This review implicates the left superior temporal gyrus and the left medial temporal lobe as key regions of structural difference in patients with schizophrenia, compared to healthy subjects. The diversity of regions reported in voxel-based morphometry studies is in part related to the choice of variables in the automated process, such as smoothing kernel size and linear versus affine transformation, as well as to differences in patient groups. Voxel-based morphometry can be used as an exploratory whole-brain approach to identify abnormal brain regions in schizophrenia, which should then be validated by using region-of-interest analyses.

Gerstmann-Sträussler syndrome is a rare familial neurodegenerative condition that is vertically transmitted, in an apparently autosomal dominant way. It can also be horizontally transmitted to non-human primates and rodents through intracerebral inoculation of brain homogenates from patients with the disease. The exact incidence of the syndrome is unknown but is estimated to be between one and ten per hundred million. Patients initially suffer from ataxia or dementia and deteriorate until they die, in one to ten years. Protease-resistant prion protein (PrP) and PrP-immunoreactive amyloid plaques with characteristic morphology accumulate in the brains of these patients. Current diagnostic criteria for Gerstmann-Sträussler syndrome incorporate clinical and neuropathological features, as animal transmission studies can be unreliable. PrP is implicated in the pathogenesis and transmission of the condition and in scrapie, an equivalent animal disease. It was discovered by enriching scrapie-infected hamster brain fractions for infectivity. Because there is compelling evidence that the scrapie isoform of PrP is a necessary component of the infectious particle, it seemed possible that the PrP gene on the short arm of human chromosome 20 in Gerstmann-Sträussler syndrome might be abnormal. We show here that PrP codon 102 is linked to the putative gene for the syndrome in two pedigrees, providing the best evidence to date that this familial condition is inherited despite also being infectious, and that substitution of leucine for proline at PrP codon 102 may lead to the development of Gerstmann-Sträussler syndrome.

Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here the ENIGMA consortium presents the largest ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and brain size (indexed by intracranial volume). Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (N = 1,443 and 1,113, respectively), we found several asymmetries showing modest but highly reliable heritability. The structural asymmetries identified, and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.Significance StatementLeft-right asymmetry is a key feature of the human brain's structure and function. It remains unclear which cortical regions are asymmetrical on average in the population, and how biological factors such as age, sex and genetic variation affect these asymmetries. Here we describe by far the largest ever study of cerebral cortical brain asymmetry, based on data from 17,141 participants. We found a global anterior-posterior 'torque' pattern in cortical thickness, together with various regional asymmetries at the population level, which have not been previously described, as well as effects of age, sex, and heritability estimates. From these data, we have created an on-line resource that will serve future studies of human brain anatomy in health and disease.

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.

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A joint and integrated analysis of multi-site diffusion MRI (dMRI) datasets can dramatically increase the statistical power of neuroimaging studies and enable comparative studies pertaining to several brain disorders. However, dMRI data sets acquired on multiple scanners cannot be naively pooled for joint analysis due to scanner specific nonlinear effects as well as differences in acquisition parameters. Consequently, for joint analysis, the dMRI data has to be harmonized, which involves removing scanner-specific differences from the raw dMRI signal. In this work, we propose a dMRI harmonization method that is capable of removing scanner-specific effects, while accounting for minor differences in acquisition parameters such as b-value, spatial resolution and number of gradient directions. We validate our algorithm on dMRI data acquired from two sites: Philadelphia Neurodevelopmental Cohort (PNC) with 800 healthy adolescents (ages 8-22 years) and Brigham and Women's Hospital (BWH) with 70 healthy subjects (ages 14-54 years). In particular, we show that gender and age-related maturation differences in different age groups are preserved after harmonization, as measured using effect sizes (small, medium and large), irrespective of the test sample size. Since we use matched control subjects from different scanners to estimate scanner-specific effects, our goal in this work is also to determine the minimum number of well-matched subjects needed from each site to achieve best harmonization results. Our results indicate that at-least 16 to 18 well-matched healthy controls from each site are needed to reliably capture scanner related differences. The proposed method can thus be used for retrospective harmonization of raw dMRI data across sites despite differences in acquisition parameters, while preserving inter-subject anatomical variability.

In this paper, we draw a link between cortical intrinsic curvature and the distributions of tangential connection lengths. We suggest that differential rates of surface expansion not only lead to intrinsic curvature of the cortical sheet, but also to differential inter-neuronal spacing. We propose that there follows a consequential change in the profile of neuronal connections: specifically an enhancement of the tendency towards proportionately more short connections. Thus, the degree of cortical intrinsic curvature may have implications for short-range connectivity.

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