Pubertal maturation and timing effects on resting state electroencephalography in autistic and comparison youth.

Autistic and comparison individuals differ in resting-state electroencephalography (EEG), such that sex and age explain variability within and between groups. Pubertal maturation and timing may further explain variation, as previous work has suggested alterations in pubertal timing in autistic youth. In a sample from two studies of 181 autistic and 94 comparison youth (8 years to 17 years and 11 months), mixed-effects linear regressions were conducted to assess differences in EEG (midline power for theta, alpha, and beta frequency bands). Alpha power was analyzed as a mediator in the relation between pubertal maturation and timing with autistic traits in the autistic groups to understand the role of puberty in brain-based changes that contribute to functional outcomes. Individuals advanced in puberty exhibited decreased power in all bands. Those who experienced puberty relatively early showed decreased power in theta and beta bands, controlling for age, sex, and diagnosis. Autistic individuals further along in pubertal development exhibited lower social skills. Alpha mediated the relation between puberty and repetitive behaviors. Pubertal maturation and timing appear to play unique roles in the development of cognitive processes for autistic and comparison youth and should be considered in research on developmental variation in resting-state EEG.

Gender, assigned sex at birth, and gender diversity: Windows into diagnostic timing disparities in autism.

LAY ABSTRACT: Later autism diagnosis is associated with risk for mental health problems. Understanding factors related to later autism diagnosis may help reduce mental health risks for autistic people. One characteristic associated with later autism diagnosis is female sex. However, studies often do not distinguish sex assigned at birth and gender identity. Gender diversity may be more common in autistic relative to neurotypical people, and autism is more common in gender-diverse populations. We studied age at autism diagnosis by sex assigned at birth, gender identity, and gender diversity (gender-diverse vs cisgender) status, separately. We studied three separate autistic samples, each of which differed in how they were diagnosed and how they were recruited. The samples included 193 persons (8.0-18.0 years) from a research-recruited academic medical center sample; 1,550 people (1.3-25.4 years) from a clinic-based sample; and 244 people (18.2-30.0 years) from a community-enriched sample. We found significant differences in the clinic-based and community-enriched samples. People assigned female sex at birth were diagnosed with autism significantly later than people assigned male at birth. People of female gender were diagnosed significantly later than people of male gender. Gender-diverse people were diagnosed significantly later than cisgender people. Sex assigned at birth, gender identity, and gender diversity may each show unique relationships with age of autism diagnosis. Differences in how autistic people are diagnosed and recruited are important to consider in studies that examine sex assigned at birth or gender identity. More research into autism diagnosis in adulthood is needed.

Gender and Autism Program: A novel clinical service model for gender-diverse/transgender autistic youth and young adults.

Objective: Situated in Children's National Hospital (CNH)'s Neuropsychology Division, the Gender and Autism Program (GAP) is the first clinical service dedicated to the needs of autistic gender-diverse/transgender youth. This study describes GAP clinical assessment profiles and presents a multi-perspective programmatic review of GAP evaluation services. Method: Seventy-five consecutive gender- and neuropsychologically-informed GAP evaluations were analyzed, including demographics, gender and autism characterization, and primary domains evaluated. Three program-based Delphi studies were conducted and identify: clinician priorities and challenges in providing care, program administrator lessons learned and ongoing barriers, and considerations adapting this model for a rural academic medical center. Results: Nearly two-thirds of referrals were transfeminine. Most youth had existing autism diagnoses; of those undiagnosed, three-quarters were found to be autistic. Five goals of evaluations were identified: Mental health was always assessed, and most evaluations also assessed gender-related needs in the context of autism neurodiversity. Neuropsychological characterization of strengths and challenges informed personalized accommodations to support youth gender-related self-advocacy. Clinicians emphasized frequent youth safety concerns. Administrators emphasized the need for specialized training for working with families. Components for adaptation of the GAP in a rural academic medical center were identified. Conclusions: Since its founding, the GAP has proven a sustainable neuropsychology-based service with consistent referral flow and insurance authorizations. Capturing staff perspectives through rigorous Delphi methods, and addressing the GAP's feasibility and replicability, this study provides a road map for replicating this service. We also highlight GAP training of specialist clinicians, fundamental to addressing the desperate shortage of providers in this field.

