Biology subjects

Gray, S. M.

Publications and source records attributed to Gray, S. M..

14 recordsLinked to original sources

bioRxiv2026

The development of slow and fast theta oscillations in the human brain

Theta oscillations are pivotal for attention and memory, with developmental shifts in theta activity and connectivity tracking memory ability across the lifespan. Building on initial evidence that the theta band separates into slow and fast sub-bands across development within the medial temporal lobe (MTL) and the prefrontal cortex (PFC), this preregistered study (https://osf.io/gsru7) characterized the frequencies of slow (~1.5-4.5 Hz) and fast (~4.5-9.0 Hz) theta oscillations across the brain in a large developmental cohort. We analyzed intracranial EEG (iEEG) recordings from widespread brain regions in 101 children and adults (5.93-54.00 years, 63 males; n electrodes = 5691) using task-based (attention to to-be-remembered visual stimuli) and task-free (resting-state) data. We reveal distinct slow and fast theta oscillations in all regions and identify a spatial gradient in both frequency ranges, with slow theta oscillations speeding up and fast theta oscillations slowing down from posterior to anterior regions. The dissociation between slow and fast theta frequencies peaks during young adulthood, mirroring the developmental trajectory of attention and memory. In the hippocampus and PFC, attentional state (task-based, task-free) modulated age effects, and individual differences in task-based slow theta frequencies predicted individual differences in memory performance, linking the development of slow theta oscillations to the development of memory. Gray matter volume was not associated with age- or task-related differences in theta frequencies, suggesting that the development of theta oscillations is independent of regional brain structure. This study establishes developmental trajectories of slow and fast theta oscillations in localized brain regions and links the maturation of hippocampal and PFC slow theta oscillations to the development of attention and memory.

neuroscience↗

bioRxiv2026

Differential roles of frontoparietal regions in working memory and decision-making

Working memory (WM) and decision-making (DM) are closely linked cognitive processes that rely on frontoparietal regions, yet their distinct and shared neural dynamics remain unclear. Using intracranial EEG recordings from 24 human subjects performing a delayed match-to-sample task, we examined high-frequency broadband (HFB) activity to dissociate WM- and DM-related processes with high spatiotemporal resolution. Principal component analysis of frontoparietal HFB activity revealed multiple temporally distinct patterns spanning stimulus presentation and delay phases. The most dominant component reflected sustained WM-related activity across task phases, consistent with persistent maintenance of internal representations. Additional components captured transient WM encoding across trial phases, as well as both stimulus-linked and ramping DM-related activity suggesting dual early and late stages of evaluative processing. These processes were distributed across frontoparietal regions but showed systematic differences in anatomical focus, with WM-related activity concentrated in dorsolateral prefrontal cortex (PFC) and DM-related activity concentrated in ventrolateral PFC, while inferior parietal cortex preferentially tracked the behavioral significance of incoming stimuli and superior parietal cortex tracked the appearance of new information that may require updating ongoing processing. Together, these findings demonstrate that WM and DM processes are separable yet interleaved over time within distributed cortical networks, revealing coordinated but functionally distinct contributions to goal-directed behavior.

neuroscience↗

bioRxiv2026

Mechanistic and machine learning models design human gut consortia that robustly inhibit Clostridioides difficile

Identifying design principles for robust inhibition of human pathogens is a major goal of microbiome engineering. By building synthetic microbial communities from the bottom-up guided by Bayesian active learning, we investigate the Clostridioides difficile growth landscape across thousands of species-metabolite conditions. Mechanistic consumer resource and machine learning models uncover significant interactions linking metabolites and species, and exhibit concordance with microbial interactions identified in human microbiome datasets. Guided by machine learning and mechanistic models, we elucidate microbial communities capable of robustly inhibiting C. difficile across diverse nutrient environments in vitro. Metabolomic profiling identified sorbitol, mannitol, and proline as key metabolites mediating community-driven C. difficile inhibition. Model-optimized communities significantly reduced C. difficile colonization in the murine gut whereas a model-designed non-inhibitory community did not exhibit this property. Communities display consistent metabolomic patterns in vitro and in vivo, suggesting that resource competition is a design principle of robust inhibition. Together, these findings establish an integrated experimental and computational framework for the rational design of microbial communities that robustly suppress pathogens across diverse environmental contexts.

