Search bioRxiv⌕ Search

Biology subjects

Calhoun, V.

Publications and source records attributed to Calhoun, V..

At least 73 records · Page 4Linked to original sources

st-DenseViT: A Weakly Supervised Spatiotemporal Vision Transformer for Dense Prediction of Dynamic Brain Networks

ObjectiveModeling dynamic neuronal activity within brain networks enables the precise tracking of rapid temporal fluctuations across different brain regions. However, current approaches in computational neuroscience fall short of capturing and representing the spatiotemporal dynamics within each brain network. We developed a novel weakly supervised spatiotemporal dense prediction model capable of generating personalized 4D dynamic brain networks from fMRI data, providing a more granular representation of brain activity over time. MethodsWe developed a model that leverages the vision transformer (ViT) as its backbone, jointly encoding spatial and temporal information from fMRI inputs using two different configurations: space-time and sequential encoders. The model generates 4D brain network maps that evolve over time, capturing dynamic changes in both spatial and temporal dimensions. In the absence of ground-truth data, we used spatially constrained windowed independent component analysis (ICA) components derived from fMRI data as weak supervision to guide the training process. The model was evaluated using large-scale resting-state fMRI datasets, and statistical analyses were conducted to assess the effectiveness of the generated dynamic maps using various metrics. ResultsOur model effectively produced 4D brain maps that captured both inter-subject and temporal variations, offering a dynamic representation of evolving brain networks. Notably, the model demonstrated the ability to produce smooth maps from noisy priors, effectively denoising the resulting brain dynamics. Additionally, statistically significant differences were observed in the temporally averaged brain maps, as well as in the summation of absolute temporal gradient maps, between patients with schizophrenia and healthy controls. For example, within the Default Mode Network (DMN), significant differences emerged in the temporally averaged space-time configurations, particularly in the thalamus, where healthy controls exhibited higher activity levels compared to subjects with schizophrenia. These findings highlight the models potential for differentiating between clinical populations. ConclusionThe proposed spatiotemporal dense prediction model offers an effective approach for generating dynamic brain maps by capturing significant spatiotemporal variations in brain activity. Leveraging weak supervision through ICA components enables the model to learn dynamic patterns without direct ground-truth data, making it a robust and efficient tool for brain mapping. SignificanceThis work presents an important new approach for dynamic brain mapping, potentially opening up new opportunities for studying brain dynamics within specific networks. By framing the problem as a spatiotemporal dense prediction task in computer vision, we leverage the spatiotemporal ViT architecture combined with weakly supervised learning techniques to efficiently and effectively estimate these maps.

neuroscience↗

Born Connected: Do Infants Already Have Adult-Like Multi-Scale Connectivity Networks?

The human brain undergoes remarkable development during the first six postnatal months, a period of dramatic structural and functional change critical for understanding neurodevelopmental trajectories. Previous infant resting-state functional MRI (rsfMRI) studies identified intrinsic connectivity networks (ICNs) but reported widely varying network numbers and organization, limiting cross-study comparisons. A recent analysis of over 100,000 subjects spanning from adolescents to adults generated a 105-network multi-scale template that greatly enhanced replicability, but the presence of these canonical ICNs in infants has not been investigated. We analysed resting-state scans from infants aged 0-6 months using two complementary approaches: burst independent component analysis (burstICA), a fully data-driven, model-order-agnostic method, and the reference-informed NeuroMark framework. burstICA successfully recovered the full set of canonical ICNs directly from infant data, and simulation-based validation confirmed that the recovered networks were biologically specific rather than methodological biases. The NeuroMark framework enhanced spatial correspondence with the reference template and maintained distinct, reproducible network profiles across scans, demonstrating high reliability for cross-study and cross-age comparisons. Networks critical for higher-order cognition, such as the default mode and salience networks, displayed adult-like topography comparable to that of primary sensory networks even within the first 6 months after birth. Subcortical networks also exhibited precise spatial organization, underscoring early maturation of deep brain structures. Functional network connectivity analyses revealed close similarity to adult profiles and clear antagonistic patterns between sensory systems and higher-order networks, indicating that foundational aspects of mature brain organization are already emerging in early infancy. Together, these findings establish a methodological foundation for early network mapping in infancy and lay critical groundwork for longitudinal and translational studies of brain development.

