A mechanistic model of connector hubs, modularity, and cognition

The human brain network is modular--comprised of communities of tightly interconnected nodes. This network contains local hubs, which have many connections within their own communities, and connector hubs, which have connections diversely distributed across communities. A mechanistic understanding of these hubs and how they support cognition has not been demonstrated. Here, we leveraged individual differences in hub connectivity and cognition. We show that a model of hub connectivity accurately predicts the cognitive performance of 476 individuals in four distinct tasks. Moreover, there is a general optimal network structure for cognitive performance--individuals with diversely connected hubs and consequent modular brain networks exhibit increased cognitive performance, regardless of the task. Critically, we find evidence consistent with a mechanistic model in which connector hubs tune the connectivity of their neighbors to be more modular while allowing for task appropriate information integration across communities, which increases global modularity and cognitive performance

Non-equilibrium dynamics and entropy production in the human brain

Living systems operate out of thermodynamic equilibrium at small scales, consuming energy and producing entropy in the environment in order to perform molecular and cellular functions. However, it remains unclear whether non-equilibrium dynamics manifest at macroscopic scales, and if so, how such dynamics support higher-order biological functions. Here we present a framework to probe for non-equilibrium dynamics by quantifying entropy production in macroscopic systems. We apply our method to the human brain, an organ whose immense metabolic consumption drives a diverse range of cognitive functions. Using whole-brain imaging data, we demonstrate that the brain fundamentally operates out of equilibrium at large scales. Moreover, we find that the brain produces more entropy -- operating further from equilibrium -- when performing physically and cognitively demanding tasks. By simulating an Ising model, we show that macroscopic non-equilibrium dynamics can arise from asymmetries in the interactions at the microscale. Together, these results suggest that non-equilibrium dynamics are vital for cognition, and provide a general tool for quantifying the non-equilibrium nature of macroscopic systems.Comment: 18 pages, 14 figure

Multiscale and multimodal network dynamics underpinning working memory

Working memory (WM) allows information to be stored and manipulated over short time scales. Performance on WM tasks is thought to be supported by the frontoparietal system (FPS), the default mode system (DMS), and interactions between them. Yet little is known about how these systems and their interactions relate to individual differences in WM performance. We address this gap in knowledge using functional MRI data acquired during the performance of a 2-back WM task, as well as diffusion tensor imaging data collected in the same individuals. We show that the strength of functional interactions between the FPS and DMS during task engagement is inversely correlated with WM performance, and that this strength is modulated by the activation of FPS regions but not DMS regions. Next, we use a clustering algorithm to identify two distinct subnetworks of the FPS, and find that these subnetworks display distinguishable patterns of gene expression. Activity in one subnetwork is positively associated with the strength of FPS-DMS functional interactions, while activity in the second subnetwork is negatively associated. Further, the pattern of structural linkages of these subnetworks explains their differential capacity to influence the strength of FPS-DMS functional interactions. To determine whether these observations could provide a mechanistic account of large-scale neural underpinnings of WM, we build a computational model of the system composed of coupled oscillators. Modulating the amplitude of the subnetworks in the model causes the expected change in the strength of FPS-DMS functional interactions, thereby offering support for a mechanism in which subnetwork activity tunes functional interactions. Broadly, our study presents a holistic account of how regional activity, functional interactions, and structural linkages together support individual differences in WM in humans

The community structure of functional brain networks exhibits scale-specific patterns of inter- and intra-subject variability

The network organization of the human brain varies across individuals, changes with development and aging, and differs in disease. Discovering the major dimensions along which this variability is displayed remains a central goal of both neuroscience and clinical medicine. Such efforts can be usefully framed within the context of the brain\u27s modular network organization, which can be assessed quantitatively using computational techniques and extended for the purposes of multi-scale analysis, dimensionality reduction, and biomarker generation. Although the concept of modularity and its utility in describing brain network organization is clear, principled methods for comparing multi-scale communities across individuals and time are surprisingly lacking. Here, we present a method that uses multi-layer networks to simultaneously discover the modular structure of many subjects at once. This method builds upon the well-known multi-layer modularity maximization technique, and provides a viable and principled tool for studying differences in network communities across individuals and within individuals across time. We test this method on two datasets and identify consistent patterns of inter-subject community variability, demonstrating that this variability - which would be undetectable using past approaches - is associated with measures of cognitive performance. In general, the multi-layer, multi-subject framework proposed here represents an advance over current approaches by straighforwardly mapping community assignments across subjects and holds promise for future investigations of inter-subject community variation in clinical populations or as a result of task constraints