Auditory Neural Responses and Communicative Functioning in Children With Microcephaly Related to Congenital Zika Syndrome.

OBJECTIVES: Children with microcephaly exhibit neurodevelopmental delays and compromised communicative functioning, yielding challenges for clinical assessment and informed intervention. This study characterized auditory neural function and communication abilities in children with microcephaly due to congenital Zika syndrome (CZS). DESIGN: Click-evoked auditory brainstem responses (ABR) at fast and slow stimulation rates and natural speech-evoked cortical auditory evoked potentials (CAEP) were recorded in 25 Brazilian children with microcephaly related to CZS (M age: 5.93 ± 0.62 years) and a comparison group of 25 healthy children (M age: 5.59 ± 0.80 years) matched on age, sex, ethnicity, and socioeconomic status. Communication abilities in daily life were evaluated using caregiver reports on Vineland Adaptive Behavior Scales-3. RESULTS: Caregivers of children with microcephaly reported significantly lower than typical adaptive functioning in the communication and socialization domains. ABR wave I latency did not differ significantly between the groups, suggesting comparable peripheral auditory function. ABR wave V absolute latency and waves I-V interwave latency were significantly shorter in the microcephaly group for both ears and rates. CAEP analyses identified reduced N2 amplitudes in children with microcephaly as well as limited evidence of speech sound differentiation, evidenced mainly by the N2 response latency. Conversely, in the comparison group, speech sound differences were observed for both the P1 and N2 latencies. Exploratory analyses in the microcephaly group indicated that more adaptive communication was associated with greater speech sound differences in the P1 and N2 amplitudes. The trimester of virus exposure did not have an effect on the ABRs or CAEPs. CONCLUSIONS: Microcephaly related to CZS is associated with alterations in subcortical and cortical auditory neural function. Reduced ABR latencies differ from previous reports, possibly due to the older age of this cohort and careful assessment of peripheral auditory function. Cortical speech sound detection and differentiation are present but reduced in children with microcephaly. Associations between communication performance in daily life and CAEPs highlight the value of auditory evoked potentials in assessing clinical populations with significant neurodevelopmental disabilities.

Electrophysiological Measures of Listening-in-Noise With and Without Remote Microphone System Use in Autistic and Non-Autistic Youth.

OBJECTIVES: This study examined the neural mechanisms by which remote microphone (RM) systems might lead to improved behavioral performance on listening-in-noise tasks in autistic and non-autistic youth. DESIGN: Cortical auditory evoked potentials (CAEPs) were recorded in autistic (n = 25) and non-autistic (n = 22) youth who were matched at the group level on chronological age ( M = 14.21 ± 3.39 years) and biological sex. Potentials were recorded during an active syllable identification task completed in quiet and in multi-talker babble noise with and without the use of an RM system. The effects of noise and RM system use on speech-sound-evoked P1-N1-P2 responses and the associations between the cortical responses and behavioral performance on syllable identification were examined. RESULTS: No group differences were observed for behavioral or CAEP measures of speech processing in quiet or in noise. In the combined sample, syllable identification in noise was less accurate and slower than in the quiet condition. The addition of the RM system to the noise condition restored accuracy, but not the response speed, to the levels observed in quiet. The CAEP analyses noted amplitude reductions and latency delays in the noise compared with the quiet condition. The RM system use increased the N1 amplitude as well as reduced and delayed the P2 response relative to the quiet and noise conditions. Exploratory brain-behavior correlations revealed that larger N1 amplitudes in the RM condition were associated with greater behavioral accuracy of syllable identification. Reduced N1 amplitude and accelerated P2 response were associated with shorter syllable identification response times when listening with the RM system. CONCLUSIONS: Findings suggest that although listening-in-noise with an RM system might remain effortful, the improved signal to noise ratio facilitates attention to the sensory features of the stimuli and increases speech sound identification accuracy.