neuroscience↗

Brain functional network connectivity interpolation characterizes neuropsychiatric continuum and heterogeneity

Psychiatric and neurodevelopmental disorders such as schizophrenia (SZ) and autism spectrum disorder (ASD) are challenging to characterize in part due to their heterogeneous presentation in individuals, with symptoms now believed to exist on a continuum. Conventional diagnostic and neuroimaging analytical approaches rely on subjective assessment or group differences but typically ignore progression between groups or heterogeneity within a group. To estimate the neuropsychiatric continuum and heterogeneity, we propose a functional network connectivity (FNC) interpolation framework based on a variational autoencoder (VAE) using static FNC (sFNC) and dynamic FNC (dFNC) data from controls and patients with SZ or ASD. We demonstrate that VAEs significantly outperform a linear baseline and a semi-supervised counterpart. For both sFNC and dFNC interpolation, the generated results effectively capture representative and generalizable properties in the original data. The interpolated continua from controls to patients in both disorders reveal group-wise gradients characterized by reduced positive correlations within the auditory, sensorimotor, and visual networks, as well as between the subcortical and cerebellar domains. In contrast, anti-correlations weaken between the subcortical domain and sensory domains, and between the cerebellar domain and sensory regions. Finally, we show examples of how to generate continuous FNC data following pathological or state-based trajectories in the VAE latent space. The proposed framework offers added advantages over traditional methods, including data-driven discovery of hidden relationships, visualization of individual differences, imputation of missing values along a continuous spectrum, and estimation of the stage where an individual falls within the continuum.

neuroscience↗

Spontaneous Brain Dynamics Associated With Acceleration Of Longterm Functional Connectome In Postnatal Development

The first six postnatal months are a critical period for brain development, marked by rapid changes in functional neural circuits. However, long-term changes in neonatal functional connectome lacks an interpretive imaging indicator for the future development due to the non-linearity characteristics. In this study, we introduce an approach to extract intrinsic brain states from short-term brain dynamics to study the long-term (longitudinal) development. We found a high association (r=0.460) between the co-activated pattern of specific brain state and the acceleration pattern of non-linear development of static functional connectome. The fractional occupancy, self-sustaining probability of this short-term state share the similar age tendency with the long-term change rate within the majority of the function connectome. These findings suggest that short-term brain dynamics could serve as potential biomarkers for predicting the long-term development of functional connectome.

neuroscience↗

Normalized Dynamic Time Warping Increases Sensitivity In Differentiating Functional Network Connectivity In Schizophrenia

Our study advances the application of dynamic time warping (DTW) as a functional connectivity measure by introducing a normalization technique which enhances the detection of schizophrenia effects in comparison to both standard DTW and traditional correlation methods. By rigorously examining the statistical validity of DTW and our proposed normalized DTW measure, we show that it effectively captures interdependencies between fMRI signals beyond linear correlation, offering a more robust, complementary and informative approach to functional connectivity analysis. Through comprehensive evaluations, we demonstrate that normalized DTW is more sensitive to differences in functional brain network connections between schizophrenia and controls, highlighting its potential to provide deeper insight into clinical research. Clinical RelevanceThis study enhances our understanding of the functional specificity of schizophrenia by emphasizing the importance of nonlinear relationships through the introduction of a normalization technique for the DTW metric.

neuroscience↗

Sex differences in deep brain shape and asymmetry persist across schizophrenia and healthy individuals: A meta-analysis from the ENIGMA-Schizophrenia Working Group