Interhemispheric transfer time and concussion in adolescents: A longitudinal study using response time and event-related potential measures.

Introduction: Concussion in children and adolescents is a public health concern with higher concussion incidence than adults and increased susceptibility to axonal injury. The corpus callosum is a vulnerable location of concussion-related white matter damage that can be associated with short- and long-term effects of concussion. Interhemispheric transfer time (IHTT) of visual information across the corpus callosum can be used as a direct measure of corpus callosum functioning that may be impacted by adolescent concussion with slower IHTT relative to matched controls. Longitudinal studies and studies testing physiological measures of IHTT following concussion in adolescents are lacking. Methods: We used the N1 and P1 components of the scalp-recorded brain event-related potential (ERP) to measure IHTT in 20 adolescents (ages 12-19 years old) with confirmed concussion and 16 neurologically-healthy control participants within 3 weeks of concussion (subacute stage) and approximately 10 months after injury (longitudinal). Results: Separate two-group (concussion, control) by two-time (3 weeks, 10 months) repeated measures ANOVAs on difference response times and IHTT latencies of the P1 and N1 components showed no significant differences by group (ps ≥ 0.25) nor by time (ps ≥ 0.64), with no significant interactions (ps ≥ 0.15). Discussion: Results from the current sample suggest that measures of IHTT may not be strongly influenced at 3 weeks or longitudinally following adolescent concussion using the current IHTT paradigm.

The Gender Self-Report: A multidimensional gender characterization tool for gender-diverse and cisgender youth and adults.

Gender identity is a core component of human experience, critical to account for in broad health, development, psychosocial research, and clinical practice. Yet, the psychometric characterization of gender has been impeded due to challenges in modeling the myriad gender self-descriptors, statistical power limitations related to multigroup analyses, and equity-related concerns regarding the accessibility of complex gender terminology. Therefore, this initiative employed an iterative multi-community-driven process to develop the Gender Self-Report (GSR), a multidimensional gender characterization tool, accessible to youth and adults, nonautistic and autistic people, and gender-diverse and cisgender individuals. In Study 1, the GSR was administered to 1,654 individuals, sampled through seven diversified recruitments to be representative across age (10-77 years), gender and sexuality diversity (∼33% each gender diverse, cisgender sexual minority, cisgender heterosexual), and autism status (> 33% autistic). A random half-split subsample was subjected to exploratory factor analytics, followed by confirmatory analytics in the full sample. Two stable factors emerged: Nonbinary Gender Diversity and Female-Male Continuum (FMC). FMC was transformed to Binary Gender Diversity based on designated sex at birth to reduce collinearity with designated sex at birth. Differential item functioning by age and autism status was employed to reduce item-response bias. Factors were internally reliable. Study 2 demonstrated the construct, convergent, and ecological validity of GSR factors. Of the 30 hypothesized validation comparisons, 26 were confirmed. The GSR provides a community-developed gender advocacy tool with 30 self-report items that avoid complex gender-related "insider" language and characterize diverse populations across continuous multidimensional binary and nonbinary gender traits. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Cognitive control and conflict adaptation in youth with high-functioning autism.

BACKGROUND: Youth diagnosed with autism spectrum disorders (ASD) often show deficits in cognitive control processes, potentially contributing to characteristic difficulties monitoring and regulating behavior. Modification of performance following conflict can be measured by examining conflict adaptation, the adjustment of cognitive resources based on previous-trial conflict. The electrophysiological correlates of these processes can be measured using the N2, a stimulus-locked component of the event-related potential (ERP). METHODS: High-density ERPs and behavioral data [i.e. response times (RTs) and error rates] were acquired while 28 youth with ASD and 36 typically developing controls completed a modified Eriksen flanker task. RESULTS: Behaviorally, groups showed similar conflict adaptation effects; youth with ASD showed larger RT slowing on switch trials. For electrophysiology, controls demonstrated larger N2 amplitudes for incongruent (high-conflict) trials following congruent (low-conflict) trials than for incongruent trials following incongruent trials. Importantly, youth with ASD showed no such differences in N2 amplitude based on previous-trial conflict. CONCLUSIONS: Lack of electrophysiological conflict adaptation effects in youth with ASD indicates irregular neural processing associated with conflict adaptation. Individuals with ASD show declines in level of conflict evaluation and adaptation. Future research is necessary to accurately characterize and understand the behavioral implications of these cognitive control deficits relative to diagnostic severity, anxiety, and personality.

