Regional structural differences in patients with schizophrenia include bilaterally reduced volume of medial temporal lobe structures. There is a need for greater integration of results from structural MRI studies to avoid redundant research activity.
We describe almost entirely automated procedures for estimation of global, voxel, and cluster-level statistics to test the null hypothesis of zero neuroanatomical difference between two groups of structural magnetic resonance imaging (MRI) data. Theoretical distributions under the null hypothesis are available for 1) global tissue class volumes; 2) standardized linear model [analysis of variance (ANOVA and ANCOVA)] coefficients estimated at each voxel; and 3) an area of spatially connected clusters generated by applying an arbitrary threshold to a two-dimensional (2-D) map of normal statistics at voxel level. We describe novel methods for economically ascertaining probability distributions under the null hypothesis, with fewer assumptions, by permutation of the observed data. Nominal Type I error control by permutation testing is generally excellent; whereas theoretical distributions may be over conservative. Permutation has the additional advantage that it can be used to test any statistic of interest, such as the sum of suprathreshold voxel statistics in a cluster (or cluster mass), regardless of its theoretical tractability under the null hypothesis. These issues are illustrated by application to MRI data acquired from 18 adolescents with hyperkinetic disorder and 16 control subjects matched for age and gender.
ADHD is associated with subnormal activation of the prefrontal systems responsible for higher-order motor control. Functional MRI is a feasible technique for investigation of neural correlates of ADHD.
It is nearly 20 years since the concept of a small-world network was first quantitatively defined, by a combination of high clustering and short path length; and about 10 years since this metric of complex network topology began to be widely applied to analysis of neuroimaging and other neuroscience data as part of the rapid growth of the new field of connectomics. Here, we review briefly the foundational concepts of graph theoretical estimation and generation of small-world networks. We take stock of some of the key developments in the field in the past decade and we consider in some detail the implications of recent studies using high-resolution tract-tracing methods to map the anatomical networks of the macaque and the mouse. In doing so, we draw attention to the important methodological distinction between topological analysis of binary or unweighted graphs, which have provided a popular but simple approach to brain network analysis in the past, and the topology of weighted graphs, which retain more biologically relevant information and are more appropriate to the increasingly sophisticated data on brain connectivity emerging from contemporary tract-tracing and other imaging studies. We conclude by highlighting some possible future trends in the further development of weighted small-worldness as part of a deeper and broader understanding of the topology and the functional value of the strong and weak links between areas of mammalian cortex.
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...
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