Biology subjects

Dave, A.

Publications and source records attributed to Dave, A..

13 recordsLinked to original sources

bioRxiv2026

Longitudinal Alterations in Sleep EEG Biomarkers of Memory Consolidation in Middle-Aged and Older Adults

The precise coordination of slow oscillations (SO) and sleep spindles during non-rapid eye movement (NREM) sleep supports memory consolidation and may serve as a sensitive marker of cognitive aging. However, longitudinal changes in their oscillatory dynamics in midlife and older age remain poorly understood. Using polysomnography with high-density EEG at two timepoints over [~]2.5 years, we examined changes in local NREM slow wave (SW), sleep spindle (occurring in the 11-16 Hz sigma range), and SO-sigma coupling strength in cognitively unimpaired middle-aged to older adults at risk for Alzheimers disease. Fronto-central SO-sigma power coupling strength significantly declined over time, independent of changes in multiple measures of SW and sleep spindle expression. Local declines in multiple sleep spindle measures were also observed. Greater baseline levels of cerebrospinal fluid (CSF) neurogranin, a postsynaptic protein abundantly expressed in the dendritic spines of the hippocampus and cerebral cortex and implicated in calcium-dependent synaptic plasticity, predicted the magnitude of longitudinal decline in SO-fast sigma coupling strength, which in turn predicted episodic memory performance changes. These findings suggest that longitudinal changes in local sleep oscillatory dynamics are related to decreased synaptic integrity and may serve as an early indicator of memory decline in older adults at risk for Alzheimers disease.

neuroscience↗

bioRxiv2026

Age-related reconfiguration of locus coeruleus-cortical functional organization

The locus coeruleus (LC) regulates attention, arousal, and adaptive behavior via widespread noradrenergic projections to cortex, yet its large-scale cortical organization and age-related vulnerability remain poorly understood. Using 7T MRI during naturalistic movie-viewing with neutral and negative emotional valence, study-specific LC delineation, and PET-derived receptor-transporter maps, we characterized LC-linked cortical organization in younger and older adults. Functional gradient analysis revealed two dominant axes: a stable primary gradient anchored by catecholaminergic receptor-transporter distributions, and a context-sensitive secondary gradient aligning with the visual-somatomotor (V-S) axis in neutral movie-viewing and the sensorimotor-association (S-A) axis in negative movie-viewing. During negative movie-viewing, older adults exhibited higher global and within-frontoparietal control network dispersion, indicating reduced functional differentiation, a pattern further associated with poorer emotional wellbeing. By revealing chemoarchitectural and context-sensitive LC-linked cortical organization, current work identifies mechanisms underlying age-related LC-linked cortical reorganization with consequences for mental health.

neuroscience↗

bioRxiv2026

Functional connectivity profile of the amygdala subfields associates with emotional well-being in aging

Amygdala-related functional connectivity plays a crucial role in human emotion, cognition, and mental well-being. The amygdala is a highly heterogeneous structure, with subregions that have both distinct and overlapping functions. However, the connectivity patterns of different amygdala subregions--and how these associations vary with age--remain poorly understood. Functional MRI data were analyzed from 68 younger adults and 66 older adults during movie watching in a 7T MRI scanner. Partial least squares (PLS) analysis was used to identify latent variables capturing variance associated with age-related differences in the functional connectivity patterns of three amygdala subregions: the basolateral (BLA), centromedial (CMA), and superficial (SFA) nuclei. In addition, covariance between behavioral measures, such as emotional resilience and cognitive function, and functional connectivity of these subregions was examined. We further explored the associated cognitive processes, correspondence with large-scale brain networks, and the underlying chemoarchitecture of the identified connectivity patterns of the BLA, CMA, and SFA. Multivariate analyses revealed age-related and subregion-specific functional connectivity patterns. Functional connectivity patterns of amygdala subregions were further associated with emotional resilience, which largely overlapped across widespread brain regions; however, their associations differed by age. Stronger coupling of amygdala subregions predicted higher resilience in older adults but lower resilience in younger adults. The identified connectivity patterns were linked to the salience, control, and default mode networks and showed spatial correspondence with mGluR5 and 5-HT6 receptor distributions. These findings highlight age-dependent reorganization of amygdala-related networks that support emotional resilience and provide novel insights into how functional and neurochemical changes of the amygdala subregions contribute to adaptive emotional and cognitive functions in aging.

