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Mintao Liu

Publications and source records attributed to Mintao Liu.

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The Genetic and Environmental Architecture of the Human Functional Connectome

Functional connectivity varies across individuals due to genetic and environmental factors, yet classical twin models typically confound non-shared environment with measurement error and are largely limited to resting-state analyses. We hypothesized that: i) explicitly modeling measurement error from repeated fMRI sessions enables more accurate application of classical twin models (ACE/ADE) to functional connectivity; ii) model applicability depends on scan-length and parcellation granularity; iii) genetic and environmental effects on functional connectomes show differentiated functional modules across conditions. We extended ACE/ADE models to include a repeated-scan derived error term by analyzing monozygotic and dizygotic twins from the Young-Adult Human Connectome Project dataset. Genetic and environment variance components were estimated for all functional couplings across resting-state and task conditions, integrated across conditions using a minimum-error criterion, and analyzed using multilayer community detection across resolution scales. Functional couplings segregated into distinct categories characterized by shared environmental, additive, dominant, or epistatic influences, with a substantial fraction not meeting twin-model assumptions. Integrating across conditions revealed hierarchical community structure in genetic and environmental components observed across community resolution scales. Incorporating measurement error into twin models improves interpretability and applicability at the functional connectome level, revealing that genetic and environmental influences are structured into coherent, multiscale brain networks.

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Resting State Functional Connectivity Patterns Associate with Alcohol Use Disorder Characteristics: Insights from the Triple Network Model

Prolonged alcohol use results in neuroadaptations that mark more severe and treatment-resistant alcohol use. The goal of this study was to identify functional connectivity brain patterns underlying Alcohol Use Disorder (AUD)-related characteristics in fifty-five adults (31 female) who endorsed heavy alcohol use. We hypothesized that resting-state functional connectivity (rsFC) of the Salience (SN), Frontoparietal (FPN), and Default Mode (DMN) networks would reflect self-reported recent and lifetime alcohol use, laboratory-based alcohol seeking, urgency, and sociodemographic characteristics related to AUD. To test our hypothesis, we combined the triple network model (TNM) of psychopathology with a multivariate data-driven approach, regularized partial least squares (rPLS), to unfold concurrent functional connectivity (FC) patterns and their association with AUD-related characteristics. We observed three concurrent associations of interest: i) drinking and age-related cross communication between the SN and both the FPN and DMN; ii) family history density of AUD and urgency anticorrelations between the SN and FPN; and iii) alcohol seeking and sex-associated SN and DMN interactions. These findings provide an integrative interpretation for many individual findings reported in the literature relating functional connectivity signatures and AUD factors. Moreover, we identified a set of neural mechanisms and brain regions concomitant with AUD-related characteristics that can serve as potential treatment targets across clinical and preclinical models.

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Tangent space functional reconfigurations in individuals at risk for alcohol use disorder

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.

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Tangent functional connectomes uncover more unique phenotypic traits

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.

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Geodesic distance on optimally regularized functional connectomes uncovers individual fingerprints

Background: Functional connectomes (FCs), have been shown to provide a reproducible individual fingerprint, which has opened the possibility of personalized medicine for neuro/psychiatric disorders. Thus, developing accurate ways to compare FCs is essential to establish associations with behavior and/or cognition at the individual-level. Methods: Canonically, FCs are compared using Pearson's correlation coefficient of the entire functional connectivity profiles. Recently, it has been proposed that the use of geodesic distance is a more accurate way of comparing functional connectomes, one which reflects the underlying non-Euclidean geometry of the data. Computing geodesic distance requires FCs to be positive-definite and hence invertible matrices. As this requirement depends on the fMRI scanning length and the parcellation used, it is not always attainable and sometimes a regularization procedure is required. Results: In the present work, we show that regularization is not only an algebraic operation for making FCs invertible, but also that an optimal magnitude of regularization leads to systematically higher fingerprints. We also show evidence that optimal regularization is dataset-dependent, and varies as a function of condition, parcellation, scanning length, and the number of frames used to compute the FCs. Discussion: We demonstrate that a universally fixed regularization does not fully uncover the potential of geodesic distance on individual fingerprinting, and indeed could severely diminish it. Thus, an optimal regularization must be estimated on each dataset to uncover the most differentiable across-subject and reproducible within-subject geodesic distances between FCs. The resulting pairwise geodesic distances at the optimal regularization level constitute a very reliable quantification of differences between subjects.

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GEFF: Graph Embedding for Functional Fingerprinting

It has been well established that Functional Connectomes (FCs), as estimated from functional MRI (fMRI) data, have an individual fingerprint that can be used to identify an individual from a population (subject-identification). Although identification rate is high when using resting-state FCs, other tasks show moderate to low values. Furthermore, identification rate is task-dependent, and is low when distinct cognitive states, as captured by different fMRI tasks, are compared. Here we propose an embedding framework, GEFF (Graph Embedding for Functional Fingerprinting), based on group-level decomposition of FCs into eigenvectors. GEFF creates an eigenspace representation of a group of subjects using one or more task FCs (Learning Stage). In the Identification Stage, we compare new instances of FCs from the Learning subjects within this eigenspace (validation dataset). The validation dataset contains FCs either from the same tasks as the Learning dataset or from the remaining tasks that were not included in Learning. Assessment of validation FCs within the eigenspace results in significantly increased subject-identification rates for all fMRI tasks tested and potentially task-independent fingerprinting process. It is noteworthy that combining resting-state with one fMRI task for GEFF Learning Stage covers most of the cognitive space for subject identification. In addition to subject-identification, GEFF was also used for identification of cognitive states, i.e. to identify the task associated to a given FC, regardless of the subject being already in the Learning dataset or not (subject-independent task-identification). In addition, we also show that eigenvectors from the Learning Stage can be characterized as task-dominant, subject dominant or neither, providing a deeper insight into the extent of variance in functional connectivity across individuals and cognitive states.

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