BackgroundSchizophrenia (SCZ) is characterized by a disconnect from reality that manifests as various clinical and cognitive symptoms, and persistent neurobiological abnormalities. Sex-related differences in clinical presentation imply separate brain substrates. The present study characterized deep brain morphology using shape features to understand the independent effects of diagnosis and sex on the brain, and to determine whether the neurobiology of schizophrenia varies as a function of sex. MethodsThis study analyzed multi-site archival data from 1,871 male (M) and 955 female (F) participants with SCZ, and 2,158 male and 1,877 female healthy controls (CON) from twenty-three cross-sectional samples from the ENIGMA Schizophrenia Workgroup. Harmonized shape analysis protocols were applied to each sites data for seven deep brain regions obtained from T1-weighted structural MRI scans. Effect sizes were calculated for the following main contrasts: 1) Sex effects;2) Diagnosis-by-Sex interaction; 3) within sex tests of diagnosis; 4) within diagnosis tests of sex differences. Meta-regression models between brain structure and clinical variables were also computed separately in men and women with schizophrenia. ResultsMass univariate meta-analyses revealed more concave-than-convex shape differences in all regions for women relative to men, across diagnostic groups (d = -0.35 to 0.20, SE = 0.02 to 0.07); there were no significant diagnosis-by-sex interaction effects. Within men and women separately, we identified more-concave-than-convex shape differences for the hippocampus, amygdala, accumbens, and thalamus, with more-convex-than-concave differences in the putamen and pallidum in SCZ (d = -0.30 to 0.30, SE = 0.03 to 0.10). Within CON and SZ separately, we found more-concave-than-convex shape differences in the thalamus, pallidum, putamen, and amygdala among females compared to males, with mixed findings in the hippocampus and caudate (d = -0.30 to 0.20, SE = 0.03 to 0.09). Meta-regression models revealed similarly small, but significant relationships, with medication and positive symptoms in both SCZ-M and SCZ-F. ConclusionsSex-specific variation is an overriding feature of deep brain shape regardless of disease status, underscoring persistent patterns of sex differences observed both within and across diagnostic categories, and highlighting the importance of including it as a critical variable in studies of neurobiology. Future work should continue to explore these dimensions independently to determine whether these patterns of brain morphology extend to other aspects of neurobiology in schizophrenia, potentially uncovering broader implications for diagnosis and treatment. Key PointsO_LIStatistical analyses revealed significant main effects for diagnosis and sex in deep brain shape morphology. Among patients with schizophrenia, there was a pattern of thinning and surface contraction in the bilateral hippocampus, amygdala, accumbens, and thalamus, and a pattern of significant thickening and surface expansion in the bilateral putamen and pallidum compared to healthy control participants. Between males and females, there was a pattern of significant thinning and surface contraction in the bilateral thalamus, pallidum, putamen, and amygdala in females compared to males. C_LIO_LIThere was no significant interaction between diagnosis and biological sex, suggesting that sex differences in deep brain shape and asymmetry among patients with schizophrenia reflect those observed in healthy individuals. C_LIO_LISmall but statistically significant relationships exist between brain structure and clinical correlates of schizophrenia were similar for both men and women with the disease, such that higher CPZ was associated with shape-derived thinning and surface contraction in the caudate, accumbens, hippocampus, amygdala, and thalamus, and elevated positive symptoms were associated with shape-derived thinning and surface contraction in the bilateral caudate, right hippocampus, and right amygdala. C_LI

neuroscience↗

Template-driven dynamic functional network connectivity predicts medication response for major depression and bipolar disorders

The process of finding reliable treatment for major depression and bipolar disorder can be arduous. The myriad behavioral symptoms presented by patients and resistance to treatment from particular medication classes complicate standard diagnostic and prescription methodologies, often requiring multiple attempted treatments during which symptoms may still be present. Physiological information such as neuroimaging scans may help to alleviate some of the uncertainty surrounding diagnosis and treatment when incorporated into a clinical setting. Changes in functional magnetic resonance imaging show particular promise, as the incorporation of dynamical information may provide insights into physiological changes prior to static, structural changes. In this work, we present a novel method for generating robust and replicable dynamic functional network connectivity (dFNC) features from neuroimaging data using a template of dynamic states derived from a large, non-affected data set. We demonstrate that this template-driven dFNC approach expands on standard dFNC approaches by allowing for the derivation of a continuous state-contribution time series. We demonstrate that the derived biomarkers can support high predictive performance for the identification of medication class and non-responders while also expanding the set of biomarkers available for studying differences in mood disorder medication response.

