivering ICMS through multiple channels at once. We found that multi-channel biomimetic ICMS gives rise to stronger and more distinguishable sensations than does its single-channel counterpart. Finally, we implemented biomimetic multi-channel feedback in a bionic hand and had the participant perform a compliance discrimination task. We found that biomimetic multi-channel tactile feedback yielded improved discrimination over its single-channel linear counterpart. We conclude that multi-channel biomimetic ICMS conveys finely graded force feedback that more closely approximates the sensitivity conferred by natural touch.

neuroscience↗

bioRxiv2023

A cell surface code mediates tissue-intrinsic defense against aberrant cells in epithelia

Tissue-intrinsic error-correction mechanisms allow epithelial cells to detect aberrant neighboring cells and cause their removal from the tissue. The molecular mechanisms which grant cells the ability to compare their internal states is unknown. Here we demonstrate that comparison of cell identity, created by cell-fate-specifying transcription factors and patterning pathways, is conveyed through a specific set of cell surface molecules. We demonstrate that Drosophila imaginal discs express a range of cell surface molecules previously implicated in neuronal axon guidance processes, such as members of the Robo, Teneurin, Ephrin, Toll-like or atypical Cadherin families. Expression of these molecules is regulated by intrinsic fate-patterning pathways of the disc but also by aberrant expression of oncogenic RasV12. Importantly, mosaic clones deregulating individual cell surface molecules are sufficient to induce all hallmarks of interface surveillance, a tissue-intrinsic error-correction mechanism previously shown to be induced by cells with aberrant activation of fate-patterning pathways. Specifically, cells with deregulated expression of Robo2 and Robo3 induce actomyosin enrichment, bilateral JNK signaling and apoptosis at mosaic clone interfaces in imaginal discs. Moreover, deregulation of Robo2 levels, which is normally expressed in a complex endogenous pattern, induces these interface surveillance hallmarks in a Robo2-pattern-specific manner. Taken together, our work indicates that these cell surface molecules mediate cell fate recognition in epithelial tissues and thereby contribute to the maintenance of epithelial health by initiating detection and removal of aberrant cells during development and adult tissue homeostasis.

cell biology↗

bioRxiv2022

Bilateral JNK activation is a hallmark of interface contractility and promotes elimination of aberrant cells

Tissue-intrinsic defence mechanisms eliminate aberrant cells from epithelia and thereby maintain the health of developing tissues or adult organisms. Interface contractility comprises one such distinct mechanism that specifically guards against aberrant cells, which undergo inappropriate cell fate and differentiation programs. The cellular mechanisms which facilitate detection and elimination of these aberrant cells are currently unknown. We find that in Drosophila imaginal discs, interface contractility is associated with bilateral JNK activation at the clonal interface of wild type and aberrant cells. Bilateral JNK activation is unique to interface contractility and is not observed in other tissue-intrinsic defence mechanisms, such as cell-cell competition. We find that JNK is activated cell-autonomously by either of the contacting cell types and drives apoptotic elimination of cells at clonal interfaces. Ultimately, JNK interface signalling provides a collective tissue-level mechanism, which ensures elimination of aberrant, misspecified cells that cannot be identified by cell fitness criteria, as in cell-cell competition. Importantly, oncogenic Ras activates interface contractility but evades apoptotic elimination by bilateral JNK activation. Combined, our work establishes bilateral JNK interface signalling and interface apoptosis as a new hallmark of interface contractility, and it highlights how oncogenic mutations evade tumour suppressor function encoded by this tissue-intrinsic surveillance system.

developmental biology↗