systems biology↗

bioRxiv2026

Multisite Evaluation of an Amplification-based Nanopore Sequencing Solution to Analyze Challenging Clinically Relevant Variants in Genes Associated with Hereditary Diseases

PurposeCarrier screening for hereditary conditions is challenged by genes with complex genomic architecture, where short-read sequencing can fail to detect clinically relevant variants. This study evaluated a unified, amplification-based nanopore sequencing workflow across multiple laboratories for comprehensive analysis of such loci. MethodsA modular long-read sequencing assay was evaluated across five laboratories using targeted PCR enrichment, Oxford Nanopore sequencing, and automated variant analysis. The workflow interrogated genes associated with spinal muscular atrophy, thalassemia, cystic fibrosis, fragile X syndrome, congenital adrenal hyperplasia, Gaucher disease, and hemophilia A. Performance was assessed against orthogonal methods for single nucleotide variants (SNVs), indels, copy-number variants, repeat expansions, and structural rearrangements. ResultsAcross 882 unique samples (1,266 tests), overall agreement with comparator methods exceeded 96% for variant-level detection and 97% for genotype status classification. Long-read sequencing enabled phasing of paralogous loci, integrated sizing and interruption analysis for FMR1 repeats, and simultaneous detection of SNVs and structural variants in globin loci and CYP21A2-TNXB region, reducing reliance on multiple workflows. ConclusionThis multisite evaluation suggests that targeted long-read sequencing can consolidate complex variant detection into a single workflow, improving analytical completeness and operational efficiency for carrier screening.

genetics↗

bioRxiv2026

Opposing effects of slow and fast theta synchrony on working memory in the human hippocampal-orbitofrontal network

Working memory (WM) enables us to maintain and manipulate information over time, but how the brain organizes sequential information locally and across networks remains unclear. Recent work suggests that slow and fast theta oscillations serve different roles in memory, yet their distinct contributions to sequential WM are unknown. Based on evidence that the hippocampus (HC) and orbitofrontal cortex (OFC) support sequential WM and that slower theta cycles provide optimal temporal windows for organizing items in WM, we predicted that these regions would coordinate via slow theta dynamics. We analyzed intracranial EEG from the HC, OFC, and amygdala (AMY) in 21 neurosurgical patients (7 female, 13-54 years of age; M {+/-} SD, 30 {+/-} 11.2 years) performing a delayed match-to-sample WM task. We assessed phase locking between regions, phase-amplitude coupling within regions, and neuronal phase coding for slow (~1-4.5 Hz) and fast (~4.5-8 Hz) theta oscillations. We found significant slow and fast theta synchrony between all regions, but identical anatomical pathways produced opposing behavioral effects depending on oscillatory frequency, particularly during higher cognitive demand. Slow theta synchrony was associated with faster response times (RTs), while fast theta synchrony between HC and OFC hindered both accuracy and RTs. Unexpectedly, AMY modulated RT through demand-dependent slow theta synchrony, where AMY-OFC synchrony predicted faster RTs during maintenance and HC-AMY synchrony predicted faster RTs during higher cognitive demand. Sustained coupling between slow theta oscillations and high-frequency broadband activity within each region suggests that local organization coincides with beneficial network behavioral effects. These results establish a frequency-opponent mechanism in which theta oscillation frequencies determine whether HC-OFC circuits facilitate or impair sequential WM.

neuroscience↗

bioRxiv2025

Distributed theta networks support the control of working memory: Evidence from scalp and intracranial EEG