neuroscience↗

Privacy-Preserving Visualization of Brain Functional Connectivity

Data visualizations are an integral part of neuroimging research, supporting activities ranging from exploratory data analysis to the interpretation and communication of findings. While essential, visualizations can also reveal private information about individual participants. In this paper, we discuss how visualizations may inadvertently lead to privacy leakage and explore methods to mitigate such risks. Our work investigates ways to securely share visualizations that faithfully preserve the patterns supporting the derived insights from data analysis, rather than deriving conclusions from the visualizations themselves. We address the problem of privacy-preserving visualization under the framework of differential privacy, focusing on commonly used visualization methods for functional network connectivity. Several perturbation-based strategies are investigated for protecting correlationrelated measures, with analyses of their privacy costs and the effects of pre- and post-processing. To achieve a better balance between privacy and visual utility, we propose workflows for connectogram and seed-based connectivity visualizations that preserve the qualitative structure of non-private results. Overall, this work illustrates how differential privacy can be effectively applied to neuroimaging visualization, highlighting its potential as a principled approach for safeguarding sensitive information.

neuroscience↗

Refining Brain Stimulation Therapies: An Active Learning Approach to Personalization

Brain stimulation holds promise for treating brain disorders, but personalizing therapy remains challenging. Effective treatment requires establishing a functional link between stimulation parameters and brain response, yet traditional methods like random sampling (RS) are inefficient and costly. To overcome this, we developed an active learning (AL) framework that identifies optimal relationships between stimulation parameters and brain response with fewer experiments. We validated this framework through three experiments: (1) in silico modeling with synthetic data from a Parkinsons disease model, (2) in silico modeling with real data from a non-human primate, and (3) in vivo modeling with a real-time rat optogenetic stimulation experiment. In each experiment, we compared AL models to RS models, using various query strategies and stimulation parameters (amplitude, frequency, pulse width). AL models consistently outperformed RS models, achieving lower error on unseen test data in silico (p<0.0056, N=1,000) and in vivo (p=0.0036, N=20). This approach represents a significant advancement in brain stimulation, potentially improving both research and clinical applications by making them more efficient and effective. Our findings suggest that AL can substantially reduce the cost and time required for developing personalized brain stimulation therapies, paving the way for more effective and accessible treatments for brain disorders.

neuroscience↗

Dev-Atlas: A reference atlas of functional brain networks for typically developing adolescents

Adolescence is a critical period for neural changes, including maturation of the brains cognitive networks, but also a period of increased vulnerability to psychopathology. It is well accepted that the brain is functionally organized into multiple interacting networks and extensive literature has demonstrated that the spatial and functional organization of these networks shows major age-related changes across the lifespan, but particularly during adolescence. Yet, there is limited option for a reference functional brain atlas derived from typically developing adolescents, which is especially problematic as the reliable and reproducible identification of functional brain networks crucially depends on the use of such reference functional atlases. In this context, we utilized resting-state functional MRI data from a total of 1,391 typically developing youth between the ages of 8 and 17 years to create a new adolescent-specific reference atlas of functional brain networks. We further investigated the impact of age and sex on these networks. Using a multiscale individual component clustering algorithm (MICCA), we identified 24 reliable functional brain networks, classified within six domains: Default-Mode (5 networks), Control (4 networks), Salience (3 networks), Attention (4 networks), Somatomotor (5 networks), and Visual (3 networks). We identified reliable and large effects of age on the spatial topography of these majority of networks, as well as on the functional network connectivity (FNC) between networks. The DMN showed reduced FNC with the other networks with older age. Sex effects were not as widespread. No significant sex-by-age interactions were detected. Overall, we created a novel brain atlas, named Dev-Atlas, focused on a typically developing sample, with the hope that this atlas can be used in future independent developmental network neuroscience studies. Dev-Atlas is freely available to the research community.

