Cognitive and behavioural flexibility: neural mechanisms and clinical considerations.

Cognitive and behavioural flexibility permit the appropriate adjustment of thoughts and behaviours in response to changing environmental demands. Brain mechanisms enabling flexibility have been examined using non-invasive neuroimaging and behavioural approaches in humans alongside pharmacological and lesion studies in animals. This work has identified large-scale functional brain networks encompassing lateral and orbital frontoparietal, midcingulo-insular and frontostriatal regions that support flexibility across the lifespan. Flexibility can be compromised in early-life neurodevelopmental disorders, clinical conditions that emerge during adolescence and late-life dementias. We critically evaluate evidence for the enhancement of flexibility through cognitive training, physical activity and bilingual experience.

Neural and psychological correlates of post-traumatic stress symptoms in a community adult sample.

A multitude of factors are associated with the symptoms of post-traumatic stress disorder. However, establishing which predictors are most strongly associated with post-traumatic stress disorder symptoms is complicated because few studies are able to consider multiple factors simultaneously across the biopsychosocial domains that are implicated by existing theoretical models. Further, post-traumatic stress disorder is heterogeneous, and studies using case-control designs may obscure which factors relate uniquely to symptom dimensions. Here we used Bayesian variable selection to identify the most important predictors for overall post-traumatic stress disorder symptoms and individual symptom dimensions in a community sample of 569 adults (18 to 85 yr of age). Candidate predictors were selected from previously established risk factors relevant for post-traumatic stress disorder and included psychological measures, behavioral measures, and resting state functional connectivity among brain regions. In a follow-up analysis, we compared results controlling for current depression symptoms in order to examine specificity. Poor sleep quality and dimensions of temperament and impulsivity were consistently associated with greater post-traumatic stress disorder symptom severity. In addition to self-report measures, brain functional connectivity among regions commonly ascribed to the default mode network, central executive network, and salience network explained the unique variability of post-traumatic stress disorder symptoms. This study demonstrates the unique contributions of psychological measures and neural substrates to post-traumatic stress disorder symptoms.

Educating the future generation of researchers: A cross-disciplinary survey of trends in analysis methods.

Methods for data analysis in the biomedical, life, and social (BLS) sciences are developing at a rapid pace. At the same time, there is increasing concern that education in quantitative methods is failing to adequately prepare students for contemporary research. These trends have led to calls for educational reform to undergraduate and graduate quantitative research method curricula. We argue that such reform should be based on data-driven insights into within- and cross-disciplinary use of analytic methods. Our survey of peer-reviewed literature analyzed approximately 1.3 million openly available research articles to monitor the cross-disciplinary mentions of analytic methods in the past decade. We applied data-driven text mining analyses to the "Methods" and "Results" sections of a large subset of this corpus to identify trends in analytic method mentions shared across disciplines, as well as those unique to each discipline. We found that the t test, analysis of variance (ANOVA), linear regression, chi-squared test, and other classical statistical methods have been and remain the most mentioned analytic methods in biomedical, life science, and social science research articles. However, mentions of these methods have declined as a percentage of the published literature between 2009 and 2020. On the other hand, multivariate statistical and machine learning approaches, such as artificial neural networks (ANNs), have seen a significant increase in the total share of scientific publications. We also found unique groupings of analytic methods associated with each BLS science discipline, such as the use of structural equation modeling (SEM) in psychology, survival models in oncology, and manifold learning in ecology. We discuss the implications of these findings for education in statistics and research methods, as well as within- and cross-disciplinary collaboration.

Structural-functional connectivity mapping of the insular cortex: a combined data-driven and meta-analytic topic mapping.

In this study, we examined structural and functional profiles of the insular cortex and mapped associations with well-described functional networks throughout the brain using diffusion tensor imaging (DTI) and resting-state functional connectivity (RSFC) data. We used a data-driven method to independently estimate the structural-functional connectivity of the insular cortex. Data were obtained from the Human Connectome Project comprising 108 adult participants. Overall, we observed moderate to high associations between the structural and functional mapping scores of 3 different insular subregions: the posterior insula (associated with the sensorimotor network: RSFC, DTI = 50% and 72%, respectively), dorsal anterior insula (associated with ventral attention: RSFC, DTI = 83% and 83%, respectively), and ventral anterior insula (associated with the frontoparietal: RSFC, DTI = 42% and 89%, respectively). Further analyses utilized meta-analytic decoding maps to demonstrate specific cognitive and affective as well as gene expression profiles of the 3 subregions reflecting the core properties of the insular cortex. In summary, given the central role of the insular in the human brain, our results revealing correspondence between DTI and RSFC mappings provide a complementary approach and insight for clinical researchers to identify dysfunctional brain organization in various neurological disorders associated with insular pathology.

