Relative brain age is associated with socioeconomic status and anxiety/depression problems in youth.

Brain age, a measure of biological aging in the brain, has been linked to psychiatric illness, principally in adult populations. Components of socioeconomic status (SES) associate with differences in brain structure and psychiatric risk across the lifespan. This study aimed to investigate the influence of SES on brain aging in childhood and adolescence, a period of rapid neurodevelopment and peak onset for many psychiatric disorders. We reanalyzed data from the Healthy Brain Network to examine the influence of SES components (occupational prestige, public assistance enrollment, parent education, and household income-to-needs ratio [INR]) on relative brain age (RBA). Analyses included 470 youth (5-17 years; 61.3% men), self-identifying as White (55%), African American (15%), Hispanic (9%), or multiracial (17.2%). Household income was 3.95 ± 2.33 (mean ± SD) times the federal poverty threshold. RBA quantified differences between chronological age and brain age using covariation patterns of morphological features and total volumes. We also examined associations between RBA and psychiatric symptoms (Child Behavior Checklist [CBCL]). Models covaried for sex, scan location, and parent psychiatric diagnoses. In a linear regression, lower RBA is associated with lower parent occupational prestige (p = .01), lower public assistance enrollment (p = .03), and more parent psychiatric diagnoses (p = .01), but not parent education or INR. Lower parent occupational prestige (p = .02) and lower RBA (p = .04) are associated with higher CBCL anxious/depressed scores. Our findings underscore the importance of including SES components in developmental brain research. Delayed brain aging may represent a potential biological pathway from SES to psychiatric risk. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Specific and common functional connectivity deficits in drug-free generalized anxiety disorder and panic disorder: A data-driven analysis.

Evidence of comparing neural network differences between anxiety disorder subtypes is limited, while it is crucial to reveal the pathogenesis of anxiety disorders. The present study aimed to investigate specific and common resting-state functional connectivity (FC) networks in generalized anxiety disorder (GAD), panic disorder (PD), and healthy controls (HC). We employed the gRAICAR algorithm to decompose the resting-state fMRI into independent components and align the components across 61 subjects (22 GAD, 18 PD and 21 HC). The default mode network and precuneus network exhibited GAD-specific aberrance, the anterior default mode network showed atypicality specific to PD, and the right fronto-parietal network showed aberrance common to GAD and PD. Between GAD-specific networks, FC between bilateral dorsolateral prefrontal cortex (DLPFC) was positively correlated with interoceptive sensitivity. In the common network, altered FCs between DLPFC and angular gyrus, and between orbitofrontal cortex and precuneus, were positively correlated with anxiety severity and interoceptive sensitivity. The pathological mechanism of PD could closely relate to the dysfunction of prefrontal cortex, while GAD could involve more extensive brain areas, which may be related to fear generalization.

ASLPrep: a platform for processing of arterial spin labeled MRI and quantification of regional brain perfusion.

Arterial spin labeled (ASL) magnetic resonance imaging (MRI) is the primary method for noninvasively measuring regional brain perfusion in humans. We introduce ASLPrep, a suite of software pipelines that ensure the reproducible and generalizable processing of ASL MRI data.

Predicting multiscan MRI outcomes in children with neurodevelopmental conditions following MRI simulator training.

Pediatric brain imaging holds significant promise for understanding neurodevelopment. However, the requirement to remain still inside a noisy, enclosed scanner remains a challenge. Verbal or visual descriptions of the process, and/or practice in MRI simulators are the norm in preparing children. Yet, the factors predictive of successfully obtaining neuroimaging data remain unclear. We examined data from 250 children (6-12 years, 197 males) with autism and/or attention-deficit/hyperactivity disorder. Children completed systematic MRI simulator training aimed to habituate to the scanner environment and minimize head motion. An MRI session comprised multiple structural, resting-state, task and diffusion scans. Of the 201 children passing simulator training and attempting scanning, nearly all (94%) successfully completed the first structural scan in the sequence, and 88% also completed the following functional scan. The number of successful scans decreased as the sequence progressed. Multivariate analyses revealed that age was the strongest predictor of successful scans in the session, with younger children having lower success rates. After age, sensorimotor atypicalities contributed most to prediction. Results provide insights on factors to consider in designing pediatric brain imaging protocols.