We combined scalp EEG and intracranial EEG (iEEG) to identify spectral and network-level signatures of executive control during a delayed match-to-sample task working memory task. To isolate executive processes, we contrasted test and sample phases, matched in perceptual input but differing in cognitive demand. Scalp EEG revealed increased frontal midline theta event-related spectral perturbations (ERSPs), dynamic increases and decreases in posterior theta-alpha ERSPs, and decreased central alpha-beta ERSPs during the test phase. These local spectral changes were accompanied by enhanced frontoposterior theta phase synchrony and network hub strength, predicting higher behavioral accuracy. Using a novel cross-modal scalp EEG-iEEG ERSP similarity approach, we localized the sources of scalp-derived frontal midline, posterior, and central control effects to medial frontal, parietal, temporal, and occipital regions. Our results integrate power and connectivity measures across scalp and iEEG, linking local spectral fluctuations to broader network organization. Together, they support a model in which executive control emerges from flexible, temporally precise coordination between medial frontal control hubs and posterior representational systems.

neuroscience↗

bioRxiv2025

Generalizing animal movement predictions across landscapes: a scalable framework grounded in empirical telemetry data

BackgroundUnderstanding animal movement across broad ecological contexts is essential for guiding management decisions in natural resource and animal disease management. However, most movement studies collect data over small spatial extents, which challenges using the data for landscape-scale management applications. MethodsWe collated relocation data from 564 wild pigs spanning 25 studies across 10 states in the United States. We derived net and daily displacement distributions for individuals in each of 4 seasons. We fit gamma distributions to displacement distributions and derived mean and dispersion parameters as metrics of displacement magnitude and variation. We modeled mean and dispersion variables using gradient-boosted regression, including landscape and weather predictors, and predicted daily and net displacement distributions across the species range. We used integrated step selection analysis to estimate habitat selection for wild pig groups sharing a common composition of habitat availability across the studied populations. ResultsFemale average ({+/-} 95% confidence interval) net displacement means varied by season, peaking in Jul-Sept at 1,152 {+/-} 140 m along with daily displacement mean distances of 650 {+/-} 41 m. Average net displacement means for males peaked in Oct.-Dec. at 1,651 {+/-} 160 m with daily displacement mean distances of 1,092 {+/-} 95 m. Extreme net displacement values ranged up to 9,649 m and 4,080 m for male and female, respectively, and extreme daily displacement distribution means of 6,616 m for males, and 3,855 m for females. Almost half of the individuals included a similar composition of habitat availability, regardless of study site location. Herbaceous wetland was the most consistently favored land type and was available for more than 70% of all individual pigs across all studies. Preference for other land types depended strongly on habitat availability. ConclusionsBy comparing movement and habitat selection across a large geographic extent, our work provides new insights about the environmental drivers and limits of wild pig movement behavior. Our workflow digests variation wild pig movement distributions and habitat selection into parameters that can be used to predict movement on heterogeneous landscapes for downstream applications such as invasive species elimination campaigns or disease management.

ecology↗

bioRxiv2025

Dietary protein source mediates colitis pathogenesis through bacterial modulation of bile acids

Introductory paragraphEvidence-based dietary recommendations for individuals with inflammatory bowel diseases (IBD) are limited. Red meat consumption is associated with increased IBD incidence and relapse in patients, suggesting that switching to a plant-based diet may limit gut inflammation. However, the mechanisms underlying the differential effects of these diets remain poorly understood. Feeding diets containing plant- or animal-derived proteins to murine colitis models revealed that mice given a beef protein (BP) diet exhibited the most severe colitis, while mice fed pea protein (PP) developed mild inflammation. The colitis-promoting effects of BP were microbially-mediated as determined by bacterial elimination or depletion and microbiota transplant studies. In the absence of colitis, BP-feeding reduced abundance of Lactobacillus johnsonii and Turicibacter sanguinis and expanded Akkermansia muciniphila, which localized to the mucus in association with decreased mucus thickness and quality. BP-fed mice had elevated primary and conjugated fecal bile acids (BAs), and taurocholic acid administration to PP-fed mice worsened colitis. Dietary psyllium protected against BP-mediated inflammation, restored BA-modulating commensals and normalized BA ratios. Collectively, these data suggest that the protein component of red meat may be responsible, in part, for the colitis-promoting effects of this food source and provide insight into dietary factors that may influence IBD severity.

