Note, the direct FC link and SC detour form a cyclic loop inherited from both SC and FC topology.

Major Depressive Disorder (MDD), affecting millions worldwide, exhibits complex pathophysiology manifested through disrupted brain network dynamics. Although graph neural networks that leverage neuroimaging data have shown promise in depression diagnosis, existing approaches are predominantly data-driven and operate largely as black-box models, lacking neurobiological interpretability. Here, we present NH-GCAT (Neurocircuitry-Inspired Hierarchical Graph Causal Attention Networks), a novel framework that bridges neuroscience domain knowledge with deep learning by explicitly and hierarchically modeling depression-specific mechanisms at different spatial scales. Our approach introduces three key technical contributions: (1) at the local brain regional level, we design a residual gated fusion module that integrates temporal blood oxygenation level dependent (BOLD) dynamics with functional connectivity patterns, specifically engineered to capture local depression-relevant low-frequency neural oscillations; (2) at the multi-regional circuit level, we propose a hierarchical circuit encoding scheme that aggregates regional node representations following established depression neurocircuitry organization, and (3) at the multi-circuit network level, we develop a variational latent causal attention mechanism that leverages a continuous probabilistic latent space to infer directed information flow among critical circuits, characterizing disease-altered whole-brain inter-circuit interactions. Rigorous leave-one-site-out cross-validation on the REST-meta-MDD dataset demonstrates NH-GCAT's state-of-the-art performance in depression classification, achieving a sample-size weighted-average accuracy of 73.3\% and an AUROC of 76.4\%, while simultaneously providing neurobiologically meaningful explanations.

Brain processes occur at various timescales, ranging from milliseconds (neurons) to minutes and hours (behavior). Characterizing functional coupling among brain regions at these diverse timescales is key to understanding how the brain produces behavior. Here, we apply instantaneous and lag-based measures of conditional linear dependence, based on Granger-Geweke causality (GC), to infer network connections at distinct timescales from functional magnetic resonance imaging (fMRI) data. Due to the slow sampling rate of fMRI, it is widely held that GC produces spurious and unreliable estimates of functional connectivity when applied to fMRI data. We challenge this claim with simulations and a novel machine learning approach. First, we show, with simulated fMRI data, that instantaneous and lag-based GC identify distinct timescales and complementary patterns of functional connectivity. Next, we analyze fMRI scans from 500 subjects and show that a linear classifier trained on either instantaneous or lag-based GC connectivity reliably distinguishes task versus rest brain states, with ~80-85% cross-validation accuracy. Importantly, instantaneous and lag-based GC exploit markedly different spatial and temporal patterns of connectivity to achieve robust classification. Our approach enables identifying functionally connected networks that operate at distinct timescales in the brain.

Functional brain networks are well described and estimated from data with Gaussian Graphical Models (GGMs), e.g.\ using sparse inverse covariance estimators. Comparing functional connectivity of subjects in two populations calls for comparing these estimated GGMs. Our goal is to identify differences in GGMs known to have similar structure. We characterize the uncertainty of differences with confidence intervals obtained using a parametric distribution on parameters of a sparse estimator. Sparse penalties enable statistical guarantees and interpretable models even in high-dimensional and low-sample settings. Characterizing the distributions of sparse models is inherently challenging as the penalties produce a biased estimator.

Here, we apply instantaneous and lag-based measures of conditional linear dependence, based on Granger-Geweke causality (GC), to infer network connections at distinct timescales from functional magnetic resonance imaging (fMRI) data.

In this work, we present an additive model for space-time data that splits the data into a temporally correlated component and a spatially correlated component.

Functional brain networks are well described and estimated from data with Gaussian Graphical Models (GGMs), e.g. using sparse inverse covariance estimators. Comparing functional connectivity of subjects in two populations calls for comparing these estimated GGMs. Our goal is to identify differences in GGMs known to have similar structure. We characterize the uncertainty of differences with confidence intervals obtained using a parametric distribution on parameters of a sparse estimator. Sparse penalties enable statistical guarantees and interpretable models even in high-dimensional and low-sample settings. Characterizing the distributions of sparse models is inherently challenging as the penalties produce a biased estimator.

Human speech production encompasses multiple modes such as perceived, overt, whispered, and imagined, each reflecting distinct neural mechanisms. Among these, theta-band synchrony has been closely associated with language processing, attentional control, and inner speech. However, previous studies have largely focused on a single mode, such as overt speech, and have rarely conducted an integrated comparison of theta synchrony across different speech modes. In this study, we analyzed differences in theta-band neural synchrony across speech modes based on connectivity metrics, focusing on region-wise variations. The results revealed that overt and whispered speech exhibited broader and stronger frontotemporal synchrony, reflecting active motor-phonological coupling during overt articulation, whereas perceived speech showed dominant posterior and temporal synchrony patterns, consistent with auditory perception and comprehension processes. In contrast, imagined speech demonstrated a more spatially confined but internally coherent synchronization pattern, primarily involving frontal and supplementary motor regions. These findings indicate that the extent and spatial distribution of theta synchrony differ substantially across modes, with overt articulation engaging widespread cortical interactions, whispered speech showing intermediate engagement, and perception relying predominantly on temporoparietal networks. Therefore, this study aims to elucidate the differences in theta-band neural synchrony across various speech modes, thereby uncovering both the shared and distinct neural dynamics underlying language perception and imagined speech.

Depression is a major cause of global mental illness and significantly influences suicide rates. Timely and accurate diagnosis is essential for effective intervention. Electroencephalography (EEG) provides a non-invasive and accessible method for examining cerebral activity and identifying disease-associated patterns. We propose a novel graph-based deep learning framework, named Edge-gated, axis-mixed Pooling Attention Network (ExPANet), for differentiating major depressive disorder (MDD) patients from healthy controls (HC). EEG recordings undergo preprocessing to eliminate artifacts and are segmented into short periods of activity. We extract 14 features from each segment, which include time, frequency, fractal, and complexity domains. Electrodes are represented as nodes, whereas edges are determined by the phase-locking value (PLV) to represent functional connectivity. The generated brain graphs are examined utilizing an adapted graph attention network. This architecture acquires both localized electrode characteristics and comprehensive functional connectivity patterns. The proposed framework attains superior performance relative to current EEG-based approaches across two different datasets. A fundamental advantage of our methodology is its explainability. We evaluated the significance of features, channels, and edges, in addition to intrinsic attention weights. These studies highlight features, cerebral areas, and connectivity associations that are especially relevant to MDD, many of which correspond with clinical data. Our findings demonstrate a reliable and transparent method for EEG-based screening of MDD, using deep learning with clinically relevant results.