Investigating Social Competence in a Pilot Randomized Clinical Trial of a Theatre-Based Intervention Enhanced for Adults with Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is characterized by challenges in social competence that persist in adulthood, yet few treatment options exist. A pilot randomized clinical trial (RCT) of a peer-mediated, theatre-based intervention with established efficacy in youth with ASD was examined in autistic adults. The final sample consisted of forty-seven 18-to-40-year-old participants randomized to the experimental (EXP N = 23) or waitlist control (WLC N = 24) condition. A multimodal, social interdependent model was employed to examine social competence changes in brain (incidental face memory (IFM) using event-related potentials), cognition (Wechsler Memory Scale-III), behavior (Contextual Assessment of Social Skills) and function (Social Responsiveness Scale (SRS); Adaptive Behavior Assessment Scale (ABAS) Social Composite). Using analysis of covariance in which pretest was controlled in the model, posttest between-group differences were observed on IFM (p = 0.016, η2 = 0.139, d = 0.79) and several social and adaptive functional (SRS, ABAS) outcomes in social communication and interaction (SCI) (p = 0.019, η2 = 0.121, d = -00.45), communication (p = 0.044 η2 = 0.09, d = -00.31), and motivation (p = 0.001, η2 = 0.229, d = -0.79) domains. At two-month follow-up, gains in social motivation remained (p = 0.041, η2 = 0.100, d = -0.77). The results offer preliminary support for a unique theatre-based social skills intervention for autistic adults who have few treatment options to enhance social competence. The trial was pre-registered with ClinicalTrials.gov (Identifier: NCT04349644).

Individual differences in neural markers of beat processing relate to spoken grammar skills in six-year-old children.

Based on the idea that neural entrainment establishes regular attentional fluctuations that facilitate hierarchical processing in both music and language, we hypothesized that individual differences in syntactic (grammatical) skills will be partly explained by patterns of neural responses to musical rhythm. To test this hypothesis, we recorded neural activity using electroencephalography (EEG) while children (N = 25) listened passively to rhythmic patterns that induced different beat percepts. Analysis of evoked beta and gamma activity revealed that individual differences in the magnitude of neural responses to rhythm explained variance in six-year-olds' expressive grammar abilities, beyond and complementarily to their performance in a behavioral rhythm perception task. These results reinforce the idea that mechanisms of neural beat entrainment may be a shared neural resource supporting hierarchical processing across music and language and suggest a relevant marker of the relationship between rhythm processing and grammar abilities in elementary-school-age children, previously observed only behaviorally.

Food cue reward salience does not explain Hyperphagia in adolescents with Prader-Willi syndrome.

Prader-Willi Syndrome (PWS) is characterized by hyperphagia, an extreme and persistent hunger that emerges in early childhood. We used event-related potentials (ERPs) to objectively investigate brain responses to low- and high-calorie foods, animals, and household objects in 20 satiated adolescents with PWS. Late Positive Potential (LPP) responses to food images did not differ from non-food images. Rather, we observed larger ERPs to high-calorie foods relative to animal images (p=.001) in an earlier time window. These responses correlated with greater severity of hyperphagia (p = .01). Thus, hyperphagia associated with PWS may be due to altered satiety regulation rather than increased motivational salience.

Peers, play, and performance to build social salience in autistic youth: A multisite randomized clinical trial.