neuroscience↗

bioRxiv2025

Frontoparietal functional dedifferentiation during naturalistic movie watching among older adults at risk of emotional vulnerability

Functional dedifferentiation, a hallmark of brain aging particularly evident within the frontoparietal network (FPN), has been extensively investigated in the context of cognitive decline, yet its implications for late-life mental health remain poorly understood. Leveraging naturalistic fMRI combined with gradient mapping techniques, the present study investigated FPN functional dedifferentiation--quantified by functional dispersion of FPN in the multidimension gradient manifold--during real-life emotional experiences and its link to affective outcomes. Here, we estimated functional dispersion during naturalistic movie watching in both younger (N=72, 34 female, 19-36 yrs) and older (N=68, 36 female, 65-82 yrs) adult groups with 7T MRI scanner and assessed their emotion regulation difficulties, anxiety, and depression symptoms as indicators of mental health status. The results demonstrated that greater FPN dispersion (i.e., more dissimilar connectivity) was linked to increased depressive symptoms in older adults and highlighted emotion regulation difficulties as a full mediator of this relationship. Moreover, FPN dispersion could distinguish emotionally resilient from vulnerable older individuals. These findings suggest that functional dedifferentiation of the FPN during ecologically valid emotional context constitutes a promising neural signature of affective vulnerability in older adults. By bridging age-related functional dedifferentiation to real-world emotional scenario, this work underscores the translational value of naturalistic paradigms in geriatric psychiatry and identifies potential intervention targets aimed at enhancing FPN specificity to promote mental health in aging population.

neuroscience↗

bioRxiv2025

Artificial Intelligence Apps for Medical Image Analysis using pyCERR and Cancer Genomics Cloud

This work introduces a user-friendly, cloud-based software framework for conducting Artificial Intelligence (AI) analyses of medical images. The framework allows users to deploy AI-based workflows by customizing software and hardware dependencies. The components of our software framework include the Python-native Computational Environment for Radiological Research (pyCERR) platform for radiological image processing, Cancer Genomics Cloud (CGC) for accessing hardware resources and user management utilities for accessing images from data repositories and installing AI models and their dependencies. GNU-GPL copyright pyCERR was ported to Python from MATLAB-based CERR to enable researchers to organize, access, and transform metadata from high dimensional, multi-modal datasets to build cloud-compatible workflows for AI modeling in radiation therapy and medical image analysis. pyCERR provides an extensible data structure to accommodate metadata from commonly used medical imaging file formats and a viewer to allow for multi-modal visualization. Analysis modules are provided to facilitate cloud-compatible AI-based workflows for image segmentation, radiomics, DCE MRI analysis, radiotherapy dose-volume histogram-based features, and normal tissue complication and tumor control models for radiotherapy. Image processing utilities are provided to help train and infer convolutional neural network-based models for image segmentation, registration and transformation. The framework allows for round-trip analysis of imaging data, enabling users to apply AI models to their images on CGC and retrieve and review results on their local machine without requiring local installation of specialized software or GPU hardware. The deployed AI models can be accessed using APIs provided by CGC, enabling their use in a variety of programming languages. In summary, the presented framework facilitates end-to-end radiological image analysis and reproducible research, including pulling data from sources, training or inferring from an AI model, utilities for data management, visualization, and simplified access to image metadata.

bioinformatics↗

bioRxiv2024

Age-related Increase in Locus Coeruleus Activity and Connectivity with Prefrontal Cortex during Ambiguity Processing