neuroscience↗

Explicitly Nonlinear Connectivity-Matrix Independent Component Analysis in Resting fMRI Data

Independent component analysis (ICA) is a widely used data-driven technique for investigating brain structure and function to extract intrinsic networks. However, the ability of ICA, a linear mixing model, to capture nonlinear relationships is inherently limited. While nonlinear ICA can be used to estimate nonlinear+ linear mixtures, it can be useful to study the degree to which there is nonlinearity above and beyond the widely studied linear resting networks. Here, we propose a way to divide the data into sources exhibiting linear-only or explicitly nonlinear dependencies in resting functional magnetic resonance imaging (fMRI) data. Such an approach can be very informative as it allows us to evaluate the degree to which a given network might be linear, nonlinear, or both linear and nonlinear. Here, we present an enhanced connectivity-domain ICA approach, connectivity-matrix ICA, incorporating normalized mutual information (NMI) after canceling the linear effects to measure explicitly nonlinear (EN) relationships within voxel connectivity. This integration enables the identification of brain spatial maps that exhibit pronounced explicitly nonlinear dependencies while excluding linear relationships. By eliminating linear dependencies and utilizing NMI, we discover highly structured resting networks that conventional functional connectivity methods would typically overlook. The results indicate that several maps show only linear or EN relationships, and the rest of the components display both linear and nonlinear patterns. We categorized these maps as linear-only, EN-only, and linear-EN maps. We also evaluate differences in the identified networks in a schizophrenia dataset. A significant global difference has been discovered between schizophrenia and controls in some linear-EN maps, such as the frontal lobe. Moreover, the temporal lobe and thalamus display linear group differences, while the visual and motor cortex display global differences in nonlinear relationships as their primary driver of these disparities. In sum, our findings emphasize the significance of accounting for explicitly nonlinear dependencies in functional connectivity analysis and demonstrate the effectiveness of the extended cmICA approach in revealing previously unrecognized brain dynamics.

neuroscience↗

Unraveling the Neural Landscape of Mental Disorders using Double Functional Independent Primitives (dFIPs)

Mental illnesses extract a high personal and societal cost, and thus explorations of the links between mental illness and functional connectivity in the brain are critical. Investigating major mental illnesses, believed to arise from disruptions in sophisticated neural connections, allows us to comprehend how these neural network disruptions may be linked to altered cognition, emotional regulation, and social interactions. Although neuroimaging has opened new avenues to explore neural alterations linked to mental illnesses, the field still requires precise and sensitive methodologies to inspect these neural substrates of various psychological disorders. In this study, we employ a hierarchical methodology to derive double functionally independent primitives (dFIPs) from resting state functional magnetic resonance neuroimaging data (rs-fMRI). These dFIPs encapsulate canonical overlapping patterns of functional network connectivity (FNC) within the brain. Our investigation focuses on the examination of how combinations of these dFIPs relate to different mental disorder diagnoses. The central aim is to unravel the complex patterns of FNC that correspond to the diverse manifestations of mental illnesses. To achieve this objective, we used a large brain imaging dataset from multiple sites, comprising 5805 total individuals diagnosed with schizophrenia (SCZ), autism spectrum disorder (ASD), bipolar disorder (BPD), major depressive disorder (MDD), and controls. The key revelations of our study unveil distinct patterns associated with each mental disorder through the combination of dFIPs. Notably, certain individual dFIPs exhibit disorder-specific characteristics, while others demonstrate commonalities across disorders. This approach offers a novel, data-driven synthesis of intricate neuroimaging data, thereby illuminating the functional changes intertwined with various mental illnesses. Our results show distinct signatures associated with psychiatric disorders, revealing unique connectivity patterns such as heightened cerebellar connectivity in SCZ and sensory domain hyperconnectivity in ASD, both contrasted with reduced cerebellar-subcortical connectivity. Utilizing the dFIP concept, we pinpoint specific functional connections that differentiate healthy controls from individuals with mental illness, underscoring its utility in identifying neurobiological markers. In summary, our findings delineate how dFIPs serve as unique fingerprints for different mental disorders.

