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Human brain function dynamically adjusts to ever-changing stimuli from the external environment. Studies characterizing brain functional reconfiguration are nevertheless scarce. Here we present a principled mathematical framework to quantify brain functional reconfiguration when engaging and disengaging from a stop signal task (SST). We apply tangent space projection (a Riemannian geometry mapping technique) to transform functional connectomes (FCs) of 54 participants and quantify functional reconfiguration using the correlation distance of the resulting tangent-FCs. Our goal was to compare functional reconfigurations in individuals at risk for alcohol use disorder (AUD). We hypothesized that functional reconfigurations when transitioning to/from a task would be influenced by family history of alcohol use disorder (FHA) and other AUD risk factors. Multilinear regression models showed that engaging and disengaging functional reconfiguration were associated with FHA and recent drinking. When engaging in the SST after a rest condition, functional reconfiguration was negatively associated with recent drinking, while functional reconfiguration when disengaging from the SST was negatively associated with FHA. In both models, several other factors contributed to the functional reconfiguration. This study 1demonstrates that tangent-FCs can characterize task-induced functional reconfiguration, and that it is related to AUD risk., Comment: 41 pages, 9 Figures, 3 Tables, 4 Supplementary Figures, 1 Supplementary Table

Functional connectomes (FCs) contain pairwise estimations of functional couplings based on pairs of brain regions activity. FCs are commonly represented as correlation matrices that are symmetric positive definite (SPD) lying on or inside the SPD manifold. Since the geometry on the SPD manifold is non-Euclidean, the inter-related entries of FCs undermine the use of Euclidean-based distances. By projecting FCs into a tangent space, we can obtain tangent functional connectomes (tangent-FCs). Tangent-FCs have shown a higher predictive power of behavior and cognition, but no studies have evaluated the effect of such projections with respect to fingerprinting. We hypothesize that tangent-FCs have a higher fingerprint than regular FCs. Fingerprinting was measured by identification rates (ID rates) on test-retest FCs as well as on monozygotic and dizygotic twins. Our results showed that identification rates are systematically higher when using tangent-FCs. Specifically, we found: (i) Riemann and log-Euclidean matrix references systematically led to higher ID rates. (ii) In tangent-FCs, Main-diagonal regularization prior to tangent space projection was critical for ID rate when using Euclidean distance, whereas barely affected ID rates when using correlation distance. (iii) ID rates were dependent on condition and fMRI scan length. (iv) Parcellation granularity was key for ID rates in FCs, as well as in tangent-FCs with fixed regularization, whereas optimal regularization of tangent-FCs mostly removed this effect. (v) Correlation distance in tangent-FCs outperformed any other configuration of distance on FCs or on tangent-FCs across the fingerprint gradient (here sampled by assessing test-retest, Monozygotic and Dizygotic twins). (vi)ID rates tended to be higher in task scans compared to resting-state scans when accounting for fMRI scan length., Comment: 31 pages, 10 figures, 2 tables

Functional connectivity, as estimated using resting state fMRI, has shown potential in bridging the gap between pathophysiology and cognition. However, clinical use of functional connectivity biomarkers is impeded by unreliable estimates of individual functional connectomes and lack of generalizability of models predicting cognitive outcomes from connectivity. To address these issues, we combine the frameworks of connectome predictive modeling and differential identifiability. Using the combined framework, we show that enhancing the individual fingerprint of resting state functional connectomes leads to robust identification of functional networks associated to cognitive outcomes and also improves prediction of cognitive outcomes from functional connectomes. Using a comprehensive spectrum of cognitive outcomes associated to Alzheimer's disease, we identify and characterize functional networks associated to specific cognitive deficits exhibited in Alzheimer's disease. This combined framework is an important step in making individual level predictions of cognition from resting state functional connectomes and in understanding the relationship between cognition and connectivity., Comment: 26 pages; 7 Figures, 2 Tables, 8 Supplementary Figures

The best approach to quantify human brain functional reconfigurations in response to varying cognitive demands remains an unresolved topic in network neuroscience. We propose that such functional reconfigurations may be categorized into three different types: i) Network Configural Breadth, ii) Task-to-Task transitional reconfiguration, and iii) Within-Task reconfiguration. In order to quantify these reconfigurations, we propose a mesoscopic framework focused on functional networks (FNs) or communities. To do so, we introduce a 2D network morphospace that relies on two novel mesoscopic metrics, Trapping Efficiency (TE) and Exit Entropy (EE), which capture topology and integration of information within and between a reference set of FNs. In this study, we use this framework to quantify the Network Configural Breadth across different tasks. We show that the metrics defining this morphospace can differentiate FNs, cognitive tasks and subjects. We also show that network configural breadth significantly predicts behavioral measures, such as episodic memory, verbal episodic memory, fluid intelligence and general intelligence. In essence, we put forth a framework to explore the cognitive space in a comprehensive manner, for each individual separately, and at different levels of granularity. This tool that can also quantify the FN reconfigurations that result from the brain switching between mental states., Comment: main article: 24 pages, 8 figures, 2 tables. supporting information: 11 pages, 5 figures

Alzheimer's disease (AD) is the only major cause of mortality in the world without an effective disease modifying treatment. Evidence supporting the so called disconnection hypothesis suggests that functional connectivity biomarkers may have clinical potential for early detection of AD. However, known issues with low test-retest reliability and signal to noise in functional connectivity may prevent accuracy and subsequent predictive capacity. We validate the utility of a novel principal component based diagnostic identifiability framework to increase separation in functional connectivity across the Alzheimer's spectrum by identifying and reconstructing FC using only AD sensitive components or connectivity modes. We show that this framework (1) increases test-retest correspondence and (2) allows for better separation, in functional connectivity, of diagnostic groups both at the whole brain and individual resting state network level. Finally, we evaluate a posteriori the association between connectivity mode weights with longitudinal neurocognitive outcomes., Comment: 8 pages, 3 tables, 3 figures

Examining task-free functional connectivity (FC) in the human brain offers insights on how spontaneous integration and segregation of information relate to human cognition, and how this organization may be altered in different conditions, and neurological disorders. This is particularly relevant for patients in disorders of consciousness (DOC) following severe acquired brain damage and coma, one of the most devastating conditions in modern medical care. We present a novel data-driven methodology, connICA, which implements Independent Component Analysis (ICA) for the extraction of robust independent FC patterns (FC-traits) from a set of individual functional connectomes, without imposing any a priori data stratification into groups. We here apply connICA to investigate associations between network traits derived from task-free FC and cognitive/clinical features that define levels of consciousness. Three main independent FC-traits were identified and linked to consciousness-related clinical features. The first one represents the functional configuration it is associated to a sedative (sevoflurane), the overall effect of the pathology and the level of arousal. The second FC-trait reflects the disconnection of the visual and sensory-motor connectivity patterns. It also relates to the time since the insult and to the ability of communicating with the external environment. The third FC-trait isolates the connectivity pattern encompassing the fronto-parietal and the default-mode network areas as well as the interaction between left and right hemispheres, which are also associated to the awareness of the self and its surroundings. Each FC-trait represents a distinct functional process with a role in the degradation of conscious states of functional brain networks, shedding further light on the functional subcircuits that get disrupted in severe brain-damage.