Atypical Brain Asymmetry in Human Situs Inversus: Gut Feeling or Real Evidence?

Abstract

The alignment of visceral and brain asymmetry observed in some vertebrate species raises the question of whether this association also exists in humans. While the visceral and brain systems may have developed asymmetry for different reasons, basic visceral left–right differentiation mechanisms could have been duplicated to establish brain asymmetry. We describe the main phenotypical anomalies and the general mechanism of left–right differentiation of vertebrate visceral and brain laterality. Next, we systematically review the available human studies that explored the prevalence of atypical behavioral and brain asymmetry in visceral situs anomalies, which almost exclusively involved participants with the mirrored visceral organization (situs inversus). The data show no direct link between human visceral and brain functional laterality as most participants with situs inversus show the typical population bias for handedness and brain functional asymmetry, although an increased prevalence of functional crowding may be present. At the same time, several independent studies present evidence for a possible relation between situs inversus and the gross morphological asymmetry of the brain torque with potential differences between subtypes of situs inversus with ciliary and non-ciliary etiologies.

Cerebral Polymorphisms for Lateralisation: Modelling the Genetic and Phenotypic Architectures of Multiple Functional Modules

“…The terminology of polymorphisms can be confusing, and in this paper I will refer to individual functional processes such as language dominance, visuo-spatial processing or handedness as modules [7], with individual modules lateralised to the right or left side of the brain; in particular, handedness will always be treated as a module. Different neural organisations have been referred to as combinations of multiple modular traits [8], phenotypes of brain functional organisation [9], or what we began to call cerebral polymorphisms [10][11][12].…”

Cognitive and Neurophysiological Models of Brain Asymmetry

“…The contribution by Guy Vingerhoets, Robin Gerrits, and Helena Verhelst, entitled "Atypical Brain Asymmetry in Human Situs Inversus: Gut Feeling or Real Evidence?" [25], is also related to the ontogenesis of handedness and other forms of hemispheric asymmetries in humans. Whether or not individuals with situs inversus also show inverted hemispheric asymmetries has been discussed for decades [26,27].…”

Recent Advances in Handedness Genetics

“…Although both hemispheres are engaged during language tasks, for the majority of people, hemispheric dominance resides in the left side. Right hemisphere dominance for language is rare and observed preferentially in left-handers [8] (see also Corballis [9] and Vingerhoets et al [10] in this issue for details on functional and anatomical brain asymmetries). This link is weak but suggests some common pathways control the establishment of brain asymmetries and contribute to both language and handedness.…”

“…Cilia are microtubule-based cellular structures with sensory and motility function. During early development, cilia are critical in pattering the left/right axis determination and mutations in genes controlling cilia formation and function lead to laterality defects (See Vingerhoets et al in this issue for a detailed explanations of this biological pathways [10]). The specific marker-trait associations from our study did not replicate in the larger GWAS for categorical measures of handedness, and it is possible that the lack of replication is due to the limited power of the original study, which led to false positives.…”