The Processing of Audiovisual Speech Is Linked with Vocabulary in Autistic and Nonautistic Children: An ERP Study.

Explaining individual differences in vocabulary in autism is critical, as understanding and using words to communicate are key predictors of long-term outcomes for autistic individuals. Differences in audiovisual speech processing may explain variability in vocabulary in autism. The efficiency of audiovisual speech processing can be indexed via amplitude suppression, wherein the amplitude of the event-related potential (ERP) is reduced at the P2 component in response to audiovisual speech compared to auditory-only speech. This study used electroencephalography (EEG) to measure P2 amplitudes in response to auditory-only and audiovisual speech and norm-referenced, standardized assessments to measure vocabulary in 25 autistic and 25 nonautistic children to determine whether amplitude suppression (a) differs or (b) explains variability in vocabulary in autistic and nonautistic children. A series of regression analyses evaluated associations between amplitude suppression and vocabulary scores. Both groups demonstrated P2 amplitude suppression, on average, in response to audiovisual speech relative to auditory-only speech. Between-group differences in mean amplitude suppression were nonsignificant. Individual differences in amplitude suppression were positively associated with expressive vocabulary through receptive vocabulary, as evidenced by a significant indirect effect observed across groups. The results suggest that efficiency of audiovisual speech processing may explain variance in vocabulary in autism.

Relations Between the McGurk Effect, Social and Communication Skill, and Autistic Features in Children with and without Autism.

Children with autism show alterations in multisensory integration that have been theoretically and empirically linked with the core and related features of autism. It is unclear, however, to what extent multisensory integration maps onto features of autism within children with and without autism. This study, thus, evaluates relations between audiovisual integration and core and related autism features across children with and without autism. Thirty-six children reported perceptions of the McGurk illusion during a psychophysical task. Parents reported on participants' autistic features. Increased report of illusory percepts tended to covary with reduced autistic features and greater communication skill. Some relations, though, were moderated by group. This work suggests that associations between multisensory integration and higher-order skills are present, but in some instances vary according to diagnostic group.

Stability of Variables Derived From Measures of Multisensory Function in Children With Autism Spectrum Disorder.

Children with autism spectrum disorder (ASD) display differences in multisensory function as quantified by several different measures. This study estimated the stability of variables derived from commonly used measures of multisensory function in school-aged children with ASD. Participants completed: a simultaneity judgment task for audiovisual speech, tasks designed to elicit the McGurk effect, listening-in-noise tasks, electroencephalographic recordings, and eye-tracking tasks. Results indicate the stability of indices derived from tasks tapping multisensory processing is variable. These findings have important implications for measurement in future research. Averaging scores across repeated observations will often be required to obtain acceptably stable estimates and, thus, to increase the likelihood of detecting effects of interest, as it relates to multisensory processing in children with ASD.

Plasticity of Temporal Binding in Children with Autism Spectrum Disorder:A Single Case Experimental Design Perceptual Training Study.

BACKGROUND: Many children with autism spectrum disorder (ASD) demonstrate atypical responses to multisensory stimuli. These disruptions, which are frequently seen in response to audiovisual speech, may produce cascading effects on the broader development of children with ASD. Perceptual training has been shown to enhance multisensory speech perception in typically developed adults. This study was the first to examine the effects of perceptual training on audiovisual speech perception in children with ASD. METHOD: A multiple baseline across participants design was utilized with four 7- to 13-year-old children with ASD. The dependent variable, which was probed outside the training task each day using a simultaneity judgment task in baseline, intervention, and maintenance conditions, was audiovisual temporal binding window (TBW), an index of multisensory temporal acuity. During perceptual training, participants completed the same simultaneity judgment task with feedback on their accuracy after each trial in easy-, medium-, and hard-difficulty blocks. RESULTS: A functional relation between the multisensory perceptual training program and TBW size was not observed. Of the three participants who were entered into training, one participant demonstrated a strong effect, characterized by a fairly immediate change in TBW trend. The two remaining participants demonstrated a less clear response (i.e., longer latency to effect, lack of functional independence). The first participant to enter the training condition demonstrated some maintenance of a narrower TBW post-training. CONCLUSIONS: Results indicate TBWs in children with ASD may be malleable, but additional research is needed and may entail further adaptation to the multisensory perceptual training paradigm.