microbiology↗

bioRxiv2025

Declarative Memory Through the Lens of Single-Trial Peaks in High-Frequency Power

Declarative memory depends on the coordination of local processing, indexed by high-frequency broadband (HFB) activity, with global network organization, indexed by theta oscillations. However, theta and HFB exhibit asynchronous timing, raising the question of how results of local processing are communicated throughout the network. Using intracranial EEG in patients performing a recognition memory task, we examined this coordination across the medial temporal lobe (MTL) and prefrontal cortex (PFC). HFB peak activity was earlier in the MTL than PFC. Anchoring analyses of theta phase clustering and connectivity to HFB peaks revealed strong phase clustering locked to HFB peaks in the PFC, as well as connectivity between the PFC and MTL that predicted individual memory performance. Graph analysis revealed specific connections amidst sparse network connectivity during memory success. This study demonstrates that transient brain states linked to internal physiological events support memory and refines our understanding of local and network-level process interactions. HighlightsO_LIMemory-linked theta activity is time-locked to internal brain events C_LIO_LINetwork connectivity changes dynamically during memory processing C_LIO_LISparse network connectivity supports successful memory C_LIO_LISpecific sequences of transient states may be critical for declarative memory C_LI

neuroscience↗

bioRxiv2024

The development of aperiodic neural activity in the human brain

The neurophysiological mechanisms supporting brain maturation are fundamental to attention and memory capacity across the lifespan. Human brain regions develop at different rates, with many regions developing into the third and fourth decades of life. Here, in this preregistered study (https://osf.io/gsru7), we analyzed intracranial EEG (iEEG) recordings from widespread brain regions in a large developmental cohort. Using task-based (i.e., attention to-be-remembered visual stimuli) and task-free (resting-state) data from 101 children and adults (5.93 - 54.00 years, 63 males; n electrodes = 5691), we mapped aperiodic (1/[f]-like) activity, a proxy of neural noise, with steeper slopes indexing less noise and flatter slopes indexing more noise. We reveal that aperiodic slopes flatten with age into young adulthood in both association and sensorimotor cortices, challenging models of early sensorimotor development based on brain structure. In prefrontal cortex (PFC), attentional state modulated age effects, revealing steeper task-based than task-free slopes in adults and the opposite in children, consistent with the development of cognitive control. Age-related differences in task-based slopes also explained age-related gains in memory performance, linking the development of PFC cognitive control to the development of memory. Last, with additional structural imaging measures, we reveal that age-related differences in gray matter volume are similarly associated with aperiodic slopes in association and sensorimotor cortices. Our findings establish developmental trajectories of aperiodic activity in localized brain regions and illuminate the development of PFC control during adolescence in the development of attention and memory.

neuroscience↗

bioRxiv2024

Neuro-immunology in a mouse model of anti-NMDAR encephalitis and assessment of treatment approaches

