Biology subjects

Harita, S.

Publications and source records attributed to Harita, S..

5 recordsLinked to original sources

bioRxiv2025

State-dependent relationship between lower and higher order networks in fMRI brain dynamics

Resting-state functional magnetic resonance imaging (fMRI) is a powerful tool for exploring the brains functional organization. Functional connectivity (FC) is a commonly studied feature of fMRI data defined as the temporal correlation between activity patterns in pairs of brain regions. A major discovery of the past two decades of FC research has been the identification of consistent modular groupings in brain region time series correlations, commonly known as resting-state networks (RSNs). A second major discovery is the observation that RSNs in cortex are organized spatially along a functional/anatomical gradient. At one end of this gradient are lower order networks (LONs), predominantly specialized for unimodal information processing. At the other end are higher order networks (HONs), responsible for integrating multimodal information. Unlike the stable structural connectivity (SC) based on fixed anatomical links, FC fluctuates over time, and varies across brain regions. FC coordination within RSNs depends on SC, forming interconnected networks that regulate cognition, emotion, and behavior. The aim of the present study was to understand better how RSNs interact and communicate, based on their underlying SC. We used a whole-brain connectome-based neural mass modelling approach to study resting-state and task-based fMRI FC data. Following virtual SC lesions in the model, we characterized the FC changes within and between RSNs, and observed how these changes varied across different cognitive states. Our findings reveal how FC dynamics depend on underlying SC, highlighting the flexibility of these interactions across different brain states. LON lesions generally decrease FC within and between other LONs, and vice-versa for HON lesions. At rest, we observed a mutual antagonism between LONs and HONs, which was reversed during task conditions, with certain tasks increasing coordination between LONs and HONs. These results highlight the dynamic nature of brain network interactions, influenced by brain states and task demands. Our findings also have implications for clinical practice, offering insights into conditions such as brain tumors and stroke. HighlightsO_LIThe reduced Wong-Wang neural mass model was implemented in a PyTorch environment and used to understand what drives resting-state network functional connectivity (FC). C_LIO_LIStructural connectivity (SC) lesions were used to isolate functional networks to see how functional networks interact in various brain states. C_LIO_LIThere is a mutual antagonism between LONs and HONs in the resting-state. C_LIO_LIThis antagonism is seen to reverse in tasks with higher cognitive load (working memory, language). C_LIO_LITasks with a lower cognitive load (motor) share a similar network interactivity profile to the resting-state following network SC lesions. C_LI

neuroscience↗

bioRxiv2024

The Role of Inhibition in fMRI Resting-State Negative Correlations

Resting-state brain activity, as observed via functional magnetic resonance imaging (fMRI), displays non-random fluctuations whose functional connectivity (FC) is commonly parsed into spatial patterns of positive and negative correlations (PCs and NCs). Mapping NC patterns for certain key seed regions has shown considerable promise in recent years as a tool for enhancing neuro-navigated targeting and clinical outcomes of repetitive transcranial magnetic stimulation (rTMS) therapies in psychiatry. These successes bring to the fore several major outstanding questions about the neurophysiological origins of fMRI NCs. In this work, we studied candidate mechanisms for the emergence of fMRI NCs using connectome-based brain network modeling. Simulations of fMRI data under manipulation of inhibitory parameters WI and {lambda}, representing local and network-mediated inhibition respectively, were explored, focusing on the impact of inhibition levels on the emergence of NCs. Despite the considerable difference in time scales between GABAergic neuronal inhibition and fMRI FC, a clear relationship was observed, whereby the greater levels of overall inhibition led to significantly greater magnitude and spatial extent of NCs. We show that this effect is due to a leftward shift in the FC correlation distribution, leading to a reduction in the number of PCs and a concomitant increase in the number of NCs. Relatedly, we observed that those connections available for recruitment as NCs were precisely those with the weakest corresponding structural connectivity. Relative to nominally default values for the models used, greater levels of inhibition also improved, quantitatively and qualitatively, single-subject fits of simulated to empirical FC matrices. Our results provide new insights into how individual variability in anatomical connectivity strengths and neuronal inhibition levels may determine individualized expression of NCs in fMRI data. These, in turn, may offer new directions for optimization and personalization of rTMS therapies and other clinical applications of fMRI NC patterns. Author SummaryResting-state brain activity, as detected through functional magnetic resonance imaging (fMRI), demonstrates non-random fluctuations in its covariance structure, often characterized as functional connectivity (FC), which is further divided into spatial patterns of positive and negative correlations (NCs). Mapping patterns of NCs of specific key seed regions have demonstrated significant potential as a method for improving the precision of neuro-navigated targeting and enhancing clinical outcomes in the application of repetitive transcranial magnetic stimulation therapies within the field of psychiatry. In our study, we employed the reduced Wong-Wang neural mass model to investigate the physiological underpinnings of NCs observed in resting-state fMRI (rs-fMRI). Our simulated data partially captures the dynamics of empirical rs-fMRI data, revealing that increased inhibition levels correlate with a higher number of NCs. We also observed differential effects on model stability and NCs with varying levels of excitation and inhibition. These findings shed light on the complex interplay between neural dynamics and rs-fMRI connectivity patterns. Importantly, our work contributes to refining model parameters and offers insights for future validation with empirical clinical data. Understanding the factors influencing NCs in rs-fMRI FC has implications for optimizing therapeutic interventions and advancing our understanding of brain function.

neuroscience↗

bioRxiv2024

Corticothalamic modelling of sleep neurophysiology with applications to mobile EEG

