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Wiafe, S.-L.

Publications and source records attributed to Wiafe, S.-L..

16 recordsLinked to original sources

A Chronnectogram-ICA Framework for Tracking Continuously Evolving and Overlapping Functional Brain States

The discrete-state model of brain dynamics has become the dominant paradigm in functional connectivity analysis, representing network activity as transitions among a fixed set of transiently recurring states while generally assuming that the states themselves do not evolve. We introduce a multilevel chronnectogram framework that relaxes this assumption and explicitly represents the higher-order temporal structure of brain dynamics, how distinct states couple and co-evolve over time, alongside the persistence of each state. The method integrates spatially guided independent component analysis (ICA) with subject-specific, state-guided dynamic ICA to capture evolving and overlapping connectivity patterns in a shared representational space. Validation on simulations with known ground truth shows recovery of continuous overlap and higher-order coupling structure invisible to discrete-state methods. Applied to resting-state functional magnetic resonance imaging from the FBIRN dataset (151 schizophrenia, 160 controls), the framework reveals that the same pair of brain states is shifted toward opposite extremes across patients, with strong synchrony in some and active anti-coupling in others, creating a redistribution of connectivity regimes invisible to conventional occupancy metrics, providing a substrate in which schizophrenia can appear both hyper- and hypo-volatile depending on the measure applied.

neuroscience↗

Spatio-dynamical decomposition: Joint spatial and dynamical criteria for FMRI Blind source separation.

Blind source separation (BSS) recovers latent sources from observed mixtures. In brain imaging, sources occur in two domains, spatial and temporal, so a criterion applied in one leaves the other unconstrained. Independent component analysis, the most used BSS tool, exploits diversity such as non-Gaussianity and sample dependence, but in one domain at a time. Methods that use both domains apply the same criterion to each and weight them against each other. We propose spatio-dynamical decomposition (SDD), scoring maps by non-Gaussianity and timecourses by dynamical independence: how much each source's dynamics depend on the others. We normalize each score by how much it can improve on the data, eliminating the need for a weight. Across simulations and 130 naturalistic fMRI runs, SDD recovers sources distinguished by either maps or dynamics and reproduces both across disjoint episodes, while baselines trade off the two; map and timescale together also better predict stimulus tracking, with the largest gain for SDD. Together, these results show that separation is strongest when spatial and temporal domains each carry their own criterion.

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TE-aware state analysis and evolution in dynamic network connectivity

Multi-echo functional magnetic resonance imaging (fMRI) acquires signals with distinct contrast profiles across echo times (TEs). Empirical evidence suggests that different TEs capture distinct signal contributions with varying sensitivity to BOLD and non-BOLD processes from long to short TEs (Stroman, 2002; Krishnamurthy, 2023; Dong, 2024). Previous literature has not yet examined how brain states extracted from temporal dynamic functional connectivity (dFNC) evolve across TEs. Here we present a methodological and empirical study of TE-dependent evolution of dynamic connectivity states, with a phenomenological two-component model for interpretation. Multiple echoes were acquired with an echo planar time-resolved imaging (EPTI) sequence. TE-specific components were extracted via atlas-based group ICA (Neuromark 1.0), and brain connectivity states were generated via windowed dFNC and spatial ICA clustering of windows. Within-subject and group-level states evolved across TEs in network organization and variance. States exhibited TE-dependent variance profiles, with distinct peak echo times; and group-level points of state transition were independently mapped to TE-dependent transitions in variance. We modified a bi-exponential model to simulate and model changes in the dFNC time-course across TEs. The bi-exponential model revealed high consistency with subject states (R2 fit=0.86, res. error=0.55, 86% model convergence rate), suggesting a two-component signal system contributing to dynamic TE-dependent connectivity changes in state. A significant correlation between relative model terms was estimated on a cell-wise basis across states (r(24) = -0.43, p=0.03, 95% CI [-0.70, -0.04]). This suggests that specific bi-exponential signal parameters (i.e., short FNC1,TE=0, long FNC2,TE=0, and long FNC2,decay) were associated with the observed TE-dependent variations in connectivity states across TEs. In sum, our analyses provide downstream implications for TE-aware state analysis dependent on connectivity magnitude (FNCTE=0) and rate of connectivity decay (FNCdecay), in a two-component signal model, with future implications for TE-dependent state biomarkers.