Estimates of locus coeruleus function with functional magnetic resonance imaging are influenced by localization approaches and the use of multi-echo data.

The locus coeruleus (LC) plays a central role in regulating human cognition, arousal, and autonomic states. Efforts to characterize the LC's function in humans using functional magnetic resonance imaging have been hampered by its small size and location near a large source of noise, the fourth ventricle. We tested whether the ability to characterize LC function is improved by employing neuromelanin-T1 weighted images (nmT1) for LC localization and multi-echo functional magnetic resonance imaging (ME-fMRI) for estimating intrinsic functional connectivity (iFC). Analyses indicated that, relative to a probabilistic atlas, utilizing nmT1 images to individually localize the LC increases the specificity of seed time series and clusters in the iFC maps. When combined with independent components analysis (ME-ICA), ME-fMRI data provided significant improvements in the temporal signal to noise ratio and DVARS relative to denoised single echo data (1E-fMRI). The effects of acquiring nmT1 images and ME-fMRI data did not appear to only reflect increases in power: iFC maps for each approach overlapped only moderately. This is consistent with findings that ME-fMRI offers substantial advantages over 1E-fMRI acquisition and denoising. It also suggests that individually identifying LC with nmT1 scans is likely to reduce the influence of other nearby brainstem regions on estimates of LC function.

Measurement reliability for individual differences in multilayer network dynamics: Cautions and considerations.

Multilayer network models have been proposed as an effective means of capturing the dynamic configuration of distributed neural circuits and quantitatively describing how communities vary over time. Beyond general insights into brain function, a growing number of studies have begun to employ these methods for the study of individual differences. However, test-retest reliabilities for multilayer network measures have yet to be fully quantified or optimized, potentially limiting their utility for individual difference studies. Here, we systematically evaluated the impact of multilayer community detection algorithms, selection of network parameters, scan duration, and task condition on test-retest reliabilities of multilayer network measures (i.e., flexibility, integration, and recruitment). A key finding was that the default method used for community detection by the popular generalized Louvain algorithm can generate erroneous results. Although available, an updated algorithm addressing this issue is yet to be broadly adopted in the neuroimaging literature. Beyond the algorithm, the present work identified parameter selection as a key determinant of test-retest reliability; however, optimization of these parameters and expected reliabilities appeared to be dataset-specific. Once parameters were optimized, consistent with findings from the static functional connectivity literature, scan duration was a much stronger determinant of reliability than scan condition. When the parameters were optimized and scan duration was sufficient, both passive (i.e., resting state, Inscapes, and movie) and active (i.e., flanker) tasks were reliable, although reliability in the movie watching condition was significantly higher than in the other three tasks. The minimal data requirement for achieving reliable measures for the movie watching condition was 20 min, and 30 min for the other three tasks. Our results caution the field against the use of default parameters without optimization based on the specific datasets to be employed - a process likely to be limited for most due to the lack of test-retest samples to enable parameter optimization.

Assessment of the impact of shared brain imaging data on the scientific literature.

Data sharing is increasingly recommended as a means of accelerating science by facilitating collaboration, transparency, and reproducibility. While few oppose data sharing philosophically, a range of barriers deter most researchers from implementing it in practice. To justify the significant effort required for sharing data, funding agencies, institutions, and investigators need clear evidence of benefit. Here, using the International Neuroimaging Data-sharing Initiative, we present a case study that provides direct evidence of the impact of open sharing on brain imaging data use and resulting peer-reviewed publications. We demonstrate that openly shared data can increase the scale of scientific studies conducted by data contributors, and can recruit scientists from a broader range of disciplines. These findings dispel the myth that scientific findings using shared data cannot be published in high-impact journals, suggest the transformative power of data sharing for accelerating science, and underscore the need for implementing data sharing universally.

