Faculty Bibliography

OBJECTIVE:This study examined the degree to which verbal and visuospatial memory abilities influence performance validity test (PVT) performance in a mixed clinical pediatric sample. METHOD/METHODS:Data from 252 consecutive clinical pediatric cases (Mage=11.23 years, SD=4.02; 61.9% male) seen for outpatient neuropsychological assessment were collected. Measures of learning and memory (e.g., The California Verbal Learning Test-Children's Version; Child and Adolescent Memory Profile [ChAMP]), performance validity (Test of Memory Malingering Trial 1 [TOMM T1]; Wechsler Intelligence Scale for Children-Fifth Edition [WISC-V] or Wechsler Adult Intelligence Scale-Fourth Edition Digit Span indices; ChAMP Overall Validity Index), and intellectual abilities (e.g., WISC-V) were included. RESULTS:Learning/memory abilities were not significantly correlated with TOMM T1 and accounted for relatively little variance in overall TOMM T1 performance (i.e., ≤6%). Conversely, ChAMP Validity Index scores were significantly correlated with verbal and visual learning/memory abilities, and learning/memory accounted for significant variance in PVT performance (12%-26%). Verbal learning/memory performance accounted for 5%-16% of the variance across the Digit Span PVTs. No significant differences in TOMM T1 and Digit Span PVT scores emerged between verbal/visual learning/memory impairment groups. ChAMP validity scores were lower for the visual learning/memory impairment group relative to the nonimpaired group. CONCLUSIONS:Findings highlight the utility of including PVTs as standard practice for pediatric populations, particularly when memory is a concern. Consistent with the adult literature, TOMM T1 outperformed other PVTs in its utility even among the diverse clinical sample with/without learning/memory impairment. In contrast, use of Digit Span indices appear to be best suited in the presence of visuospatial (but not verbal) learning/memory concerns. Finally, the ChAMP's embedded validity measure was most strongly impacted by learning/memory performance.

Differences in speech prosody are a widely observed feature of Autism Spectrum Disorder (ASD). However, it is unclear how prosodic differences in ASD manifest across different languages that demonstrate cross-linguistic variability in prosody. Using a supervised machine-learning analytic approach, we examined acoustic features relevant to rhythmic and intonational aspects of prosody derived from narrative samples elicited in English and Cantonese, two typologically and prosodically distinct languages. Our models revealed successful classification of ASD diagnosis using rhythm-relative features within and across both languages. Classification with intonation-relevant features was significant for English but not Cantonese. Results highlight differences in rhythm as a key prosodic feature impacted in ASD, and also demonstrate important variability in other prosodic properties that appear to be modulated by language-specific differences, such as intonation.

BACKGROUND:Social attention differences, expressed through gaze patterns, have been documented in autism spectrum disorder (ASD), with subtle differences also reported among first-degree relatives, suggesting a shared genetic link. Findings have mostly been derived from standard eye-tracking methods (total fixation count or total fixation duration). Given the dynamics of visual attention, these standard methods may obscure subtle, yet core, differences in visual attention mechanisms, particularly those presenting sub-clinically. This study applied a constellation of eye-tracking analyses to gaze data from individuals with ASD and their parents. METHODS:This study included n = 156 participants across groups, including ASD (n = 24) and control (n = 32) groups, and parents of individuals with ASD (n = 61) and control parents (n = 39). A complex scene with social/non-social elements was displayed and gaze tracked via an eye tracker. Eleven analytic methods from the following categories were analyzed: (1) standard variables, (2) temporal dynamics (e.g., gaze over time), (3) fixation patterns (e.g., perseverative or regressive fixations), (4) first fixations, and (5) distribution patterns. MANOVAs, growth curve analyses, and Chi-squared tests were applied to examine group differences. Finally, group differences were examined on component scores derived from a principal component analysis (PCA) that reduced variables to distinct dimensions. RESULTS:No group differences emerged among standard, first fixation, and distribution pattern variables. Both the ASD and ASD parent groups demonstrated on average reduced social attention over time and atypical perseverative fixations. Lower social attention factor scores derived from PCA strongly differentiated the ASD and ASD parent groups from controls, with parent findings driven by the subset of parents demonstrating the broad autism phenotype. LIMITATIONS:To generalize these findings, larger sample sizes, extended viewing contexts (e.g., dynamic stimuli), and even more eye-tracking analytical methods are needed. CONCLUSIONS:Fixations over time and perseverative fixations differentiated ASD and the ASD parent groups from controls, with the PCA most robustly capturing social attention differences. Findings highlight their methodological utility in studies of the (broad) autism spectrum to capture nuanced visual attention differences that may relate to clinical symptoms in ASD, and reflect genetic liability in clinically unaffected relatives. This proof-of-concept study may inform future studies using eye tracking across populations where social attention is impacted.