Interpreting ambiguous environmental cues, like facial expressions, becomes increasingly challenging with age, especially as cognitive resources decline. Managing these challenges requires adaptive neural mechanisms that are essential for maintaining mental well-being. The locus coeruleus (LC), the brains main norepinephrine source, regulates attention, arousal, and stress response. With extensive cortical connections, the LC supports adapting to cognitive demands and resolving conflicting cues from environment, particularly in later life. Previous research suggests that LC interacts with the prefrontal cortex (PFC) during high-conflict tasks. However, whether LC activity and its connectivity with the PFC support emotional ambiguity processing and contributes to emotional well-being in healthy aging remains unclear. To address this gap, we used 7T-MRI to examine LC function in 75 younger (25.8 {+/-} 4.02years, 35females) and 69 older adults (71.3 {+/-} 4.1 years, 35females) during facial-emotion-recognition task morphed with varying ambiguity: anchor (unambiguous happy or fearful), intermediate-ambiguity (30%happy-70%fearful and 40%happy-60%fearful expressions), and absolute-ambiguity (50%happy-fearful). Behaviorally, participants had longer response times and lower confidence during the absolute-ambiguity condition, while older adults perceived ambiguous faces as happy more frequently than younger adults. Neuroimaging results revealed older adults exhibited greater LC activity and enhanced connectivity with dorsolateral PFC (dlPFC) during absolute-ambiguity compared to younger adults. This heightened connectivity in older adults was linked to better task-independent self-reported mental well-being questionnaires and greater emotional resilience scores derived from principal component analysis. Overall, these findings suggest that greater LC activity supports managing cognitively demanding tasks, while enhanced LC-dlPFC connectivity promotes emotional well-being, highlighting this neural pathways role in healthy aging. Significance StatementUnderstanding how the brain adapts to cognitive and emotional demands with age is key to promoting healthy aging. This study examined whether the locus coeruleus (LC), a brain region critical for regulating attention and arousal, undergoes adaptive changes with age, especially during emotional ambiguity task. Using ultra-high-field imaging, we explored younger and older adults recognize facial expressions with varying ambiguity levels. Our findings indicated that compared to young, older adults showed heightened LC activity and LC-dorsolateral prefrontal cortex (dlPFC) connectivity when processing absolute-ambiguous facial expressions, with enhanced connectivity linked to improved mental well-being. These results suggest higher LC activity supports cognitive demands of ambiguity processing with LC-dlPFC connectivity promoting emotional well-being and resilience, offering insights into mechanisms underlying healthy aging.

neuroscience↗

bioRxiv2024

Engagement in moderate-intensity physical activity supports overnight emotional memory retention in older adults

ImportancePreserving the ability to vividly recall emotionally rich experiences contributes to quality of life in older adulthood. While prior work suggests that moderate-intensity physical activity (MPA) may bolster memory, it is unclear whether this extends to emotionally salient memories consolidated during sleep. ObjectiveTo investigate associations between engagement in physical activity (PA) and overnight emotional memory retention and examine whether theoretically replacing 30-minutes of lower-intensity activity with MPA is associated with better consolidation. Design, Setting, and ParticipantsA cross-sectional study of 40 community-dwelling older adults free of neurological and psychiatric disorders. Data were collected from May 2018 to July 2022 and analyzed from January to July 2024. ExposuresParticipants completed an overnight polysomnography (PSG) with emotional memory tested before and after sleep and a self-report questionnaire assessing habitual PA. Main Outcome(s) and Measures(s)Emotional memory performance was assessed via recognition memory or mnemonic discrimination performance. Overnight memory retention was calculated by subtracting immediate test from delayed test performance for both recognition memory and mnemonic discrimination, with more negative scores indicating lower memory retention. Frequency and duration of MPA, light-intensity PA, non-exertive activity, and sedentary behavior were calculated from the Community Health Activities Model Program for Seniors (CHAMPS) Activities Questionnaire for Older Adults. Isotemporal substitution modelling evaluated whether statistically reallocating time spent in sedentary and lower-intensity activity to MPA was associated with better overnight memory retention. ResultsData from 40 participants were analyzed ({square}age=72.3{+/-}5.8, 26 female). Better overnight emotional recognition memory retention was associated with the frequency ({beta}=0.663, SE=0.212, p=0.003) and duration ({beta}=0.214, SE=0.101, p=0.042) of MPA. No relationships were found with mnemonic discrimination or neutral recognition memory. Statistically modelling the replacement of 30 minutes of lower-intensity activity with MPA was associated with better overnight retention of emotional memories ({beta}=0.108, SE=0.048, p=0.030), but not neutral ({beta}=-0.029, SE=0.069, p=0.679). Conclusions and RelevanceMPA may enhance sleep-dependent consolidation of emotional memories in older adults. Modest increases in MPA may yield significant benefits for sleep-dependent emotional memory retention. These findings may guide interventions to preserve memory function and inform public health recommendations by demonstrating that substituting even short durations of low-intensity activity for MPA could produce significant cognitive gains relevant for maintaining quality of life in older adulthood.