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a disorder mediated by autoantibodies against the GluN1 subunit of NMDAR. It occurs with severe neuropsychiatric symptoms that often improve with immunotherapy. Clinical studies and animal models based on patients antibody transfer or NMDAR immunization suggest that the autoantibodies play a major pathogenic role. Yet, there is an important need of models offering an all-inclusive neuro-immunobiology of the disease together with a clinical course long enough to facilitate the assessment of potential new treatments. Toward this end, eight-week-old female mice (C57BL/6J) were immunized (days 1 and 28) with GluN1356-385 peptide or saline with AddaVax adjuvant and pertussis toxin. After symptom development ([~]day 35), subsets of mice were treated with an anti-CD20 (day 35), a positive allosteric modulator (PAM) of NMDAR (NMDAR-PAM, SGE-301) from days 45 to 71, or both. GluN1-antibody synthesis, epitope spreading, effects of antibodies on density and function of NMDAR, brain immunological infiltrates, microglial activation and NMDAR phagocytosis, and antibody synthesis in cultured inguinal and deep cervical lymph nodes (DCLN) were assessed with techniques including immunohistochemistry, calcium imaging, confocal and super-resolution microscopy, electrophysiology, or flow cytometry. Changes of memory and behaviour were assessed with a panel of behavioural tests, and clinical/subclinical seizures with brain-implanted electrodes. Immunized mice, but not controls, developed serum and CSF NMDAR-antibodies (IgG1 predominant) against the immunizing peptide and other GluN1 regions (epitope spreading) resulting in a decrease of synaptic and extrasynaptic NMDAR clusters and reduction of hippocampal plasticity. These findings were associated with brain inflammatory infiltrates, mainly B- and plasma cells, microglial activation, colocalization of NMDAR-IgG complexes with microglia, and presence of these complexes within microglial endosomes. Cultures of DCLC showed GluN1-antibody production. These findings were associated with psychotic-like behaviour (predominant at disease onset), memory deficit, depressive-like behaviour, abnormal movements (15% of mice), and lower threshold for developing pentylenetetrazole-induced seizures (hypoactivity, myoclonic jerks, continuous tonic-clonic) which correlated with regional cFOS expression. Most symptoms and neurobiological alterations were reversed by the anti-CD20 and PAM, alone or combined. Initial repopulation of B cells, by the end of the study, was associated with re-emergence of clinical-neurobiological alterations, which were abrogated by PAM. Overall, this model offers an all-inclusive neuro-immunobiology of the disease, allowing testing novel treatments, supporting the potential therapeutic role of NMDAR-PAM, and suggesting an immunological paradigm of systemic antigen presentation and brain NMDAR epitope spreading, which along the DCLN might contribute to fine-tune the polyclonal immune response.

neuroscience↗

bioRxiv2024

Microbial community function increases host plant leaf growth in a pitcher plant experimental system

Across diverse ecosystems, bacteria and their host organisms engage in complex relationships having negative, neutral, or positive interactions. However, the specific effects of leaf- associated bacterial community functions on plant growth are poorly understood. To address this gap, we explored the relationships between bacterial community function and host plant growth in the purple pitcher plant (Sarracenia purpurea). The main aim of our research was to investigate how different bacterial community functions affect the growth and nutrient content in the plant. Previous research had suggested that microbial communities may aid in prey decomposition and subsequent nutrient acquisition in carnivorous plants, including S. purpurea. However, the specific functional roles of these bacterial communities in plant growth and nutrient uptake are not well known. In this study, sterile, freshly opened leaves (pitchers) were inoculated with three functionally distinct, pre-assembled bacterial communities and effects examined over 8 weeks. Bacterial community composition and function were measured using physiological assays, metagenomics, and metatranscriptomics. Distinct bacterial functions affected plant traits; a bacterial community enriched in decomposition and secondary metabolite production traits was associated with larger leaves with almost double the biomass of control pitchers. Physiological differences in bacterial communities were supported by metatranscriptomic analysis; for example, the bacterial community with the highest chitinase activity had greater expression of transcripts associated with chitinase enzymes. The relationship between bacterial community function and plant growth observed here indicates potential mechanisms for host-associated bacterial functions to support plant health and growth. ImportanceThis study addresses a gap in understanding the relationships between bacterial community function and plant growth. We inoculated sterile, freshly opened pitcher plant leaves with three functionally distinct bacterial communities to uncover potential mechanisms through which bacterial functions support plant health and growth. Our findings demonstrate that distinct bacterial functions significantly influence plant traits, with some bacterial communities supporting more growth than in control pitchers. These results highlight the ecological roles of microbial communities in plants and thus ecosystems, and suggest potential pathways in which microbes support host plant health. This research provides valuable insights into plant-microbe interactions and effects of diverse microbial community functions.