AO_SCPLOWBSTRACTC_SCPLOWRecent developments in mathematical modelling of EEG enable the tracking of otherwise-inaccessible neurophysiological parameters throughout sleep. Likewise, advancements in wearable electronics have enabled easy & affordable collection of sleep EEG at home. The convergence of these two advances, namely neurophysiological modelling for mobile sleep EEG, can boost preclinical and clinical assessments of sleep. However, this subject area has received limited attention in existing literature. To address this, we used an established model of the corticothalamic system to analyze EEG power spectra from 5 datasets, spanning from research-grade systems to at-home mobile EEG. In the present work, we compare the convergent and divergent features of the data and the estimated physiological model parameters. While data quality and characteristics differ considerably, key patterns consistent with previous theoretical and empirical work are observed. During the transition from lighter to deeper NREM, i) exponent of the aperiodic (1/f) spectral component is increased, ii) bottom-up thalamocortical drive is reduced, iii) corticocortical connection strengths are increased. This effect is observed in healthy subjects but is interestingly absent when taking SSRI antidepressants, suggesting possible effects of ascending neuromodulation on corticothalamic oscillations. We further show a month-long increase in REM% in one mobile EEG subject, associated with boosted high-frequency activity in spectra and higher thalamothalamic gains in the model, pointing to possible changes of thalamic inhibition in REM parasomnias. Our results provide a proof-of-principle for the utility and feasibility of this physiological modelling-based approach to analyzing mobile EEG data, providing a mechanistic measure of brain physiology during sleep. Statement of significanceWe employ a physiological model of the corticothalamic circuitry to model the EEG power spectra in sleep. We fit this model to 5 EEG datasets, and demonstrate that while mobile and non-mobile EEG recordings differ in their characteristics and quality, they can both robustly represent the changes along sleep stages using the aperiodic (1/f) component. We observe an increased corticocortical connection strength and decreased corticothalamic connection strength as the subject goes into deeper stages of NREM sleep; an effect that is, importantly, not observed in subjects taking SSRIs. This work provides a proof-of-concept for using mathematical modelling, working well for large mobile and non-mobile datasets providing valuable insight into the mechanisms generating sleep EEG.

neuroscience↗

bioRxiv2023

Sleep-insomnia superposition: opposing brain signatures of sleep in task-based and resting-state conditions

Sleep and depression have a complex, bidirectional relationship, with sleep-associated alterations in brain dynamics and structure impacting a range of symptoms and cognitive abilities. Previous work describing these relationships has provided an incomplete picture by investigating only one or two types of sleep measures, depression, or neuroimaging modalities in parallel. We analyzed the correlations between task and resting-state brain-wide signatures of sleep, cognition, and depression in over 30,000 individuals. Neural signatures of insomnia and depression were negatively correlated with neural signatures of sleep duration in the task condition but positively correlated in the resting-state condition, showing that resting-state neural signatures of insomnia and depression resemble that of rested wakefulness. This was further supported by our finding of hypoconnectivity in task but hyperconnectivity in resting-state data in association with insomnia and depression This information disputes conventional assumptions about the neurofunctional manifestations of hyper- and hypo-somnia, and may explain inconsistent findings in the literature.

neuroscience↗

bioRxiv2021

Mapping inter-individual functional connectivity variability in TMS targets for major depressive disorder

Transcranial magnetic stimulation (TMS) is an emerging alternative to existing treatments for major depressive disorder (MDD). The effects of TMS on both brain physiology and therapeutic outcomes are known to be highly variable from subject to subject, however. Proposed reasons for this variability include individual differences in neurophysiology, in cortical geometry, and in brain connectivity. Standard approaches to TMS target site definition tend to focus on coordinates or landmarks within the individual brain regions implicated in MDD, such as the dorsolateral prefrontal cortex (dlPFC) and orbitofrontal cortex (OFC). Additionally considering the network connectivity of these sites has the potential to improve subject-specificity of TMS targeting and, in turn, improve treatment outcomes. We looked at the functional connectivity (FC) of dlPFC and OFC TMS targets, based on induced electrical field (E-field) maps, estimated using the SimNIBS library. We generated individualized E-field maps on the cortical surface for 121 subjects from the Human Connectome Project database using tetrahedral head models generated from T1-weighted MR images. We analyzed inter-subject variability in the shape and location of these TMS target E-field patterns, their FC, and the major functional networks to which they belong. Our results revealed the key differences in TMS target FC between the dlPFC and OFC, and also how this connectivity varies across subjects. Three major functional networks were targeted across the dlPFC and OFC: the ventral attention, fronto-parietal and default-mode networks in the dlPFC, and the fronto-parietal and default mode networks in the OFC. Inter-subject variability in cortical geometry and in FC was high. Our results characterize the FC patterns of canonical therapeutic TMS targets, and the key dimensions of their variability across subjects. The high inter-individual variability in cortical geometry and FC, leading to high variability in distributions of targeted brain networks, may account for the high levels of variability in physiological and therapeutic TMS outcomes. These insights should, we hope, prove useful as part of the broader effort by the psychiatry, neurology, and neuroimaging communities to help improve and refine TMS therapy, through a better understanding of the technology and its neurophysiological effects. HighlightsO_LIE-field modelling and functional connectivity used to study TMS targets (dlPFC,OFC) C_LIO_LIConsiderable variability in TMS target E-field patterns seen across subjects C_LIO_LILarge inter-subject differences in target connectivity observed and characterized C_LIO_LIMajor functional networks targeted by dlPFC, OFC TMS were the VAN, FPN and DMN C_LIO_LIInsights can contribute to improved and more personalized TMS therapies in the future C_LI

neuroscience↗