Default mode network scaffolds immature frontoparietal network in cognitive development.

The default mode network (DMN) is a workspace for convergence of internal and external information. The frontal parietal network (FPN) is indispensable to executive functioning. Yet, how they interplay to support cognitive development remains elusive. Using longitudinal developmental fMRI with an n-back paradigm, we show a heterogeneity of maturational changes in multivoxel activity and network connectivity among DMN and FPN nodes in 528 children and 103 young adults. Compared with adults, children exhibited prominent longitudinal improvement but still inferior behavioral performance, which paired with less pronounced DMN deactivation and weaker FPN activation in children, but stronger DMN coupling with FPN regions. Children's DMN reached an adult-like level earlier than FPN at both multivoxel activity pattern and intranetwork connectivity levels. Intrinsic DMN-FPN internetwork coupling in children mediated the relationship between age and working memory-related functional coupling of these networks, with posterior cingulate cortex (PCC)-dorsolateral prefrontal cortex (DLPFC) coupling emerging as most prominent pathway. Coupling of PCC-DLPFC may further work together with task-invoked activity in PCC to account for longitudinal improvement in behavioral performance in children. Our findings suggest that the DMN provides a scaffolding effect in support of an immature FPN that is critical for the development of executive functions in children.

A Brain Network by Any Other Name.

Network neuroscientists generally agree with Pessoa's contention that human brain function is context-dependent and interactionally complex, and that we should embrace brain networks as the functional units of interest. The more contentious issue for the field is how to define brain networks in ways that will facilitate further discovery. A group including members from the Organization for Human Brain Mapping is working toward cataloging best practices and providing concrete reporting guidelines for the scientific community.

A spatio-temporal decomposition framework for dynamic functional connectivity in the human brain.

Much recent attention has been directed toward investigating the spatial and temporal organization of brain dynamics, but the rules which constrain the variation of spatio-temporal organization in functional connectivity under different brain states remain unclear. Here, we developed a novel computational approach based on tensor decomposition and regularization to represent dynamic functional connectivity as a linear combination of dynamic modules and time-varying weights. In this approach, dynamic modules represent co-activating functional connectivity patterns, and time-varying weights represent the temporal expression of dynamic modules. We applied this dynamic decomposition model (DDM) on a resting-state fMRI dataset and found that whole-brain dynamic functional connectivity can be decomposed as a linear combination of eight dynamic modules which we summarize as 'high order modules' and 'primary-high order modules', according to their spatial attributes and correspondence with existing intrinsic functional brain networks. By clustering the time-varying weights, we identified five brain states including three major states and two minor states. We found that state transitions mainly occurred between the three major states, and that temporal variation of dynamic modules may contribute to brain state transitions. We then conceptualized the variability of weights as the flexibility of the corresponding dynamic modules and found that different dynamic modules exhibit different amounts of flexibility and contribute to different cognitive measures. Finally, we applied DDM to a schizophrenia resting-state fMRI dataset and found that atypical flexibility of dynamic modules correlates with impaired cognitive flexibility in schizophrenia. Overall, this work provides a quantitative framework that characterizes temporal variation in the topology of dynamic functional connectivity.

Reconfiguration of Directed Functional Connectivity Among Neurocognitive Networks with Aging: Considering the Role of Thalamo-Cortical Interactions.

A complete picture of how subcortical nodes, such as the thalamus, exert directional influence on large-scale brain network interactions across age remains elusive. Using directed functional connectivity and weighted net causal outflow on resting-state fMRI data, we provide evidence of a comprehensive reorganization within and between neurocognitive networks (default mode: DMN, salience: SN, and central executive: CEN) associated with age and thalamocortical interactions. We hypothesize that thalamus subserves both modality-specific and integrative hub role in organizing causal weighted outflow among large-scale neurocognitive networks. To this end, we observe that within-network directed functional connectivity is driven by thalamus and progressively weakens with age. Secondly, we find that age-associated increase in between CEN- and DMN-directed functional connectivity is driven by both the SN and the thalamus. Furthermore, left and right thalami act as a causal integrative hub exhibiting substantial interactions with neurocognitive networks with aging and play a crucial role in reconfiguring network outflow. Notably, these results were largely replicated on an independent dataset of matched young and old individuals. Our findings strengthen the hypothesis that the thalamus is a key causal hub balancing both within- and between-network connectivity associated with age and maintenance of cognitive functioning with aging.