Medical utilization surrounding initial opioid-related diagnoses by coding method.

OBJECTIVES: To identify methods for coding initial opioid-related disorder (ORD) diagnoses in administrative claims and determine whether coding methods correspond to acute medical utilization patterns. STUDY DESIGN: Retrospective analysis of Blue Health Intelligence commercial data. METHODS: We included members with 2 years of continuous coverage around the first appearance of an ORD diagnosis code (initial ORD) in medical or pharmacy claims with dates of service between October 2015 and March 2016. Initial ORD was identified by International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) F11 codes or buprenorphine for medication-assisted treatment (BUP-MAT) with a duration of 3 or more days. Descriptive analyses were evaluated prediagnosis, in the month of diagnosis, and post diagnosis and included mean cost per member per month (PMPM); mean monthly percentage of members with at least 1 opioid agonist prescription (OAP), inpatient visit, or emergency department (ED) visit; and percentage of members with at least 1 ICD-10-CM Z79.891 code (long-term [current] use of opiate analgesic). RESULTS: A total of 6426 initial ORD diagnoses were identified by F11.20 (65.2%), F11.x (28.7%), and BUP-MAT (6.1%). PMPM costs for BUP-MAT ($2054) were lower than for F11.20 ($5053) and F11.x ($6597) in the diagnosis month. Mean monthly percentage of members with at least 1 OAP declined from pre- to post initial ORD diagnosis (F11.20, 52.5% to 50.0%; F11.x, 44.1% to 37.9%; BUP-MAT, 34.0% to 12.7%). Members with initial ORD coded as F11.x had the highest mean percentage with at least 1 inpatient or ED visit in the diagnosis month (30.9% and 26.8%, respectively) versus F11.20 (19.3% and 10.8%) and BUP-MAT (5.1% and 3.5%). Percentage of members with at least 1 Z79.891 code was higher post diagnosis than in the month of diagnosis (F11.20, 34.6% vs 25.7%; F11.x, 16.5% vs 8.1%; BUP-MAT, 19.5% vs 8.1%). CONCLUSIONS: Medical utilization patterns of members with ORD differ by the coding method used to document their initial diagnosis in administrative claims.

Brief Report: Differences in Multisensory Integration Covary with Sensory Responsiveness in Children with and without Autism Spectrum Disorder.

Research shows that children with autism spectrum disorder (ASD) differ in their behavioral patterns of responding to sensory stimuli (i.e., sensory responsiveness) and in various other aspects of sensory functioning relative to typical peers. This study explored relations between measures of sensory responsiveness and multisensory speech perception and integration in children with and without ASD. Participants were 8-17 year old children, 18 with ASD and 18 matched typically developing controls. Participants completed a psychophysical speech perception task, and parents reported on children's sensory responsiveness. Psychophysical measures (e.g., audiovisual accuracy, temporal binding window) were associated with patterns of sensory responsiveness (e.g., hyporesponsiveness, sensory seeking). Results indicate that differences in multisensory speech perception and integration covary with atypical patterns of sensory responsiveness.

