Sensory Assessments Reveal Phenotypic Heterogeneity in Autism

Background: Adults with autism exhibit inhibitory deficits that are often manifested in behavioral excesses, such as repetitive behaviors, and/or sensory hyper-responsiveness. If such behaviors are the result of a generalized deficiency in inhibitory neurotransmission, then it stands to reason that deficits involving localized cortical-cortical interactions – such as in sensory discrimination tasks – could be detected and quantified.  Quantification of systemic alterations in information processing strategies could reveal differences within the autism spectrum.

Objectives: This study describes several methods for quantifiable biologically based sensory perceptual metrics. These sensory discrimination tests may provide (a) an effective means for biobehavioral assessment of deficits specific to autism and (b) an efficient and sensitive measure of change following treatment.

Methods: The sensory discriminative capacity of individuals with autism (n=56, age range 16-40) and age matched controls (n=150) were obtained by delivering several different protocols that utilized vibrotactile stimuli applied to the finger tips.  Specific information processing mechanisms were targeted by each of several sets of protocols.  Mechanistically, the protocols were designed to be sensitive to (1) feed-forward inhibition, (2) lateral inhibition, (3) adaptation, and (4) functional connectivity by delivering combinations of stimuli that were either “static” (did not change in amplitude) or “dynamic” (amplitudes of stimuli were dynamically modulated during a trial).  Multi-parametric approaches (e.g., PCA) were used to combine the data from several tests.

Results: Although protocols that utilized dynamic modulation of the testing stimuli demonstrated a pronounced but consistent impact on the discriminative capacity of the typically developing subjects in a wide array of protocols, there was a pronounced difference on the observations obtained from within the cohort of autism subjects.  Moreover, there appears to be a distinct heterogeneity within the autism spectrum in terms of sensory information processing strategies, particularly for the protocols that utilized amplitude modulated stimuli in a rate dependent fashion.  Additionally, although sorting the autism cohort into two groups could be best accomplished with protocols utilizing dynamic stimuli, the group differences remained intact and were significant across all protocols, both static and dynamic.  Multi-parametric analysis of the sensory based data revealed two distinct groups within the autism spectrum independent of IQ.

Conclusions: The changes observed with different parameters of stimulation, and in particular the increased impact of the rate of change of amplitude modulated vibrotactile stimuli on the responses of  subjects within the autism spectrum, was interpreted to be consistent with the reduced GABAergic mediated inhibition described in previous reports and could be interpreted as a more sensitive means of assessing information processing strategies.  One significant aspect of this study is that the methods could prove to be a useful and efficient way to detect specific neural deficits within the autism spectrum and perhaps monitor the efficacy of pharmacological or behavioral treatments.

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