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Wiafe, S.-L.

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

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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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