Feedback and reward processing in high-functioning autism.

Individuals with high-functioning autism often display deficits in social interactions and high-level cognitive functions. Such deficits may be influenced by poor ability to process feedback and rewards. The feedback-related negativity (FRN) is an event-related potential (ERP) that is more negative following losses than gains. We examined FRN amplitude in 25 individuals with Autism Spectrum Disorder (ASD) and 25 age- and IQ-matched typically developing control participants who completed a guessing task with monetary loss/gain feedback. Both groups demonstrated a robust FRN that was more negative to loss trials than gain trials; however, groups did not differ in FRN amplitude as a function of gain or loss trials. N1 and P300 amplitudes did not differentiate groups. FRN amplitude was positively correlated with age in individuals with ASD, but not measures of intelligence, anxiety, behavioral inhibition, or autism severity. Given previous findings of reduced-amplitude error-related negativity (ERN) in ASD, we propose that individuals with ASD may process external, concrete, feedback similar to typically developing individuals, but have difficulty with internal, more abstract, regulation of performance.

Dimensions of anxiety and depression and neurophysiological indicators of error-monitoring: Relationship with delta and theta oscillatory power and error-related negativity amplitude.

Error-monitoring processes may be affected by transdiagnostic dimensions of psychopathology symptoms including trait anxiety, worry, and severity of depressive symptoms. We tested the relationship between continuous measures of anxiety and depressive symptomology and neural correlates of error-monitoring as measured by time-frequency domain delta and theta oscillatory power and time-domain error-related negativity (ERN) amplitude extracted from the electroencephalogram (EEG). Secondary analyses tested for diagnostic group differences in error-related neural responses in individuals with generalized anxiety disorder (GAD), major depressive disorder (MDD), and comorbid psychiatric disorders. About 178 participants (104 female, M[SD]age  = 21.7[4.6]) with a wide range of psychopathology symptoms completed a modified version of the Eriksen flanker task and symptom questionnaires. Residualized difference values between correct and error trials for delta/theta power and error/correct ERN amplitude were used as dependent variables. Linear regression analyses adjusted for age, sex, and task accuracy showed nonsignificant associations of symptom dimension measures with error-related residualized delta/theta power or residualized ERN amplitude. Subset analyses on those with confirmed psychopathology diagnoses also did not predict residualized error-related delta/theta power nor residualized ERN amplitude (nGAD  = 14, nMDD  = 28, nComorbid  = 19, nControl  = 85). Taken in the context of the previous literature, results suggest a heterogeneous relationship between depressive and anxiety symptom dimensions and neurophysiological indices of error-monitoring.

Parent-Child Concordance on the Pubertal Development Scale in Typically Developing and Autistic Youth.

BACKGROUND: Characterizing puberty in autism spectrum disorder (ASD) is critical given the direct impacts of pubertal progression on neural, cognitive, and physical maturation. Limited information is available about the utility and parent-child concordance of the self-report and parent-report Pubertal Development Scale (PDS) in ASD, an economical and easily administered measure. METHOD: The primary aim of this study was to examine the concordance between self-report and parent-report PDS ratings in autistic males and females ages 8-17y compared to typically developing (TD) youth, including using the PDS to derive informant-based estimates of adrenal and gonadal development. We hypothesized that there would be greater parent-youth discrepancies in pubertal ratings among autistic males. Our second aim was exploratory; we examined whether individual characteristics impact PDS concordance and hypothesized that lower intellectual and adaptive skills, higher autistic traits, and reduced self-awareness/monitoring would correlate with lower concordance. RESULTS: There were no significant diagnostic group differences in parent-youth concordance for overall PDS scores among males and females. Autistic males had significantly lower inter-item agreement with their parents than TD males and had lower agreement for both adrenal and gonadal aspects of pubertal maturation (adrenal κ=.48; gonadal κ=.55). CONCLUSIONS: The PDS is a feasible measure in ASD. Greater parent-youth discrepancies in autistic males may be due to reduced parental awareness or reduced insight into pubertal maturation among autistic males. Future research is needed to further elucidate individual and/or environmental characteristics that influence youth- and parent-reported PDS scores, including differences in self-perception and insight.