OBJECTIVE: Individuals with autism spectrum disorder (ASD) have significant impairment in social competence and reduced social salience. SENSE Theatre, a peer-mediated, theater-based intervention has demonstrated posttreatment gains in face memory and social communication. The multisite randomized clinical trial compared the Experimental (EXP; SENSE Theatre) to an Active Control Condition (ACC; Tackling Teenage Training, TTT) at pretest, posttest, and follow-up. It was hypothesized that the EXP group would demonstrate greater incidental face memory (IFM) and better social behavior (interaction with novel peers) and social functioning (social engagement in daily life) than the ACC group, and posttest IFM would mediate the treatment effect on follow-up social behavior and functioning. METHOD: Two hundred ninety participants were randomized to EXP (N = 144) or ACC (N = 146). Per protocol sample (≥ 7/10 sessions) resulted in 207 autistic children 10-16 years. Event-related potentials measured IFM. Naive examiners measured social behavior (Vocal Expressiveness, Quality of Rapport, Social Anxiety) and functioning (Social Communication). Structural equation modeling was used to assess treatment effects. RESULTS: SENSE Theatre participants showed significantly better IFM (b = .874, p = .039) at posttest, and significant indirect effects on follow-up Vocal Expressiveness a × b = .064, with 90% CI [.014, .118] and Quality of Rapport a × b = .032, with 90% CI [.002, .087] through posttest IFM. CONCLUSIONS: SENSE Theatre increases social salience as reflected by IFM, which in turn affected Vocal Expressiveness and Quality of Rapport. Results indicate that a neural mechanism supporting social cognition and driven by social salience is engaged by the treatment and has a generalized, indirect effect on clinically meaningful functional outcomes related to core symptoms of autism. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Comparison of evoked potentials across four related developmental encephalopathies.

BACKGROUND: Developing biomarkers is a priority for drug development for all conditions, but vital in the rare neurodevelopmental disorders where sensitive outcome measures are lacking. We have previously demonstrated the feasibility and tracking of evoked potentials to disease severity in Rett syndrome and CDKL5 deficiency disorder. The aim of the current study is to characterize evoked potentials in two related developmental encephalopathies, MECP2 duplication syndrome and FOXG1 syndrome, and compare across all four groups to better understand the potential of these measures to serve as biomarkers of clinical severity for the developmental encephalopathies. METHODS: Visual and auditory evoked potentials were acquired from participants with MECP2 duplication syndrome and FOXG1 syndrome across five sites of the Rett Syndrome and Rett-Related Disorders Natural History Study. A group of age-matched individuals (mean = 7.8 years; range = 1-17) with Rett syndrome, CDKL5 deficiency disorder, and typically-developing participants served as a comparison group. The analysis focused on group-level differences as well as associations between the evoked potentials and measures of clinical severity from the Natural History Study. RESULTS: As reported previously, group-level comparisons revealed attenuated visual evoked potentials (VEPs) in participants with Rett syndrome (n = 43) and CDKL5 deficiency disorder (n = 16) compared to typically-developing participants. VEP amplitude was also attenuated in participants with MECP2 duplication syndrome (n = 15) compared to the typically-developing group. VEP amplitude correlated with clinical severity for Rett syndrome and FOXG1 syndrome (n = 5). Auditory evoked potential (AEP) amplitude did not differ between groups, but AEP latency was prolonged in individuals with MECP2 duplication syndrome (n = 14) and FOXG1 syndrome (n = 6) compared to individuals with Rett syndrome (n = 51) and CDKL5 deficiency disorder (n = 14). AEP amplitude correlated with severity in Rett syndrome and CDKL5 deficiency disorder. AEP latency correlated with severity in CDKL5 deficiency disorder, MECP2 duplication syndrome, and FOXG1 syndrome. CONCLUSIONS: There are consistent abnormalities in the evoked potentials in four developmental encephalopathies some of which correlate with clinical severity. While there are consistent changes amongst these four disorders, there are also condition specific findings that need to be further refined and validated. Overall, these results provide a foundation for further refinement of these measures for use in future clinical trials for these conditions.

Plasticity Changes in Central Auditory Systems of School-Age Children Following a Brief Training With a Remote Microphone System.

