How Genetically Induced Enhanced Synaptic Plasticity and Regional Cortical Rededications Account for Autistic Superior Performances: The Trigger-Threshold-Target-Neglect Model for Autism

Background:  Autism is characterized by enhanced synaptic as well as enhanced regional plasticity. This phenomenon seem to be the result of genetic mutations involved in the disorder which mostly up-regulate early synaptic development. This cascade of genetic as well as biological events seem to account for the pattern of enhanced regional activity in visual associative cortex that systematically occurs during perceptual processing tasks in individuals with autism. Yet, not all individuals with autism present enhanced perceptual functioning, and there is tremendous heterogeneity across the spectrum. This leads to examine the hypothesis of a causal link between increased synaptic and regional plasticity, and the effect of variability in perceptual activity on different subgroups within the autism spectrum.

Objectives:  We here aim at investigating how enhanced synaptic and regional plasticity are responsible for opposite patterns of cognitive enhancements across subgroups within the autism spectrum.

Methods:  We use two complimentary theoretical accounts of functional plasticity in autism: (i) microstructural plasticity wherein synaptic plasticity is the byproduct of the genetic mutations involved in autism, and (ii) regional plasticity wherein differences in functional and structural patterns of brain activity and grey matter integrity trigger heterogeneity in brain activity during perceptual tasks. Specifically, the latter account examines the overlap between regions of structural differences between autistic and control individuals, enhanced activation during visual and auditory perceptual processing, and regions identified as extremely plastic in rededicating functions within the context of cross modal plasticity models following congenital sensory impairment.

Results:  (i) the main cognitive domains enhanced in autism are sub-served by the most plastic cortical brain region, the multimodal associative cortex; (ii) autistic cognitive enhancements and cortical rededications are overlapping with those involved in cross modal plasticity following sensory impairment; (iii) autism is associated with enhanced topographical variability of task-related activation in perceptual and motor associative regions, suggesting  enhanced regional plasticity in functional allocation; (iv) regions of enhanced activity during perceptual auditory tasks differ in autistics individuals with and without speech onset delay.

Conclusions:  According to the Trigger-Threshold-Target-Neglect (TTTN) model, autism is the result of a plastic reaction triggered by heterogeneous alterations, largely genetic in nature. These genetic mutations are responsible for setting a lower threshold of brain reorganization targeting ‘’sensitive’’ cerebral territories. Within this account, the plastic reaction would be the only consequence of the genetic alteration in non-syndromic (or primary) autism, whereas syndromic (or secondary) autism would occur when the mutation alters typical plasticity mechanisms, resulting in intellectual disability and dysmorphism. Differences in the regional target (perceptual vs. linguistic) of brain reorganization might account for the widespread heterogeneity characterizing the autistic spectrum phenotype. As a result, functions that are not targeted within and by this reorganization would be responsible for autistic deficits or lack of expertise. The TTTN model accounts for pairs of specific strengths and deficits in the phenotype of autism, such as the coupling between speech delay and perceptual strengths in classical autism, as well as the coupling between precocious speech strengths and motor clumsiness in Asperger syndrome.