Widespread Autonomic Physiological Coupling Across the Brain-Body Axis.

The brain is closely attuned to visceral signals from the body's internal environment, as evidenced by the numerous associations between neural, hemodynamic, and peripheral physiological signals. We show that these brain-body co-fluctuations can be captured by a single spatiotemporal pattern. Across several independent samples, as well as single-echo and multi-echo fMRI data acquisition sequences, we identify widespread co-fluctuations in the low-frequency range (0.01 - 0.1 Hz) between resting-state global fMRI signals, neural activity, and a host of autonomic signals spanning cardiovascular, pulmonary, exocrine and smooth muscle systems. The same brain-body co-fluctuations observed at rest are elicited by arousal induced by cued deep breathing and intermittent sensory stimuli, as well as spontaneous phasic EEG events during sleep. Further, we show that the spatial structure of global fMRI signals is maintained under experimental suppression of end-tidal carbon dioxide (PETCO2) variations, suggesting that respiratory-driven fluctuations in arterial CO2 accompanying arousal cannot explain the origin of these signals in the brain. These findings establish the global fMRI signal as a significant component of the arousal response governed by the autonomic nervous system.

Increasing the representation of minoritized youth for inclusive and reproducible brain-behavior associations.

Population neuroscience datasets allow researchers to estimate reliable effect sizes for brain-behavior associations because of their large sample sizes. However, these datasets undergo strict quality control to mitigate sources of noise, such as head motion. This practice often excludes a disproportionate number of minoritized individuals. We employ motion-ordering and motion-ordering+resampling (bagging) to test if these methods preserve functional MRI (fMRI) data in the Adolescent Brain Cognitive Development Study ( N = 5,733 ). Black and Hispanic youth exhibited excess head motion relative to data collected from White youth, and were discarded disproportionately when using conventional approaches. Both methods retained more than 99% of Black and Hispanic youth. They produced reproducible brain-behavior associations across low-/high-motion racial/ethnic groups based on motion-limited fMRI data. The motion-ordering and bagging methods are two feasible approaches that can enhance sample representation for testing brain-behavior associations and fulfill the promise of consortia datasets to produce generalizable effect sizes across diverse populations.

A network correspondence toolbox for quantitative evaluation of novel neuroimaging results.

Decades of neuroscience research has shown that macroscale brain dynamics can be reliably decomposed into a subset of large-scale functional networks, but the specific spatial topographies of these networks and the names used to describe them can vary across studies. Such discordance has hampered interpretation and convergence of research findings across the field. To address this problem, we have developed the Network Correspondence Toolbox (NCT) to permit researchers to examine and report spatial correspondence between their novel neuroimaging results and sixteen widely used functional brain atlases, consistent with recommended reporting standards developed by the Organization for Human Brain Mapping. The atlases included in the toolbox show some topographical convergence for specific networks, such as those labeled as default or visual. Network naming varies across atlases, particularly for networks spanning frontoparietal association cortices. For this reason, quantitative comparison with multiple atlases is recommended to benchmark novel neuroimaging findings. We provide several exemplar demonstrations using the Human Connectome Project task fMRI results and UK Biobank independent component analysis maps to illustrate how researchers can use the NCT to report their own findings through quantitative evaluation against multiple published atlases. The NCT provides a convenient means for computing Dice coefficients with spin test permutations to determine the magnitude and statistical significance of correspondence among user-defined maps and existing atlas labels. The NCT also includes functionality to incorporate additional atlases in the future. The adoption of the NCT will make it easier for network neuroscience researchers to report their findings in a standardized manner, thus aiding reproducibility and facilitating comparisons between studies to produce interdisciplinary insights.

Racial Discrimination and Risk for Internalizing and Externalizing Symptoms Among Black Youths.