Pupil response to social-emotional material is associated with rumination and depressive symptoms in adults with autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD) is marked by repetitive thinking and high rates of depression. Understanding the extent to which repetitive negative thinking in ASD reflects autistic stereotypy versus general depressive thinking patterns (e.g., rumination) could help guide treatment research to improve emotional health in ASD. We compared associations between rumination, depressive symptoms, and pupil response to social-emotional material in adults with ASD and typically developing (TD) adults with and without depression. METHODS: N = 53 verbally fluent young adults were recruited to three cohorts: ASD, n = 21; TD-depressed, n = 13; never-depressed TD-controls, n = 19. Participants completed Ruminative Response Scale and Beck Depression Inventory self-reports and a passive-viewing task employing emotionally-expressive faces, during which pupillary motility was assessed to quantify cognitive-affective load. Main and interactive effects of cohort, emotion condition, and time on pupil amplitude were tested via a linear mixed effects analysis of variance using restricted maximum likelihood estimation. Similar procedures were used to test for effects of rumination and depressive symptoms on pupil amplitude over time within ASD. RESULTS: Responsive pupil dilation in the ASD cohort tended to be significantly lower than TD-depressed initially but increased to comparable levels by trial end. When viewing sad faces, individuals with ASD who had higher depression scores resembled TD-depressed participants' faster, larger, and sustained pupil response. Within ASD, depressive symptoms uniquely predicted early pupil response to sad faces, while rumination and depression scores each independently predicted sustained pupil response. CONCLUSIONS: People with elevated depressive symptoms appear to have faster and greater increases in pupil-indexed neural activation following sad stimuli, regardless of ASD status, suggesting the utility of conceptualizing rumination as depression-like in treatment. Ruminative processes may increase more slowly in ASD, suggesting the potential utility of interventions that decrease reactions before they are uncontrollable. Findings also reinforce the importance of testing for effects of internalizing variables in broader ASD research.

Single Trial Plasticity in Evidence Accumulation Underlies Rapid Recalibration to Asynchronous Audiovisual Speech.

Asynchronous arrival of audiovisual information at the peripheral sensory organs is a ubiquitous property of signals in the natural environment due to differences in the propagation time of light and sound. As these cues are constantly changing their distance from the observer, rapid adaptation to asynchronies is crucial for their appropriate integration. We investigated the neural basis of rapid recalibration to asynchronous audiovisual speech in humans using a combination of psychophysics, drift diffusion modeling, and electroencephalography (EEG). Consistent with previous reports, we found that perception of audiovisual temporal synchrony depends on the temporal ordering of the previous trial. Drift diffusion modelling indicated that this recalibration effect is well accounted for by changes in the rate of evidence accumulation (i.e. drift rate). Neural responses as indexed via evoked potentials were similarly found to vary based on the temporal ordering of the previous trial. Within and across subject correlations indicated that the observed changes in drift rate and the modulation of evoked potential magnitude were related. These results indicate that the rate and direction of evidence accumulation are affected by immediate sensory history and that these changes contribute to single trial recalibration to audiovisual temporal asynchrony.

Developmental sequelae and neurophysiologic substrates of sensory seeking in infant siblings of children with autism spectrum disorder.

It has been proposed that early differences in sensory responsiveness arise from atypical neural function and produce cascading effects on development across domains. This longitudinal study prospectively followed infants at heightened risk for autism spectrum disorder (ASD) based on their status as younger siblings of children diagnosed with ASD (Sibs-ASD) and infants at relatively lower risk for ASD (siblings of typically developing children; Sibs-TD) to examine the developmental sequelae and possible neurophysiological substrates of a specific sensory response pattern: unusually intense interest in nonsocial sensory stimuli or "sensory seeking." At 18 months, sensory seeking and social orienting were measured with the Sensory Processing Assessment, and a potential neural signature for sensory seeking (i.e., frontal alpha asymmetry) was measured via resting state electroencephalography. At 36 months, infants' social symptomatology was assessed in a comprehensive diagnostic evaluation. Sibs-ASD showed elevated sensory seeking relative to Sibs-TD, and increased sensory seeking was concurrently associated with reduced social orienting across groups and resting frontal asymmetry in Sibs-ASD. Sensory seeking also predicted later social symptomatology. Findings suggest that sensory seeking may produce cascading effects on social development in infants at risk for ASD and that atypical frontal asymmetry may underlie this atypical pattern of sensory responsiveness.

Integration and Temporal Processing of Asynchronous Audiovisual Speech.