OBJECTIVES: The objective of this study was to investigate whether a brief speech-in-noise training with a remote microphone (RM) system (favorable listening condition) would contribute to enhanced post-training plasticity changes in the auditory system of school-age children. DESIGN: Before training, event-related potentials (ERPs) were recorded from 49 typically developing children, who actively identified two syllables in quiet and in noise (+5 dB signal-to-noise ratio [SNR]). During training, children completed the same syllable identification task as in the pre-training noise condition, but received feedback on their performance. Following random assignment, half of the sample used an RM system during training (experimental group), while the other half did not (control group). That is, during training' children in the experimental group listened to a more favorable speech signal (+15 dB SNR) than children from the control group (+5 dB SNR). ERPs were collected after training at +5 dB SNR to evaluate the effects of training with and without the RM system. Electrical neuroimaging analyses quantified the effects of training in each group on ERP global field power (GFP) and topography, indexing response strength and network changes, respectively. Behavioral speech-perception-in-noise skills of children were also evaluated and compared before and after training. We hypothesized that training with the RM system (experimental group) would lead to greater enhancement of GFP and greater topographical changes post-training than training without the RM system (control group). We also expected greater behavioral improvement on the speech-perception-in-noise task when training with than without the RM system. RESULTS: GFP was enhanced after training only in the experimental group. These effects were observed on early time-windows corresponding to traditional P1-N1 (100 to 200 msec) and P2-N2 (200 to 400 msec) ERP components. No training effects were observed on response topography. Finally, both groups increased their speech-perception-in-noise skills post-training. CONCLUSIONS: Enhanced GFP after training with the RM system indicates plasticity changes in the neural representation of sound resulting from listening to an enriched auditory signal. Further investigation of longer training or auditory experiences with favorable listening conditions is needed to determine if that results in long-term speech-perception-in-noise benefits.

Rapid Interactions of Widespread Brain Networks Characterize Semantic Cognition.

Language comprehension requires the rapid retrieval and integration of contextually appropriate concepts ("semantic cognition"). Current neurobiological models of semantic cognition are limited by the spatial and temporal restrictions of single-modality neuroimaging and lesion approaches. This is a major impediment given the rapid sequence of processing steps that have to be coordinated to accurately comprehend language. Through the use of fused functional magnetic resonance imaging and electroencephalography analysis in humans (n = 26 adults; 15 females), we elucidate a temporally and spatially specific neurobiological model for real-time semantic cognition. We find that semantic cognition in the context of language comprehension is supported by trade-offs between widespread neural networks over the course of milliseconds. Incorporation of spatial and temporal characteristics, as well as behavioral measures, provide convergent evidence for the following progression: a hippocampal/anterior temporal phonological semantic retrieval network (peaking at ∼300 ms after the sentence final word); a frontotemporal thematic semantic network (∼400 ms); a hippocampal memory update network (∼500 ms); an inferior frontal semantic syntactic reappraisal network (∼600 ms); and nodes of the default mode network associated with conceptual coherence (∼750 ms). Additionally, in typical adults, mediatory relationships among these networks are significantly predictive of language comprehension ability. These findings provide a conceptual and methodological framework for the examination of speech and language disorders, with additional implications for the characterization of cognitive processes and clinical populations in other cognitive domains.SIGNIFICANCE STATEMENT The present study identifies a real-time neurobiological model of the meaning processes required during language comprehension (i.e., "semantic cognition"). Using a novel application of fused magnetic resonance imaging and electroencephalography in humans, we found that semantic cognition during language comprehension is supported by a rapid progression of widespread neural networks related to meaning, meaning integration, memory, reappraisal, and conceptual cohesion. Relationships among these systems were predictive of individuals' language comprehension efficiency. Our findings are the first to use fused neuroimaging analysis to elucidate language processes. In so doing, this study provides a new conceptual and methodological framework in which to characterize language processes and guide the treatment of speech and language deficits/disorders.

Typical and atypical neural mechanisms support spoken word processing in Angelman syndrome.

