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The emergence of distributed patterns of neural activity supporting brain functions and behavior can be understood by study of the brain's low-dimensional topology. Functional neuroimaging demonstrates that brain activity linked to adaptive behavior is constrained to low-dimensional manifolds. In human participants, we tested whether these low-dimensional constraints preserve working memory performance following local neuronal perturbations. We combined multi-session functional magnetic resonance imaging, non-invasive transcranial magnetic stimulation (TMS), and methods translated from the fields of complex systems and computational biology to assess the functional link between changes in local neural activity and the reshaping of task-related low dimensional trajectories of brain activity. We show that specific reconfigurations of low-dimensional trajectories of brain activity sustain effective working memory performance following TMS manipulation of local activity on, but not off, the space traversed by these trajectories. We highlight an association between the multi-scale changes in brain activity underpinning cognitive function., (© 2022. The Author(s).)

The ability to solve cognitive tasks depends upon adaptive changes in the organization of whole-brain functional networks. However, the link between task-induced network reconfigurations and their underlying energy demands is poorly understood. We address this by multimodal network analyses integrating functional and molecular neuroimaging acquired concurrently during a complex cognitive task. Task engagement elicited a marked increase in the association between glucose consumption and functional brain network reorganization. This convergence between metabolic and neural processes was specific to feedforward connections linking the visual and dorsal attention networks, in accordance with task requirements of visuo-spatial reasoning. Further increases in cognitive load above initial task engagement did not affect the relationship between metabolism and network reorganization but only modulated existing interactions. Our findings show how the upregulation of key computational mechanisms to support cognitive performance unveils the complex, interdependent changes in neural metabolism and neuro-vascular responses., Competing Interests: AH, MB, LR, GG, VP, PM, TV, LC No competing interests declared, WW WW declares to having received speaker honoraria from the GE Healthcare and research grants from Ipsen Pharma, Eckert-Ziegler AG, Scintomics, and ITG; and working as a part time employee of CBmed Ltd. (Center for Biomarker Research in Medicine, Graz, Austria). MH MH received consulting fees and/or honoraria from Bayer Healthcare BMS, Eli Lilly, EZAG, GE Healthcare, Ipsen, ITM, Janssen, Roche, and Siemens Healthineers. SK SK received grants/research support, consulting fees and/or honoraria within the last three years from Angelini, AOP Orphan Pharmaceuticals AG, Celgene GmbH, Eli Lilly, Janssen-Cilag Pharma GmbH, KRKA-Pharma, Lundbeck A/S, Mundipharma, Neuraxpharm, Pfizer, Sage, Sanofi, Schwabe, Servier, Shire, Sumitomo Dainippon Pharma Co. Ltd., Sun Pharmaceutical Industries Ltd. and Takeda. RL RL received conference speaker honorarium within the last three years from Shire and support from Siemens Healthcare regarding clinical research using PET/MR. He is shareholder of BM Health GmbH since 2019., (© 2020, Hahn et al.)

