A characteristic feature of human cognition is our ability to ‘multi-task’—performing two or more tasks in parallel—particularly when one task is well learned. How the brain supports this capacity remains poorly understood. Most past studies have focussed on identifying the areas of the brain—typically the dorsolateral prefrontal cortex—that are required to navigate information-processing bottlenecks. In contrast, we take a systems neuroscience approach to test the hypothesis that the capacity to conduct effective parallel processing relies on a distributed architecture that interconnects the cerebral cortex with the cerebellum. The latter structure contains over half of the neurons in the adult human brain and is well suited to support the fast, effective, dynamic sequences required to perform tasks relatively automatically. By delegating stereotyped within-task computations to the cerebellum, the cerebral cortex can be freed up to focus on the more challenging aspects of performing the tasks in parallel. To test this hypothesis, we analysed task-based fMRI data from 50 participants who performed a task in which they either balanced an avatar on a screen (balance), performed serial-7 subtractions (calculation) or performed both in parallel (dual task). Using a set of approaches that include dimensionality reduction, structure-function coupling, and time-varying functional connectivity, we provide robust evidence in support of our hypothesis. We conclude that distributed interactions between the cerebral cortex and cerebellum are crucially involved in parallel processing in the human brain. Author Summary How does the brain support the performance of multiple complex tasks, in parallel? The distributed architecture of the cerebellum is ideally placed to interact with the cerebral cortex, creating complex channels for segregated information processing that afford the execution of parallel tasks. Here, we apply time-resolved functional connectivity analyses to functional MRI data collected while individuals performed a dual task that required either balancing, calculating, or the two in tandem. We found robust evidence for distinct patterns of cortico-cerebellar connectivity as a function of task performance.

Author Summary The study of dynamical systems offers a powerful framework for interpreting neuroimaging data from a range of different contexts, however, as a field, we have yet to fully embrace the power of this approach. Here, we offer a brief overview of some key terms from the dynamical systems literature, and then highlight three ways in which neuroimaging studies can begin to embrace the dynamical systems approach: by shifting from local to global descriptions of activity, by moving from static to dynamic analyses, and by transitioning from descriptive to generative models of neural activity patterns. Abstract Most human neuroscience research to date has focused on statistical approaches that describe stationary patterns of localized neural activity or blood flow. While these patterns are often interpreted in light of dynamic, information-processing concepts, the static, local, and inferential nature of the statistical approach makes it challenging to directly link neuroimaging results to plausible underlying neural mechanisms. Here, we argue that dynamical systems theory provides the crucial mechanistic framework for characterizing both the brain’s time-varying quality and its partial stability in the face of perturbations, and hence, that this perspective can have a profound impact on the interpretation of human neuroimaging results and their relationship with behavior. After briefly reviewing some key terminology, we identify three key ways in which neuroimaging analyses can embrace a dynamical systems perspective: by shifting from a local to a more global perspective, by focusing on dynamics instead of static snapshots of neural activity, and by embracing modeling approaches that map neural dynamics using “forward” models. Through this approach, we envisage ample opportunities for neuroimaging researchers to enrich their understanding of the dynamic neural mechanisms that support a wide array of brain functions, both in health and in the setting of psychopathology.

Previous research has shown that the autonomic nervous system provides essential constraints over ongoing cognitive function. However, there is currently a relative lack of direct empirical evidence for how this interaction manifests in the brain at the macroscale level. Here, we examine the role of ascending arousal and attentional load on large-scale network dynamics by combining pupillometry, functional MRI, and graph theoretical analysis to analyze data from a visual motion-tracking task with a parametric load manipulation. We found that attentional load effects were observable in measures of pupil diameter and in a set of brain regions that parametrically modulated their BOLD activity and mesoscale network-level integration. In addition, the regional patterns of network reconfiguration were correlated with the spatial distribution of the α2a adrenergic receptor. Our results further solidify the relationship between ascending noradrenergic activity, large-scale network integration, and cognitive task performance. Author Summary In our daily lives, it is usual to encounter highly demanding cognitive tasks. They have been traditionally regarded as challenges that are solved mainly through cerebral activity, specifically via information-processing steps carried by neurons in the cerebral cortex. Activity in cortical networks thus constitutes a key factor for improving our understanding of cognitive processes. However, recent evidence has shown that evolutionary older players in the central nervous system, such as brain stem’s ascending modulatory systems, might play an equally important role in diverse cognitive mechanisms. Our article examines the role of the ascending arousal system on large-scale network dynamics by combining pupillometry, functional MRI, and graph theoretical analysis.