Angelman syndrome (AS) is known to affect expressive and receptive communication abilities. This study examined individual differences in neural mechanisms underlying speech processing in children with AS (n = 24, M age = 10.01 years) and typical development (n = 30, M age = 10.82 years) using auditory event-related potentials during passive listening to common English words and novel pseudowords. A group of adults with AS (n = 7, M = 31.78 years) provided data about the upper developmental range. The typically developing group demonstrated the expected more negative amplitudes in response to words than pseudowords within 250-500 ms after stimulus onset at the left temporal scalp region. Children and adults with AS exhibited a similar left-lateralized pattern of word-pseudoword differentiation at temporal and parietal regions, but not the midline parietal memory response for known words observed in the typically developing group, suggesting typical-like word-pseudoword differentiation along with possible alterations in the automatic recall of word meaning. These results have important implications for understanding receptive and expressive communication processes in AS and support the use of auditory neural responses for characterizing individual differences in neurodevelopmental disorders with limited speech.

Spoken language comprehension in children and adults with Angelman Syndrome.

INTRODUCTION: Objective evaluation of receptive communication abilities in nonspeaking individuals using standardized behavioral measures can be complicated by co-occurring intellectual disabilities and motor difficulties. Eye tracking during listening may offer an informative complementary approach to directly evaluate receptive language skills. METHOD: This study examined feasibility of eye gaze measures as an index of spoken language comprehension in nonspeaking children and adults with Angelman syndrome (AS; n = 23) using a looking-while-listening procedure. Typically developing children (n = 34) provided a reference data set. Primary caregivers of participants with AS completed standardized informant reports (MacArthur-Bates Communicative Development Inventory: Words and Gestures; Vineland Adaptive Behavior Scales-3; Aberrant Behavior Checklist-2) to characterize communicative skills and general adaptive functioning. RESULTS: Gaze data in participants with AS, particularly in the individuals reported by caregivers to have larger receptive vocabularies and stronger adaptive communicative functioning, demonstrated the expected pattern of comprehension reflected by the increased probability of looks to the target images after vs. before they were named in a spoken sentence. However, processing speed (gaze reaction time) was significantly slower in participants with AS than in the typically developing group. CONCLUSIONS: Gaze-based paradigms could be an informative measure of receptive communication processes in participants who are unable to complete traditional standardized behavioral assessments.

Electrophysiological biomarkers of brain function in CDKL5 deficiency disorder.

CDKL5 deficiency disorder is a debilitating developmental and epileptic encephalopathy for which no targeted treatment exists. A number of promising therapeutics are under development for CDKL5 deficiency disorder but a lack of validated biomarkers of brain function and clinical severity may limit the ability to objectively assess the efficacy of new treatments as they become available. To address this need, the current study quantified electrophysiological measures in individuals with CDKL5 deficiency disorder and the association between these parameters and clinical severity. Visual and auditory evoked potentials, as well as resting EEG, were acquired across 5 clinical sites from 26 individuals with CDKL5 deficiency disorder. Evoked potential and quantitative EEG features were calculated and compared with typically developing individuals in an age- and sex-matched cohort. Baseline and Year 1 data, when available, were analysed and the repeatability of the results was tested. Two clinician-completed severity scales were used for evaluating the clinical relevance of the electrophysiological parameters. Group-level comparisons revealed reduced visual evoked potential amplitude in CDKL5 deficiency disorder individuals versus typically developing individuals. There were no group differences in the latency of the visual evoked potentials or in the latency or amplitude of the auditory evoked potentials. Within the CDKL5 deficiency disorder group, auditory evoked potential amplitude correlated with disease severity at baseline as well as Year 1. Multiple quantitative EEG features differed between CDKL5 deficiency disorder and typically developing participants, including amplitude standard deviation, 1/f slope and global delta, theta, alpha and beta power. Several quantitative EEG features correlated with clinical severity, including amplitude skewness, theta/delta ratio and alpha/delta ratio. The theta/delta ratio was the overall strongest predictor of severity and also among the most repeatable qEEG measures from baseline to Year 1. Together, the present findings point to the utility of evoked potentials and quantitative EEG parameters as objective measures of brain function and disease severity in future clinical trials for CDKL5 deficiency disorder. The results also underscore the utility of the current methods, which could be similarly applied to the identification and validation of electrophysiological biomarkers of brain function for other developmental encephalopathies.