Whole-Brain Functional Dynamics Track Depressive Symptom Severity.

Depressive symptoms are reported by 20% of the population and are related to altered functional integrity of large-scale brain networks. The link between moment-to-moment brain function and depressive symptomatology, and the implications of these relationships for clinical and community populations alike, remain understudied. The present study examined relationships between functional brain dynamics and subclinical-to-mild depressive symptomatology in a large community sample of adults with and without psychiatric diagnoses. This study used data made available through the Enhanced Nathan Kline Institute-Rockland Sample; 445 participants between 18 and 65 years of age completed a 10-min resting-state functional MRI scan. Coactivation pattern analysis was used to examine the dimensional relationship between depressive symptoms and whole-brain states. Elevated levels of depressive symptoms were associated with increased frequency and dwell time of the default mode network, a brain network associated with self-referential thought, evaluative judgment, and social cognition. Furthermore, increased depressive symptom severity was associated with less frequent occurrences of a hybrid brain network implicated in cognitive control and goal-directed behavior, which may impair the inhibition of negative thinking patterns in depressed individuals. These findings demonstrate how temporally dynamic techniques offer novel insights into time-varying neural processes underlying subclinical and clinically meaningful depressive symptomatology.

Linked Social-Communication Dimensions and Connectivity in Functional Brain Networks in Autism Spectrum Disorder.

Much recent attention has been directed toward elucidating the structure of social interaction-communication dimensions and whether and how these symptom dimensions coalesce with each other in individuals with autism spectrum disorder (ASD). However, the underlying neurobiological basis of these symptom dimensions is unknown, especially the association of social interaction and communication dimensions with brain networks. Here, we proposed a method of whole-brain network-based regression to identify the functional networks linked to these symptom dimensions in a large sample of children with ASD. Connectome-based predictive modeling (CPM) was established to explore neurobiological evidence that supports the merging of communication and social interaction deficits into one symptom dimension (social/communication deficits). Results showed that the default mode network plays a core role in communication and social interaction dimensions. A primary sensory perceptual network mainly contributed to communication deficits, and high-level cognitive networks mainly contributed to social interaction deficits. CPM revealed that the functional networks associated with these symptom dimensions can predict the merged dimension of social/communication deficits. These findings delineate a link between brain functional networks and symptom dimensions for social interaction and communication and further provide neurobiological evidence supporting the merging of communication and social interaction deficits into one symptom dimension.

Variability in Brain Structure and Function Reflects Lack of Peer Support.

Humans are a highly social species. Complex interactions for mutual support range from helping neighbors to building social welfare institutions. During times of distress or crisis, sharing life experiences within one's social circle is critical for well-being. By translating pattern-learning algorithms to the UK Biobank imaging-genetics cohort (n = ~40 000 participants), we have delineated manifestations of regular social support in multimodal whole-brain measurements. In structural brain variation, we identified characteristic volumetric signatures in the salience and limbic networks for high- versus low-social support individuals. In patterns derived from functional coupling, we also located interindividual differences in social support in action-perception circuits related to binding sensory cues and initiating behavioral responses. In line with our demographic profiling analysis, the uncovered neural substrates have potential implications for loneliness, substance misuse, and resilience to stress.

Brain Dynamics Underlying Cognitive Flexibility Across the Lifespan.

The neural mechanisms contributing to flexible cognition and behavior and how they change with development and aging are incompletely understood. The current study explored intrinsic brain dynamics across the lifespan using resting-state fMRI data (n = 601, 6-85 years) and examined the interactions between age and brain dynamics among three neurocognitive networks (midcingulo-insular network, M-CIN; medial frontoparietal network, M-FPN; and lateral frontoparietal network, L-FPN) in relation to behavioral measures of cognitive flexibility. Hierarchical multiple regression analysis revealed brain dynamics among a brain state characterized by co-activation of the L-FPN and M-FPN, and brain state transitions, moderated the relationship between quadratic effects of age and cognitive flexibility as measured by scores on the Delis-Kaplan Executive Function System (D-KEFS) test. Furthermore, simple slope analyses of significant interactions revealed children and older adults were more likely to exhibit brain dynamic patterns associated with poorer cognitive flexibility compared with younger adults. Our findings link changes in cognitive flexibility observed with age with the underlying brain dynamics supporting these changes. Preventative and intervention measures should prioritize targeting these networks with cognitive flexibility training to promote optimal outcomes across the lifespan.