Delineating the Macroscale Areal Organization of the Macaque Cortex In Vivo.

Complementing long-standing traditions centered on histology, fMRI approaches are rapidly maturing in delineating brain areal organization at the macroscale. The non-human primate (NHP) provides the opportunity to overcome critical barriers in translational research. Here, we establish the data requirements for achieving reproducible and internally valid parcellations in individuals. We demonstrate that functional boundaries serve as a functional fingerprint of the individual animals and can be achieved under anesthesia or awake conditions (rest, naturalistic viewing), though differences between awake and anesthetized states precluded the detection of individual differences across states. Comparison of awake and anesthetized states suggested a more nuanced picture of changes in connectivity for higher-order association areas, as well as visual and motor cortex. These results establish feasibility and data requirements for the generation of reproducible individual-specific parcellations in NHPs, provide insights into the impact of scan state, and motivate efforts toward harmonizing protocols.

Pointwise influence matrices for functional-response regression.

We extend the notion of an influence or hat matrix to regression with functional responses and scalar predictors. For responses depending linearly on a set of predictors, our definition is shown to reduce to the conventional influence matrix for linear models. The pointwise degrees of freedom, the trace of the pointwise influence matrix, are shown to have an adaptivity property that motivates a two-step bivariate smoother for modeling nonlinear dependence on a single predictor. This procedure adapts to varying complexity of the nonlinear model at different locations along the function, and thereby achieves better performance than competing tensor product smoothers in an analysis of the development of white matter microstructure in the brain.

Human Connectomics across the Life Span.

Connectomics has enhanced our understanding of neurocognitive development and decline by the integration of network sciences into studies across different stages of the human life span. However, these studies commonly occurred independently, missing the opportunity to test integrated models of the dynamical brain organization across the entire life span. In this review article, we survey empirical findings in life-span connectomics and propose a generative framework for computationally modeling the connectome over the human life span. This framework highlights initial findings that across the life span, the human connectome gradually shifts from an 'anatomically driven' organization to one that is more 'topological'. Finally, we consider recent advances that are promising to provide an integrative and systems perspective of human brain plasticity as well as underscore the pitfalls and challenges.

Neural correlates of self-perceptions in adolescents with major depressive disorder.

Alteration in self-perception is a salient feature in major depression. Hyperactivity of anterior cortical midline regions has been implicated in this phenomenon in depressed adults. Here, we extend this work to depressed adolescents during a developmental time when neuronal circuitry underlying the sense of self matures by using task-based functional magnetic resonance imaging (fMRI) and connectivity analyses. Twenty-three depressed adolescents and 18 healthy controls (HC) viewed positive and negative trait words in a scanner and judged whether each word described them ('self' condition) or was a good trait to have ('general' condition). Self-perception scores were based on participants' endorsements of positive and negative traits during the fMRI task. Depressed adolescents exhibited more negative self-perceptions than HC. Both groups activated cortical midline regions in response to self-judgments compared to general-judgments. However, depressed adolescents recruited the posterior cingulate cortex/precuneus more for positive self-judgments. Additionally, local connectivity of the dorsal medial prefrontal cortex was reduced during self-reflection in depressed adolescents. Our findings highlight differences in self-referential processing network function between depressed and healthy adolescents and support the need for further investigation of brain mechanisms associated with the self, as they may be paramount to understanding the etiology and development of major depressive disorder.

An integrated framework for targeting functional networks via transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) is a powerful investigational tool for in vivo manipulation of regional or network activity, with a growing number of potential clinical applications. Unfortunately, the vast majority of targeting strategies remain limited by their reliance on non-realistic brain models and assumptions that anatomo-functional relationships are 1:1. Here, we present an integrated framework that combines anatomically realistic finite element models of the human head with resting functional MRI to predict functional networks targeted via TMS at a given coil location and orientation. Using data from the Human Connectome Project, we provide an example implementation focused on dorsolateral prefrontal cortex (DLPFC). Three distinct DLPFC stimulation zones were identified, differing with respect to the network to be affected (default, frontoparietal) and sensitivity to coil orientation. Network profiles generated for DLPFC targets previously published for treating depression revealed substantial variability across studies, highlighting a potentially critical technical issue.