Importance: Racial discrimination is a psychosocial stressor associated with youths' risk for psychiatric symptoms. Scarce data exist on the moderating role of amygdalar activation patterns among Black youths in the US. Objective: To investigate the association between racial discrimination and risk for psychopathology moderated by neuroaffective processing. Design, Setting, and Participants: This cohort study used longitudinal self-report and functional magnetic resonance imaging (fMRI) data from Black youth participants in the US from the Adolescent Brain Cognitive Development (ABCD) study. Data were analyzed from January 2023 to May 2024. Exposures: At time 1 of the current study (12 months after baseline), youths self-reported on their experiences of interpersonal racial discrimination and their feelings of marginalization. Amygdalar response was measured during an emotionally valenced task that included blocks of faces expressing either neutral or negative emotion. Main Outcomes and Measures: At 24 and 36 months after baseline, youths reported their internalizing (anxiety and depressive symptoms) and externalizing symptoms (aggression and rule-breaking symptoms). Results: A total of 1596 youths were a mean (SD) age of 10.92 (0.63) years, and 803 were female (50.3%). Families in the study had a mean annual income range of $25 000 to $34 999. Two factors were derived from factor analysis: interpersonal racial discrimination and feelings of marginalization (FoM). Using structural equation modeling in a linear regression, standardized ß coefficients were obtained. Neural response to faces expressing negative emotion within the right amygdala significantly moderated the association between FoM and changes in internalizing symptoms (ß = -0.20; 95% CI, -0.32 to -0.07; P < .001). The response to negative facial emotion within the right amygdala significantly moderated the association between FoM and changes in externalizing symptoms (ß = 0.24; 95% CI, 0.04 to 0.43; P = .02). Left amygdala response to negative emotion significantly moderated the association between FoM and changes in externalizing symptoms (ß = -0.16; 95% CI, -0.32 to -0.01; P = .04). Conclusions and Relevance: In this cohort study of Black adolescents in the US, findings suggest that amygdala function in response to emotional stimuli can both protect and intensify the affective outcomes of feeling marginalized on risk for psychopathology, informing preventive interventions aimed at reducing the adverse effects of racism on internalizing and externalizing symptoms among Black youths.

Resting state functional brain connectivity in child and adolescent psychiatry: where are we now?

Approaching the 30th anniversary of the discovery of resting state functional magnetic resonance imaging (rsfMRI) functional connectivity, we reflect on the impact of this neuroimaging breakthrough on the field of child and adolescent psychiatry. The study of intrinsic functional brain architecture that rsfMRI affords across a wide range of ages and abilities has yielded numerous key insights. For example, we now know that many neurodevelopmental conditions are associated with more widespread circuit alterations across multiple large-scale brain networks than previously suspected. The emergence of population neuroscience and effective data-sharing initiatives have made large rsfMRI datasets publicly available, providing sufficient power to begin to identify brain-based subtypes within heterogeneous clinical conditions. Nevertheless, several methodological and theoretical challenges must still be addressed to fulfill the promises of personalized child and adolescent psychiatry. In particular, incomplete understanding of the physiological mechanisms driving developmental changes in intrinsic functional connectivity remains an obstacle to further progress. Future directions include cross-species and multimodal neuroimaging investigations to illuminate such mechanisms. Data collection and harmonization efforts that span multiple countries and diverse cohorts are urgently needed. Finally, incorporating naturalistic fMRI paradigms such as movie watching should be a priority for future research efforts.

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.

Brain signal variability and executive functions across the life span.

Neural variability is thought to facilitate survival through flexible adaptation to changing environmental demands. In humans, such capacity for flexible adaptation may manifest as fluid reasoning, inhibition of automatic responses, and mental set-switching-skills falling under the broad domain of executive functions that fluctuate over the life span. Neural variability can be quantified via the BOLD signal in resting-state fMRI. Variability of large-scale brain networks is posited to underpin complex cognitive activities requiring interactions between multiple brain regions. Few studies have examined the extent to which network-level brain signal variability across the life span maps onto high-level processes under the umbrella of executive functions. The present study leveraged a large publicly available neuroimaging dataset to investigate the relationship between signal variability and executive functions across the life span. Associations between brain signal variability and executive functions shifted as a function of age. Limbic-specific variability was consistently associated with greater performance across subcomponents of executive functions. Associations between executive function subcomponents and network-level variability of the default mode and central executive networks, as well as whole-brain variability, varied across the life span. Findings suggest that brain signal variability may help to explain to age-related differences in executive functions across the life span.

Traditionally, regional variability in brain signals has been viewed as a source of noise in human neuroimaging research. Our study demonstrates that brain signal variability may contain meaningful information related to psychological processes. We demonstrate that brain signal variability, particularly whole-brain variability, may serve as a reliable indicator of cognitive functions across the life span. Global variability and network-level variability play differing roles in supporting executive functions. Findings suggest that brain signal variability serves as a meaningful indicator of development and cognitive aging.

Disentangling the Individual-Shared and Individual-Specific Subspace of Altered Brain Functional Connectivity in Autism Spectrum Disorder.

