The discovery of population differences in network community structure: New methods and applications to brain functional networks in schizophrenia

The modular organization of the brain network can vary in two fundamental ways. The amount of interversus intra-modular connections between network nodes can be altered, or the community structure itself can be perturbed, in terms of which nodes belong to which modules (or communities). Alterations have previously been reported in modularity, which is a function of the proportion of intra-modular edges over all modules in the network. For example, we have reported that modularity is decreased in functional brain networks in schizophrenia: There are proportionally more inter-modular edges and fewer intra-modular edges. However, despite numerous and increasing studies of brain modular organization, it is not known how to test for differences in the community structure, i.e., the assignment of regional nodes to specific modules. Here, we introduce a method based on the normalized mutual information between pairs of modular networks to show that the community structure of the brain network is significantly altered in schizophrenia, using resting-state fMRI in 19 participants with childhood-onset schizophrenia and 20 healthy participants. We also develop tools to show which specific nodes (or brain regions) have significantly different modular communities between groups, a subset that includes right insular and perisylvian cortical regions. The methods that we propose are broadly applicable to other experimental contexts, both in neuroimaging and other areas of network science

Mapping cortical anatomy in preschool aged children with autism using surface-based morphometry☆

The challenges of gathering in-vivo measures of brain anatomy from young children have limited the number of independent studies examining neuroanatomical differences between children with autism and typically developing controls (TDCs) during early life, and almost all studies in this critical developmental window focus on global or lobar measures of brain volume. Using a novel cohort of young males with Autistic Disorder and TDCs aged 2 to 5 years, we (i) tested for group differences in traditional measures of global anatomy (total brain, total white, total gray and total cortical volume), and (ii) employed surface-based methods for cortical morphometry to directly measure the two biologically distinct sub-components of cortical volume (CV) at high spatial resolution—cortical thickness (CT) and surface area (SA). While measures of global brain anatomy did not show statistically significant group differences, children with autism showed focal, and CT-specific anatomical disruptions compared to TDCs, consisting of relative cortical thickening in regions with central roles in behavioral regulation, and the processing of language, biological movement and social information. Our findings demonstrate the focal nature of brain involvement in early autism, and provide more spatially and morphometrically specific anatomical phenotypes for subsequent translational study

Differential tangential expansion as a mechanism for cortical gyrification.

Gyrification, the developmental buckling of the cortex, is not a random process-the forces that mediate expansion do so in such a way as to generate consistent patterns of folds across individuals and even species. Although the origin of these forces is unknown, some theories have suggested that they may be related to external cortical factors such as axonal tension. Here, we investigate an alternative hypothesis, namely, whether the differential tangential expansion of the cortex alone can account for the degree and pattern-specificity of gyrification. Using intrinsic curvature as a measure of differential expansion, we initially explored whether this parameter and the local gyrification index (used to quantify the degree of gyrification) varied in a regional-specific pattern across the cortical surface in a manner that was replicable across independent datasets of neurotypicals. Having confirmed this consistency, we further demonstrated that within each dataset, the degree of intrinsic curvature of the cortex was predictive of the degree of cortical folding at a global and regional level. We conclude that differential expansion is a plausible primary mechanism for gyrification, and propose that this perspective offers a compelling mechanistic account of the co-localization of cytoarchitecture and cortical folds

Leveraging big data for causal understanding in mental health: a research framework

Over the past 30 years there have been numerous large-scale and longitudinal psychiatric research efforts to improve our understanding and treatment of mental health conditions. However, despite the huge effort by the research community and considerable funding, we still lack a causal understanding of most mental health disorders. Consequently, the majority of psychiatric diagnosis and treatment still operates at the level of symptomatic experience, rather than measuring or addressing root causes. This results in a trial-and-error approach that is a poor fit to underlying causality with poor clinical outcomes. Here we discuss how a research framework that originates from exploration of causal factors, rather than symptom groupings, applied to large scale multi-dimensional data can help address some of the current challenges facing mental health research and, in turn, clinical outcomes. Firstly, we describe some of the challenges and complexities underpinning the search for causal drivers of mental health conditions, focusing on current approaches to the assessment and diagnosis of psychiatric disorders, the many-to-many mappings between symptoms and causes, the search for biomarkers of heterogeneous symptom groups, and the multiple, dynamically interacting variables that influence our psychology. Secondly, we put forward a causal-orientated framework in the context of two large-scale datasets arising from the Adolescent Brain Cognitive Development (ABCD) study, the largest long-term study of brain development and child health in the United States, and the Global Mind Project which is the largest database in the world of mental health profiles along with life context information from 1.4 million people across the globe. Finally, we describe how analytical and machine learning approaches such as clustering and causal inference can be used on datasets such as these to help elucidate a more causal understanding of mental health conditions to enable diagnostic approaches and preventative solutions that tackle mental health challenges at their root cause

The impact of sound field systems on learning and attention in elementary school classrooms