Imaging human connectomes at the macroscale.

At macroscopic scales, the human connectome comprises anatomically distinct brain areas, the structural pathways connecting them and their functional interactions. Annotation of phenotypic associations with variation in the connectome and cataloging of neurophenotypes promise to transform our understanding of the human brain. In this Review, we provide a survey of magnetic resonance imaging­based measurements of functional and structural connectivity. We highlight emerging areas of development and inquiry and emphasize the importance of integrating structural and functional perspectives on brain architecture.

A comprehensive assessment of regional variation in the impact of head micromovements on functional connectomics.

Functional connectomics is one of the most rapidly expanding areas of neuroimaging research. Yet, concerns remain regarding the use of resting-state fMRI (R-fMRI) to characterize inter-individual variation in the functional connectome. In particular, recent findings that "micro" head movements can introduce artifactual inter-individual and group-related differences in R-fMRI metrics have raised concerns. Here, we first build on prior demonstrations of regional variation in the magnitude of framewise displacements associated with a given head movement, by providing a comprehensive voxel-based examination of the impact of motion on the BOLD signal (i.e., motion-BOLD relationships). Positive motion-BOLD relationships were detected in primary and supplementary motor areas, particularly in low motion datasets. Negative motion-BOLD relationships were most prominent in prefrontal regions, and expanded throughout the brain in high motion datasets (e.g., children). Scrubbing of volumes with FD>0.2 effectively removed negative but not positive correlations; these findings suggest that positive relationships may reflect neural origins of motion while negative relationships are likely to originate from motion artifact. We also examined the ability of motion correction strategies to eliminate artifactual differences related to motion among individuals and between groups for a broad array of voxel-wise R-fMRI metrics. Residual relationships between motion and the examined R-fMRI metrics remained for all correction approaches, underscoring the need to covary motion effects at the group-level. Notably, global signal regression reduced relationships between motion and inter-individual differences in correlation-based R-fMRI metrics; Z-standardization (mean-centering and variance normalization) of subject-level maps for R-fMRI metrics prior to group-level analyses demonstrated similar advantages. Finally, our test-retest (TRT) analyses revealed significant motion effects on TRT reliability for R-fMRI metrics. Generally, motion compromised reliability of R-fMRI metrics, with the exception of those based on frequency characteristics - particularly, amplitude of low frequency fluctuations (ALFF). The implications of our findings for decision-making regarding the assessment and correction of motion are discussed, as are insights into potential differences among volume-based metrics of motion.

The extrinsic and intrinsic functional architectures of the human brain are not equivalent.

The brain's intrinsic functional architecture, revealed in correlated spontaneous activity, appears to constitute a faithful representation of its repertoire of evoked, extrinsic functional interactions. Here, using broad task contrasts to probe evoked patterns of coactivation, we demonstrate tight coupling between the brain's intrinsic and extrinsic functional architectures for default and task-positive regions, but not for subcortical and limbic regions or for primary sensory and motor cortices. While strong correspondence likely reflects persistent or recurrent patterns of evoked coactivation, weak correspondence may exist for regions whose patterns of evoked functional interactions are more adaptive and context dependent. These findings were independent of task. For tight task contrasts (e.g., incongruent vs. congruent trials), evoked patterns of coactivation were unrelated to the intrinsic functional architecture, suggesting that high-level task demands are accommodated by context-specific modulations of functional interactions. We conclude that intrinsic approaches provide only a partial understanding of the brain's functional architecture. Appreciating the full repertoire of dynamic neural responses will continue to require task-based functional magnetic resonance imaging approaches.

Differential development of human brain white matter tracts.