Sex differences in automatic emotion regulation in adolescents with autism spectrum disorder.

Autism may be underdiagnosed in females because their social difficulties are often less noticeable. This study explored sex differences in automatic facial emotion processing in 45 adolescents with autism spectrum disorder (22 female, 23 male), age 10-16 years, performing active target detection task and Go/NoGo tasks where faces with positive and negative emotional expressions served as irrelevant distractors. The combined sample demonstrated more accurate performance on the target detection (response initiation) than the Go/NoGo task (response inhibition), replicating findings previously reported in typical participants. Females exhibited greater difficulty than males with response initiation in the target detection task, especially in the context of angry faces, while males found withholding a response in the Go/NoGo block with happy faces more challenging. Electrophysiological data revealed no sex differences or emotion discrimination effects during the early perceptual processing of faces indexed by the occipitotemporal N170. Autistic males demonstrated increased frontal N2 and parietal P3 amplitudes compared to females, suggesting greater neural resource allocation to automatic emotion regulation processes. The associations between standardized behavioral measures (autism severity, theory of mind skills) and brain responses also varied by sex: more adaptive social functioning was related to the speed of perceptual processing (N170 latency) in females and the extent of deliberate attention allocation (P3 amplitudes) in males. Together, these findings suggest that males and females with autism may rely on different strategies for social functioning and highlight the importance of considering sex differences in autism. LAY SUMMARY: Females with autism may exhibit less noticeable social difficulties than males. This study demonstrates that autistic females are more successful than males at inhibiting behavioral responses in emotional contexts, while males are more likely to initiate a response. At the neural level, social functioning in females is related to the speed of automatic perceptual processing of facial cues, and in males, to the extent of active attention allocation to the stimuli. These findings highlight the importance of considering sex differences in autism diagnosis and treatment selection.

Electrophysiological biomarkers and age characterize phenotypic heterogeneity among individuals with major depressive disorder.

Introduction: Despite the high need for effective treatments for major depressive disorder (MDD), the development of novel medicines is hampered by clinical, genetic and biological heterogeneity, unclear links between symptoms and neural dysfunction, and tenuous biomarkers for clinical trial contexts of use. Methods: In this study, we examined the International Study to Predict Optimized Treatment in Depression (iSPOT-D) clinical trial database for new relationships between auditory event-related potential (ERP) responses, demographic features, and clinical symptoms and behavior, to inform strategies for biomarker-driven patient stratification that could be used to optimize future clinical trial design and drug development strategy in MDD. Results: We replicate findings from previous analyses of the classic auditory oddball task in the iSPOT-D sample showing smaller than typical N1 and P300 response amplitudes and longer P300 latencies for target and standard stimuli in patients with MDD, suggesting altered bottom-up sensory and top-down attentional processes. We further demonstrate that age is an important contributor to clinical group differences, affecting both topographic distribution of the clinically informative ERP responses and the types of the stimuli sensitive to group differences. In addition, the observed brain-behavior associations indicate that levels of anxiety and stress are major contributing factors to atypical sensory and attentional processing among patients with MDD, particularly in the older subgroups. Discussion: Our novel findings support the possibility of accelerated cognitive aging in patients with MDD and identify the frontal P300 latency as an additional candidate biomarker of MDD. These results from a large, well-phenotyped sample support the view that heterogeneity of the clinical population with MDD can be systematically characterized based on age and neural biomarkers of sensory and attentional processing, informing patient stratification strategies in the design of clinical trials.

Cross-disorder comparison of sensory over-responsivity in chronic tic disorders and obsessive-compulsive disorder.

