Biology subjects

Ross, T. J.

Publications and source records attributed to Ross, T. J..

13 recordsLinked to original sources

bioRxiv2026

Human striatal population state dynamics

Animal models reveal that striatal projection neurons (SPNs) fluctuate between discrete electrophysiological states with distinct levels of cortical interaction. These dynamics and their behavioral relevance remain uncharacterized in humans. Leveraging neurobiologically informed modeling of over 3 billion voxel-frame-wise striatal coactivation profiles with cortex in functional magnetic resonance imaging (fMRI), we identified population-level striatal states in humans resembling canonical SPN states that reorganized systematically with task demands, arousal and behavior. A background of low- and moderate-coactivation "down-like" and "up-like" striatal rest states with high transition reciprocity modulated task reaction times and reward reactivity. Meanwhile, sparse, disproportionately high-magnitude bursts of striatal coactivation with cortex, which emerged preferentially from the up-like rest state and whose cortical input composition varied with task context, tracked task engagement and arousal level. Findings bring a critical feature of corticostriatal neurobiology into systems-level view in humans and reveal a subthreshold state architecture whose balance encodes behaviorally relevant information.

neuroscience↗

bioRxiv2026

Brain morphological pattern is associated with the presence, severity, and transition of transdiagnostic psychiatric disorders in preadolescents

Cognitive function, psychological processes, mental states, and behaviors are key dimensions of human subjective experience that separately relate to mental disorders across diagnostic categories. However, whether these dimensions are linked to common or distinct brain morphological patterns that convey risk or resilience for psychiatric disorders remains unclear. The current study is a longitudinal investigation on 11,875 youths from the Adolescent Brain Cognitive Development (ABCD) Study aged 9-10 years at baseline. A machine learning approach based on canonical correlation analysis was used to identify latent dimensional associations of cortical morphology (4 metrics: surface area, cortical and subcortical volume, cortical thickness, and sulcal/gyral depth) with multidomain behavioral assessments including cognitive scores and psychological measures indexing motivation, impulse control, mental states, and behaviors across a normative continuum from healthy to pathological. Across morphological measures, we identified a robust latent brain structural variate that correlated positively with cognitive performance and negatively with psychological measures indexing greater psychology. Notably, higher scores on this brain variate reflected larger cortical surface area and cortical volume--especially in the temporal gyri--together with a posterior-anterior gradient in cortical thickness, showing relatively greater thickness in occipital, parietal, and temporal cortices and lower thickness in cingulate and frontal regions. This brain variate and the related cognitive-psychological-behavioral variate remained stable at the 2-year follow-up, demonstrating temporal consistency. Importantly, the brain variate showed a dose-dependent relationship with the cumulative number of psychiatric diagnoses assessed concurrently and at 2-year follow-up, with lower brain variate scores being associated with higher numbers of comorbid diagnoses. In addition, the brain scores were associated with longitudinal transitions between healthy and diagnosed states over the 2-year study period, in which lower scores at baseline were associated with persistent psychiatric diagnoses whereas higher scores at baseline were associated with persistent healthy states, suggesting that the brain scores capture a vulnerability- resilience continuum for psychopathology. By revealing shared brain structural substrates across conventional diagnostic boundaries, these findings advance the neurodevelopmental understanding of psychiatric disorders and highlight the potential utility of morphology-informed approaches for early screening and intervention in youth.

developmental biology↗

bioRxiv2025

Physiological Arousal as a Predominant Source of Individual Differences in Functional Brain Networks

Individual differences in brain network function and organization are promising targets for fMRI-based biomarkers in precision psychiatry, yet the sources of individual variability remain poorly understood. We show that arousal, assessed by systemic low-frequency oscillation (sLFO) amplitude in the fMRI signal, accounts for a substantial portion of variance in brain network properties (e.g.: R= 0.70 for default mode network (DMN)-dorsal attention connectivity; R= -0.63 for DMN dynamics). These relationships replicated across sessions, across independent samples, and when assessed with traditional arousal indices. Critically, associations persisted after sLFO denoising, indicating a genuine brain-physiology relationship rather than hemodynamic artifact. Pharmacological manipulation showed that drug-induced sLFO-assessed arousal changes were accompanied by corresponding shifts in network connectivity and dynamics. This work identifies arousal as a prominent determinant of variability in functional brain networks, providing a new perspective on brain-based individual differences while offering an approach to measure arousal directly from fMRI data.

