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Neurosci Biobehav Rev. 2014 Nov;47:735-52. doi: 10.1016/j.neubiorev.2014.07.012. Epub 2014 Aug 22.

Linking neocortical, cognitive, and genetic variability in autism with alterations of brain plasticity: the Trigger-Threshold-Target model.

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Centre d'excellence en Troubles envahissants du développement de l'Université de Montréal (CETEDUM), Canada; Hôpital Rivière-des-Prairies, Département de Psychiatrie, Montréal, Canada; Centre de recherche de l'Institut Universitaire de Psychiatrie de l'Université de Montréal, Montréal, Canada; Université de Montréal, Canada. Electronic address:
Université de Montréal, Canada; Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal, Canada.
Montreal Neurological Institute, Université of McGiIl, Montréal, Canada.
Centre for Mind/Brain Sciences, University of Trento, Italy.


The phenotype of autism involves heterogeneous adaptive traits (strengths vs. disabilities), different domains of alterations (social vs. non-social), and various associated genetic conditions (syndromic vs. nonsyndromic autism). Three observations suggest that alterations in experience-dependent plasticity are an etiological factor in autism: (1) the main cognitive domains enhanced in autism are controlled by the most plastic cortical brain regions, the multimodal association cortices; (2) autism and sensory deprivation share several features of cortical and functional reorganization; and (3) genetic mutations and/or environmental insults involved in autism all appear to affect developmental synaptic plasticity, and mostly lead to its upregulation. We present the Trigger-Threshold-Target (TTT) model of autism to organize these findings. In this model, genetic mutations trigger brain reorganization in individuals with a low plasticity threshold, mostly within regions sensitive to cortical reallocations. These changes account for the cognitive enhancements and reduced social expertise associated with autism. Enhanced but normal plasticity may underlie non-syndromic autism, whereas syndromic autism may occur when a triggering mutation or event produces an altered plastic reaction, also resulting in intellectual disability and dysmorphism in addition to autism. Differences in the target of brain reorganization (perceptual vs. language regions) account for the main autistic subgroups. In light of this model, future research should investigate how individual and sex-related differences in synaptic/regional brain plasticity influence the occurrence of autism.


Asperger; Autism; Cortical reallocation; Cross-modal plasticity; Double-hit mechanism; Enhanced perceptual functioning; Intellectual disability; Language; Perception; Speech; Synaptic plasticity; Syndromic autism; Veridical mapping

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