BACKGROUND: Sensory over-responsivity (SOR) refers to excessively intense and/or prolonged behavioral responses to environmental stimuli typically perceived as non-aversive. SOR is prevalent in several neurodevelopmental disorders, including chronic tic disorders (CTDs) and obsessive-compulsive disorder (OCD). Few studies have examined the extent and clinical correlates of SOR across disorders, limiting insights into the phenomenon's transdiagnostic clinical and biological relevance. Such cross-disorder comparisons are of particular interest for CTDs and OCD given their frequent co-occurrence. OBJECTIVE: We sought to compare the magnitude of SOR between adults with CTD and adults with OCD and to identify the clinical factors most strongly associated with SOR across these disorders. METHODS: We enrolled 207 age- and sex-matched participants across four diagnostic categories: CTD without OCD (designated "CTD/OCD-"; n = 37), CTD with OCD ("CTD/OCD+"; n = 32), OCD without tic disorder ("OCD"; n = 69), and healthy controls (n = 69). Participants completed a self-report battery of rating scales assessing SOR (Sensory Gating Inventory, SGI), obsessive-compulsive symptoms (Dimensional Obsessive-Compulsive Scale, DOCS), inattention and hyperactivity (Adult ADHD Self-Report Screening Scale for DSM-5, ASRS-5), anxiety (Generalized Anxiety Disorder-7), and depression (Patient Health Questionnaire-9). CTD participants were also administered the Yale Global Tic Severity Scale (YGTSS). To examine between-group differences in SOR, we compared SGI score across all groups and between pairs of groups. To examine the relationship of SOR with other clinical factors, we performed multivariable linear regression. RESULTS: CTD/OCD-, CTD/OCD+, and OCD participants were 86.7%, 87.6%, and 89.5%, respectively, more likely to have higher SGI total scores than healthy controls. SGI total score did not differ between CTD/OCD-, CTD/OCD+, and OCD groups. In the regression model of log-transformed SGI total score, OCD diagnosis, DOCS score, and ASRS-5 score each contributed significantly to model goodness-of-fit, whereas CTD diagnosis and YGTSS total tic score did not. CONCLUSION: SOR is prevalent in adults with CTD and in adults with OCD but does not significantly differ in magnitude between these disorders. Across CTD, OCD, and healthy control adult populations, SOR is independently associated with both obsessive-compulsive and ADHD symptoms, suggesting a transdiagnostic relationship between these sensory and psychiatric manifestations. Future cross-disorder, longitudinal, and translational research is needed to clarify the role and prognostic import of SOR in CTDs, OCD, and other neurodevelopmental disorders.

Searching for a "Brain Signature" of Neurodevelopmental Disorders: Event-Related Potentials and the Quest for Biomarkers of Cognition.

SUMMARY: This review summarizes main applications of event-related potentials (ERPs) to the study of cognitive processes in persons with neurodevelopmental disorders, for whom traditional behavioral assessments may not be suitable. A brief introduction to the ERPs is followed by a review of empirical studies using passive ERP paradigms to address three main questions: characterizing individual differences, predicting risk for poor developmental outcomes, and documenting treatment effects in persons with neurodevelopmental disorders. Evidence across studies reveals feasibility of ERP methodology in a wide range of clinical populations and notes consistently stronger brain-behavior associations involving ERP measures of higher-order cognition compared with sensory-perceptual processes. The final section describes the current limitations of ERP methodology that need to be addressed before it could be used as a clinical tool and highlights the needed steps toward translating ERPs from group-level research applications to individually interpretable clinical use.

Speech Processing in Autism Spectrum Disorder: An Integrative Review of Auditory Neurophysiology Findings.