Individuals with autism spectrum disorder (ASD) and their first-degree relatives demonstrate automaticity deficits reflected in reduced eye-voice coordination during rapid automatized naming (RAN), suggesting that RAN deficits may be a genetically meaningful marker of ASD language-related impairments. This study investigated whether RAN deficits in ASD extend to a language typologically distinct from English. Participants included 23 Cantonese-speaking individuals with ASD and 39 controls from Hong Kong (HK), and age- and IQ-comparable groups of previously-studied English-speaking individuals with ASD (n = 45) and controls (n = 44) from the US. Participants completed RAN on an eye tracker. Analyses examined naming time, error rate, measures of eye movement reflecting language automaticity, including eye-voice span (EVS; location of eyes versus the named item) and refixations. The HK-ASD group exhibited longer naming times and more refixations than HK-Controls, in a pattern similar to that observed in the US-ASD group. Cultural effects revealed that both HK groups showed longer EVS and more fixations than US groups. Naming time and refixation differences may be ASD-specific impairments spanning cultures/languages, whereas EVS and fixation frequency may be more variably impacted. A potential underlying mechanism of visual "stickiness" may be contributing to this breakdown in language automaticity in ASD.

The FMR1 gene in its premutation (PM) state has been linked to a range of clinical and subclinical phenotypes among FMR1 PM carriers, including some subclinical traits associated with autism spectrum disorder (ASD). This study attempted to further characterize the phenotypic profile associated with the FMR1 PM by studying a battery of assessments examining clinical-behavioral traits, social-cognitive, and executive abilities in women carrying the FMR1 PM, and associations with FMR1-related variability. Participants included 152 female FMR1 PM carriers and 75 female controls who were similar in age and IQ, and screened for neuromotor impairments or signs of fragile X-associated tremor/ataxia syndrome. The phenotypic battery included assessments of ASD-related personality and language (i.e., pragmatic) traits, symptoms of anxiety and depression, four different social-cognitive tasks that tapped the ability to read internal states and emotions based on different cues (e.g., facial expressions, biological motion, and complex social scenes), and a measure of executive function. Results revealed a complex phenotypic profile among the PM carrier group, where subtle differences were observed in pragmatic language, executive function, and social-cognitive tasks that involved evaluating basic emotions and trustworthiness. The PM carrier group also showed elevated rates of ASD-related personality traits. In contrast, PM carriers performed similarly to controls on social-cognitive tasks that involved reliance on faces and biological motion. The PM group did not differ from controls on self-reported depression or anxiety symptoms. Using latent profile analysis, we observed three distinct subgroups of PM carriers who varied considerably in their performance across tasks. Among PM carriers, CGG repeat length was a significant predictor of pragmatic language violations. Results suggest a nuanced phenotypic profile characterized by subtle differences in select clinical-behavioral, social-cognitive, and executive abilities associated with the FMR1 PM in women.

Atypical visual attention patterns have been observed among carriers of the fragile X mental retardation gene (FMR1) premutation (PM), with some similarities to visual attention patterns observed in autism spectrum disorder (ASD) and among clinically unaffected relatives of individuals with ASD. Patterns of visual attention could constitute biomarkers that can help to inform the neurocognitive profile of the PM, and that potentially span diagnostic boundaries. This study examined patterns of eye movement across an array of fixation measurements from three distinct eye-tracking tasks in order to investigate potentially overlapping profiles of visual attention among PM carriers, ASD parents, and parent controls. Logistic regression analyses were conducted to examine whether variables constituting a PM-specific looking profile were able to effectively predict group membership. Participants included 65PM female carriers, 188 ASD parents, and 84 parent controls. Analyses of fixations across the eye-tracking tasks, and their corresponding areas of interest, revealed a distinct visual attention pattern in carriers of the FMR1 PM, characterized by increased fixations on the mouth when viewing faces, more intense focus on bodies in socially complex scenes, and decreased fixations on salient characters and faces while narrating a wordless picture book. This set of variables was able to successfully differentiate individuals with the PM from controls (Sensitivity = 0.76, Specificity = 0.85, Accuracy = 0.77) as well as from ASD parents (Sensitivity = 0.70, Specificity = 0.80, Accuracy = 0.72), but did not show a strong distinction between ASD parents and controls (Accuracy = 0.62), indicating that this set of variables comprises a profile that is unique to PM carriers. Regarding predictive power, fixations toward the mouth when viewing faces was able to differentiate PM carriers from both ASD parents and controls, whereas fixations toward other social stimuli did not differentiate PM carriers from ASD parents, highlighting some overlap in visual attention patterns that could point toward shared neurobiological mechanisms. Results demonstrate a profile of visual attention that appears strongly associated with the FMR1 PM in women, and may constitute a meaningful biomarker.

