Natalie Russo

Deconstructing executive deficits among persons with autism: Implications for cognitive neuroscience

Individuals with autism demonstrate impairments on measures of executive function (EF) relative to typically developing comparison participants. EF is comprised of several processes including inhibition, working memory and set shifting that develop throughout the lifespan. Impairments in EF may appear early in development and persist, or may represent a more transient delay which resolves with time. Given the unevenness of the cognitive profile of persons with autism, understanding the development of EF poses methodological challenges. These issues include those related to matching measures and the choice of comparison participants to which the performance of persons with autism will be compared. In the current review, we attempt to break down the processes of inhibition, working memory and set shifting among persons with autism. We propose to do this within a developmental perspective that highlights how matching measures and comparison participants can affect the interpretation of research findings.

The Development of Multisensory Integration in High-Functioning Autism: High-Density Electrical Mapping and Psychophysical Measures Reveal Impairments in the Processing of Audiovisual Inputs

Successful integration of auditory and visual inputs is crucial for both basic perceptual functions and for higher-order processes related to social cognition. Autism spectrum disorders (ASD) are characterized by impairments in social cognition and are associated with abnormalities in sensory and perceptual processes. Several groups have reported that individuals with ASD are impaired in their ability to integrate socially relevant audiovisual (AV) information, and it has been suggested that this contributes to the higher-order social and cognitive deficits observed in ASD. However, successful integration of auditory and visual inputs also influences detection and perception of nonsocial stimuli, and integration deficits may impair earlier stages of information processing, with cascading downstream effects. To assess the integrity of basic AV integration, we recorded high-density electrophysiology from a cohort of high-functioning children with ASD (7-16 years) while they performed a simple AV reaction time task. Children with ASD showed considerably less behavioral facilitation to multisensory inputs, deficits that were paralleled by less effective neural integration. Evidence for processing differences relative to typically developing children was seen as early as 100 ms poststimulation, and topographic analysis suggested that children with ASD relied on different cortical networks during this early multisensory processing stage.

Multisensory processing in children with autism: high-density electrical mapping of auditory–somatosensory integration

Successful integration of signals from the various sensory systems is crucial for normal sensory–perceptual functioning, allowing for the perception of coherent objects rather than a disconnected cluster of fragmented features. Several prominent theories of autism suggest that automatic integration is impaired in this population, but there have been few empirical tests of this thesis. A standard electrophysiological metric of multisensory integration (MSI) was used to test the integrity of auditory–somatosensory integration in children with autism (N=17, aged 6–16 years), compared to age‐ and IQ‐matched typically developing (TD) children. High‐density electrophysiology was recorded while participants were presented with either auditory or somatosensory stimuli alone (unisensory conditions), or as a combined auditory–somatosensory stimulus (multisensory condition), in randomized order. Participants watched a silent movie during testing, ignoring concurrent stimulation. Significant differences between neural responses to the multisensory auditory–somatosensory stimulus and the unisensory stimuli (the sum of the responses to the auditory and somatosensory stimuli when presented alone) served as the dependent measure. The data revealed group differences in the integration of auditory and somatosensory information that appeared at around 175 ms, and were characterized by the presence of MSI for the TD but not the autism spectrum disorder (ASD) children. Overall, MSI was less extensive in the ASD group. These findings are discussed within the framework of current knowledge of MSI in typical development as well as in relation to theories of ASD.

Severe Multisensory Speech Integration Deficits in High-Functioning School-Aged Children with Autism Spectrum Disorder (ASD) and Their Resolution During Early Adolescence

Under noisy listening conditions, visualizing a speakers articulations substantially improves speech intelligibility. This multisensory speech integration ability is crucial to effective communication, and the appropriate development of this capacity greatly impacts a childs ability to successfully navigate educational and social settings. Research shows that multisensory integration abilities continue developing late into childhood. The primary aim here was to track the development of these abilities in children with autism, since multisensory deficits are increasingly recognized as a component of the autism spectrum disorder (ASD) phenotype. The abilities of high-functioning ASD children (n = 84) to integrate seen and heard speech were assessed cross-sectionally, while environmental noise levels were systematically manipulated, comparing them with age-matched neurotypical children (n = 142). Severe integration deficits were uncovered in ASD, which were increasingly pronounced as background noise increased. These deficits were evident in school-aged ASD children (5-12 year olds), but were fully ameliorated in ASD children entering adolescence (13-15 year olds). The severity of multisensory deficits uncovered has important implications for educators and clinicians working in ASD. We consider the observation that the multisensory speech system recovers substantially in adolescence as an indication that it is likely amenable to intervention during earlier childhood, with potentially profound implications for the development of social communication abilities in ASD children.

The Development of Audiovisual Multisensory Integration Across Childhood and Early Adolescence: A High-Density Electrical Mapping Study

The integration of multisensory information is essential to forming meaningful representations of the environment. Adults benefit from related multisensory stimuli but the extent to which the ability to optimally integrate multisensory inputs for functional purposes is present in children has not been extensively examined. Using a cross-sectional approach, high-density electrical mapping of event-related potentials (ERPs) was combined with behavioral measures to characterize neurodevelopmental changes in basic audiovisual (AV) integration from middle childhood through early adulthood. The data indicated a gradual fine-tuning of multisensory facilitation of performance on an AV simple reaction time task (as indexed by race model violation), which reaches mature levels by about 14 years of age. They also revealed a systematic relationship between age and the brain processes underlying multisensory integration (MSI) in the time frame of the auditory N1 ERP component (∼ 120 ms). A significant positive correlation between behavioral and neurophysiological measures of MSI suggested that the underlying brain processes contributed to the fine-tuning of multisensory facilitation of behavior that was observed over middle childhood. These findings are consistent with protracted plasticity in a dynamic system and provide a starting point from which future studies can begin to examine the developmental course of multisensory processing in clinical populations.