neuroscience↗

A Novel Registration Framework for Aligning Longitudinal Infant Brain Tensor Images

Registering longitudinal infant brain images is challenging, as the infant brain undergoes rapid changes in size, shape and tissue contrast in the first months and years of life. Diffusion tensor images (DTI) have relatively consistent tissue properties over the course of infancy compared to commonly used T1 or T2- weighted images, presenting great potential for infant brain registration. Moreover, groupwise registration has been widely used in infant neuroimaging studies to reduce bias introduced by predefined atlases that may not be well representative of samples under study. To date, however, no methods have been developed for groupwise registration of tensor-based images. Here, we propose a novel registration approach to groupwise align longitudinal infant DTI images to a sample-specific common space. Longitudinal infant DTI images are first clustered into more homogenous subgroups based on image similarity using Louvain clustering. DTI scans are then aligned within each subgroup using standard tensor-based registration. The resulting images from all subgroups are then further aligned onto a sample-specific common space. Results show that our approach significantly improved registration accuracy both globally and locally compared to standard tensor-based registration and standard fractional anisotropy-based registration. Additionally, clustering based on image similarity yielded significantly higher registration accuracy compared to no clustering, but comparable registration accuracy compared to clustering based on chronological age. By registering images groupwise to reduce registration bias and capitalizing on the consistency of features in tensor maps across early infancy, our groupwise registration framework facilitates more accurate alignment of longitudinal infant brain images.

bioengineering↗

Dynamic functional connectivity correlates of trait mindfulness in early adolescence

BackgroundTrait mindfulness, the tendency to attend to present-moment experiences without judgement, is negatively correlated with adolescent anxiety and depression. Understanding the neural mechanisms underlying trait mindfulness may inform the neural basis of psychiatric disorders. However, few studies have identified brain connectivity states that correlate with trait mindfulness in adolescence, nor have they assessed the reliability of such states. MethodsTo address this gap in knowledge, we rigorously assessed the reliability of brain states across 2 functional magnetic resonance imaging (fMRI) scan from 106 adolescents aged 12 to 15 (50% female). We performed both static and dynamic functional connectivity analyses and evaluated the test-retest reliability of how much time adolescents spent in each state. For the reliable states, we assessed associations with self-reported trait mindfulness. ResultsHigher trait mindfulness correlated with lower anxiety and depression symptoms. Static functional connectivity (ICCs from 0.31-0.53) was unrelated to trait mindfulness. Among the dynamic brains states we identified, most were unreliable within individuals across scans. However, one state, an hyperconnected state of elevated positive connectivity between networks, showed good reliability (ICC=0.65). We found that the amount of time that adolescents spent in this hyperconnected state positively correlated with trait mindfulness. ConclusionsBy applying dynamic functional connectivity analysis on over 100 resting-state fMRI scans, we identified a highly reliable brain state that correlated with trait mindfulness. The brain state may reflect a state of mindfulness, or awareness and arousal more generally, which may be more pronounced in those who are higher in trait mindfulness.

neuroscience↗

Providing context: Extracting non-linear and dynamic temporal motifs from brain activity

