Asymmetries of the cerebral cortex are found across diverse phyla and are particularly pronounced in humans, with important implications for brain function and disease. However, many prior studies have confounded asymmetries due to size with those due to shape. Here, we introduce a novel approach to characterize asymmetries of the whole cortical shape, independent of size, across different spatial frequencies using magnetic resonance imaging data in three independent datasets. We find that cortical shape asymmetry is highly individualized and robust, akin to a cortical fingerprint, and identifies individuals more accurately than size-based descriptors, such as cortical thickness and surface area, or measures of inter-regional functional coupling of brain activity. Individual identifiability is optimal at coarse spatial scales (~37 mm wavelength), and shape asymmetries show scale-specific associations with sex and cognition, but not handedness. While unihemispheric cortical shape shows significant heritability at coarse scales (~65 mm wavelength), shape asymmetries are determined primarily by subject-specific environmental effects. Thus, coarse-scale shape asymmetries are highly personalized, sexually dimorphic, linked to individual differences in cognition, and are primarily driven by stochastic environmental influences.

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Asymmetries of the cerebral cortex are found across diverse phyla and occur at multiple spatial scales, from the global morphology of the two hemispheres to fine-grained sulcal and gyral anatomy. Cortical asymmetries are particularly pronounced in humans and have important implications for brain function and disease. However, most studies conflate asymmetries in regional size and shape and only consider effects at fairly fine-grained resolutions, such as image voxels or a priori regions-of-interest. As such, whether asymmetries are preferentially expressed at specific spatial resolutions over others remains unclear. Here, we apply a spectral shape analysis to magnetic resonance imaging (MRI) data from three independent samples to derive a multiscale description of asymmetries in cortical shape that is distinct from regional size-related descriptors such as volume or thickness. We show that our proposed shape asymmetry signature (SAS) is a highly individualized feature, akin to a cortical fingerprint, that more accurately identifies individuals than size-based descriptors or measures of inter-regional functional coupling of brain activity. Notably, individual identifiability is optimal at coarse spatial scales (~37 mm wavelength), and shape asymmetries at specific scales show differences between males and females but are unrelated to the handedness. We further demonstrate that while unihemispheric shape descriptors show significant heritability at coarse scales, the SAS are determined primarily by unique environmental effects across all scales considered. Our findings thus identify coarse-scale scale asymmetries of cortical shape as being highly unique to individuals, sexually dimorphic, and largely driven by stochastic environmental influences.

The rates of cannabis use have been narrowing between sexes over the past decade, and there are sex differences in the perception of cannabis use-related risks, yet it remains unexamined whether sex and risk perception interact to predict cannabis consumption levels. We aimed to examine for the first time how sex, risk perception, and their interaction affect cannabis consumption, accounting for age, alcohol use, mode of administration, education, employment status, and country via general linear mixed models. We conducted the European Web Survey on Drugs in 16 countries from 2016 to 2018. People who used cannabis at the time of the study included 6500 males and 2921 females, with a median age of 22 years. There was no risk perception-by-sex interaction effect on cannabis consumption. Greater past-month cannabis dosage in grams and frequency (days used/past month) were reported by males and by persons who reported having a perception of no risk and of a slight risk versus a moderate-to-high-risk perception. The findings may inform discussions on public health messaging aimed at alleviating cannabis-related harms in males and females who use cannabis.

It remains elusive how and why some people born with profound brain structure abnormalities develop high levels of intellect and near normal behaviour, while others with what appears to be the same or similar structural abnormalities experience far more concerning phenotypical outcomes. To begin to address this issue, a high-functioning female (aged 17 years at testing) born with complete callosal agenesis (ACC1) was tested on a series of psychophysical tests requiring unimanual-sequential or bimanual object weight discrimination; the latter of which is believed to depend on the integrity of the corpus callosum. In all five variants of the weight-discrimination task, ACC1’s performance was well within two standard deviations of the sample distribution mean. Arguably within the normal range, her performance warrants further investigation. Results suggest that individuals like ACC1 hold the secret to future understanding of the elusive neuro-compensatory processes of the human brain.

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