Multisensory integration of visual mouth movements with auditory speech is known to offer substantial perceptual benefits, particularly under challenging (i.e., noisy) acoustic conditions. Previous work characterizing this process has found that ERPs to auditory speech are of shorter latency and smaller magnitude in the presence of visual speech. We sought to determine the dependency of these effects on the temporal relationship between the auditory and visual speech streams using EEG. We found that reductions in ERP latency and suppression of ERP amplitude are maximal when the visual signal precedes the auditory signal by a small interval and that increasing amounts of asynchrony reduce these effects in a continuous manner. Time-frequency analysis revealed that these effects are found primarily in the theta (4-8 Hz) and alpha (8-12 Hz) bands, with a central topography consistent with auditory generators. Theta effects also persisted in the lower portion of the band (3.5-5 Hz), and this late activity was more frontally distributed. Importantly, the magnitude of these late theta oscillations not only differed with the temporal characteristics of the stimuli but also served to predict participants' task performance. Our analysis thus reveals that suppression of single-trial brain responses by visual speech depends strongly on the temporal concordance of the auditory and visual inputs. It further illustrates that processes in the lower theta band, which we suggest as an index of incongruity processing, might serve to reflect the neural correlates of individual differences in multisensory temporal perception.

Neural Correlates of Sensory Hyporesponsiveness in Toddlers at High Risk for Autism Spectrum Disorder.

Altered patterns of sensory responsiveness are a frequently reported feature of Autism Spectrum Disorder (ASD). Younger siblings of individuals with ASD are at a greatly elevated risk of a future diagnosis of ASD, but little is known about the neural basis of sensory responsiveness patterns in this population. Younger siblings (n = 20) of children diagnosed with ASD participated in resting electroencephalography (EEG) at an age of 18 months. Data on toddlers' sensory responsiveness were obtained using the Sensory Experiences Questionnaire. Correlations were present between hyporesponsiveness and patterns of oscillatory power, functional connectivity, and signal complexity. Our findings suggest that neural signal features hold promise for facilitating early identification and targeted remediation in young children at risk for ASD.

Event Related Potentials Index Rapid Recalibration to Audiovisual Temporal Asynchrony.

Asynchronous arrival of multisensory information at the periphery is a ubiquitous property of signals in the natural environment due to differences in the propagation time of light and sound. Rapid adaptation to these asynchronies is crucial for the appropriate integration of these multisensory signals, which in turn is a fundamental neurobiological process in creating a coherent perceptual representation of our dynamic world. Indeed, multisensory temporal recalibration has been shown to occur at the single trial level, yet the mechanistic basis of this rapid adaptation is unknown. Here, we investigated the neural basis of rapid recalibration to audiovisual temporal asynchrony in human participants using a combination of psychophysics and electroencephalography (EEG). Consistent with previous reports, participant's perception of audiovisual temporal synchrony on a given trial (t) was influenced by the temporal structure of stimuli on the previous trial (t-1). When examined physiologically, event related potentials (ERPs) were found to be modulated by the temporal structure of the previous trial, manifesting as late differences (>125 ms post second-stimulus onset) in central and parietal positivity on trials with large stimulus onset asynchronies (SOAs). These findings indicate that single trial adaptation to audiovisual temporal asynchrony is reflected in modulations of late evoked components that have previously been linked to stimulus evaluation and decision-making.

Rhythmic Modulation of Entrained Auditory Oscillations by Visual Inputs.

Temporal structure is ubiquitous in sensory signals, and the brain has been shown to robustly represent information about temporal structure in the phase of low frequency neural oscillations. In a related construct, the integration of information across the different senses has been proposed to be at least partly due to the phase resetting of these low frequency oscillations. As a consequence, oscillations represent a potential contributor to the encoding of complex multisensory signals with informative temporal structures. Here we investigated these interactions using electroencephalography (EEG). We entrained low frequency (3 Hz) delta oscillations using a repetitive auditory stimulus-broadband amplitude modulated noise. Following entrainment, we presented auditory and audiovisual stimuli at variable delays. We examined whether the power of oscillations at the entrained frequency was dependent on the delay (and thus, potentially, phase) at which subsequent stimulation was delivered, and whether this relationship was different for subsequent multisensory (i.e., audiovisual) stimuli when compared with auditory stimuli alone. Our findings demonstrate that, when the subsequent stimuli are solely auditory, the power of oscillations at the entrained frequency is rhythmically modulated by when the stimulus was delivered. For audiovisual stimuli, however, no such dependency is present, yielding consistent power modulations. These effects indicate that reciprocal oscillatory mechanisms may be involved in the continuous encoding of complex temporally structured multisensory inputs such as speech.

