ABSTRACT 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 the 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 AUD (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 demonstrates that tangent-FCs can characterize task-induced functional reconfiguration and that it is related to AUD risk. AUTHOR SUMMARY Human brain function constantly adapts to the external environment stimuli and transitions between cognitive states, which can be hindered by alcohol misuse and family history of alcohol use disorder (AUD). In this work, we used a novel methodology that applies Riemannian geometry concepts to functional connectivity to quantify functional reconfiguration of rest-to-task (engaging) and task-to-rest (disengaging) transitions. We ultimately aimed to determine the relationship between AUD risk factors and functional reconfiguration. Our findings showed that engaging functional reconfiguration was diminished in participants with a family history of AUD, whereas disengaging functional reconfiguration was diminished with greater recent drinking behavior. This study suggests that analysis of functional reconfiguration using Riemannian geometry is a promising avenue to better understand rest-to-task and task-to-rest brain transitions.

Author Summary Understanding and measuring the ways in which human brain connectivity changes to accommodate a broad range of cognitive and behavioral goals is an important undertaking. We put forth a mesoscopic framework that captures such changes by tracking the topology and integration of information within and between functional networks (FNs) of the brain. Canonically, when FNs are characterized, they are separated from the rest of the brain network. The two metrics proposed in this work, trapping efficiency and exit entropy, quantify the topological and information integration characteristics of FNs while they are still embedded in the overall brain network. Trapping efficiency measures the module’s ability to preserve an incoming signal from escaping its local topology, relative to its total exiting weights. Exit entropy measures the module’s communication preferences with other modules/networks using information theory. When these two metrics are plotted in a 2D graph as a function of different brain states (i.e., cognitive/behavioral tasks), the resulting morphospace characterizes the extent of network reconfiguration between tasks (functional reconfiguration), and the change when moving from rest to an externally engaged “task-positive” state (functional preconfiguration), to collectively define network configural breadth. We also show that these metrics are sensitive to subject, task, and functional network identities. Overall, this method is a promising approach to quantify how human brains adapt to a range of tasks, and potentially to help improve precision clinical neuroscience. Abstract The quantification of human brain functional (re)configurations across varying cognitive demands remains an unresolved topic. We propose that such functional configurations may be categorized into three different types: (a) network configural breadth, (b) task-to task transitional reconfiguration, and (c) within-task reconfiguration. Such functional reconfigurations are rather subtle at the whole-brain level. Hence, we propose a mesoscopic framework focused on functional networks (FNs) or communities to quantify functional (re)configurations. 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. 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.