Atypical processing and integration of sensory inputs are hypothesized to play a role in unusual sensory reactions and social-cognitive deficits in autism spectrum disorder (ASD). Reports on the relationship between objective metrics of sensory processing and clinical symptoms, however, are surprisingly sparse. Here we examined the relationship between neurophysiological assays of sensory processing and 1) autism severity and 2) sensory sensitivities, in individuals with ASD aged 6–17. Multiple linear regression indicated significant associations between neural markers of auditory processing and multisensory integration, and autism severity. No such relationships were apparent for clinical measures of visual/auditory sensitivities. These data support that aberrant early sensory processing contributes to autism symptoms, and reveal the potential of electrophysiology to objectively subtype autism.

This study examined the development of neural processing of auditorally presented words in high functioning children with autism. The purpose was to test the hypothesis that electrophysiological abnormalities associated with impairments in early cortical processing and in semantic processing persist into early adolescence in autistic individuals. Eighteen children with autism and 18 normally developing children participated in the study. Ten of the children in each group were 8-9 years old, and 8 in each group were 11-12 years old (n = 36). Lists of words were presented auditorally; half were words belonging to a specified semantic category and half were words outside the category. Results revealed that while early cortical processing abnormalities appeared to resolve with development, children with autism in both age groups failed to exhibit differential semantic processing of in-versus out-of-category words. Further, while 8 year-olds with autism generated a large N4 (a late cognitive ERP component, which is sensitive to semantic deviance from a context) to words in both stimulus classes the 11 year-olds showed attenuated N4 relative to normal controls in response to both stimulus types. An attempt is made to integrate findings with current cognitive theories toward a parsimonious explanation of semantic classification deficits in autism.

Neurodevelopmental disorders, including autism spectrum disorder, have complex polygenic etiologies. Single-gene mutations in patients can help define genetic factors and molecular mechanisms underlying neurodevelopmental disorders. Here we describe individuals with monogenic heterozygous microdeletions in ANKS1B , a predicted risk gene for autism and neuropsychiatric diseases. Affected individuals present with a spectrum of neurodevelopmental phenotypes, including autism, attention-deficit hyperactivity disorder, and speech and motor deficits. Neurons generated from patient-derived induced pluripotent stem cells demonstrate loss of the ANKS1B -encoded protein AIDA-1, a brain-specific protein highly enriched at neuronal synapses. A transgenic mouse model of Anks1b haploinsufficiency recapitulates a range of patient phenotypes, including social deficits, hyperactivity, and sensorimotor dysfunction. Identification of the AIDA-1 interactome using quantitative proteomics reveals protein networks involved in synaptic function and the etiology of neurodevelopmental disorders. Our findings formalize a link between the synaptic protein AIDA-1 and a rare, previously undefined genetic disease we term ANKS1B haploinsufficiency syndrome.

Background: Maladaptive reactivity to sensory inputs is commonly observed in neurodevelopmental disorders (e.g., autism, ADHD). Little is known, however, about the underlying neural mechanisms. For some children, atypical sensory reactivity is the primary complaint, despite absence of another identifiable neurodevelopmental diagnosis. Studying Sensory Processing Disorder (SPD) may well provide a window into the neuropathology of these symptoms. It has been proposed that a deficit in sensory integration underlies the SPD phenotype, but objective quantification of sensory integration is lacking. Here we used neural and behavioral measures of multisensory integration (MSI), which would be affected by impaired sensory integration and for which there are well accepted objective measures, to test whether failure to integrate across the senses is associated with atypical sensory reactivity in SPD. An autism group served to determine if observed differences were unique to SPD. Methods: We tested whether children aged 6-16 years with SPD (N = 14) integrate multisensory inputs differently from age-matched typically developing controls (TD: N = 54), or from children with an autism spectrum disorder (ASD: N = 44). Participants performed a simple reaction-time task to the occurrence of auditory, visual, and audiovisual stimuli presented in random order, while high-density recordings of electrical brain activity were made. Results: Children with SPD showed large reductions in the extent to which they benefited from multisensory inputs compared to TDs. The ASD group showed similarly reduced response speeding to multisensory relative to unisensory inputs. Neural evidence for MSI was seen across all three groups, with the multisensory response differing from the sum of the unisensory responses. Post hoc tests suggested the possibility of enhanced MSI in SPD in timeframes consistent with cortical sensory registration (∼60 ms), followed by reduced MSI during a timeframe consistent with