neuroscience↗

bioRxiv2024

Cerebrovascular pathology mediates associations between hypoxemia during rapid eye movement sleep and medial temporal lobe structure and function in older adults

Obstructive sleep apnea (OSA) is common in older adults and is associated with medial temporal lobe (MTL) degeneration and memory decline in aging and Alzheimers disease (AD). However, the underlying mechanisms linking OSA to MTL degeneration and impaired memory remains unclear. By combining magnetic resonance imaging (MRI) assessments of cerebrovascular pathology and MTL structure with clinical polysomnography and assessment of overnight emotional memory retention in older adults at risk for AD, cerebrovascular pathology in fronto-parietal brain regions was shown to statistically mediate the relationship between OSA-related hypoxemia, particularly during rapid eye movement (REM) sleep, and entorhinal cortical thickness. Reduced entorhinal cortical thickness was, in turn, associated with impaired overnight retention in mnemonic discrimination ability across emotional valences for high similarity lures. These findings identify cerebrovascular pathology as a contributing mechanism linking hypoxemia to MTL degeneration and impaired sleep-dependent memory in older adults.

neuroscience↗

bioRxiv2023

Medial temporal lobe functional network architecture supports sleep-related emotional memory processing in older adults

Memory consolidation occurs via reactivation of a hippocampal index during non-rapid eye movement slow-wave sleep (NREM SWS) which binds attributes of an experience existing within cortical modules. For memories containing emotional content, hippocampal-amygdala dynamics facilitate consolidation over a sleep bout. This study tested if modularity and centrality--graph theoretical measures that index the level of segregation/integration in a system and the relative import of its nodes--map onto central tenets of memory consolidation theory and sleep-related processing. Findings indicate that greater network integration is tied to overnight emotional memory retention via NREM SWS expression. Greater hippocampal and amygdala influence over network organization supports emotional memory retention, and hippocampal or amygdala control over information flow are differentially associated with distinct stages of memory processing. These centrality measures are also tied to the local expression and coupling of key sleep oscillations tied to sleep-dependent memory consolidation. These findings suggest that measures of intrinsic network connectivity may predict the capacity of brain functional networks to acquire, consolidate, and retrieve emotional memories.

neuroscience↗

bioRxiv2023

Intratumoral immune triads are required for adoptive T cell therapy-mediated elimination of solid tumors

Tumor-reactive CD8 T cells found in cancer patients are frequently dysfunctional, unable to halt tumor growth. Adoptive T cell transfer (ACT), the administration of large numbers of in vitro-generated cytolytic tumor-reactive CD8 T cells, is an important cancer immune therapy being pursued. However, a limitation of ACT is that transferred CD8 T cells often rapidly lose effector function, and despite exciting results in certain malignancies, few ACT clinical trials have shown responses in solid tumors. Here, we developed preclinical cancer mouse models to investigate if and how tumor-specific CD4 T cells can be enlisted to overcome CD8 T cell dysfunction in the setting of ACT. In situ confocal microscopy of color-coded cancer cells, tumor-specific CD8 and CD4 T cells, and antigen presenting cells (APC), combined with functional studies, revealed that the spatial positioning and interactions of CD8 and CD4 T cells, but not their numbers, dictates ACT efficacy and anti-tumor responses. We uncover a new role of antigen-specific CD4 T cells in addition to the known requirement for CD4 T cells during priming/activation of naive CD8 T cells. CD4 T cells must co-engage with CD8 T cells and APC cross-presenting CD8-and CD4-tumor antigens during the effector phase, forming a three-cell-cluster (triad), to license CD8 T cell cytotoxicity and mediate cancer cell elimination. Triad formation transcriptionally and epigenetically reprogram CD8 T cells, prevent T cell dysfunction/exhaustion, and ultimately lead to the elimination of large established tumors and confer long-term protection from recurrence. When intratumoral triad formation was disrupted, adoptively transferred CD8 T cells could not be reprogrammed, and tumors progressed despite equal numbers of tumor-infiltrating CD8 and CD4 T cells. Strikingly, the formation of CD4 T cell::CD8 T cell::APC triads in tumors of patients with lung cancers treated with immune checkpoint blockade was associated with clinical responses, but not CD4::APC dyads or overall numbers of CD8 or CD4 T cells, demonstrating the importance of triads in non-ACT settings in humans. Our work uncovers intratumoral triads as a key requirement for anti-tumor immunity and a new role for CD4 T cells in CD8 T cell cytotoxicity and cancer cell eradication.

