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

Abstract

Recent fMRI and fTCD studies have found that functional modules for aspects of language, praxis, and visuo-spatial functioning, while typically left, left and right hemispheric respectively, frequently show atypical lateralisation. Studies with increasing numbers of modules and participants are finding increasing numbers of module combinations, which here are termed cerebral polymorphisms—qualitatively different lateral organisations of cognitive functions. Polymorphisms are more frequent in left-handers than right-handers, but it is far from the case that right-handers all show the lateral organisation of modules described in introductory textbooks. In computational terms, this paper extends the original, monogenic McManus DC (dextral-chance) model of handedness and language dominance to multiple functional modules, and to a polygenic DC model compatible with the molecular genetics of handedness, and with the biology of visceral asymmetries found in primary ciliary dyskinesia. Distributions of cerebral polymorphisms are calculated for families and twins, and consequences and implications of cerebral polymorphisms are explored for explaining aphasia due to cerebral damage, as well as possible talents and deficits arising from atypical inter- and intra-hemispheric modular connections. The model is set in the broader context of the testing of psychological theories, of issues of laterality measurement, of mutation-selection balance, and the evolution of brain and visceral asymmetries.

Atypical language network lateralization is reflected throughout the macroscale functional organization of cortex

“…Across development, the maturation of lateralized functions is associated with improved visuospatial and language abilities and enhanced cognitive efficiency 71,72 . Although the precise timing of these developmental cascades remains largely unknown 14,15 , some markers of lateralization are already apparent during gestation, for instance the leftward asymmetrical folding of the Sylvian fissure 73 . At birth, intra-hemispheric white matter connectivity across the language network is reduced in favor of strong inter-hemispheric coordination 74 , an organizational property that is consistent with the presence of prominent homotopic intrinsic connectivity from 3 to 6 months of life 75 .…”

“…However, while the lateralization of brain functions and associated behaviors has fascinated neuroscientists for over a century 9,10 , the origins, mechanisms, and consequences of hemispheric specialization are still largely unknown [11][12][13][14] . In this regard, the extent to which the asymmetrical organization of discrete processes may be evident throughout the macroscale functional organization of the cortical sheet remains an open question 15 .…”

Light-induced asymmetries in embryonic retinal gene expression are mediated by the vascular system and extracellular matrix

“…Moreover, additive genetic factors explain only one quarter of the variance in human handedness, and it has been suggested that nonshared environmental factors can explain part of the remaining variance 20 , 115 (but see Refs. 116 – 118 ). Hence, to understand the ontogeny of functional and brain lateralization we must elucidate the interaction between endogenous and environmental factors 2 , 3 , 11 , 14 , 17 , 66 , 67 , 69 – 71 .…”

Cognitive and Neurophysiological Models of Brain Asymmetry

“…As mentioned above, the McManus DC model of handedness and language dominance [15] was one of the most influential models of handedness ontogenesis. In his contribution to the Special Issue, entitled "Cerebral Polymorphisms for Lateralisation: Modelling the Genetic and Phenotypic Architectures of Multiple Functional Modules", McManus presents an update and extension of this model with two central changes [22]. Building upon the 2014 polygenic revision of the DC model [21], McManus presents an extended polygenic DC model informed by recent studies on the genetics of handedness and, in particular, the role of cilia.…”