Electrophysiological Endophenotypes and the Error-Related Negativity (ERN) in Autism Spectrum Disorder: A Family Study.

We examined the error-related negativity (ERN) as an endophenotype of ASD by comparing the ERN in families of ASD probands to control families. We hypothesized that ASD probands and families would display reduced-amplitude ERN relative to controls. Participants included 148 individuals within 39 families consisting of a mother, father, sibling, and proband. Robust ANOVAs revealed non-significant differences in ERN amplitude and behavioral performance among ASD probands relative to control youth. In subsequent multiple regression analyses group and kinship (proband, sibling, mother, father) did not significantly predict ΔERN (error minus correct ERN) or behavioral performance. Results do not provide evidence for the ERN as an endophenotype of ASD. Future research is needed to examine state- or trait-related factors influencing ERN amplitudes in ASD.

Conflict and performance monitoring throughout the lifespan: An event-related potential (ERP) and temporospatial component analysis.

Cognitive control includes higher-level cognitive processes used to evaluate environmental conflict. Given the importance of cognitive control in regulating behavior, understanding the developmental course of these processes may contribute to a greater understanding of normal and abnormal development. We examined behavioral (response times [RTs], error rates) and event-related potential data (N2, error-related negativity [ERN], correct-response negativity [CRN], error positivity [Pe]) during a flanker task in cross-sectional groups of 45 youth (ages 8-18), 52 younger adults (ages 20-28), and 58 older adults (ages 56-91). Younger adults displayed the most efficient processing, including significantly reduced CRN and N2 amplitude, increased Pe amplitude, and significantly better task performance than youth or older adults (e.g., faster RTs, fewer errors). Youth displayed larger CRN and N2, attenuated Pe, and significantly worse task performance than younger adults. Older adults fell either between youth and younger adults (e.g., CRN amplitudes, N2 amplitudes) or displayed neural and behavioral performance that was similar to youth (e.g., Pe amplitudes, error rates). These findings point to underdeveloped neural and cognitive processes early in life and reduced efficiency in older adulthood, contributing to poor implementation and modulation of cognitive control in response to conflict. Thus, cognitive control processing appears to reach peak performance and efficiency in younger adulthood, marked by improved task performance with less neural activation.

An electrophysiological investigation of interhemispheric transfer time in children and adolescents with high-functioning autism spectrum disorders.

Little is known about the functional impact of putative deficits in white-matter connectivity across the corpus callosum (CC) in individuals with autism spectrum disorders (ASDs). We utilized the temporal sensitivity of event-related potentials to examine the interhemispheric transfer time (IHTT) of basic visual information across the CC in youth with high-functioning ASD relative to healthy controls. We conducted two experiments: a visual letter matching experiment (n = 46) and a visual picture matching experiment, (n = 48) and utilized both electrophysiological (N1 and P1 amplitudes and latencies) and behavioral [response times (RTs), error rates] indices of IHTT. There were no significant group differences on either experiment for RTs, error rates, or N1 and P1 latencies, suggesting that on basic tasks the timing of information flow across the CC may not be altered in high functioning ASD.

Making sense of all the conflict: a theoretical review and critique of conflict-related ERPs.