neuroscience↗

bioRxiv2025

Maturation of Dorsal Association Tracts during Preadolescence Links to Concurrent and Future Cognitive Performance and Transdiagnostic Psychopathology

Many psychiatric disorders begin during adolescence, coinciding with the rapid development of brain white matter (WM). However, it remains unclear whether deviations from normal WM maturation during this age period contribute to the development of psychopathology. In this study, we developed and validated normative models of brain age based on specific WM tracts using three large-scale developmental datasets (a total of [~]10,000 subjects). We found that tract-specific deviations in WM development of association and limbic/subcortical systems were linked to concurrent cognition and psychopathology. The spatial pattern of the association system aligned closely with distributions of high-order brain networks, and with mitochondrial content and respiratory capacity. The maturation of the association system contributed significantly to better cognitive performance assessed two or three years later. Importantly, delayed WM development especially in dorsal association tracts predicted psychiatric disorders across diagnoses and disorder onset over a 2-year follow-up. By identifying tract-specific WM development during preadolescence as a predictor of cognitive capacity and psychiatric disorder risks, this study provides a valuable framework for tracking individualized brain maturation and understanding the neurobiological underpinnings of cognitive performance and transdiagnostic psychopathology.

neuroscience↗

bioRxiv2023

Small but significant genetic differentiation among populations of Phyllachora maydis in the midwestern United States revealed by microsatellite (SSR) markers.

Phyllachora maydis Maubl, the causal pathogen of tar spot of corn (Zea mays L.), has emerged recently in the United States and Canada. Studies related to its genetic diversity and population structure are limited and are necessary to improve our understanding of this pathogens biology, ecology, epidemiology, and evolutionary potential within this region. This study developed and used 13 microsatellites (SSR markers) to assess the genetic population structure, diversity, gene flow and reproductive mode of 181 P. maydis samples across five states in the Midwest U.S. The polymorphic information content (PIC) of loci ranged from 0.32 to 0.72 per locus, indicating their high utility for assessing the dynamics of P. maydis populations. Analysis of molecular variance (AMOVA) detected a significantly low, but statistically significant genetic differentiation (FST = 0.15) among populations, where 85% of the variance resided within populations. P. maydis populations were highly diverse (He = 0.55), with moderate gene flow (Nm = 2.80), and showed evidence of sexual recombination ([r]d; p = > 0.001). Structure analysis showed the samples were not geographically structured but rather grouped into two genetic clusters (k =2) of severe genetic admixture suggesting possible long-distance dispersal of aerial spores or infected corn materials among the five Midwest states. Both principal coordinate analysis (PCoA) and discriminate analysis of principal component (DAPC) supported the STRUCTURE analysis of the two clusters. These 13 highly polymorphic molecular markers could be used for future investigations of this pathogens population dynamics within the U.S., and possibly populations outside.

pathology↗

bioRxiv2023

In vivo disentanglement of diffusion frequency-dependence, tensor shape, and relaxation using multidimensional MRI

Diffusion MRI with free gradient waveforms, combined with simultaneous relaxation encoding, referred to as multidimensional MRI (MD-MRI), offers microstructural specificity in complex biological tissue. This approach delivers intravoxel information about the microstructure, local chemical composition, and importantly, how these properties are coupled within heterogeneous tissue containing multiple microenvironments. Recent theoretical advances incorporated diffusion time dependency and integrated MD-MRI with concepts from oscillating gradients. This framework probes the diffusion frequency,{omega} , in addition to the diffusion tensor, D, and relaxation, R1, R2, correlations. A D({omega})-R1-R2 clinical imaging protocol was then introduced, with limited brain coverage and 3 mm3 voxel size, which hinder brain segmentation and future cohort studies. In this study, we introduce an efficient, sparse in vivo MD-MRI acquisition protocol providing whole brain coverage at 2 mm3 voxel size. We demonstrate its feasibility and robustness using a well-defined phantom and repeated scans of five healthy individuals. Additionally, we test different denoising strategies to address the sparse nature of this protocol, and show that efficient MD-MRI encoding design demands a nuanced denoising approach. The MD-MRI framework provides rich information that allows resolving the diffusion frequency dependence into intravoxel components based on their D({omega})-R1-R2 distribution, enabling the creation of microstructure-specific maps in the human brain. Our results encourage the broader adoption and use of this new imaging approach for characterizing healthy and pathological tissues.