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Large-scale brain dynamics are organized by a directional coordination hierarchy

The cortical hierarchy is a central organizing feature of brain structure and function, yet whether it is continuously expressed in spontaneous neural activity remains unresolved. Here, we show that resting-state brain dynamics are organized along a directional coordination axis that recapitulates hierarchical information flow. Focusing on the directional dynamics of interregional coordination, we identify three recurrent coordination regimes: a feedback-dominated mode in which transmodal cortex leads sensory systems, a feedforward-dominated mode reflecting the reverse, and an integrative mode of balanced bidirectional exchange. These modes define a low-dimensional coordination landscape that replicates across four independent cohorts, establishing directional structure as a stable property of the adult brain. In schizophrenia, this landscape is selectively reorganized: feedback-dominated coordination becomes less persistent, integrative coordination becomes more persistent, and global dynamics shift toward faster convergence and reduced entropy, reflecting a loss of directional constraint and dynamical flexibility. These alterations track symptom severity, cognitive performance, and medication exposure. Mediation analyses suggest that medication-related reductions in integrative coordination are statistically routed through feedforward dynamics, consistent with dopaminergic modulation of recurrent cortical loops as a candidate mechanism. Together, these findings identify directional functional dynamics as a fundamental and clinically informative axis of large-scale brain organization.

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Functional Connectivity Changes in Major Depressive Disorder

Major depressive disorder (MDD) is associated with brain-wide network disruptions. This study investigates a large resting-state functional magnetic resonance imaging dataset (N = 519) to analyze static and dynamic functional network connectivity (FNC). Using independent component analysis, our analysis revealed hyperconnectivity within sensorimotor and temporal subdomains, hypoconnectivity from higher cognitive networks, and hyperconnectivity from the default mode and sensorimotor domains in MDD. A novel frequency-sensitive dynamic approach identified disruptions in the temporal synchrony of brain states engaging the default mode-paralimbic, sensorimotor, and frontal regions, as well as the subcortical limbic, frontal, and salience regions. Overall, the findings highlight the utility of combining static and dynamic approaches in large neuroimaging datasets to elucidate the neural underpinnings of MDD pathology.

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Structural co-modulation: An individualized measure of inter-component interactions in source-based morphometry

Source-based morphometry (SBM) is a powerful multivariate method for identifying covarying structural brain networks. However, standard SBM provides only a single loading value per component for each subject, which limits the characterization of relationships between these components. We propose a novel technical co-modulation approach to derive an individualized, network-like measure of structural brain organization. This method transforms the subject-specific SBM loading vector into a symmetric co-modulation matrix by computing the vectors outer product. Each element of this matrix quantifies the pairwise interaction between structural components, creating a subject-specific fingerprint. Similar to functional connectivity that maps the temporal synchronization between networks, this matrix maps their joint structural prominence, reflecting how strongly two networks co-occur within an individual. To demonstrate the utility of this method, we applied it to structural MRI data from 210 patients with schizophrenia (SZ) and 195 healthy controls (HC) from the fBIRN psychosis dataset using functional networks as priors for SBM. We observed widespread reductions in structural co-modulation in the SZ group, particularly within and between visual, default-mode, and cognitive control networks. Furthermore, co-modulation patterns were significantly correlated with cognitive performance and clinical symptom severity in patients. Structural co-modulation provides a robust framework for quantifying individualized relationships between structural brain features, overcoming key limitations of standard SBM and offering a new avenue for integrating structural and functional brain analyses.

bioengineering↗

Dynamic Co-Modulation (DyCoM): A Unified Operator Framework for Time-Varying Interactions

Dynamic connectivity is central to understanding time-varying interactions between brain regions. Despite decades of methodological development, approaches to measuring dynamic connectivity remain fragmented, leading to inconsistent findings, limited comparability across studies, and difficulty attributing observed effects to computational choices. Here, we introduce dynamic co-modulation (DyCoM), a compact operator-level framework that expresses dynamic connectivity estimators as compositions of a small set of fundamental signal processing operations. Using simulations and resting-state fMRI data, we show that DyCoM disentangles previously conflated findings by revealing that lower-order sensory and higher-order executive control neurobiological signatures, state-transition sensitivity, and medication-linked clinical associations arise from distinct operator choices within a single unified framework. Together, these results establish DyCoM as a unifying foundation for dynamic interaction analysis, revealing how differences in estimator design give rise to divergent biological interpretations and offering a principled and extensible framework for coherence, interpretability, and estimator development.

bioengineering↗

The Role of Sleep Duration and Age in Neural Reactivation and Episodic Memory Performance Across the Adult Lifespan