Cognitive control theory suggests that goal-directed behavior is governed by a dynamic interplay between areas of the prefrontal cortex. Critical to cognitive control is the detection and resolution of competing stimulus or response representations (i.e., conflict). Event-related potential (ERP) research provides a window into the nature and precise temporal sequence of conflict monitoring. We critically review the research on conflict-related ERPs, including the error-related negativity (ERN), Flanker N2, Stroop N450 and conflict slow potential (conflict SP or negative slow wave [NSW]), and provide an analysis of how these ERPs inform conflict monitoring theory. Overall, there is considerable evidence that amplitude of the ERN is sensitive to the degree of response conflict, consistent with a role in conflict monitoring. It remains unclear, however, to what degree contextual, individual, affective, and motivational factors influence ERN amplitudes and how ERN amplitudes are related to regulative changes in behavior. The Flanker N2, Stroop N450, and conflict SP ERPs represent distinct conflict-monitoring processes that reflect conflict detection (N2, N450) and conflict adjustment or resolution processes (N2, conflict SP). The investigation of conflict adaptation effects (i.e., sequence or sequential trial effects) shows that the N2 and conflict SP reflect post-conflict adjustments in cognitive control, but the N450 generally does not. Conflict-related ERP research provides a promising avenue for understanding the effects of individual differences on cognitive control processes in healthy, neurologic and psychiatric populations. Comparisons between the major conflict-related ERPs and suggestions for future studies to clarify the nature of conflict-related neural processes are provided.

How about watching others? Observation of error-related feedback by others in autism spectrum disorders.

Research indicates that individuals with autism spectrum disorders (ASD) may have a reduced ability to utilize performance feedback to regulate their behavior; however, it is unclear to what degree alterations in the environmental context affect feedback processing and contribute to the symptoms of ASD. We utilized the observational FRN (oFRN), an event-related potential (ERP) component that putatively indexes feedback processing while observing feedback directed toward another person, to examine the influence of motivational and social demands on feedback processing in ASD. High-density electroencephalogram recordings were collected from 38 youth with ASD and 31 control participants similar on age and IQ while they observed a confederate performing a modified Eriksen Flanker task. Participants were instructed to count the confederate's errors and were told that they would be awarded based on performance: the confederate would either earn points for the participant or herself. Both groups showed robust oFRN activity on traditional scalp-electrode waveforms and waveforms identified using temporospatial principal components analysis. Amplitude of oFRN did not differentiate groups. Results remained non-significant when comparing medicated to non-medicated participants. There were no significant correlations between oFRN amplitudes, autism symptom severity, and anxiety symptoms. Findings suggest that the social context of the task and motivational significance of the confederate's performance did not limit feedback processing in ASD. Future research in which the context is manipulated further is warranted to determine whether increased environmental complexity influences feedback processing in ASD.

Cognitive control adjustments and conflict adaptation in major depressive disorder.

Individuals with major depressive disorder (MDD) show alterations in the cognitive control function of conflict processing. We examined the influence of these deficits on behavioral and event-related potential (ERP) indices of conflict adaptation, a cognitive control process wherein previous-trial congruency modulates current-trial performance, in 55 individuals with MDD and 55 matched controls. ERPs were calculated while participants completed a modified flanker task. There were nonsignificant between-groups differences in response time, error rate, and N2 indices of conflict adaptation. Higher depressive symptom scores were associated with smaller mean N2 conflict adaptation scores for individuals with MDD and when collapsed across groups. Results were consistent when comorbidity and medications were analyzed. These findings suggest N2 conflict adaptation is associated with depressive symptoms rather than clinical diagnosis alone.

Cognitive conflict adaptation in generalized anxiety disorder.

Individuals with generalized anxiety disorder (GAD) display poor emotional conflict adaptation, a cognitive control process requiring the adjustment of performance based on previous-trial conflict. It is unclear whether GAD-related conflict adaptation difficulties are present during tasks without emotionally-salient stimuli. We examined conflict adaptation using the N2 component of the event-related potential (ERP) and behavioral responses on a Flanker task from 35 individuals with GAD and 35 controls. Groups did not differ on conflict adaptation accuracy; individuals with GAD also displayed intact RT conflict adaptation. In contrast, individuals with GAD showed decreased amplitude N2 principal component for conflict adaptation. Correlations showed increased anxiety and depressive symptoms were associated with longer RT conflict adaptation effects and lower ERP amplitudes, but not when separated by group. We conclude that individuals with GAD show reduced conflict-related component processes that may be influenced by compensatory activity, even in the absence of emotionally-salient stimuli.