Purpose Investigations into the nature of communication disorders in autistic individuals increasingly evaluate neural responses to speech stimuli. This integrative review aimed to consolidate the available data related to speech and language processing across levels of stimulus complexity (from single speech sounds to sentences) and to relate it to the current theories of autism. Method An electronic database search identified peer-reviewed articles using event-related potentials or magnetoencephalography to investigate auditory processing from single speech sounds to sentences in autistic children and adults varying in language and cognitive abilities. Results Atypical neural responses in autistic persons became more prominent with increasing stimulus and task complexity. Compared with their typically developing peers, autistic individuals demonstrated mostly intact sensory responses to single speech sounds, diminished spontaneous attentional orienting to spoken stimuli, specific difficulties with categorical speech sound discrimination, and reduced processing of semantic content. Atypical neural responses were more often observed in younger autistic participants and in those with concomitant language disorders. Conclusions The observed differences in neural responses to speech stimuli suggest that communication difficulties in autistic individuals are more consistent with the reduced social interest than the auditory dysfunction explanation. Current limitations and future directions for research are also discussed.

Nutritional Formulation for Patients with Angelman Syndrome: A Randomized, Double-Blind, Placebo-Controlled Study of Exogenous Ketones.

BACKGROUND: Angelman syndrome (AS) patients often respond to low glycemic index therapy to manage refractory seizures. These diets significantly affect quality of life and are challenging to implement. These formulations may have benefits in AS even in the absence of biomarkers suggesting ketosis. OBJECTIVES: We aimed to compare an exogenous medical food ketone formulation (KF) with placebo for the dietary management of AS. METHODS: This randomized, double-blind, placebo-controlled, crossover clinical trial was conducted in an academic center from 15 November, 2018 to 6 January, 2020. Thirteen participants with molecularly confirmed AS aged 4-11 y met the criteria and completed the 16-wk study. The study consisted of four 4-wk phases: a baseline phase, a blinded KF or placebo phase, a washout phase, and the crossover phase with alternate blinded KF or placebo. Primary outcomes were safety and tolerability rated by retention in the study and adherence to the formulation. Additional secondary outcomes of safety in this nonverbal population included blood chemistry, gastrointestinal health, seizure burden, cortical irritability, cognition, mobility, sleep, and developmental staging. RESULTS: Data were compared between the baseline, KF, and placebo epochs. One participant exited the trial owing to difficulty consuming the formulation. Adverse events included an increase in cholesterol in 1 subject when consuming KF and a decrease in albumin in 1 subject when consuming placebo. Stool consistency improved with KF consumption, from 6.04 ± 1.61 at baseline and 6.35 ± 1.55 during placebo to 4.54 ± 1.19 during KF (P = 0.0027). Electroencephalograph trends showed a decrease in Δ frequency power during the KF arm and event-related potentials suggested a change in the frontal memory response. Vineland-3 showed improved fine motor skills in the KF arm. CONCLUSIONS: The exogenous KF appears safe. More data are needed to determine the utility of exogenous ketones as a nutritional approach in children with AS.This trial was registered at clinicaltrials.gov as NCT03644693.

A prospective study of neurodevelopmental trends between 3 and 24 months in normocephalic infants with prenatal Zika virus exposure: Evidence of emerging communication delays in the NATZIG cohort.

Developmental trends between 3 and 24 months were assessed in 194 normocephalic infants with prenatal Zika virus exposure. Bayley Scales of Infant and Toddler Development Screening Test-3rd Edition cognitive scores remained in the typical range. Communication skills developed at a slower rate suggesting that neurodevelopmental delays may emerge at older ages.

Visual food cue processing in children with Prader-Willi Syndrome.

Hyperphagia and the associated interest in food is a characteristic feature of Prader-Willi syndrome (PWS) that emerges during childhood and remains a life-long concern. This study examined neural responses reflecting food cue salience in children with PWS and typical controls, age 3-12 years. Visual event-related potentials were recorded while participants in satiated state passively viewed photographs of high- and low-calorie foods, animals, and neutral objects. Contrary to the prediction, children with PWS did not demonstrate greater than typical neural responses to food, suggesting that it is not an exceptionally motivationally salient stimulus in PWS. Caregiver reports of greater hyperphagia were associated with neural responses to low-calorie foods suggesting accelerated and more fine-grained visual stimulus categorization in terms of edibility and caloric content. Overall, the findings align more closely with the altered satiety rather than increased food reward models of hyperphagia in PWS.