The human brain is organized into large-scale functional modules that have been shown to evolve in childhood and adolescence. However, it remains unknown whether the underlying white matter ...architecture is similarly refined during development, potentially allowing for improvements in executive function. In a sample of 882 participants (ages 8–22) who underwent diffusion imaging as part of the Philadelphia Neurodevelopmental Cohort, we demonstrate that structural network modules become more segregated with age, with weaker connections between modules and stronger connections within modules. Evolving modular topology facilitates global network efficiency and is driven by age-related strengthening of hub edges present both within and between modules. Critically, both modular segregation and network efficiency are associated with enhanced executive performance and mediate the improvement of executive functioning with age. Together, results delineate a process of structural network maturation that supports executive function in youth.
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•Structural brain modules become more segregated during youth•Targeted strengthening of hub edges simultaneously promotes network efficiency•Enhanced modular segregation mediates improvements in executive function in youth
Baum et al. apply network analytic techniques to demonstrate that human white matter networks become increasingly modular during adolescent development. Furthermore, targeted strengthening of hub connections facilitates global network integration. This process of network evolution mediates improvements in executive functioning during youth.
•1st Neuroimaging Workgroup Meeting in Functional Neurological Disorder (FND).•Underscores the importance of FND cohort characterization in brain imaging research.•Details methodological approaches ...taken in FND neuroimaging research to date.•Research agenda proposed to definitely elucidate the neural circuitry of FND.•Discussions underway regarding having FND researchers join the ENIGMA consortium.
Functional neurological disorder (FND) was of great interest to early clinical neuroscience leaders. During the 20th century, neurology and psychiatry grew apart – leaving FND a borderland condition. Fortunately, a renaissance has occurred in the last two decades, fostered by increased recognition that FND is prevalent and diagnosed using “rule-in” examination signs. The parallel use of scientific tools to bridge brain structure - function relationships has helped refine an integrated biopsychosocial framework through which to conceptualize FND. In particular, a growing number of quality neuroimaging studies using a variety of methodologies have shed light on the emerging pathophysiology of FND. This renewed scientific interest has occurred in parallel with enhanced interdisciplinary collaborations, as illustrated by new care models combining psychological and physical therapies and the creation of a new multidisciplinary FND society supporting knowledge dissemination in the field. Within this context, this article summarizes the output of the first International FND Neuroimaging Workgroup meeting, held virtually, on June 17th, 2020 to appraise the state of neuroimaging research in the field and to catalyze large-scale collaborations. We first briefly summarize neural circuit models of FND, and then detail the research approaches used to date in FND within core content areas: cohort characterization; control group considerations; task-based functional neuroimaging; resting-state networks; structural neuroimaging; biomarkers of symptom severity and risk of illness; and predictors of treatment response and prognosis. Lastly, we outline a neuroimaging-focused research agenda to elucidate the pathophysiology of FND and aid the development of novel biologically and psychologically-informed treatments.
Having gained a tremendous amount of popularity since its introduction in 2006, tract-based spatial statistics (TBSS) can now be considered as the standard approach for voxel-based analysis (VBA) of ...diffusion tensor imaging (DTI) data. Aiming to improve the sensitivity, objectivity, and interpretability of multi-subject DTI studies, TBSS includes a skeletonization step that alleviates residual image misalignment and obviates the need for data smoothing. Although TBSS represents an elegant and user-friendly framework that tackles numerous concerns existing in conventional VBA methods, it has limitations of its own, some of which have already been detailed in recent literature. In this work, we present general methodological considerations on TBSS and report on pitfalls that have not been described previously. In particular, we have identified specific assumptions of TBSS that may not be satisfied under typical conditions. Moreover, we demonstrate that the existence of such violations can severely affect the reliability of TBSS results. With TBSS being used increasingly, it is of paramount importance to acquaint TBSS users with these concerns, such that a well-informed decision can be made as to whether and how to pursue a TBSS analysis. Finally, in addition to raising awareness by providing our new insights, we provide constructive suggestions that could improve the validity and increase the impact of TBSS drastically.
•We investigate tract-based spatial statistics (TBSS) considering potential pitfalls.•TBSS is not tract-specific and we show how this may falsify results.•User defined parameters strongly influence the final TBSS-derived results.•We provide suggestions that improve the validity and increase the impact of TBSS.
Very preterm human neonates are exposed to numerous invasive procedures as part of life-saving care. Evidence suggests that repetitive neonatal procedural pain precedes long-term alterations in brain ...development. However, to date the link between pain and brain development has limited temporal and anatomic specificity. We hypothesized that early exposure to painful stimuli during a period of rapid brain development, before pain modulatory systems reach maturity, will predict pronounced changes in thalamic development, and thereby cognitive and motor function. In a prospective cohort study, 155 very preterm neonates (82 males, 73 females) born 24-32 weeks' gestation underwent two MRIs at median postmenstrual ages 32 and 40 weeks that included structural, metabolic, and diffusion imaging. Detailed day-by-day clinical data were collected. Cognitive and motor abilities were assessed at 3 years, corrected age. The association of early (skin breaks, birth-Scan 1) and late pain (skin breaks, Scans 1-2) with thalamic volumes and
-acetylaspartate (NAA)/choline (Cho), and fractional anisotropy of white-matter pathways was assessed. Early pain was associated with slower thalamic macrostructural growth, most pronounced in extremely premature neonates. Deformation-based morphometry analyses confirmed early pain-related volume losses were localized to somatosensory regions. In extremely preterm neonates early pain was associated with decreased thalamic NAA/Cho and microstructural alterations in thalamocortical pathways. Thalamic growth was in turn related to cognitive and motor outcomes. We observed regionally-specific alterations in the lateral thalamus and thalamocortical pathways in extremely preterm neonates exposed to more procedural pain. Findings suggest a sensitive period leading to lasting alterations in somatosensory-system development.