immunology↗

bioRxiv2022

Technical Note: STRATIS: A Cloud-enabled Software Toolbox for Radiotherapy and Imaging Analysis

PurposeRecent advances in computational resources, including software libraries and hardware, have enabled the use of high-dimensional, multi-modal datasets to build Artificial Intelligence (AI) models and workflows for radiation therapy and image analysis. The purpose of Software Toolbox for RAdioTherapy and Imaging analysiS (STRATIS) is to provide cloud-enabled, easy-to-share software workflows to train and deploy AI models for transparency and multi-institutional collaboration. MethodSTRATIS leverages open source medical image informatics software for application-specific analysis. Jupyter notebooks for AI modeling workflows are provided with Python language as the base kernel. In addition to Python, workflows use software written in other languages, such as MATLAB, GNU-Octave, R, and C++, with the help of bridge libraries. The workflows can be run on a cloud platform, local workstation, or an institutional HPC cluster. Computational environments are provided in the form of publicly available docker images -and build scripts for local Anaconda environments. Utilities provided with STRATIS simplify bookkeeping of associations between imaging objects and allow chaining data processing operations defined via a setting file for AI models. ResultsWorkflows available on STRATIS can be broadly categorized into image segmentation, deformable image registration, and outcomes modeling for radiotherapy toxicity and tumor control using radiomics and dosimetry features. The STRATIS-forge GitHub organization https://www.github.com/stratis-forge hosts build-scripts for Docker and Anaconda as well as Jupyter notebooks for analysis workflows. The software for building environments and workflow notebooks has open source-GNU-GPL copyright, and AI models retain the copyright chosen by their original developers. ConclusionSTRATIS enables researchers to deploy and share AI modeling workflows for radiotherapy and image analysis. STRATIS is publicly available on Terra.bios FireCloud platform with a pre-deployed computational environment and on GitHub organization for users pursuing local deployment.

bioinformatics↗

bioRxiv2018

Multiparameter cell characterization using nanofluidic technology facilitates real-time phenotypic and genotypic elucidation of intratumor heterogeneity

Genetic and functional complexity of bulk tumor has become evident through rapid advances in sequencing technologies. As a unique integrated approach to characterizing tumor heterogeneity, we demonstrate the multifaceted capabilities of a novel nanofluidic platform to enable single-cell phenotypic and genetic profiling of ovarian cancer patient-derived tumor cells. This approach has enabled increased resolution of tumor cell phenotypic and genetic heterogeneity, providing a better understanding of underlying biological drivers of the disease. A range of CA-125 expression levels is observed within cells from individuals, demonstrating clonal diversity consistent with other phenotypic data. Further, TP53 mutation analysis demonstrates a sub-population of cells exhibiting high mutation frequency that likely drives downstream growth kinetics and protein expression. Finally, genomic data is orthogonally used to address clonal heterogeneity across ovarian tumors when compared to bulk sequencing, illustrating the potential for single-cell sequencing data integrated with cellular functional and growth data toward future therapeutic intervention.

genomics↗

bioRxiv2018

Unmodified, autologous adipose-derived regenerative cells improve cardiac function, structure and revascularization in a porcine model of chronic myocardial infarction

Numerous studies have investigated cell-based therapies for myocardial infarction (MI), with mixed results. In the present study the left anterior descending (LAD) artery of pigs was occluded for 180 min. Four weeks later, the mean left ventricular ejection fraction (LVEF) was shown to have been reduced to approximately 35%. At that time, 18x106 unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) were delivered into the LAD vein (control: delivery of saline). Six weeks following UA-ADRCs/saline delivery, the mean LVEF had increased by 18% (p<0.01) after delivery of UA-ADRCs, but was unchanged after delivery of saline. This is among the best outcome ever reported in studies on porcine animal models of cell-based therapies for MI in which functional outcome was assessed with cardiac magnetic resonance imaging. The unique combination of the procedure used for isolating UA-ADRCs, the late cell delivery time and the uncommon cell delivery route applied in the present study may open new horizons for cell-based therapies for MI.

molecular biology↗