BACKGROUND:Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental disorder that encompasses a complex and heterogeneous set of traits. Subclinical traits that mirror the core features of ASD, referred to as the broad autism phenotype (BAP), have been documented repeatedly in unaffected relatives and are believed to reflect underlying genetic liability to ASD. The BAP may help inform the etiology of ASD by allowing the stratification of families into more phenotypically and etiologically homogeneous subgroups. This study explores polygenic scores related to the BAP. METHODS:Phenotypic and genotypic information were obtained from 2614 trios from the Simons Simplex Collection. Polygenic scores of ASD (ASD-PGSs) were generated across the sample to determine the shared genetic overlap between the BAP and ASD. Maternal and paternal ASD-PGSs were explored in relation to BAP traits and their child's ASD symptomatology. RESULTS:Maternal pragmatic language was related to child's social communicative atypicalities. In fathers, rigid personality was related to increased repetitive behaviors in children. Maternal (but not paternal) ASD-PGSs were related to the pragmatic language and rigid BAP domains. CONCLUSIONS:Associations emerged between parent and child phenotypes, with more associations emerging in mothers than in fathers. ASD-PGS associations emerged with BAP in mothers only, highlighting the potential for a female protective factor, and implicating the polygenic etiology of ASD-related phenotypes in the BAP.

This study examined prosody through characterization of acoustic properties of the speech of individuals with ASD and their parents, during narration. A subset of utterances were low-pass filtered and rated for differences in intonation, speech rate, and rhythm. Listener ratings were minimally related to acoustic measures, underscoring the complexity of atypical prosody in ASD. Acoustic analyses revealed greater utterance-final fundamental frequency excursion size and slower speech rate in the ASD group. Slower speech rate was also evident in the ASD parent group, particularly parents with the broad autism phenotype. Overlapping prosodic differences in ASD and ASD Parent groups suggest that prosodic differences may constitute an important phenotype contributing to ASD features and index genetic liability to ASD among first-degree relatives.

The FMR1 gene is associated with a wide range of clinical and cognitive phenotypes, ranging from intellectual disability and autism symptoms in fragile X syndrome (caused by the FMR1 full mutation), to a more varied, and still poorly understood range of clinical and cognitive phenotypes among carriers of the gene in its premutation state. Because the FMR1 premutation is relatively common among women (as high as 1 in 150), investigations of its phenotypic impact could have broad implications for understanding gene-behavior relationships underlying complex human traits, with potential clinical implications. This study investigated physiological regulation measured by pupillary responses, along with fixation patterns while viewing facial expressions among women who carry the FMR1 premutation (PM group; n = 47), to examine whether the FMR1 gene may relate to physiological regulation, social-emotional functioning, and social language skills (where subclinical differences have been previously reported among PM carriers that resemble those documented in autism-related conditions). Relative to controls (n = 25), the PM group demonstrated atypical pupillary responses and fixation patterns, controlling for IQ. In the PM group, pupillary response and fixation patterns were related to social cognition, social language abilities, and FMR1-related variation. Results indicate a pattern of atypical attention allocation among women who carry the FMR1 PM that could reflect different emotion-processing strategies mediated by autonomic dysregulation and the FMR1 gene. These findings lend insight into the FMR1 gene's potential contributions to complex human traits such as social emotional processing and social language.

This study examined the perception of an ASD label compared to Asperger's syndrome or no diagnosis. Seventy-one undergraduates read an adapted vignette (Ohan et al. J Autism Dev Disord 45:3384-3389, 2015) about an undergraduate with ASD, Asperger's Syndrome, or No Diagnosis. Participants also completed questionnaires. More positive ratings emerged for the Asperger's and ASD labels than No Diagnosis in low contact scenarios, particularly when involving greater social versus professional interaction. In contrast, more positive ratings emerged for the Asperger's compared to the ASD and No Diagnosis on high contact items. Ratings between low and high contact items differed only for ASD. Results demonstrate the impact of diagnostic labels across social contexts and support the need for education surrounding changes in nosology.