neuroscience↗

bioRxiv2023

Uncovering the Environmental Conditions Required for Phyllachora maydis Infection and Tar Spot Development on Corn in the United States for Use as Predictive Models for Future Epidemics

Phyllachora maydis is a fungal pathogen causing tar spot of corn (Zea mays L.), a new and emerging, yield-limiting disease in the United States. Since being first reported in Illinois and Indiana in 2015, P. maydis can now be found across much of the corn growing of the United States. Knowledge of the epidemiology of P. maydis is limited but could be useful in developing tar spot prediction tools. The research presented here aims to elucidate the environmental conditions necessary for the development of tar spot in the field and the creation of predictive models to anticipate future tar spot epidemics. Extended periods (30-day windowpanes) of moderate ambient temperature were most significant for explaining the development of tar spot. Shorter periods (14- to 21-day windowpanes) of moisture (relative humidity, dew point, number of hours with predicted leaf wetness) were negatively correlated with tar spot development. These weather variables were used to develop multiple logistic regression models, an ensembled model, and two machine learning models for the prediction of tar spot development. This work has improved the understanding of P. maydis epidemiology and provided the foundation for the development of a predictive tool for anticipating future tar spot epidemics.

plant biology↗

bioRxiv2022

Dissociable misconfigurations of striatal functional connectivity profiles in smokers

Corticostriatal circuits are central to reward processing and reinforcement learning functions that often become dysregulated in substance use disorder (SUD) and drive compulsive drug use. Human neuroimaging research seeking to identify how corticostriatal circuits become altered in SUD has primarily focused on evaluating connectivity between cortex-striatum node-pairs. Yet, striatal nodes receive appreciable input from many cortical nodes, and the morphological and electrophysiological properties of striatal nodes dictate that combinational features of their multivariate "connectivity profiles" shape their activity more so than any individual cortical node. Here, we introduce an approach for quantifying and statistically evaluating different types of multivariate connectivity profile configuration differences (i.e., aggregate divergence, rank order arrangement, and entropy shift) that may reflect different forms of circuit plasticity, and apply it to nicotine dependent smokers (n=46) as an exemplar SUD. Foremost, we find evidence of significant connectivity profile misconfiguration throughout much of the striatum, suggesting that prior findings of abnormal connections between individual striatal-cortical node-pairs may only represent the "tip of the iceberg" of corticostriatal circuit alteration in nicotine dependence. Moreover, we find that dorsolateral and ventromedial striatum display distinct types of connectivity profile misconfiguration. Whereas dorsolateral striatum almost exclusively displays abnormal rank order arrangement that is present in both the nicotine sated and acutely abstinent states - indicative of a "trait" misconfiguration - ventromedial striatum almost exclusively displays abnormal aggregate divergence that only manifests during acute abstinence - indicative of a "state" misconfiguration. Further, we identify a unique striatal site in the right caudal ventral putamen that displays multiple forms of connectivity profile misconfiguration, where connections with cognitive processing cortical areas overtake those with motor/premotor control cortical areas as the strongest in the connectivity profile, and acute abstinence significantly strengthens this abnormal arrangement. Moreover, the interactive magnitude of these misconfigurations during acute abstinence is significantly linked to dependence severity. Collectively, the present findings underscore the need for increased examination of connectivity profile misconfigurations as a mechanism of SUD etiology and as a potential guide for identifying therapeutic intervention targets.

neuroscience↗

bioRxiv2021

Brain functional connectome defines a transdiagnostic dimension associated with cognition and psychopathology in youth