Early exposure to repetitive procedural pain in very preterm neonates may disrupt the development of regions involved in somatosensory processing, leading to poor functional outcomes. We demonstrate that early pain is associated with thalamic volume loss in the territory of the somatosensory thalamus and is accompanied by disruptions thalamic metabolic growth and thalamocortical pathway maturation, particularly in extremely preterm neonates. Thalamic growth was associated with cognitive and motor outcome at 3 years corrected age. Findings provide evidence for a developmentally sensitive period whereby subcortical structures in young neonates may be most vulnerable to procedural pain. Furthermore, results suggest that the thalamus may play a key role underlying the association between neonatal pain and poor neurodevelopmental outcomes in these high-risk neonates.
•Abnormal white matter is associated with MDD in adolescents and young adults.•Lower FA mainly located in the corpus callosum and frontal-subcortical circuits.•Impairments of white matter integrity ...may contribute to the pathogenesis of MDD.
Adolescents and young adults are at a critical stage of life development, and depression can have serious consequences. In recent decades, an increasing number of diffusion tensor imaging (DTI) studies of major depressive disorder (MDD) have reported inconsistent alterations in white matter (WM) microarchitecture. To rule out the confounding effects of age, we conducted a meta-analysis of fractional anisotropy (FA) in adolescents and young adults with MDD to identify abnormalities in WM involved in the pathogenesis of MDD using anisotropic effect-size signed differential mapping (AES-SDM). The pooled meta-analysis revealed significantly lower FA mainly in the corpus callosum (CC) extending to the left anterior thalamic projections (ATP) and left cortico-spinal projection (CSP) in depressed adolescents and young adults than that in healthy controls. A reduction in FA was also identified in the right frontal orbito-polar tract (FOPT) extending to the right inferior fronto-occipital fasciculus (IFOF). In the meta-regression analysis, the mean age of patients, percentage of female patients and duration of depression were not linearly associated with abnormalities in FA. These results constitute robust evidence that abnormalities in WM microarchitecture in the interhemispheric connections and frontal-subcortical neuronal circuits may contribute to the pathogenesis of MDD during adolescence and young adulthood.
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects approximately 8%-12% of children worldwide. Throughout an individual's lifetime, ADHD can significantly ...increase risk for other psychiatric disorders, educational and occupational failure, accidents, criminality, social disability and addictions. No single risk factor is necessary or sufficient to cause ADHD. The multifactorial causation of ADHD is reflected in the heterogeneity of this disorder, as indicated by its diversity of psychiatric comorbidities, varied clinical profiles, patterns of neurocognitive impairment and developmental trajectories, and the wide range of structural and functional brain anomalies. Although evidence-based treatments can reduce ADHD symptoms in a substantial portion of affected individuals, there is yet no curative treatment for ADHD. A number of theoretical models of the emergence and developmental trajectories of ADHD have been proposed, aimed at providing systematic guides for clinical research and practice. We conducted a comprehensive review of the current status of research in understanding the heterogeneity of ADHD in terms of etiology, clinical profiles and trajectories, and neurobiological mechanisms. We suggest that further research focus on investigating the impact of the etiological risk factors and their interactions with developmental neural mechanisms and clinical profiles in ADHD. Such research would have heuristic value for identifying biologically homogeneous subgroups and could facilitate the development of novel and more tailored interventions that target underlying neural anomalies characteristic of more homogeneous subgroups.
Schizophrenia is frequently characterized as a disorder of brain connectivity. Neuroimaging has played a central role in supporting this view, with nearly two decades of research providing abundant ...evidence of structural and functional connectivity abnormalities in the disorder. In recent years, our understanding of how schizophrenia affects brain networks has been greatly advanced by attempts to map the complete set of inter-regional interactions comprising the brain's intricate web of connectivity; i.e., the human connectome. Imaging connectomics refers to the use of neuroimaging techniques to generate these maps which, combined with the application of graph theoretic methods, has enabled relatively comprehensive mapping of brain network connectivity and topology in unprecedented detail. Here, we review the application of these techniques to the study of schizophrenia, focusing principally on magnetic resonance imaging (MRI) research, while drawing attention to key methodological issues in the field. The published findings suggest that schizophrenia is associated with a widespread and possibly context-independent functional connectivity deficit, upon which are superimposed more circumscribed, context-dependent alterations associated with transient states of hyper- and/or hypo-connectivity. In some cases, these changes in inter-regional functional coupling dynamics can be related to measures of intra-regional dysfunction. Topological disturbances of functional brain networks in schizophrenia point to reduced local network connectivity and modular structure, as well as increased global integration and network robustness. Some, but not all, of these functional abnormalities appear to have an anatomical basis, though the relationship between the two is complex. By comprehensively mapping connectomic disturbances in patients with schizophrenia across the entire brain, this work has provided important insights into the highly distributed character of neural abnormalities in the disorder, and the potential functional consequences that these disturbances entail.
► Schizophrenia is a prototypical connectivity disorder. ► This article reviews imaging connectomic studies of schizophrenia. ► A primer on basic principles and methods of the field is provided. ► Key methodological issues in the literature are highlighted.
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