Purpose: An evaluation of the installation and use of sound field systems (SFS) was carried out to investigate their impact on teaching and learning in elementary school classrooms. Methods: The evaluation included acoustic surveys of classrooms, questionnaire surveys of students and teachers and experimental testing of students with and without the use of SFS. Students ’ perceptions of classroom environments and objective data evaluating change in performance on cognitive and academic assessments with amplification over a six month period are reported. Results: Teachers were positive about the use of SFS in improving children’s listening and attention to verbal instructions. Over time students in amplified classrooms did not differ from those in nonamplified classrooms in their reports of listening conditions, nor did their performance differ in measures of numeracy, reading or spelling. Use of SFS in the classrooms resulted in significantly larger gains in performance in the number of correct items on the nonverbal measure of speed of processing and the measure of listening comprehension. Analysis controlling for classroom acoustics indicated that students ’ listening comprehension score

Adolescent brain maturation and cortical folding: evidence for reductions in gyrification

Evidence from anatomical and functional imaging studies have highlighted major modifications of cortical circuits during adolescence. These include reductions of gray matter (GM), increases in the myelination of cortico-cortical connections and changes in the architecture of large-scale cortical networks. It is currently unclear, however, how the ongoing developmental processes impact upon the folding of the cerebral cortex and how changes in gyrification relate to maturation of GM/WM-volume, thickness and surface area. In the current study, we acquired high-resolution (3 Tesla) magnetic resonance imaging (MRI) data from 79 healthy subjects (34 males and 45 females) between the ages of 12 and 23 years and performed whole brain analysis of cortical folding patterns with the gyrification index (GI). In addition to GI-values, we obtained estimates of cortical thickness, surface area, GM and white matter (WM) volume which permitted correlations with changes in gyrification. Our data show pronounced and widespread reductions in GI-values during adolescence in several cortical regions which include precentral, temporal and frontal areas. Decreases in gyrification overlap only partially with changes in the thickness, volume and surface of GM and were characterized overall by a linear developmental trajectory. Our data suggest that the observed reductions in GI-values represent an additional, important modification of the cerebral cortex during late brain maturation which may be related to cognitive development

Human development of the ability to learn from bad news

Humans show a natural tendency to discount bad news while incorporating good news into beliefs (the “good news–bad news effect”), an effect that may help explain seemingly irrational risk taking. Understanding how this bias develops with age is important because adolescents are prone to engage in risky behavior; thus, educating them about danger is crucial. We reveal a striking valence-dependent asymmetry in how belief updating develops with age. In the ages tested (9–26 y), younger age was associated with inaccurate updating of beliefs in response to undesirable information regarding vulnerability. In contrast, the ability to update beliefs accurately in response to desirable information remained relatively stable with age. This asymmetry was mediated by adequate computational use of positive but not negative estimation errors to alter beliefs. The results are important for understanding how belief formation develops and might help explain why adolescents do not respond adequately to warnings

A four-dimensional probabilistic atlas of the human brain

The authors describe the development of a four-dimensional atlas and reference system that includes both macroscopic and microscopic information on structure and function of the human brain in persons between the ages of 18 and 90 years. Given the presumed large but previously unquantified degree of structural and functional variance among normal persons in the human population, the basis for this atlas and reference system is probabilistic. Through the efforts of the International Consortium for Brain Mapping (ICBM), 7,000 subjects will be included in the initial phase of database and atlas development. For each subject, detailed demographic, clinical, behavioral, and imaging information is being collected. In addition, 5,800 subjects will contribute DNA for the purpose of determining genotype-phenotype-behavioral correlations. The process of developing the strategies, algorithms, data collection methods, validation approaches, database structures, and distribution of results is described in this report. Examples of applications of the approach are described for the normal brain in both adults and children as well as in patients with schizophrenia. This project should provide new insights into the relationship between microscopic and macroscopic structure and function in the human brain and should have important implications in basic neuroscience, clinical diagnostics, and cerebral disorders

Adolescent Engagement in Dangerous Behaviors Is Associated with Increased White Matter Maturity of Frontal Cortex

Background: Myelination of white matter in the brain continues throughout adolescence and early adulthood. This cortical immaturity has been suggested as a potential cause of dangerous and impulsive behaviors in adolescence. Methodology/Principal Findings: We tested this hypothesis in a group of healthy adolescents, age 12–18 (N = 91), who underwent diffusion tensor imaging (DTI) to delineate cortical white matter tracts. As a measure of real-world risk taking, participants completed the Adolescent Risk Questionnaire (ARQ) which measures engagement in dangerous activities. After adjusting for age-related changes in both DTI and ARQ, engagement in dangerous behaviors was found to be positively correlated with fractional anisotropy and negatively correlated with transverse diffusivity in frontal white matter tracts, indicative of increased myelination and/or density of fibers (ages 14–18, N = 60). Conclusions/Significance: The direction of correlation suggests that rather than having immature cortices, adolescents who engage in dangerous activities have frontal white matter tracts that are more adult in form than their more conservative peers