Comparing directed functional connectivity between groups with confirmatory subgrouping GIMME.

Connectivity modeling in functional neuroimaging has become widely used method of analysis for understanding functional architecture. One method for deriving directed connectivity models is Group Iterative Multiple Model Estimation (GIMME; Gates and Molenaar, 2012). GIMME looks for commonalities across the sample to detect signal from noise and arrive at edges that exist across the majority in the group ("group-level edges") and individual-level edges. In this way, GIMME obtains generalizable results via the group-level edges while also allowing for between subject heterogeneity in connectivity, moving the field closer to obtaining reliable personalized connectivity maps. In this article, we present a novel extension of GIMME, confirmatory subgrouping GIMME, which estimates subgroup-level edges for a priori known groups (e.g. typically developing controls vs. clinical group). Detecting edges that consistently exist for individuals within predefined subgroups aids in interpretation of the heterogeneity in connectivity maps and allows for subgroup-specific inferences. We describe this algorithm, as well as several methods to examine the results. We present an empirical example that finds similarities and differences in resting state functional connectivity among four groups of children: typically developing controls (TDC), children with autism spectrum disorder (ASD), children with Inattentive (ADHD-I) and Combined (ADHD-C) Type ADHD. Findings from this study suggest common involvement of the left Broca's area in all the clinical groups, as well as several unique patterns of functional connectivity specific to a given disorder. Overall, the current approach and proof of principle findings highlight a novel and reliable tool for capturing heterogeneity in complex mental health disorders.

Path and Directionality Discovery in Individual Dynamic Models: A Regularized Unified Structural Equation Modeling Approach for Hybrid Vector Autoregression.

There recently has been growing interest in the study of psychological and neurological processes at an individual level. One goal in such endeavors is to construct person-specific dynamic assessments using time series techniques such as Vector Autoregressive (VAR) models. However, two problems exist with current VAR specifications: (1) VAR models are restricted in that contemporaneous relations are typically modeled either as undirected relations among residuals or directed relations among observed variables, but not both; (2) current estimation frameworks are limited by the reliance on stepwise model building procedures. This study adopts a new modeling approach. We first extended the current unified SEM (uSEM) framework, a widely used structural VAR model, to a hybrid representation (i.e., "huSEM") to include both undirected and directed contemporaneous effects, and then replaced the stepwise modeling with a LASSO-type regularization for a global search of the optimal sparse model. Our simulation study showed that regularized huSEM performed uniformly the best over alternative VAR representations and/or modeling approaches, with respect to accurately recovering the presence and directionality of hybrid relations and reliably removing false relations when the data are generated to have two types of contemporaneous relations. The present study to our knowledge is the first application of the recently developed regularized SEM technique to the estimation of huSEM, which points to a promising future for statistical learning in psychometric models.

Age and Gender Effects on Intrinsic Connectivity in Autism Using Functional Integration and Segregation.

BACKGROUND: The objective of this study was to examine intrinsic whole-brain functional connectivity in autism spectrum disorder (ASD) using the framework of functional segregation and integration. Emphasis was given to potential gender and developmental effects as well as identification of specific networks that may contribute to the global results. METHODS: We leveraged an open data resource (N = 1587) of resting-state functional magnetic resonance imaging data in the Autism Brain Imaging Data Exchange (ABIDE) initiative, combining data from more than 2100 unique cross-sectional datasets in ABIDE I and ABIDE II collected at different sites. Modularity and global efficiency were utilized to assess functional segregation and integration, respectively. A meta-analytic approach for handling site differences was used. The effects of age, gender, and diagnostic category on segregation and integration were assessed using linear regression. RESULTS: Modularity decreased nonlinearly in the ASD group with age, as evidenced by an increase and then decrease over development. Global efficiency had an opposite relationship with age by first decreasing and then increasing in the ASD group. Both modularity and global efficiency remained largely stable in the typically developing control group during development, representing a significantly different effect than seen in the ASD group. Age effects on modularity were localized to the somatosensory network. Finally, a marginally significant interaction between age, gender, and diagnostic category was found for modularity. CONCLUSIONS: Our results support prior work that suggested a quadratic effect of age on brain development in ASD, while providing new insights about the specific characteristics of developmental and gender effects on intrinsic connectivity in ASD.