Dysfunction of sensory oscillations in Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is a highly prevalent developmental disability characterized by deficits in social communication and interaction, restricted interests, and repetitive behaviors. Recently, anomalous sensory and perceptual function has gained an increased level of recognition as an important feature of ASD. A specific impairment in the ability to integrate information across brain networks has been proposed to contribute to these disruptions. A crucial mechanism for these integrative processes is the rhythmic synchronization of neuronal excitability across neural populations; collectively known as oscillations. In ASD there is believed to be a deficit in the ability to efficiently couple functional neural networks using these oscillations. This review discusses evidence for disruptions in oscillatory synchronization in ASD, and how disturbance of this neural mechanism contributes to alterations in sensory and perceptual function. The review also frames oscillatory data from the perspective of prevailing neurobiologically-inspired theories of ASD.

Examining associations between anxiety and cortisol in high functioning male children with autism.

BACKGROUND: Autism spectrum disorder (ASD) is characterized by deficits in communication and social ability, as well as restricted interests and repetitive behavior. Anxiety is a persistent anticipation or apprehension about one or more situations to which a person is exposed, and affects many people, including children with ASD. Stress, by contrast, is a response to situations that are threatening, uncontrollable, or unexpected. Indices of anxiety are often measured through informants, with parents and teachers serving as the primary sources of reported anxiety in children. However, self-report measures exist, allowing current (state) and persistent (trait) anxiety to be assessed. The current study was designed to evaluate whether children with autism could identify their own levels of anxiety and the degree to which these levels were associated with symptom profile and physiological arousal. METHODS: Self-reported state and trait anxiety were collected during exposure to different stress paradigms for 40 children (21 typically developing, 19 with autistic disorder) and compared to parent reported social ability (Social Responsiveness Scale) and stress responsivity (cortisol). RESULTS: Significant differences were found between typically developing and children with autism for both state and trait anxiety across all conditions. Associations were identified between severity of parent-reported social impairment and both types of self-report anxiety. No relationship was found between stress (salivary cortisol) and anxiety in children with autism. CONCLUSIONS: Children with autism are able to consistently report their persistent level of anxiety symptoms in stressful situations of benign character. Therefore, the inclusion of such measures may be useful in identifying and tracking symptoms in children with autism under appropriate circumstances.

Recurrent CMV retinitis in a non-HIV patient with drug-resistant CMV.

BACKGROUND: We report a case of recurrent cytomegalovirus (CMV) retinitis in an HIV-negative patient with CD4+ T lymphocytopenia. METHODS: Case report. RESULTS: A 41-year-old HIV-negative woman with a history of systemic lupus erythematosus, idiopathic thrombocytopenic purpura requiring splenectomy, and diabetes presented with primary CMV infection, high-grade viremia, CMV pneumonia followed by CMV retinitis (CMVR) and a CD4+ T lymphocyte (CD4) count of 12 cells/mm(3) after therapy with rituximab, prednisone, and methotrexate. Persistent CMV viremia led to genotypic analysis of the circulating virus, which revealed UL97 and UL54 mutations known to be associated with resistance to ganciclovir (GCV) and cidofovir. CMV clearance from the bloodstream followed systemic antiviral therapy and recovery of CD4 cell count. However, CMVR recurred multiple times despite GCV implants, systemic valganciclovir, intravitreal GCV injections, and persistent CD4 counts greater than 100 cells/mm(3). Recurrent episodes of CMVR responded to multiple high dose intravitreal GCV injections (5000-6000 micrograms) and recovery of CD4 cell counts to greater than 200 cells/mm(3). CONCLUSION: This case demonstrates that recurrent CMVR occurs in HIV-negative patients at CD4 cell counts thought to be protective in HIV patients, and suggests that an ineffective local immune response to retinal infection combined with CMV drug resistance may have been important factors leading to recurrent disease in this patient. Treatment producing high local concentrations of GCV may be effective therapy for CMV retinitis due to GCV-resistant virus.