Mosaic Epigenetic Dysregulation of Ectodermal Cells in Autism Spectrum Disorder

DNA mutational events are increasingly being identified in autism spectrum disorder (ASD), but the potential additional role of dysregulation of the epigenome in the pathogenesis of the condition remains unclear. The epigenome is of interest as a possible mediator of environmental effects during development, encoding a cellular memory reflected by altered function of progeny cells. Advanced maternal age (AMA) is associated with an increased risk of having a child with ASD for reasons that are not understood. To explore whether AMA involves covert aneuploidy or epigenetic dysregulation leading to ASD in the offspring, we tested a homogeneous ectodermal cell type from 47 individuals with ASD compared with 48 typically developing (TD) controls born to mothers of ≥35 years, using a quantitative genome-wide DNA methylation assay. We show that DNA methylation patterns are dysregulated in ectodermal cells in these individuals, having accounted for confounding effects due to subject age, sex and ancestral haplotype. We did not find mosaic aneuploidy or copy number variability to occur at differentially-methylated regions in these subjects. Of note, the loci with distinctive DNA methylation were found at genes expressed in the brain and encoding protein products significantly enriched for interactions with those produced by known ASD-causing genes, representing a perturbation by epigenomic dysregulation of the same networks compromised by DNA mutational mechanisms. The results indicate the presence of a mosaic subpopulation of epigenetically-dysregulated, ectodermally-derived cells in subjects with ASD. The epigenetic dysregulation observed in these ASD subjects born to older mothers may be associated with aging parental gametes, environmental influences during embryogenesis or could be the consequence of mutations of the chromatin regulatory genes increasingly implicated in ASD. The results indicate that epigenetic dysregulatory mechanisms may complement and interact with DNA mutations in the pathogenesis of the disorder.

Atypical cortical representation of peripheral visual space in children with an autism spectrum disorder

A key feature of early visual cortical regions is that they contain discretely organized retinotopic maps. Titration of these maps must occur through experience, and the fidelity of their spatial tuning will depend on the consistency and accuracy of the eye movement system. Anomalies in fixation patterns and the ballistics of eye movements are well documented in autism spectrum disorder (ASD), with off‐center fixations a hallmark of the phenotype. We hypothesized that these atypicalities might affect the development of visuo‐spatial maps and specifically that peripheral inputs might receive altered processing in ASD. Using high‐density recordings of visual evoked potentials (VEPs) and a novel system‐identification approach known as VESPA (visual evoked spread spectrum analysis), we assessed sensory responses to centrally and peripherally presented stimuli. Additionally, input luminance was varied to bias responsiveness to the magnocellular system, given previous suggestions of magnocellular‐specific deficits in ASD. Participants were 22 ASD children (7–17 years of age) and 31 age‐ and performance‐IQ‐matched neurotypical controls. Both VEP and VESPA responses to central presentations were indistinguishable between groups. In contrast, peripheral presentations resulted in significantly greater early VEP and VESPA amplitudes in the ASD cohort. We found no evidence that anomalous enhancement was restricted to magnocellular‐biased responses. The extent of peripheral response enhancement was related to the severity of stereotyped behaviors and restricted interests, cardinal symptoms of ASD. The current results point to differential visuo‐spatial cortical mapping in ASD, shedding light on the consequences of peculiarities in gaze and stereotyped visual behaviors often reported by clinicians working with this population.

Change Detection in Naturalistic Pictures Among Children with Autism

Persons with autism often show strong reactions to changes in the environment, suggesting that they may detect changes more efficiently than typically developing (TD) persons. However, Fletcher-Watson et al. (Br J Psychol 97:537–554, 2006) reported no differences between adults with autism and TD adults with a change-detection task. In this study, we also found no initial differences in change-detection between children with autism and NVMA-matched TD children, although differences emerged when detection failures were related to the developmental level of the participants. Whereas detection failures decreased with increasing developmental level for TD children, detection failures remained constant over the same developmental range for children with autism, pointing to an atypical developmental trajectory for change-detection among children with autism.

Cognitive Flexibility Among Individuals With Down Syndrome: Assessing the Influence of Verbal and Nonverbal Abilities

The influences of verbal mental age (VMA) and performance mental age (PMA) on cognitive flexibility were examined among a group of participants with Down syndrome (DS), in order to disentangle the relative contributions of each. The impaired cognitive flexibility typically observed among individuals with DS in combination with uneven VMA and PMA development suggests an opportunity to further understand the developmental relationship between VMA, PMA, and cognitive flexibility. We examined the performance of 22 participants with DS on the Flexible Item Selection Task (FIST), used for measuring cognitive flexibility among preschoolers. Partial correlations revealed that only VMA was related to the FIST after controlling for PMA, highlighting the role of verbal abilities in the development of cognitive flexibility.

Differences in Visual Orienting between Persons with Down or Fragile X Syndrome.

The voluntary and reflexive orienting abilities of persons with Down syndrome and fragile X syndrome, at average MA levels of approximately 4 and 7 years, were compared with an RT task. Reflexive orienting abilities appeared to develop in accordance with MA for the participants with Down syndrome but not for those with fragile X syndrome. However, both groups showed delayed voluntary orienting. The group differences in reflexive orienting at the low MA level reinforce the practice of separating etiologies and highlight the contribution of rudimentary attentional processes in the study of individuals with mental retardation.