Sleep is essential for episodic memory consolidation, involving the reactivation of neural patterns during encoding and retrieval. This study examined how sleep duration influences encoding-retrieval similarity (ERS) and memory performance across the adult lifespan. Fifty-five adults (18-79 years) participated in a seven-day protocol, combining actigraphy-based sleep monitoring with EEG and memory assessments during a paired associate learning task. Significant correlations between sleep duration and ERS were observed, with clusters showing positive and negative associations across brain regions. In match context trials, ERS in the left frontal region correlated with sleep duration, and age moderated these effects. In mismatch context trials, positive correlations were identified in the left posterior, left frontal, and right posterior regions. These results highlight the role of sleep in modulating neural reactivation patterns during memory retrieval and emphasize the influence of age. The study advances our understanding of how sleep variability impacts memory consolidation and provides a basis for exploring targeted sleep interventions. Clinical RelevanceThis study highlights the impact of habitual sleep variability on neural reactivation patterns and memory retrieval across the adult lifespan. The findings emphasize the moderating role of age and suggest that improving sleep duration may enhance episodic memory performance. These insights could guide clinicians in developing personalized sleep interventions to support cognitive health and mitigate age-related memory decline.

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SPATIAL DISSIMILARITY TRAJECTORIES REVEAL RAPID FUNCTIONAL NETWORK REFINEMENT DURING EARLY INFANCY

The first six months of life mark a critical window for human brain development, characterized by rapid synaptic formation, axonal growth, and network reorganization. During this period, large-scale functional networks progressively mature. Although prior infant fMRI studies have characterized temporal functional connectivity, the spatial organization and refinement of brain networks during early infancy remain underexplored. In this study, we analyzed longitudinal resting-state fMRI from 74 typically developing infants (0-6 months; 137 scans) using group independent component analysis (ICA) with group-information-guided ICA (GIG-ICA) back-reconstruction. Spatial dissimilarity between each infants spatial map and the group-level map was quantified using cosine dissimilarity and Euclidean distance. Generalized additive models were applied to model age-related trends. Both cosine and Euclidean dissimilarity metrics showed significant decreases with age, indicating a progressive convergence of individual network topographies toward the group-level architecture. These findings reveal increasing spatial coherence and refinement of large-scale brain networks during early infancy, suggesting that spatial maturation complements the well-established functional integration observed in temporal connectivity studies.

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Functional Inertia Index of Memory-Retaining Brain Dynamics: A Measure of Large-Scale Brain Adaptability

The brain does not process the present in isolation. Its responses are shaped by the accumulating weight of prior states, yet existing frameworks treat large-scale brain dynamics as sequences of transient configurations, leaving the constraining influence of history formally unspecified. Here we show that the brain possesses an intrinsic, representation-agnostic organizing constraint, the degree to which accumulated prior states resist ongoing reorganization, which we term functional inertia. Using an inertial state-space model replicated across two independent observational frameworks, we demonstrate that functional inertia operates coherently across three levels of brain organization: it structures activity into dynamical regimes, links these regimes to clinical and cognitive expression through a system-level inertial magnitude, and distributes across circuits in patterns that reconcile the longstanding coexistence of associative rigidity and sensory volatility in schizophrenia. Critically, removing the cumulative integration collapses this multilevel organization. Strikingly, the system-level inertial magnitude carries opposite cognitive signatures across diagnostic contexts, predicting better performance in healthy individuals but greater symptom severity in schizophrenia, reflecting context-dependent expression of a single constraint. These findings position functional inertia as a unifying, multilevel constraint on brain reorganization, recasting stability and volatility not as opposing properties but as context-dependent expressions of a single constraint.

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Neural flexibility in metabolic demand dynamics reveals sex-specific differences and supports cognition in late childhood

Dynamic coordination of metabolic demand across brain networks supports emerging cognitive abilities and may drive overall cognitive development, yet how these dynamics vary by sex and relate to cognition in late childhood remains unclear. Using resting-state fMRI from 2,000 healthy 9-to 11-year-olds in the ABCD study, we applied time-resolved dynamic time warping to quantify amplitude mismatches, a proxy of relative energy demand across brain intrinsic networks. Clustering revealed three recurring states: convergent (globally balanced), divergent (imbalanced), and mixed (intermediate). Females spent engaged more with the flexible mixed state, whereas males lingered longer in convergent and divergent states. Across the cohort, better performance on cognitive flexibility, processing speed, and long-term memory tasks correlated with greater overall time in the mixed state and with higher transition rates, but with shorter dwell in any single state. These findings indicate that neural flexibility, rather than prolonged stability, supports cognition during late childhood and that sex differences in dynamic energy coordination emerge well before adolescence.