BackgroundCognitive dysfunction and high-order psychopathologic dimensions are two main classes of transdiagnostic factors related to psychiatric disorders. They may link to common or distinct core brain networks underlying developmental risk of psychiatric disorders. MethodThe current study is a longitudinal investigation with 11,875 youths aged 9-to 10-years-old at study onset, from the Adolescent Brain Cognitive Development study. A machine-learning approach based on canonical correlation analysis was used to identify latent dimensional associations of the resting-state functional connectome with multi-domain behavioral assessments of cognitive functions and psychopathological problems. For the latent rsFC factor showing a robust behavioral association, its ability to predict psychiatric disorders was assessed using two-year follow-up data and its genetic association was evaluated using twin data from the same cohort. ResultA latent functional connectome pattern was identified that showed a strong and generalizable association with the multi-domain behavioral assessments (5-fold cross validation: {rho} = 0.68~0.73, for the training set (N = 5096); {rho} = 0.56 ~ 0.58, for the test set (N = 1476)). This functional connectome pattern was highly heritable (h2 = 74.42%, 95% CI: 56.76%-85.42%), exhibited a dose-response relationship with cumulative number of psychiatric disorders assessed concurrently and 2-years post-MRI-scan, and predicted the transition of diagnosis across disorders over the 2-year follow-up period. ConclusionThese findings provide preliminary evidence for a transdiagnostic connectome-based measure that underlies individual differences in developing psychiatric disorders in early adolescence.

neuroscience↗

bioRxiv2021

Not all smokers are alike: The hidden cost of sustained attention during nicotine abstinence

BackgroundNicotine Withdrawal Syndrome (NWS)-associated cognitive deficits are heterogeneous, suggesting underlying endophenotypic subgroups. We identified smoker subgroups based on response accuracy during a cognitively demanding Parametric Flanker Task (PFT) and characterized their distinct neuroimaging endophenotypes using a nicotine state manipulation (sated, abstinent). MethodsForty-five smokers completed the 25-min PFT in two fMRI sessions (nicotine sated, abstinent). Task-evoked NWS-associated errors of omission (EOm), brain activity, underlying functional connectivity (FC), and brain-behavior correlations between subgroups were assessed. ResultsBased on their response accuracy in the high demand PFT condition, smokers split into high (HTP, n=21) and low task performer (LTP, n=24) subgroups. Behaviorally, HTPs showed greater response accuracy independent of nicotine state and greater vulnerability to abstinence-induced EOm. HTPs showed greater BOLD responses in attentional control brain regions for the [correct responses (-) errors of commission] PFT contrast across states. A whole-brain FC analysis with these subgroup-derived regions as seeds revealed two circuits: L Precentral : R Insula and L Insula : R Occipital, with abstinence-induced FC strength increases only in HTPs. Finally, abstinence-induced brain (FC) and behavior (EOm) differences were positively correlated for HTPs in a L Precentral : R Orbitofrontal cortical circuit. ConclusionWe used a cognitive stressor (PFT) to fractionate smokers into two subgroups (HTP/LTP). Only the HTPs demonstrated sustained attention deficits during nicotine abstinence, a stressor in dependent smokers. Unpacking underlying smoker heterogeneity with this dual stressor approach revealed distinct smoker subgroups with differential attention deficit responses to withdrawal that could be novel targets for therapeutic interventions to improve cessation outcomes.

neuroscience↗

bioRxiv2020

Time varying connectivity across the brain changes as a function of nicotine abstinence state

BackgroundThe Nicotine Withdrawal Syndrome (NWS) includes affective and cognitive disruptions whose incidence and severity vary across time during acute abstinence. However, most network-level neuroimaging employs static measures of resting state functional connectivity (rsFC), assuming time-invariance, and unable to capture dynamic brain-behavior relationships. Recent advances in rsFC signal processing allow characterization of "time varying connectivity" (TVC), which characterizes network communication between sub-networks that reconfigure over the course of data collection. As such, TVC may more fully describe network dysfunction related to the NWS. MethodsTo isolate alterations in the frequency and diversity of communication across network boundaries as a function of acute nicotine abstinence we scanned cigarette smokers in the nicotine sated and abstinent states and applied a previously-validated method to characterize TVC at a network and nodal level within the brain. ResultsDuring abstinence, we found brain wide decreases in the frequency of interactions between network nodes in different modular communities (i.e. temporal flexibility; TF). In addition, within a subset of the networks examined the variability of these interactions across community boundaries (i.e. spatiotemporal diversity; STD) also decreased. Finally, within two of these networks the decrease in STD was significantly related to NWS clinical symptoms. ConclusionsEmploying multiple measures of TVC in a within subjects design, we characterized a novel set of changes in network communication and link these changes to specific behavioral symptoms of the NWS. These reductions in TVC provide a meso-scale network description of the relative inflexibility of specific large-scale brain networks as a result of acute abstinence.

