Developmental Brain Asymmetry. The Good and the Bad Sides

Brain asymmetry is a hallmark of the human brain. Recent studies report a certain degree of abnormal asymmetry of brain lateralization between left and right brain hemispheres can be associated with many neuropsychiatric conditions. In this regard, some questions need answers. First, the accelerated brain asymmetry is programmed during the pre-natal period that can be called “accelerated brain decline clock”. Second, can we find the right biomarkers to predict these changes? Moreover, can we establish the dynamics of these changes in order to identify the right time window for proper interventions that can reverse or limit the neurological decline? To find answers to these questions, we performed a systematic online search for the last 10 years in databases using keywords. Conclusion: we need to establish the right in vitro model that meets human conditions as much as possible. New biomarkers are necessary to establish the “good” or the “bad” borders of brain asymmetry at the epigenetic and functional level as early as possible.

Brain Asymmetry: Towards an Asymmetrical Neurovisceral Integration

Despite the ancestral evidence of an asymmetry in motor predominance, going through the inspiring discoveries of Broca and Wernicke on the localization of language processing, continuing with the subsequent noise coinciding with the study of brain function in commissurotomized patients—and the subsequent avalanche of data on the asymmetric distribution of multiple types of neurotransmitters in physiological and pathological conditions—even today, the functional significance of brain asymmetry is still unknown. Currently, multiple evidence suggests that functional asymmetries must have a neurochemical substrate and that brain asymmetry is not a static concept but rather a dynamic one, with intra- and inter-hemispheric interactions between its various processes, and that it is modifiable depending on changing endogenous and environmental conditions. Furthermore, based on the concept of neurovisceral integration in the overall functioning of an organism, some evidence has emerged suggesting that this integration could be organized asymmetrically, using the autonomic nervous system as a bidirectional communication pathway, whose performance would also be asymmetric. However, the functional significance of this distribution, as well as the evolutionary advantage of an asymmetric nervous organization, is still unknown.

Structural and functional asymmetry of the neonatal cerebral cortex

Features of brain asymmetry have been implicated in a broad range of cognitive processes; however, their origins are still poorly understood. Using a new left-right symmetric, spatiotemporal cortical surface atlas, we investigated cortical asymmetries in 442 healthy newborn infants soon after birth, using structural and functional magnetic resonance images from the Developing Human Connectome Project. We identified previously unrecognised structural and functional asymmetries in auditory, visual and sensorimotor cortices, which closely resemble known asymmetries in adults. These findings show that cortical asymmetries are largely determined prenatally and suggest that they may constrain the development of lateralised functions in later life. In adults, deviations in brain asymmetry have been implicated in a broad range of developmental and psychiatric disorders, some of which have been associated with abnormal perinatal neurodevelopment. To test the hypothesis that normal cortical asymmetry is disrupted in the perinatal period by severe environmental stress, we compared cortical asymmetries between the same group of term neonates and 103 preterm neonates imaged at term-equivalent age. No significant differences were seen between these two cohorts, showing that the development of cortical asymmetries proceeds largely unaffected by preterm birth.

Patterns of brain asymmetry associated with polygenic risks for autism and schizophrenia implicate language and executive functions but not brain masculinization

Autism spectrum disorder (ASD) and schizophrenia have been conceived as partly opposing disorders in terms of systemizing vs. empathizing cognitive styles, with resemblances to male vs. female average sex differences. Left–right asymmetry of the brain is an important aspect of its organization that shows average differences between the sexes and can be altered in both ASD and schizophrenia. Here we mapped multivariate associations of polygenic risk scores for ASD and schizophrenia with asymmetries of regional cerebral cortical surface area, thickness, and subcortical volume measures in 32,256 participants from the UK Biobank. Polygenic risks for the two disorders were positively correlated (r = 0.08, p = 7.13 × 10−50) and both were higher in females compared to males, consistent with biased participation against higher-risk males. Each polygenic risk score was associated with multivariate brain asymmetry after adjusting for sex, ASD r = 0.03, p = 2.17 × 10−9, and schizophrenia r = 0.04, p = 2.61 × 10−11, but the multivariate patterns were mostly distinct for the two polygenic risks and neither resembled average sex differences. Annotation based on meta-analyzed functional imaging data showed that both polygenic risks were associated with asymmetries of regions important for language and executive functions, consistent with behavioral associations that arose in phenome-wide association analysis. Overall, the results indicate that distinct patterns of subtly altered brain asymmetry may be functionally relevant manifestations of polygenic risks for ASD and schizophrenia, but do not support brain masculinization or feminization in their etiologies.