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Dynamic Inter-Modality Source Coupling Reveals Sex Differences in Children based on Brain Structural-Functional Network Connectivity: A Multimodal MRI Study of the ABCD Dataset

BackgroundSex differences in brain development are well-documented, yet the dynamic coupling between structure and function remains underexplored. We introduce dynamic inter-modality source coupling (dIMSC), extending our previous work to link structural MRI source-based morphometry (SBM) with dynamic functional network connectivity (dFNC). MethodsWe used data from the Adolescent Brain Cognitive Development (ABCD) study (ages 9-11) and combined SBM-derived gray matter sources with sliding-window dFNC. dIMSC was computed as the time-resolved cross-correlation between these modalities to quantify structure-function coupling strength. We evaluated sex differences in these profiles and their interaction with cognitive performance. ResultsSignificant sex-specific patterns emerged: males exhibited stronger positive coupling in sensorimotor regions (postcentral gyrus), while females showed stronger coupling in higher-order associative regions (inferior parietal lobule). These configurations were functionally distinct: higher positive coupling occupancy predicted better crystallized cognition (vocabulary) in females, whereas it predicted better fluid cognition (working memory) in males. ConclusionTogether, these findings suggest that males and females utilize distinct structural-functional configurations to support cognitive processing, males relying on a sensorimotor-anchored organization and females on an associative-anchored one. The dIMSC method advances our earlier work by enabling time-resolved analysis of brain coupling, providing a powerful framework for investigating sex-specific neurodevelopmental mechanisms.

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Brain State Convergence and Divergence as Resting State FMRI Biomarkers: A Large-Scale Study of Continuous, Overlapping, Time-resolved States Differentiates Four Psychiatric Disorders

AO_SCPLOWBSTRACTC_SCPLOWBrain function is inherently dynamic, characterized by transient, overlapping functional states rather than static connectivity patterns. Current clustering-based dynamic functional network connectivity methods often fail to capture overlapping states; meanwhile, independent component analysis (ICA)-based methods typically rely on group-level analysis, limiting subject-specific accuracy. To address this gap, we introduce a novel analytical framework estimating individualized dynamic double functional independent primitives (ddFIP)-based states. Our methodological innovation includes: (1) a two-stage ICA combining spatially constrained ICA to define group-level intrinsic connectivity networks (ICNs), followed by constrained ICA to estimate subject-specific states and timecourses; (2) calibration ensuring derived states preserve original correlation scales, enabling meaningful cross-subject and group-level comparisons; and (3) novel metrics leveraging this calibrated representation, including amplitude convergence (uniformity of simultaneous state contributions), amplitude divergence (variability of states independent of state dominance), and dynamic state density (number of concurrently active states at any given time). Validating our framework on an extensive resting-state fMRI dataset (N > 5.5K) spanning four neuropsychiatric conditions revealed disorder-specific connectivity signatures: schizophrenia exhibited extensive variability (increased divergence), while autism displayed pronounced stability (increased convergence). In summary, our proposed method uniquely integrates subject-specific ICA estimation, unit-preserving calibration, and novel convergence-divergence metrics, providing data-driven biomarkers that differentiating psychiatric disorders.

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Mapping Dynamic Metabolic Energy Distribution in Brain Networks using fMRI: A Novel Dynamic Time Warping Framework

Schizophrenia has long been linked to impaired coordination of brain activity, yet most frameworks overlook two key dimensions: the amplitude of brain signals and the differing timescales on which regions operate. These factors are critical in disorders where neural activity is exaggerated and slowed. In healthy adults, networks compensate for mismatched processing speeds to maintain proportionate activity, but this process is poorly understood in schizophrenia. We developed a timescale-aligned, time-resolved framework that separates temporal distortions from genuine amplitude differences, enabling measurement of amplitude balance between networks across timescales. This approach was applied to large-scale fMRI datasets, including the Human Connectome Project and a multi-site schizophrenia cohort. Patients with schizophrenia showed greater amplitude imbalance, especially during fast fluctuations, along with more frequent re-entry into unbalanced states and slower recovery to stable coordination. We further identified a flexible intermediate state that patients occupied more often, and that predicted better working-memory performance. Across cohorts, amplitude imbalance was associated with greater symptom severity and poorer reasoning ability. These findings provide a new mechanistic view of dyscoordination in schizophrenia grounded in timescale-normalized amplitude dynamics, highlight aberrant recovery of amplitude balance as a core feature of the illness, and suggest that timescale-aligned amplitude imbalance may serve as a promising target for biomarker development.

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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.

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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

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