Multi-center studies using magnetic resonance imaging facilitate studying small effect sizes, global population variance and rare diseases. The reliability and sensitivity of these multi-center studies crucially depend on the comparability of the data generated at different sites and time points. The level of inter-site comparability is still controversial for conventional anatomical T1-weighted MRI data. Quantitative multi-parameter mapping (MPM) was designed to provide MR parameter measures that are comparable across sites and time points, i.e., 1 mm high-resolution maps of the longitudinal relaxation rate (R1 = 1/T1), effective proton density (PD*), magnetization transfer saturation (MT) and effective transverse relaxation rate (R2* = 1/T2*). MPM was validated at 3T for use in multi-center studies by scanning five volunteers at three different sites. We determined the inter-site bias, inter-site and intra-site coefficient of variation (CoV) for typical morphometric measures [i.e., gray matter (GM) probability maps used in voxel-based morphometry] and the four quantitative parameters. The inter-site bias and CoV were smaller than 3.1 and 8%, respectively, except for the inter-site CoV of R2* (<20%). The GM probability maps based on the MT parameter maps had a 14% higher inter-site reproducibility than maps based on conventional T1-weighted images. The low inter-site bias and variance in the parameters and derived GM probability maps confirm the high comparability of the quantitative maps across sites and time points. The reliability, short acquisition time, high resolution and the detailed insights into the brain microstructure provided by MPM makes it an efficient tool for multi-center imaging studies.

How does human brain structure mature during adolescence? We used MRI to measure cortical thickness and intracortical myelination in 297 population volunteers aged 14-24 y old. We found and replicated that association cortical areas were thicker and less myelinated than primary cortical areas at 14 y. However, association cortex had faster rates of shrinkage and myelination over the course of adolescence. Age-related increases in cortical myelination were maximized approximately at the internal layer of projection neurons. Adolescent cortical myelination and shrinkage were coupled and specifically associated with a dorsoventrally patterned gene expression profile enriched for synaptic, oligodendroglial-and schizophrenia-related genes. Topologically efficient and biologically expensive hubs of the brain anatomical network had greater rates of shrinkage/myelination and were associated with overexpression of the same transcriptional profile as cortical consolidation. We conclude that normative human brain maturation involves a genetically patterned process of consolidating anatomical network hubs. We argue that developmental variation of this consolidation process may be relevant both to normal cognitive and behavioral changes and the high incidence of schizophrenia during human brain adolescence. A dolescence is associated with major behavioral, social, and sexual changes as well as increased risk for many psychiatric disorders (1). However, human brain maturation during adolescence is not yet so well understood. Historically, pioneering studies used histological techniques to show that distinct areas of cortex were differentially myelinated in postmortem examination of perinatal tissue, suggesting "myelinogenesis" as an important process in human brain development (2, 3). MRI can measure human brain development more comprehensively and over a wider age range than is possible for postmortem anatomists. The thickness of human cortex can be reliably and replicably measured by MRI (4), and longitudinal studies have shown that cortical thickness (CT; millimeters) monotonically shrinks over the course of postnatal development, with variable shrinkage rates estimated for different age ranges (5-11; review in ref. 12). CT typically shrinks from about 3.5 mm at age 13 y old (9) to about 2.2 mm at age 75 y old (10, 11). Rates of cortical shrinkage are faster during adolescence (approximately −0.05 mm/y) than in later adulthood or earlier childhood (9).What does this MRI phenomenon of cortical shrinkage represent at a cellular level? There are broadly two tenable models: pruning and myelination. Basic physical principles of MRI predict that shorter longitudinal (T1) relaxation times reflect either a reduction in the fraction of "watery" cytoplasmic material, like cell bodies, synapses, or extracellular fluid, or an increase in the fraction of "fatty" myelinated material, like axons. Pruning models propose that cortical shrinkage in adolescence represents loss or remodeling of synapses, dendrites, or cell bodies (13). Myelin...

BackgroundA World Health Organization 2017 report stated that major depression affects almost 5% of the human population. Major depression is associated with impaired psychosocial functioning and reduced quality of life. Challenges such as shortage of mental health personnel, long waiting times, perceived stigma, and lower government spends pose barriers to the alleviation of mental health problems. Face-to-face psychotherapy alone provides only point-in-time support and cannot scale quickly enough to address this growing global public health challenge. Artificial intelligence (AI)-enabled, empathetic, and evidence-driven conversational mobile app technologies could play an active role in filling this gap by increasing adoption and enabling reach. Although such a technology can help manage these barriers, they should never replace time with a health care professional for more severe mental health problems. However, app technologies could act as a supplementary or intermediate support system. Mobile mental well-being apps need to uphold privacy and foster both short- and long-term positive outcomes.ObjectiveThis study aimed to present a preliminary real-world data evaluation of the effectiveness and engagement levels of an AI-enabled, empathetic, text-based conversational mobile mental well-being app, Wysa, on users with self-reported symptoms of depression.MethodsIn the study, a group of anonymous global users were observed who voluntarily installed the Wysa app, engaged in text-based messaging, and self-reported symptoms of depression using the Patient Health Questionnaire-9. On the basis of the extent of app usage on and between 2 consecutive screening time points, 2 distinct groups of users (high users and low users) emerged. The study used mixed-methods approach to evaluate the impact and engagement levels among these users. The quantitative analysis measured the app impact by comparing the average improvement in symptoms of depression between high and low users. The qualitative analysis measured the app engagement and experience by analyzing in-app user feedback and evaluated the performance of a machine learning classifier to detect user objections during conversations.ResultsThe average mood improvement (ie, difference in pre- and post-self-reported depression scores) between the groups (ie, high vs low users; n=108 and n=21, respectively) revealed that the high users group had significantly higher average improvement (mean 5.84 [SD 6.66]) compared with the low users group (mean 3.52 [SD 6.15]); Mann-Whitney P=.03 and with a moderate effect size of 0.63. Moreover, 67.7% of user-provided feedback responses found the app experience helpful and encouraging.ConclusionsThe real-world data evaluation findings on the effectiveness and engagement levels of Wysa app on users with self-reported symptoms of depression show promise. However, further work is required to validate these initial findings in much larger samples and across longer periods.

Autism Spectrum Disorders (ASDs) are neurodevelopmental syndromes characterised by repetitive behaviours and restricted interests, impairments in social behavior and relations, and in language and communication. These symptoms are also observed in a number of developmental disorders of known origin, including Fragile X Syndrome, Rett syndrome, and Fetal Anticonvulsant Syndrome. While these conditions have diverse etiologies, and poorly understood pathologies, emerging evidence suggests that they may all be linked to dysfunction in particular aspects of GABAergic inhibitory signalling in the brain. We review evidence from genetics, molecular neurobiology and systems neuroscience relating to the role of GABA in these conditions. We conclude by discussing how these deficits may relate to the specific symptoms observed.

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