Approaches studying the dynamics of resting-state functional magnetic resonance imaging (rs-fMRI) activity often focus on time-resolved functional connectivity (tr-FC). While many approaches have been proposed, these typically focus on linear approaches like computing the linear correlation at a timestep or within a window. In this work, we propose to use a generative non-linear deep learning model, a disentangled variational autoencoder (DSVAE), that factorizes out window-specific (context) information from timestep-specific (local) information. This has the advantage of allowing our model to capture differences at multiple temporal scales. For the timestep-specific scale, which has higher temporal precision, we find significant differences between schizophrenia patients and control subjects in their temporal step distance through our models latent space. We also find that window-specific embeddings, or as we refer to them, context embeddings, more accurately separate windows from schizophrenia patients and control subjects than the standard tr-FC approach. Moreover, we find that for individuals with schizophrenia, our models context embedding space is significantly correlated with both age and symptom severity. Interestingly, patients appear to spend more time in three clusters, one closer to controls which shows increased visual-sensorimotor, cerebellar-subcortical, and reduced cerebellar-sensorimotor functional network connectivity (FNC), an intermediate station showing increased subcortical-sensorimotor FNC, and one that shows decreased visual-sensorimotor, decreased subcortical-sensorimotor, and increased visual-subcortical domains. We verify that our model captures features that are complementary to - but not the same as - standard tr-FC features. Our model can thus help broaden the neuroimaging toolset in analyzing fMRI dynamics and shows potential as an approach for finding psychiatric links that are more sensitive to individual and group characteristics. Author summaryWe introduce a powerful new temporal representation learning model for resting-state fMRI data that can find novel and interesting temporal motifs that relate brain activity to schizophrenia diagnosis. Our model uses factorizes out local (timestep-specific) and context (window-specific) information in a latent space. We find that the context embeddings are more linearly predictive of whether someone has a schizophrenia diagnosis, and the context embedding space significantly correlates with age and symptom severity. We verify that our model captures features that are complementary to but not the same as time-resolved functional connectivity features. Our model can thus help broaden the neuroimaging toolset in analyzing fMRI dynamics and shows potential as an approach for finding psychiatric links that are more sensitive to individual and group characteristics.

neuroscience↗

Functionally Adaptive Structural Basis Sets of the Brain: A Dynamic Fusion Approach

The precise relationship between brain structure and function has been investigated through a multitude of lenses, but one detail that is held constant across most neuroimaging studies in this space is the identification of a singular structural basis set of the brain, upon which functional activation signals can be reconstructed to examine the linkage between structure and function. Such basis sets can be considered "functionally independent", as they are derived through structural data alone and have no explicit association to functional data. Recent work in multimodal fusion has facilitated a more integrated view of structure-function linkages by enabling the equal contribution of both modalities to the joint decomposition, resulting in components that are independent within modality but co-vary closely across modalities. These existing symmetric fusion approaches thus identify structural bases given an associated functional context. In this work we consider an additional layer of precision to the investigation of structure-function coupling by studying these context-dependent linkages in a time-resolved manner. In other words, we ask which features of brain structure become (or remain) salient given the dynamically changing functional contexts (i.e., dynamic functional connectivity states, task structure, etc.) the brain may pass through during a given fMRI scan. We introduce "dynamic fusion", an ICA-based symmetric fusion approach that enables flexible, time-resolved linkages between brain structure and dynamic brain function. We show evidence that temporally resolved, and functionally contextualized, structural basis sets can accurately reflect dynamic functional processes and capture diagnostically relevant structure-functional coupling while detecting nuanced functionally-driven structural components that cannot be captured with traditionally computed structural bases. Lastly, differential analysis of component stability across repeated scans from a control cohort reveals organization of static and dynamic structure/function coupling falls along unimodal/transmodal hierarchical lines.

neuroscience↗

Studying time-resolved functional connectivity via communication theory: on the complementary nature of phase synchronization and sliding window Pearson correlation.

