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. 2015 Jun 5:6:33.
doi: 10.1186/s13229-015-0024-1. eCollection 2015.

Sex differences in brain plasticity: a new hypothesis for sex ratio bias in autism

Laurent Mottron #  1   2   3   4 , Pauline Duret #  1   2   3   4   5 , Sophia Mueller  6   7   8 , Robert D Moore  4   9   10 , Baudouin Forgeot d'Arc  1   2   3   4 , Sebastien Jacquemont  4   11   12 , Lan Xiong #  3   4
Affiliations

Sex differences in brain plasticity: a new hypothesis for sex ratio bias in autism

Laurent Mottron et al. Mol Autism. .

Abstract

Several observations support the hypothesis that differences in synaptic and regional cerebral plasticity between the sexes account for the high ratio of males to females in autism. First, males are more susceptible than females to perturbations in genes involved in synaptic plasticity. Second, sex-related differences in non-autistic brain structure and function are observed in highly variable regions, namely, the heteromodal associative cortices, and overlap with structural particularities and enhanced activity of perceptual associative regions in autistic individuals. Finally, functional cortical reallocations following brain lesions in non-autistic adults (for example, traumatic brain injury, multiple sclerosis) are sex-dependent. Interactions between genetic sex and hormones may therefore result in higher synaptic and consecutively regional plasticity in perceptual brain areas in males than in females. The onset of autism may largely involve mutations altering synaptic plasticity that create a plastic reaction affecting the most variable and sexually dimorphic brain regions. The sex ratio bias in autism may arise because males have a lower threshold than females for the development of this plastic reaction following a genetic or environmental event.

Keywords: Autism spectrum; Enhanced perceptual functioning; Male bias; Perceptual associative cortex; Regional plasticity; Sex ratio; Sexual dimorphism; Synaptic plasticity.

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Figures

Figure 1
Figure 1
Convergence between functional (A), structural (B, C), and connectivity (D) regions of interest in autism and regions of maximal variability (E) and sexual dimorphism (F) in typical individuals in a visual associative area (G). (A) Regions showing more activity in autistic individuals than in non-autistic controls when processing visual information. Qualitative meta-analysis, whole brain FDR corrected [16]. (B) Regions showing greater cortical gyrification in autistic individuals than in non-autistic individuals. The warmer the color, the greater the significance of the group differences [152]. (C) Regions showing higher thickness in autistic versus non-autistic individuals. More than 1,000 brains analyzed, FDR corrected [151]. (D) Regions of enhanced resting-state local connectivity density in autistic individuals. Warm colors show the regions with greater connectivity in the autistic individuals than in non-autistic individuals, and cool colors regions of lower connectivity [134]. (E) High inter-individual variability in resting-state functional connectivity in non-autistic individuals. Values above or below the global mean are displayed in warm and cool colors, respectively [17]. (F) Regions of higher resting-state functional connectivity in males (blue) and females (pink). Seed-based analysis on more than 1,000 brains corrected with Gaussian random-field theory [118]. (G) Bilateral visual associative cortex: Brodmann Areas 18 (green) and 19 (red).
Figure 2
Figure 2
Topographical overlap between functional, structural, and connectomic particularities in the autistic left-hemisphere (A) and regions of high variability (B) and sexual dimorphism (C) in the general population in a visual associative area (D). Patterns of this schematic representation were obtained by manual alignment, distortion and superimposition of the results from the different relevant studies presented in Figure 1. (A) Overlap between two (light blue) or more (dark blue) autistic particularities out of four studies reporting higher thickness [151], gyrification [152], functional activity [16], and connectivity [134] in autism (left panel in Figure 1). (B) Overlap between the autism-specific region defined in A and regions of high inter-individual variability in connectivity ([17] and Figure 1E). (C) Overlap between the autism-specific region defined in A and regions of higher connectivity in males ([118] and Figure 1F). (D) Overlap between the region defined in C and the visual associative regions (Brodmann Areas 18 and 19, Figure 1G).
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References

    1. Fombonne E. Epidemiology of pervasive developmental disorders. Pediatr Res. 2009;65:591–8. - PubMed
    1. Werling DM, Geschwind DH. Understanding sex bias in autism spectrum disorder. Proc Natl Acad Sci U S A. 2013;110:4868–9. - PMC - PubMed
    1. Jacquemont S, Coe BP, Hersch M, Duyzend MH, Krumm N, Bergmann S, et al. A higher mutational burden in females supports a "female protective model" in neurodevelopmental disorders. Am J Hum Genet. 2014;94(3):415-25. doi:10.1016/j.ajhg.2014.02.001. - PMC - PubMed
    1. Betancur C. Etiological heterogeneity in autism spectrum disorders: more than 100 genetic and genomic disorders and still counting. Brain Res. 2011;1380:42–77. - PubMed
    1. Lim ET, Raychaudhuri S, Sanders SJ, Stevens C, Sabo A, MacArthur DG, et al. Rare complete knockouts in humans: population distribution and significant role in autism spectrum disorders. Neuron. 2013;77:235–42. - PMC - PubMed

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