The Neurodevelopment Of Basic Sensory Processing And Integration In Autism Spectrum Disorder

This thesis presents three studies that together explore the neurophysiological basis for the sensory processing and integration abnormalities that have been observed in autism spectrum disorder (ASD) since the disorder was first described over half a century ago. In designing these studies we seek to fill a hole that currently exists in the research community‟s knowledge of the neurodevelopment of basic multisensory integration -- both in children with autism and as well as in those with typical development. The first study applied event related potentials (ERPs) and behavioral measures of multisensory integration to a large group of healthy participants ranging in age from 7 to 29 years, with the goal of detailing the developmental trajectory of basic audiovisual integration in the brain. Our behavioral results revealed a gradual fine-tuning of multisensory facilitation of reaction time which reached mature levels by about 14 years of age. A similarly protracted period of maturation was seen in the brain processes thought to underlie to multisensory integration. Using the results of this cross-sectional study as a guide, the second study employed a between groups design to assess differences in the neural activity and behavioral facilitation associated with integrating basic audiovisual stimuli in groups of children and adolescents with ASD and typical development (aged 7-16 years). Deficits in basic audiovisual integration were seen at the earliest stages of cortical sensory processing in the ASD groups. In the concluding study we assessed whether neurophysiological measures of sensory processing and integration predict autistic symptom severity and parent-reported visual/auditory sensitivities. The data revealed that a combination of neural indices of auditory and visual processing and integration were predictive of severity of autistic symptoms in a group of children and adolescents with ASD. A particularly robust relationship was observed between severity of autism and the integrity of basic auditory processing and audiovisual integration. In contrast, our physiological indices did not predict visual/auditory sensitivities as assessed by parent responses on a questionnaire

Atypical multisensory integration in Niemann-Pick type C disease – towards potential biomarkers

Background: Niemann-Pick type C (NPC) is an autosomal recessive disease in which cholesterol and glycosphingolipids accumulate in lysosomes due to aberrant cell-transport mechanisms. It is characterized by progressive and ultimately terminal neurological disease, but both pre-clinical studies and direct human trials are underway to test the safety and efficacy of cholesterol clearing compounds, with good success already observed in animal models. Key to assessing the effectiveness of interventions in patients, however, is the development of objective neurobiological outcome measures. Multisensory integration mechanisms present as an excellent candidate since they necessarily rely on the fidelity of long-range neural connections between the respective sensory cortices (e.g. the auditory and visual systems). Methods: A simple way to test integrity of the multisensory system is to ask whether individuals respond faster to the occurrence of a bisensory event than they do to the occurrence of either of the unisensory constituents alone. Here, we presented simple auditory, visual, and audio-visual stimuli in random sequence. Participants responded as fast as possible with a button push. One 11-year-old and two 14-year-old boys with NPC participated in the experiment and their results were compared to those of 35 age-matched neurotypical boys. Results: Reaction times (RTs) to the stimuli when presented simultaneously were significantly faster than when they were presented alone in the neurotypical children, a facilitation that could not be accounted for by probability summation, as evidenced by violation of the so-called ‘race’ model. In stark contrast, the NPC boys showed no such speeding, despite the fact that their unisensory RTs fell within the distribution of RTs observed in the neurotypicals. Conclusions: These results uncover a previously undescribed deficit in multisensory integrative abilities in NPC, with implications for ongoing treatment of the clinical symptoms of these children. They also suggest that multisensory processes may represent a good candidate biomarker against which to test the efficacy of therapeutic interventions