Consistency and interpretation of changes in millimeter-scale cortical intrinsic curvature across three independent datasets in schizophrenia

Abstract

Several studies have sought to test the neurodevelopmental hypothesis of schizophrenia through analysis of cortical gyrification. However, to date, results have been inconsistent. A possible reason for this is that gyrification measures at the centimeter scale may be insensitive to subtle morphological changes at smaller scales. The lack of consistency in such studies may impede further interpretation of cortical morphology as an aid to understanding the etiology of schizophrenia.In this study we developed a new approach, examining whether millimeter-scale measures of cortical curvature are sensitive to changes in fundamental geometric properties of the cortical surface in schizophrenia. We determined and compared millimeter-scale and centimeter-scale curvature in three separate case–control studies; specifically two adult groups and one adolescent group. The datasets were of different sizes, with different ages and gender-spreads. The results clearly show that millimeter-scale intrinsic curvature measures were more robust and consistent in identifying reduced gyrification in patients across all three datasets.To further interpret this finding we quantified the ratio of expansion in the upper and lower cortical layers. The results suggest that reduced gyrification in schizophrenia is driven by a reduction in the expansion of upper cortical layers. This may plausibly be related to a reduction in short-range connectivity.

Intrinsic gray-matter connectivity of the brain in adults with autism spectrum disorder

“…Thus, depending on different geometries, a patch of uniform area may be achieved by either an increased or decreased ratio of radius to perimeter. Our results therefore further suggest that the brain has negative curvature, which supports previous observations using alternative measures of intrinsic cortical morphometry (25,30). The molecular and genetic mechanisms underlying the atypical expansion and wiring of the cortex in ASD remain largely unknown.…”

“…Differences in intrinsic geometry of the cortex have previously also been related to the density of neural units defining the surface architecture of individual cortical regions (25,30). Theoretically (Fig.…”

“…Although these connections can extend up to a few millimeters (19,21), intrinsic connections are difficult to measure in vivo as they are not explicitly quantifiable by conventional measures of brain volume or cortical thickness. Intrinsic connections are, however, well documented in the in vitro literature and have previously been implicated in other neurodevelopmental/neuropsychiatric conditions, such as schizophrenia (29)(30)(31), where more postmortem data are currently available to allow histological characterization relative to ASD. We therefore used a surface-based approach to brain morphometry (24) to investigate the horizontal organization of the cortex in ASD.…”

“…As assessed here, wiring costs do not represent the actual length of axonal connections but are indicative of the intrinsic "wiring potential" of a brain region (i.e., reduced costs may facilitate the formation of intrinsic cortico-cortical circuits). As such, intrinsic measures reflect the actual intrinsic architecture of the brain, which may differ across different regions and may also include different neural components characterizing the lateral (i.e., horizontal) architecture of the cortex (30,32).…”

“…For example, the distance between two points on a sheet of paper remains the same regardless of whether the sheet is folded or unfolded. Thus, intrinsic measures are distinguished from extrinsic features such as cortical folding, which affect the 3D alignment of the cortex but does not alter distances between surface points (25,30).…”