Both natural and engineered networks are often modular. Whether a network node interacts with only nodes from its own module or nodes from multiple modules provides insight into its functional role. The participation coefficient ( PC ) is typically used to measure this attribute, although its value also depends on the size and connectedness of the module it belongs to and may lead to nonintuitive identification of highly connected nodes. Here, we develop a normalized PC that reduces the influence of intramodular connectivity compared with the conventional PC . Using brain, C. elegans , airport, and simulated networks, we show that our measure of participation is not influenced by the size or connectedness of modules, while preserving conceptual and mathematical properties, of the classic formulation of PC . Unlike the conventional PC , we identify London and New York as high participators in the air traffic network and demonstrate stronger associations with working memory in human brain networks, yielding new insights into nodal participation across network modules. Author Summary It is challenging to reliably quantify how single elements (i.e., nodes) in a network are connected to different subcomponents (i.e., modules) of a network; this is important as intermodular connectivity contribute to efficient and distributed information processing. Participation coefficient ( PC ) calculates how distributed nodes are across modules. But PC is influenced by modularity algorithms that tend to favor large modules with strong intramodule connectivity, that in turn generate low PC values, even if a node has strong intermodule connectivity. We use a network randomization approach and show that by reducing the influence of intramodular connectivity, we obtain node participation results unaffected by size and connectedness of modules. This provides network scientists with new insights into the intermodular connectivity configurations of complex networks.

The brain is a complex, multiscale dynamical system composed of many interacting regions. Knowledge of the spatiotemporal organization of these interactions is critical for establishing a solid understanding of the brain’s functional architecture and the relationship between neural dynamics and cognition in health and disease. The possibility of studying these dynamics through careful analysis of neuroimaging data has catalyzed substantial interest in methods that estimate time-resolved fluctuations in functional connectivity (often referred to as “dynamic” or time-varying functional connectivity; TVFC). At the same time, debates have emerged regarding the application of TVFC analyses to resting fMRI data, and about the statistical validity, physiological origins, and cognitive and behavioral relevance of resting TVFC. These and other unresolved issues complicate interpretation of resting TVFC findings and limit the insights that can be gained from this promising new research area. This article brings together scientists with a variety of perspectives on resting TVFC to review the current literature in light of these issues. We introduce core concepts, define key terms, summarize controversies and open questions, and present a forward-looking perspective on how resting TVFC analyses can be rigorously and productively applied to investigate a wide range of questions in cognitive and systems neuroscience.

Inefficient integration between bottom-up visual input and higher order visual processing regions is implicated in visual hallucinations in Parkinson’s disease (PD). Here, we investigated white matter contributions to this perceptual imbalance hypothesis. Twenty-nine PD patients were assessed for hallucinatory behavior. Hallucination severity was correlated to connectivity strength of the network using the network-based statistic approach. The results showed that hallucination severity was associated with reduced connectivity within a subnetwork that included the majority of the diverse club. This network showed overall greater between-module scores compared with nodes not associated with hallucination severity. Reduced between-module connectivity in the lateral occipital cortex, insula, and pars orbitalis and decreased within-module connectivity in the prefrontal, somatosensory, and primary visual cortices were associated with hallucination severity. Conversely, hallucination severity was associated with increased between- and within-module connectivity in the orbitofrontal and temporal cortex, as well as regions comprising the dorsal attentional and default mode network. These results suggest that hallucination severity is associated with marked alterations in structural network topology with changes in participation along the perceptual hierarchy. This may result in the inefficient transfer of information that gives rise to hallucinations in PD. Author Summary Inefficient integration of information between external stimuli and internal perceptual predictions may lead to misperceptions or visual hallucinations in Parkinson’s disease (PD). In this study, we show that hallucinatory behavior in PD patients is associated with marked alterations in structural network topology. Severity of hallucinatory behavior was associated with decreased connectivity in a large subnetwork that included the majority of the diverse club, nodes with a high number of between-module connections. Furthermore, changes in between-module connectivity were found across brain regions involved in visual processing, top-down prediction centers, and endogenous attention, including the occipital, orbitofrontal, and posterior cingulate cortex. Together, these findings suggest that impaired integration across different sides across different perceptual processing regions may result in inefficient transfer of information.

The human brain is able to flexibly adapt its information processing capacity to meet a variety of cognitive challenges. Recent evidence suggests that this flexibility is reflected in the dynamic reorganization of the functional connectome. The ascending catecholaminergic arousal systems of the brain are a plausible candidate mechanism for driving alterations in network architecture, enabling efficient deployment of cognitive resources when the environment demands them. We tested this hypothesis by analyzing both resting-state and task-based fMRI data following the administration of atomoxetine, a noradrenaline reuptake inhibitor, compared with placebo, in two separate human fMRI studies. Our results demonstrate that the manipulation of central catecholamine levels leads to a reorganization of the functional connectome in a manner that is sensitive to ongoing cognitive demands. Author Summary There is emerging evidence that the flexible network structure of the brain is related to activity within the ascending arousal systems of the brain, such as the noradrenergic locus coeruleus. Here, we explored the role of catecholaminergic activity on network architecture by analyzing the graph structure of the brain measured using functional MRI following the administration of atomoxetine, a selective noradrenaline reuptake inhibitor. We estimated functional network topology in two double-blind, placebo-controlled datasets: one from the resting state and another from a parametric N-back task. Our results demonstrate that the nature of catecholaminergic network reconfiguration is differentially related to cognitive state and provide confirmatory evidence for the hypothesis that the functional network signature of the brain is sensitive to the ascending catecholaminergic arousal system.