The effects of induced state negative affect on performance monitoring processes.

Previous research suggests that performance-monitoring processes are related to personality traits; relationships with affective states, however, remain unclear. The purpose of this study was to replicate and extend previous findings that induced state negative affect alters electrophysiological reflections of performance monitoring. High-density event-related potentials (ERPs) were obtained from 69 healthy individuals (41 female, 28 male) who completed an Eriksen flanker task and received either encouraging or derogatory feedback based on mean reaction times (RTs) for 30-trial sub-blocks. Affective state, behavioral measures (i.e. error rates, RTs) and ERP measures [i.e. error-related negativity (ERN), post-error positivity (Pe) and N2] were assessed. Reaction times did not differ between feedback groups. Participants who received derogatory feedback committed more errors over time. Despite changes in affect, no significant group differences were demonstrated for behavioral or ERP measures of performance monitoring. Increases in vigilance were associated with more negative N2 amplitudes; no other changes in affective state were associated with changes in ERP measures. Results are consistent with findings suggesting performance-monitoring processes are only slightly affected by changes in affective state and fail to replicate previous studies suggesting the ERN is related to state changes in affect-supporting the possibility of the ERN as an endophenotype.

Cognitive control and conflict adaptation similarities in children and adults.

Conflict adaptation effects occur when previous-trial congruency affects current-trial performance. We examined developmental differences in response time (RT), error rate, and electrophysiological (N450 and conflict slow-potential [conflict SP] event-related potentials [ERPs]) indices of conflict adaptation in 21 typically developing children and 26 adults during a Stroop task. Children exhibited significantly slower RTs, increased error rates, and increased ERP amplitudes relative to adults. Groups did not differ in magnitude of conflict adaptation for RTs, error rates, or the conflict SP. Neither group showed significant N450 conflict adaptation. Results suggest current indices of conflict adaptation do not differ between children and adults.

Sex differences in electrophysiological indices of conflict monitoring.

The purpose of this study was to investigate sex differences in cognitive control as measured by the stimulus-locked N2 component of the event-related potential (ERP). High-density ERPs were obtained from 114 healthy individuals (60 females, 54 males) who completed a modified Eriksen Flanker Task. Behavioral measures (i.e., error rates, reaction times) and N2 amplitudes were analyzed. On the flanker task, females responded significantly slower and committed more errors than males. For N2 amplitude, there was a significant main effect of congruency, with increased amplitude to incongruent trials. Importantly, sexes differed as a function of congruency, with males showing significantly larger incongruent N2 amplitudes than females. Sex differences in N2 amplitude remained in a subgroup of participants that did not differ for behavioral, demographic, and affective variables. No sex differences were shown for electrophysiological or behavioral indices of conflict adaptation. Results indicate sex differences in brain activation associated with conflict monitoring. Findings may be explained by two contradictory possibilities: (1) females more effectively monitor conflict as indicated by less neural activation than males for similar behavioral performance in a matched subsample, or, (2) females less effectively monitor conflict than males.

Error processing in high-functioning Autism Spectrum Disorders.

Studies report error-processing abnormalities in high-functioning individuals with Autism Spectrum Disorders (ASD) that may be influenced by intelligence and autism severity. Error processing can be measured using the error-related negativity (ERN) and post-error positivity (Pe) components of the event-related potential (ERP), along with behavioral indices such as post-error reaction time (RT) slowing. We used a modified Flanker task to test the hypothesis that high-functioning individuals with ASD would show decreased amplitude ERN in 24 individuals with ASD and 21 age- and IQ-matched typically-developing control participants. Behaviorally, individuals with ASD committed more errors than controls, but groups did not significantly differ on RTs, although there was a trend-level difference in post-error slowing. For ERPs, ERN amplitude was significantly attenuated in individuals with ASD relative to controls; groups did not differ in Pe amplitude. Amplitude of the ERN was not significantly correlated with measures of intelligence, anxiety, behavioral inhibition, or general autism severity.