Cognitive activity emerges from large-scale neuronal dynamics that are constrained to a low-dimensional manifold. How this low-dimensional manifold scales with cognitive complexity, and which brain regions regulate this process, are not well understood. We addressed this issue by analyzing sub-second high-field fMRI data acquired during performance of a task that systematically varied the complexity of cognitive reasoning. We show that task performance reconfigures the low-dimensional manifold and that deviations from these patterns relate to performance errors. We further demonstrate that individual differences in thalamic activity relate to reconfigurations of the low-dimensional architecture during task engagement., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Cognitive reasoning is thought to require functional interactions between whole-brain networks. Such networks rely on both cerebral hemispheres, with the corpus callosum providing cross-hemispheric communication. Here we used high-field functional magnetic resonance imaging (7 T fMRI), a well validated cognitive task, and brain network analyses to investigate the functional networks underlying cognitive reasoning in individuals with corpus callosum dysgenesis (CCD), an anatomical abnormality that affects the corpus callosum. Participants with CCD were asked to solve cognitive reasoning problems while their brain activity was measured using fMRI. The complexity of these problems was parametrically varied by changing the complexity of relations that needed to be established between shapes within each problem matrix. Behaviorally, participants showed a typical reduction in task performance as problem complexity increased. Task-evoked neural activity was observed in brain regions known to constitute two key cognitive control systems: the fronto-parietal and cingulo-opercular networks. Under low complexity demands, network topology and the patterns of local neural activity in the CCD group closely resembled those observed in neurotypical controls. By contrast, when asked to solve more complex problems, participants with CCD showed a reduction in neural activity and connectivity within the fronto-parietal network. These complexity-induced, as opposed to resting-state, differences in functional network activity help resolve the apparent paradox between preserved network architecture found at rest in CCD individuals, and the heterogeneous deficits they display in response to cognitive task demands [preprint: https://doi.org/10.1101/312629]., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Cognitive function requires the coordination of neural activity across many scales, from neurons and circuits to large-scale networks. As such, it is unlikely that an explanatory framework focused upon any single scale will yield a comprehensive theory of brain activity and cognitive function. Modelling and analysis methods for neuroscience should aim to accommodate multiscale phenomena. Emerging research now suggests that multi-scale processes in the brain arise from so-called critical phenomena that occur very broadly in the natural world. Criticality arises in complex systems perched between order and disorder, and is marked by fluctuations that do not have any privileged spatial or temporal scale. We review the core nature of criticality, the evidence supporting its role in neural systems and its explanatory potential in brain health and disease., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Our capacity for higher cognitive reasoning has a measurable limit. This limit is thought to arise from the brain's capacity to flexibly reconfigure interactions between spatially distributed networks. Recent work, however, has suggested that reconfigurations of task-related networks are modest when compared with intrinsic "resting-state" network architecture. Here we combined resting-state and task-driven functional magnetic resonance imaging to examine how flexible, task-specific reconfigurations associated with increasing reasoning demands are integrated within a stable intrinsic brain topology. Human participants (21 males and 28 females) underwent an initial resting-state scan, followed by a cognitive reasoning task involving different levels of complexity, followed by a second resting-state scan. The reasoning task required participants to deduce the identity of a missing element in a 4 × 4 matrix, and item difficulty was scaled parametrically as determined by relational complexity theory. Analyses revealed that external task engagement was characterized by a significant change in functional brain modules. Specifically, resting-state and null-task demand conditions were associated with more segregated brain-network topology, whereas increases in reasoning complexity resulted in merging of resting-state modules. Further increments in task complexity did not change the established modular architecture, but affected selective patterns of connectivity between frontoparietal, subcortical, cingulo-opercular, and default-mode networks. Larger increases in network efficiency within the newly established task modules were associated with higher reasoning accuracy. Our results shed light on the network architectures that underlie external task engagement, and highlight selective changes in brain connectivity supporting increases in task complexity. SIGNIFICANCE STATEMENT Humans have clear limits in their ability to solve complex reasoning problems. It is thought that such limitations arise from flexible, moment-to-moment reconfigurations of functional brain networks. It is less clear how such task-driven adaptive changes in connectivity relate to stable, intrinsic networks of the brain and behavioral performance. We found that increased reasoning demands rely on selective patterns of connectivity within cortical networks that emerged in addition to a more general, task-induced modular architecture. This task-driven architecture reverted to a more segregated resting-state architecture both immediately before and after the task. These findings reveal how flexibility in human brain networks is integral to achieving successful reasoning performance across different levels of cognitive demand., (Copyright © 2017 the authors 0270-6474/17/378399-13$15.00/0.)

The human brain is characterized by a remarkable ability to adapt its information processing based on current goals. This ability, which is encompassed by the psychological construct of cognitive control, involves activity throughout large-scale, specialized brain systems that support segregated functions at rest and during active task performance. Based on recent research, we propose an account in which control functions rely on transitory changes in patterns of cooperation and competition between neural systems. This account challenges current conceptualizations of control as relying on segregated or antagonistic activity of specialized brain systems. Accordingly, we argue that the study of transitory task-based interactions between brain systems is critical to understanding the flexibility of normal cognitive control and its disruption in pathological conditions., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: Neuroimaging studies have consistently implicated alterations of the basal ganglia and orbitofrontal cortex in the pathophysiology of OCD, however, recent work also emphasizes more diffuse patterns of brain alteration as occurring in this disorder. The goal of this study was to extend such observations by investigating large-scale brain functional network correlates of cognitive-control performance in OCD patients., Experimental Design: We combined fMRI with a validated task of cognitive control and a multivariate statistical method to assess multiple functional networks encompassing broad task-relevant cortical regions in OCD patients and matched controls. Functional networks of interest were targeted a priori and the groups were compared in terms of the spatiotemporal profile of network responses (functional connectivity) during the task performance in a data-driven manner., Principal Observations: Task performance was equivalent in both groups and each distinct network demonstrated strong overlap in its general response during task. However, significant differences in functional connectivity were also observed between groups that appeared driven by specific phases of task performance. Such differences were most pronounced during rest-task transitions and mainly involved dorsal anterior cingulate and insular cortices within the paralimbic network. Relative heightened functional connectivity of insula in patients during task correlated with a measure of patients' state anxiety., Conclusions: Our findings provide a novel functional imaging characterization of brain network alterations associated with cognitive-control in OCD. Additionally, these findings raise questions about the role of patients' arousal states on the performance of cognitive imaging tasks that are otherwise assumed to be emotionally neutral., (Copyright © 2011 Wiley-Liss, Inc.)