Inter-regional BOLD signal variability is an organizational feature of functional brain networks.

Neuronal variability patterns promote the formation and organization of neural circuits. Macroscale similarities in regional variability patterns may therefore be linked to the strength and topography of inter-regional functional connections. To assess this relationship, we used multi-echo resting-state fMRI and investigated macroscale connectivity-variability associations in 154 adult humans (86 women; mean age = 22yrs). We computed inter-regional measures of moment-to-moment BOLD signal variability and related them to inter-regional functional connectivity. Region pairs that showed stronger functional connectivity also showed similar BOLD signal variability patterns, independent of inter-regional distance and structural similarity. Connectivity-variability associations were predominant within all networks and followed a hierarchical spatial organization that separated sensory, motor and attention systems from limbic, default and frontoparietal control association networks. Results were replicated in a second held-out fMRI run. These findings suggest that macroscale BOLD signal variability is an organizational feature of large-scale functional networks, and shared inter-regional BOLD signal variability may underlie macroscale brain network dynamics.

What have we really learned from functional connectivity in clinical populations?

Functional connectivity (FC), or the statistical interdependence of blood-oxygen dependent level (BOLD) signals between brain regions using fMRI, has emerged as a widely used tool for probing functional abnormalities in clinical populations due to the promise of the approach across conceptual, technical, and practical levels. With an already vast and steadily accumulating neuroimaging literature on neurodevelopmental, psychiatric, and neurological diseases and disorders in which FC is a primary measure, we aim here to provide a high-level synthesis of major concepts that have arisen from FC findings in a manner that cuts across different clinical conditions and sheds light on overarching principles. We highlight that FC has allowed us to discover the ubiquity of intrinsic functional networks across virtually all brains and clarify typical patterns of neurodevelopment over the lifespan. This understanding of typical FC maturation with age has provided important benchmarks against which to evaluate divergent maturation in early life and degeneration in late life. This in turn has led to the important insight that many clinical conditions are associated with complex, distributed, network-level changes in the brain, as opposed to solely focal abnormalities. We further emphasize the important role that FC studies have played in supporting a dimensional approach to studying transdiagnostic clinical symptoms and in enhancing the multimodal characterization and prediction of the trajectory of symptom progression across conditions. We highlight the unprecedented opportunity offered by FC to probe functional abnormalities in clinical conditions where brain function could not be easily studied otherwise, such as in disorders of consciousness. Lastly, we suggest high priority areas for future research and acknowledge critical barriers associated with the use of FC methods, particularly those related to artifact removal, data denoising and feasibility in clinical contexts.

Embracing diversity and inclusivity in an academic setting: Insights from the Organization for Human Brain Mapping.

Scientific research aims to bring forward innovative ideas and constantly challenges existing knowledge structures and stereotypes. However, women, ethnic and cultural minorities, as well as individuals with disabilities, are systematically discriminated against or even excluded from promotions, publications, and general visibility. A more diverse workforce is more productive, and thus discrimination has a negative impact on science and the wider society, as well as on the education, careers, and well-being of individuals who are discriminated against. Moreover, the lack of diversity at scientific gatherings can lead to micro-aggressions or harassment, making such meetings unpleasant, or even unsafe environments for early career and underrepresented scientists. At the Organization for Human Brain Mapping (OHBM), we recognized the need for promoting underrepresented scientists and creating diverse role models in the field of neuroimaging. To foster this, the OHBM has created a Diversity and Inclusivity Committee (DIC). In this article, we review the composition and activities of the DIC that have promoted diversity within OHBM, in order to inspire other organizations to implement similar initiatives. Activities of the committee over the past four years have included (a) creating a code of conduct, (b) providing diversity and inclusivity education for OHBM members, (c) organizing interviews and symposia on diversity issues, and (d) organizing family-friendly activities and providing childcare grants during the OHBM annual meetings. We strongly believe that these activities have brought positive change within the wider OHBM community, improving inclusivity and fostering diversity while promoting rigorous, ground-breaking science. These positive changes could not have been so rapidly implemented without the enthusiastic support from the leadership, including OHBM Council and Program Committee, and the OHBM Special Interest Groups (SIGs), namely the Open Science, Student and Postdoc, and Brain-Art SIGs. Nevertheless, there remains ample room for improvement, in all areas, and even more so in the area of targeted attempts to increase inclusivity for women, individuals with disabilities, members of the LGBTQ+ community, racial/ethnic minorities, and individuals of lower socioeconomic status or from low and middle-income countries. Here, we present an overview of the DIC's composition, its activities, future directions and challenges. Our goal is to share our experiences with a wider audience to provide information to other organizations and institutions wishing to implement similar comprehensive diversity initiatives. We propose that scientific organizations can push the boundaries of scientific progress only by moving beyond existing power structures and by integrating principles of equity and inclusivity in their core values.