BACKGROUND: Despite considerable effort toward understanding the neural basis of autism spectrum disorder (ASD) using case-control analyses of resting-state functional magnetic resonance imaging data, findings are often not reproducible, largely due to biological and clinical heterogeneity among individuals with ASD. Thus, exploring the individual-shared and individual-specific altered functional connectivity (AFC) in ASD is important to understand this complex, heterogeneous disorder. METHODS: We considered 254 individuals with ASD and 295 typically developing individuals from the Autism Brain Imaging Data Exchange to explore the individual-shared and individual-specific subspaces of AFC. First, we computed AFC matrices of individuals with ASD compared with typically developing individuals. Then, common orthogonal basis extraction was used to project AFC of ASD onto 2 subspaces: an individual-shared subspace, which represents altered connectivity patterns shared across ASD, and an individual-specific subspace, which represents the remaining individual characteristics after eliminating the individual-shared altered connectivity patterns. RESULTS: Analysis yielded 3 common components spanning the individual-shared subspace. Common components were associated with differences of functional connectivity at the group level. AFC in the individual-specific subspace improved the prediction of clinical symptoms. The default mode network-related and cingulo-opercular network-related magnitudes of AFC in the individual-specific subspace were significantly correlated with symptom severity in social communication deficits and restricted, repetitive behaviors in ASD. CONCLUSIONS: Our study decomposed AFC of ASD into individual-shared and individual-specific subspaces, highlighting the importance of capturing and capitalizing on individual-specific brain connectivity features for dissecting heterogeneity. Our analysis framework provides a blueprint for parsing heterogeneity in other prevalent neurodevelopmental conditions.

Longitudinal Development of Thalamocortical Functional Connectivity in 22q11.2 Deletion Syndrome.

BACKGROUND: The 22q11.2 deletion syndrome (22qDel) is a genetic copy number variant that strongly increases risk for schizophrenia and other neurodevelopmental disorders. Disrupted functional connectivity between the thalamus and the somatomotor/frontoparietal cortex has been implicated in cross-sectional studies of 22qDel, idiopathic schizophrenia, and youths at clinical high risk for psychosis. Here, we used a novel functional atlas approach to investigate longitudinal age-related changes in network-specific thalamocortical functional connectivity (TCC) in participants with 22qDel and typically developing (TD) control participants. METHODS: TCC was calculated for 9 functional networks derived from resting-state functional magnetic resonance imaging scans collected from 65 participants with 22qDel (63.1% female) and 69 demographically matched TD control participants (49.3% female) ages 6 to 23 years. Analyses included 86 longitudinal follow-up scans. Nonlinear age trajectories were characterized with generalized additive mixed models. RESULTS: In participants with 22qDel, TCC in the frontoparietal network increased until approximately age 13, while somatomotor TCC and cingulo-opercular TCC decreased from age 6 to 23. In contrast, no significant relationships between TCC and age were found in TD control participants. Somatomotor connectivity was significantly higher in participants with 22qDel than in TD control participants in childhood, but lower in late adolescence. Frontoparietal TCC showed the opposite pattern. CONCLUSIONS: 22qDel is associated with aberrant development of functional network connectivity between the thalamus and cortex. Younger individuals with 22qDel have lower frontoparietal connectivity and higher somatomotor connectivity than control individuals, but this phenotype may normalize or partially reverse by early adulthood. Altered maturation of this circuitry may underlie elevated neuropsychiatric disease risk in this syndrome.

Pre-pandemic Executive Function Protects Against Pandemic Anxiety in Children with and Without Autism Spectrum Disorder.

The COVID-19 pandemic may have exacerbated depression, anxiety, and executive function (EF) difficulties in children with autism spectrum disorder (ASD). EF skills have been positively associated with mental health outcomes. Here, we probed the psychosocial impacts of pandemic responses in children with and without ASD by relating pre-pandemic EF assessments with anxiety and depression symptoms several months into the pandemic. We found that pre-pandemic inhibition and shifting difficulties, measured by the Behavior Rating Inventory of Executive Function, predicted higher risk of anxiety symptoms. These findings are critical for promoting community recovery and maximizing clinical preparedness to support children at increased risk for adverse psychosocial outcomes.

The biological role of local and global fMRI BOLD signal variability in human brain organization.

Variability drives the organization and behavior of complex systems, including the human brain. Understanding the variability of brain signals is thus necessary to broaden our window into brain function and behavior. Few empirical investigations of macroscale brain signal variability have yet been undertaken, given the difficulty in separating biological sources of variance from artefactual noise. Here, we characterize the temporal variability of the most predominant macroscale brain signal, the fMRI BOLD signal, and systematically investigate its statistical, topographical and neurobiological properties. We contrast fMRI acquisition protocols, and integrate across histology, microstructure, transcriptomics, neurotransmitter receptor and metabolic data, fMRI static connectivity, and empirical and simulated magnetoencephalography data. We show that BOLD signal variability represents a spatially heterogeneous, central property of multi-scale multi-modal brain organization, distinct from noise. Our work establishes the biological relevance of BOLD signal variability and provides a lens on brain stochasticity across spatial and temporal scales.

Controversies and progress on standardization of large-scale brain network nomenclature.