Neuroscience is increasingly focusing on developmental factors related to human structural and functional connectivity. Unfortunately, to date, diffusion-based imaging approaches have only contributed modestly to these broad objectives, despite the promise of diffusion-based tractography. Here, we report a novel data-driven approach to detect similarities and differences among white matter tracts with respect to their developmental trajectories, using 64-direction diffusion tensor imaging. Specifically, using a cross-sectional sample comprising 144 healthy individuals (7 to 48 years old), we applied k-means cluster analysis to separate white matter voxels based on their age-related trajectories of fractional anisotropy. Optimal solutions included 5-, 9- and 14-clusters. Our results recapitulate well-established tracts (e.g., internal and external capsule, optic radiations, corpus callosum, cingulum bundle, cerebral peduncles) and subdivisions within tracts (e.g., corpus callosum, internal capsule). For all but one tract identified, age-related trajectories were curvilinear (i.e., inverted 'U-shape'), with age-related increases during childhood and adolescence followed by decreases in middle adulthood. Identification of peaks in the trajectories suggests that age-related losses in fractional anisotropy occur as early as 23 years of age, with mean onset at 30 years of age. Our findings demonstrate that data-driven analytic techniques may be fruitfully applied to extant diffusion tensor imaging datasets in normative and neuropsychiatric samples.

Toward discovery science of human brain function.

Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (<0.1 Hz) fluctuations in the fMRI signal that are temporally correlated across functionally related areas. Referred to as functional connectivity, these correlations yield detailed maps of complex neural systems, collectively constituting an individual's "functional connectome." Reproducibility across datasets and individuals suggests the functional connectome has a common architecture, yet each individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain-behavior relationships, will require multicenter collaborative datasets. Here we initiate this endeavor by gathering R-fMRI data from 1,414 volunteers collected independently at 35 international centers. We demonstrate a universal architecture of positive and negative functional connections, as well as consistent loci of inter-individual variability. Age and sex emerged as significant determinants. These results demonstrate that independent R-fMRI datasets can be aggregated and shared. High-throughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/.

Age-related differences in regional brain volumes: a comparison of optimized voxel-based morphometry to manual volumetry.

Regional manual volumetry is the gold standard of in vivo neuroanatomy, but is labor-intensive, can be imperfectly reliable, and allows for measuring limited number of regions. Voxel-based morphometry (VBM) has perfect repeatability and assesses local structure across the whole brain. However, its anatomic validity is unclear, and with its increasing popularity, a systematic comparison of VBM to manual volumetry is necessary. The few existing comparison studies are limited by small samples, qualitative comparisons, and limited selection and modest reliability of manual measures. Our goal was to overcome those limitations by quantitatively comparing optimized VBM findings with highly reliable multiple regional measures in a large sample (N=200) across a wide agespan (18-81). We report a complex pattern of similarities and differences. Peak values of VBM volume estimates (modulated density) produced stronger age differences and a different spatial distribution from manual measures. However, when we aggregated VBM-derived information across voxels contained in specific anatomically defined regions (masks), the patterns of age differences became more similar, although important discrepancies emerged. Notably, VBM revealed stronger age differences in the regions bordering CSF and white matter areas prone to leukoaraiosis, and VBM was more likely to report nonlinearities in age-volume relationships. In the white matter regions, manual measures showed stronger negative associations with age than the corresponding VBM-based masks. We conclude that VBM provides realistic estimates of age differences in the regional gray matter only when applied to anatomically defined regions, but overestimates effects when individual peaks are interpreted. It may be beneficial to use VBM as a first-pass strategy, followed by manual measurement of anatomically defined regions.

The implications of cortical recruitment and brain morphology for individual differences in inhibitory function in aging humans.

The authors assessed individual differences in cortical recruitment, brain morphology, and inhibitory task performance. Similar to previous studies, older adults tended toward bilateral activity during task performance more than younger adults. However, better performing older adults showed less bilateral activity than poorer performers, contrary to the idea that additional activity is universally compensatory. A review of the results and of extant literature suggests that compensatory activity in prefrontal cortex may only be effective if the additional cortical processors brought to bear on the task can play a complementary role in task performance. Morphological analyses revealed that frontal white matter tracts differed as a function of performance in older adults, suggesting that hemispheric connectivity might impact both patterns of recruitment and cognitive performance.