Time-resolved functional network connectivity (trFNC) assesses the time-resolved coupling between brain regions using functional magnetic resonance imaging (fMRI) data. This study aims to compare two techniques used to estimate trFNC, to investigate their similarities and differences when applied to fMRI data. These techniques are the sliding window Pearson correlation (SWPC), an amplitude-based approach, and phase synchronization (PS), a phase-based technique. To accomplish our objective, we used resting-state fMRI data from the Human Connectome Project (HCP) with 827 subjects (repetition time: 0.7s) and the Function Biomedical Informatics Research Network (fBIRN) with 311 subjects (repetition time: 2s), which included 151 schizophrenia patients and 160 controls. Our simulations reveal distinct strengths in two connectivity methods: SWPC captures high-magnitude, low-frequency connectivity, while PS detects low-magnitude, high-frequency connectivity. Stronger correlations between SWPC and PS align with pronounced fMRI oscillations. For fMRI data, higher correlations between SWPC and PS occur with matched frequencies and smaller SWPC window sizes ([~]30s), but larger windows ([~]88s) sacrifice clinically relevant information. Both methods identify a schizophrenia-associated brain network state but show different patterns: SWPC highlights low anti-correlations between visual, subcortical, auditory, and sensory-motor networks, while PS shows reduced positive synchronization among these networks. In sum, our findings underscore the complementary nature of SWPC and PS, elucidating their respective strengths and limitations without implying the superiority of one over the other. Impact StatementThis study demonstrates that SWPC and PS provide complementary insights into dynamic functional connectivity, revealing different aspects of brain dynamics based on signal focus. For tasks involving slow dynamics, SWPC amplitude is ideal, while the PS phase is more suitable for transient dynamics. In schizophrenia, typically associated with general dysconnectivity, we uncover a dual dysconnectivity profile depending on phase or amplitude dynamics. This novel approach offers researchers a platform to explore task-specific dysconnectivity profiles, enabling more targeted interventions. These findings will guide methodology choices, deepen understanding of brain dynamics, and support the development of precise neuropsychiatric biomarkers. HighlightsO_LITime-resolved functional network connectivity (trFNC) is widely used; here we study two approaches often pit against one another: 1) phase synchrony (PS), a phase-based method, and 2) sliding window Pearson correlation (SWPC), an amplitude-based method. C_LIO_LISWPC is sensitive to the choice of window size, while PS requires a narrow frequency band. Both can result in the loss of relevant information. C_LIO_LIWe find through simulation that SWPC better captures high-magnitude slow-varying amplitude-encoded connectivity while PS better captures low-magnitude fast-varying phase-encoded connectivity. C_LIO_LIWe find that while both SWPC and PS detect disconnected states mostly associated with schizophrenia they exhibit unique complementary patterns. C_LIO_LIWe conclude that SWPC and PS are complementary techniques, each with distinct assumptions and constraints, which should be selected based on the focus of the study. C_LI

neuroscience↗

SpaDE: Semantic Locality Preserving Biclusteringfor Neuroimaging Data

The most discriminative and revealing patterns in the neuroimaging population are often confined to smaller subdivisions of the samples and features. Especially in neuropsychiatric conditions, symptoms are expressed within micro subgroups of individuals and may only underly a subset of neurological mechanisms. As such, running a whole-population analysis yields suboptimal outcomes leading to reduced specificity and interpretability. Biclustering is a potential solution since subject heterogeneity makes one-dimensional clustering less effective in this realm. Yet, high dimensional sparse input space and semantically incoherent grouping of attributes make post hoc analysis challenging. Therefore, we propose a deep neural network called semantic locality preserving auto decoder (SpaDE), for unsupervised feature learning and biclustering. SpaDE produces coherent subgroups of subjects and neural features preserving semantic locality and enhancing neurobiological interpretability. Also, it regularizes for sparsity to improve representation learning. We employ SpaDE on human brain connectome collected from schizophrenia (SZ) and healthy control (HC) subjects. The model outperforms several state-of-the-art biclustering methods. Our method extracts modular neural communities showing significant (HC/SZ) group differences in distinct brain networks including visual, sensorimotor, and subcortical. Moreover, these biclustered connectivity substructures exhibit substantial relations with various cognitive measures such as attention, working memory, and visual learning.

neuroscience↗