Progress in scientific disciplines is accompanied by standardization of terminology. Network neuroscience, at the level of macroscale organization of the brain, is beginning to confront the challenges associated with developing a taxonomy of its fundamental explanatory constructs. The Workgroup for HArmonized Taxonomy of NETworks (WHATNET) was formed in 2020 as an Organization for Human Brain Mapping (OHBM)-endorsed best practices committee to provide recommendations on points of consensus, identify open questions, and highlight areas of ongoing debate in the service of moving the field toward standardized reporting of network neuroscience results. The committee conducted a survey to catalog current practices in large-scale brain network nomenclature. A few well-known network names (e.g., default mode network) dominated responses to the survey, and a number of illuminating points of disagreement emerged. We summarize survey results and provide initial considerations and recommendations from the workgroup. This perspective piece includes a selective review of challenges to this enterprise, including (1) network scale, resolution, and hierarchies; (2) interindividual variability of networks; (3) dynamics and nonstationarity of networks; (4) consideration of network affiliations of subcortical structures; and (5) consideration of multimodal information. We close with minimal reporting guidelines for the cognitive and network neuroscience communities to adopt.

Variability in Cognitive Task Performance in Early Adolescence Is Associated With Stronger Between-Network Anticorrelation and Future Attention Problems.

Background: Intraindividual variability (IIV) during cognitive task performance is a key behavioral index of attention and a consistent marker of attention-deficit/hyperactivity disorder. In adults, lower IIV has been associated with anticorrelation between the default mode network (DMN) and dorsal attention network (DAN)-thought to underlie effective allocation of attention. However, whether these behavioral and neural markers of attention are 1) associated with each other and 2) can predict future attention-related deficits has not been examined in a developmental, population-based cohort. Methods: We examined relationships at the baseline visit between IIV on 3 cognitive tasks, DMN-DAN anticorrelation, and parent-reported attention problems using data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 11,878 participants, ages 9 to 10 years, female = 47.8%). We also investigated whether behavioral and neural markers of attention at baseline predicted attention problems 1, 2, and 3 years later. Results: At baseline, greater DMN-DAN anticorrelation was associated with lower IIV across all 3 cognitive tasks (B = 0.22 to 0.25). Older age at baseline was associated with stronger DMN-DAN anticorrelation and lower IIV (B = -0.005 to -0.0004). Weaker DMN-DAN anticorrelation and IIV were cross-sectionally associated with attention problems (B = 1.41 to 7.63). Longitudinally, lower IIV at baseline was associated with less severe attention problems 1 to 3 years later, after accounting for baseline attention problems (B = 0.288 to 0.77). Conclusions: The results suggest that IIV in early adolescence is associated with worsening attention problems in a representative cohort of U.S. youth. Attention deficits in early adolescence may be important for understanding and predicting future cognitive and clinical outcomes.

Individual differences in time-varying and stationary brain connectivity during movie watching from childhood to early adulthood: Age, sex, and behavioral associations.

Spatially remote brain regions exhibit dynamic functional interactions across various task conditions. While time-varying functional connectivity during movie watching shows sensitivity to movie content, stationary functional connectivity remains relatively stable across videos. These findings suggest that dynamic and stationary functional interactions may represent different aspects of brain function. However, the relationship between individual differences in time-varying and stationary connectivity and behavioral phenotypes remains elusive. To address this gap, we analyzed an open-access functional MRI dataset comprising participants aged 5-22 years, who watched two cartoon movie clips. We calculated regional brain activity, time-varying connectivity, and stationary connectivity, examining associations with age, sex, and behavioral assessments. Model comparison revealed that time-varying connectivity was more sensitive to age and sex effects compared with stationary connectivity. The preferred age models exhibited quadratic log age or quadratic age effects, indicative of inverted-U shaped developmental patterns. In addition, females showed higher consistency in regional brain activity and time-varying connectivity than males. However, in terms of behavioral predictions, only stationary connectivity demonstrated the ability to predict full-scale intelligence quotient. These findings suggest that individual differences in time-varying and stationary connectivity may capture distinct aspects of behavioral phenotypes.

Laterality and hemispheric specialization of self-face recognition.

Inspired by the pioneering work of Eran Zaidel beginning in the early 1970's on the role of the two cerebral hemispheres of the human brain in self-related cognition, we review research on self-face recognition from a laterality perspective. The self-face is an important proxy of the self, and self-face recognition has been used as an indicator of self-awareness more broadly. Over the last half century, behavioral and neurological data, along with over two decades of neuroimaging research evidence have accumulated on this topic, generally concluding a right-hemisphere dominance for self-face recognition. In this review, we briefly revisit the pioneering roots of this work by Sperry, Zaidel & Zaidel, and focus on the important body of neuroimaging literature on self-face recognition it has inspired. We conclude with a brief discussion of current models of self-related processing and future directions for research in this area.