animal behavior and cognition↗

bioRxiv2019

Nicotine dependence (trait) and acute nicotinic stimulation (state) modulate attention but not cognitive control: converging fMRI evidence from Go-Nogo and Flanker tasks

AO_SCPCAPBSTRACTC_SCPCAPCognitive deficits during nicotine withdrawal may contribute to smoking relapse. However, interacting effects of chronic nicotine dependence and acute nicotine withdrawal on cognitive control are poorly understood. Here, we examine the effects of nicotine dependence (trait; smokers versus non-smoking controls), and acute nicotinic stimulation (state; administration of nicotine and varenicline, two FDA-approved smoking cessation aids, during abstinence), on two well-established tests of cognitive control, the Go-Nogo task and the Flanker task, during fMRI scanning. We compared performance and neural responses between these four pharmacological manipulations in a double-blind, placebo-controlled crossover design. As expected, performance in both tasks was modulated by nicotine dependence, abstinence and pharmacological manipulation. However, effects were driven entirely by conditions that required less cognitive control. When demand for cognitive control was high, abstinent smokers showed no deficits. By contrast, acutely abstinent smokers showed performance deficits in easier conditions and missed more trials. Go-Nogo fMRI results showed decreased inhibition-related neural activity in right anterior insula and right putamen in smokers and decreased dorsal anterior cingulate cortex activity on nicotine across groups. No effects were found on inhibition-related activity during the Flanker task, or on error-related activity in either task. Given robust nicotinic effects on physiology and behavioral deficits in attention, we are confident that pharmacological manipulations were effective. Thus, findings fit a recent proposal that abstinent smokers show decreased ability to divert cognitive resources at low or intermediate cognitive demand, while performance at high cognitive demand remains relatively unaffected, suggesting a primary attentional deficit during acute abstinence.

neuroscience↗

bioRxiv2019

Habenular and striatal activity during performance feedback are differentially linked with state-like and trait-like aspects of tobacco use disorder

Although tobacco use disorder is linked with functional alterations in the striatum, anterior cingulate cortex (ACC), and insula, preclinical evidence also implicates the habenula as a contributor to negative reinforcement mechanisms maintaining nicotine use. The habenula is a small and understudied epithalamic nucleus involved in reward and aversive processing that is hypothesized to be hyperactive during nicotine withdrawal thereby contributing to anhedonia. In a pharmacologic fMRI study involving administration of nicotine and varenicline, two relatively efficacious cessation aids, we utilized a positive and negative performance feedback task previously shown to differentially activate the striatum and habenula. By administering these nicotinic drugs (vs. placebos) to both overnight abstinent smokers (n=24) and nonsmokers (n=20), we delineated feedback-related functional alterations both as a function of a chronic smoking history (trait: smokers vs. nonsmokers) and as a function of drug administration (state: nicotine, varenicline). We observed that smokers showed less ventral striatal responsivity to positive feedback, an alteration not mitigated by drug administration, but rather correlated with higher trait-level addiction severity among smokers and elevated self-reported negative affect across all participants. Conversely, nicotine administration reduced habenula activity following both positive and negative feedback among abstinent smokers, but not nonsmokers; greater habenula activity correlated with elevated abstinence-induced, state-level tobacco craving among smokers and elevated social anhedonia across all participants. These outcomes highlight a dissociation between neurobiological processes linked with the trait of dependence severity and with the state of acute nicotine withdrawal. Interventions simultaneously targeting both aspects may improve currently poor cessation outcomes.\n\nOne-sentence teaserIn a pharmacological fMRI study, e dissociate brain alterations in the habenula linked with nicotine withdrawal and striatal alterations linked with addiction.

neuroscience↗