ecology↗

bioRxiv2024

Mouse Adaptation of Human Inflammatory Bowel Diseases Microbiota Enhances Colonization Efficiency and Alters Microbiome Aggressiveness Depending on Recipient Colonic Inflammatory Environment

Understanding the cause vs consequence relationship of gut inflammation and microbial dysbiosis in inflammatory bowel diseases (IBD) requires a reproducible mouse model of human-microbiota-driven experimental colitis. Our study demonstrated that human fecal microbiota transplant (FMT) transfer efficiency is an underappreciated source of experimental variability in human microbiota associated (HMA) mice. Pooled human IBD patient fecal microbiota engrafted germ-free (GF) mice with low amplicon sequence variant (ASV)-level transfer efficiency, resulting in high recipient-to-recipient variation of microbiota composition and colitis severity in HMA Il-10-/- mice. In contrast, mouse-to-mouse transfer of mouse-adapted human IBD patient microbiota transferred with high efficiency and low compositional variability resulting in highly consistent and reproducible colitis phenotypes in recipient Il-10-/- mice. Human-to-mouse FMT caused a population bottleneck with reassembly of microbiota composition that was host inflammatory environment specific. Mouse-adaptation in the inflamed Il-10-/-host reassembled a more aggressive microbiota that induced more severe colitis in serial transplant to Il-10-/- mice than the distinct microbiota reassembled in non-inflamed WT hosts. Our findings support a model of IBD pathogenesis in which host inflammation promotes aggressive resident bacteria, which further drives a feed-forward process of dysbiosis exacerbated gut inflammation. This model implies that effective management of IBD requires treating both the dysregulated host immune response and aggressive inflammation-driven microbiota. We propose that our mouse-adapted human microbiota model is an optimized, reproducible, and rigorous system to study human microbiome-driven disease phenotypes, which may be generalized to mouse models of other human microbiota-modulated diseases, including metabolic syndrome/obesity, diabetes, autoimmune diseases, and cancer.

microbiology↗

bioRxiv2020

The innate immunity protein C1QBP functions as a negative regulator of circulative transmission of Potato leafroll virus by aphids

The vast majority of plant viruses are transmitted by insect vectors with many crucial aspects of the transmission process being mediated by key protein-protein interactions. Yet, very few vector proteins interacting with virus have been identified and functionally characterized. Potato leafroll virus (PLRV) is transmitted most effectively by Myzus persicae, the green peach aphid, in a circulative, non-propagative manner. Using an affinity purification strategy coupled to high-resolution mass spectrometry (AP-MS), we identified 11 proteins from M. persicae displaying high probability of interaction with PLRV and an additional 23 vector proteins with medium confidence interaction scores. Two of these proteins were confirmed to directly interact with the structural proteins of PLRV and other luteovirid species via yeast two-hybrid with an additional vector protein displaying binding specificity. Immunolocalization of one of these direct PLRV-interacting proteins, an orthologue of the human innate immunity protein complement component 1 Q subcomponent-binding protein (C1QBP), shows that MpC1QBP partially co-localizes with PLRV within cytoplasmic puncta and along the periphery of aphid gut epithelial cells. Chemical inhibition of C1QBP in the aphid leads to increased PLRV acquisition and subsequently increased titer in inoculated plants, supporting the role of C1QBP as a negative regulator of PLRV accumulation in M. persicae. We hypothesize that the innate immune function of C1QBP is conserved in aphids and represents the first instance of aphids mounting an immune response to a non-propagative plant virus. This study presents the first use of AP-MS for the in vivo isolation of functionally relevant insect vector-virus protein complexes.

microbiology↗