Dynamic functional connectivity profile of the salience network across the life span.

The insular cortex and anterior cingulate cortex together comprise the salience or midcingulo-insular network, involved in detecting salient events and initiating control signals to mediate brain network dynamics. The extent to which functional coupling between the salience network and the rest of the brain undergoes changes due to development and aging is at present largely unexplored. Here, we examine dynamic functional connectivity (dFC) of the salience network in a large life span sample (n = 601; 6-85 years old). A sliding-window analysis and k-means clustering revealed five states of dFC formed with the salience network, characterized by either widespread asynchrony or different patterns of synchrony between the salience network and other brain regions. We determined the frequency, dwell time, total transitions, and specific state-to-state transitions for each state and subject, regressing the metrics with subjects' age to identify life span trends. A dynamic state characterized by low connectivity between the salience network and the rest of the brain had a strong positive quadratic relationship between age and both frequency and dwell time. Additional frequency, dwell time, total transitions, and state-to-state transition trends were observed with other salience network states. Our results highlight the metastable dynamics of the salience network and its role in the maturation of brain regions critical for cognition.

Structure-Function Connectomics Reveals Aberrant Developmental Trajectory Occurring at Preadolescence in the Autistic Brain.

Accumulating neuroimaging evidence shows that age estimation obtained from brain connectomics reflects the level of brain maturation along with neural development. It is well known that autism spectrum disorder (ASD) alters neurodevelopmental trajectories of brain connectomics, but the precise relationship between chronological age (ChA) and brain connectome age (BCA) during development in ASD has not been addressed. This study uses neuroimaging data collected from 50 individuals with ASD and 47 age- and gender-matched typically developing controls (TDCs; age range: 5-18 years). Both functional and structural connectomics were assessed using resting-state functional magnetic resonance imaging and diffusion tensor imaging data from the Autism Brain Imaging Data Exchange repository. For each participant, BCA was estimated from structure-function connectomics through linear support vector regression. We found that BCA matched well with ChA in TDC children and adolescents, but not in ASD. In particular, our findings revealed that individuals with ASD exhibited accelerated brain maturation in youth, followed by a delay of brain development starting at preadolescence. Our results highlight the critical role of BCA in understanding aberrant developmental trajectories in ASD and provide the new insights into the pathophysiological mechanisms of this disorder.

COVID-19 and Its Global Economic Impact.

Pandemics are enormous threats to the world that impact all aspects of our lives, especially the global economy. The COVID-19 pandemic has emerged since December 2019 and has affected the global economy in many ways. As the world becomes more interconnected, the economic impacts of the pandemic become more serious. In addition to increased health expenditures and reduced labor force, the pandemic has hit the supply and demand chain massively and caused trouble for manufacturers who have to fire some of their employees or delay their economic activities to prevent more loss. With the closure of manufacturers and companies and reduced travel rates, usage of oil after the beginning of the pandemic has decreased significantly that was unprecedented in the last 30 years. The mining industry is a critical sector in several developing countries, and the COVID-19 pandemic has hit this industry too. Also, world stock markets declined as investors started to become concerned about the economic impacts of the COVID-19 pandemic. The tourism industry and airlines have also experienced an enormous loss too. The GDP has reduced, and this pandemic will cost the world more than 2 trillion at the end of 2020.