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469 Electroencephalographic Correlate of Sensory Over-Responsivity in Adults with Chronic Tic Disorders
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- David A. Isaacs, Alexander C. Conley, Alexandra P. Key, Carissa J. Cascio, Harrison C. Walker, Mark T. Wallace, Daniel O. Claassen
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- Journal:
- Journal of Clinical and Translational Science / Volume 7 / Issue s1 / April 2023
- Published online by Cambridge University Press:
- 24 April 2023, p. 137
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OBJECTIVES/GOALS: To identify an electroencephalographic (EEG) signature of SOR in adults with TS METHODS/STUDY POPULATION: We will recruit 60 adults with CTD and 60 sex- and age-matched healthy controls to complete scales assessing severity of SOR (Sensory Gating Inventory, SGI), tics, and psychiatric symptoms. Subjects will then be monitored on dense-array scalp EEG during sequential auditory and tactile sensory gating paradigms, as such paradigms have been shown to correlate with self-report measures of SOR in other populations. Single-trial EEG data will be segmented into 100-ms epochs and spectrally deconvoluted into standard frequency bands (delta, theta, alpha, beta, gamma) for pre-defined regions of interest. We will conduct between-group contrasts (Wilcoxon rank-sum) of band-specific sensory gating indices and within-group correlations (Spearman rank correlations) between sensory gating indices and SGI scores. RESULTS/ANTICIPATED RESULTS: We hypothesize that, relative to controls, adults with CTD exhibit impaired sensory gating and that extent of impairment correlates with severity of SOR. 14 adults with CTD (9 men, 5 women) and 16 controls (10 men, 6 women) have completed the protocol to date. Within this sample, adults with CTD showed significantly reduced sensory gating compared to controls in frontal (CTD median 0.12 dB (interquartile range -0.15–0.70 dB); control -0.37 dB (-0.80–-0.13 dB); p = 0.01) and parietal (CTD 0.17 dB (-0.08–0.50 dB); control -0.20 dB (-0.43–0.10 dB); p = 0.01) gamma band during the 100-200 ms epoch in the tactile paradigm. No significant between-group differences were evident for the auditory paradigm. Among adults with CTD, multiple sensory gating indices significantly correlated with SGI scores. Enrollment continues. DISCUSSION/SIGNIFICANCE: Results aim to clarify the extent of sensory gating impairment in TS and identify a clinical correlate of neurophysiologic dysfunction in the disorder. Such knowledge has direct implications for identification of candidate neurophysiologic biomarkers, an express goal of the National Institutes of Health.
4420 Characterizing medical comorbidity prior to autism diagnosis in children before age two.
- Michelle D Failla, Kyle Schwartz, Shikha Chaganti, Tiffany G Woynaroski, Laurie Cutting, Bennett Landman, Carissa Cascio
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- Journal:
- Journal of Clinical and Translational Science / Volume 4 / Issue s1 / June 2020
- Published online by Cambridge University Press:
- 29 July 2020, p. 46
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OBJECTIVES/GOALS: Autism spectrum disorder (ASD) is a developmental disorder with a high financial and personal burden. Individuals with ASD experience significant comorbid medical conditions. We identified conditions that appear prior to ASD diagnosis in order to potentially improve early screening practices. METHODS/STUDY POPULATION: We used electronic health record data from an anonymized database at Vanderbilt University Medical Center for individuals with ASD and matched controls to analyze comorbid conditions prior to an ASD diagnosis. Data were censored to include only individuals who first appeared in the databank prior to two years of age (ntotal = 1551, ncontrols = 976, nASD = 575). Comorbidities (~1800 conditions) were compared between the ASD and matched control group using a novel tool (pyPheWAS) to examine presence, count, and duration of comorbidities that occurred between 0-2 years old and before ASD diagnosis. RESULTS/ANTICIPATED RESULTS: Convulsions (p = 0.000404, ß = 0.807), constipation (p = 0.000789, ß = 0.894), and strabismus (p = 0.00243, ß = 1.155) were the most significant comorbid conditions prior to age 2 in individuals who would later be diagnosed with ASD. The group with ASD also had more visits associated with convulsions (p = 0.00511, ß = 0.195), diseases of the esophagus (p = 0.0117, ß = 1.675), and allergic reactions to food (p = 0.0119, ß = 0.540) prior to their diagnosis. The ASD group was also seen for a longer duration regarding convulsions (p = 0.000273, ß = 0.695), constipation (p = 0.00157, ß = 0.712), and malaise and fatigue (p = 0.00188, ß = 0.903) before ASD diagnosis. DISCUSSION/SIGNIFICANCE OF IMPACT: Precise comorbid condition profiles in early childhood may help uncover biomarkers leading to better prediction of a future ASD diagnosis. Medical conditions that precede the onset of measurable behavioral symptoms may enhance early screening, treatment, and intervention in ASD.
2091 Neurophysiological substrates and developmental sequelae of sensory differences in infants at high risk for autism spectrum disorder
- Tiffany G. Woynaroski, Cara Damiano, David Simon, Lisa Ibanez, Michael Murias, Mark Wallace, Wendy Stone, Carissa Cascio
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- Journal:
- Journal of Clinical and Translational Science / Volume 2 / Issue S1 / June 2018
- Published online by Cambridge University Press:
- 21 November 2018, p. 22
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OBJECTIVES/SPECIFIC AIMS: Background: Children with autism spectrum disorder (ASD) show a broad range of unusual responses to sensory stimuli and experiences. It has been hypothesized that early differences in sensory responsiveness arise from atypical neural function and produce “cascading effects” on development across a number of domains, impacting social and communication skill, as well as broader development in children affected by ASD. A primary challenge to confirming these hypotheses is that ASD cannot be definitely diagnosed in the earliest stages of development (i.e., infancy). A potential solution is to prospectively follow infants at heightened risk for ASD based on their status as infant siblings of children who are diagnosed. We examined the developmental sequelae and possible neurophysiological substrates of three different patterns of sensory responsiveness—hyporesponsiveness (reduced or absent responding to sensory stimuli) and hyperresponsiveness (exaggerated responding to sensory stimuli), as well as sensory seeking (craving of or fascination with certain sensory experiences). Infants at high risk (HR) for ASD were compared with a control group of infants at relatively lower risk for ASD (LR; siblings of children with typical developmental histories). Objectives: Research questions included: (a) Do HR infants differ from LR infants in early sensory responsiveness?, (b) Does sensory responsiveness predict future ASD and related symptomatology? and (c) Is sensory responsiveness predicted by resting brain states? METHODS/STUDY POPULATION: Methods: To answer these questions, we carried out a longitudinal correlational investigation in which 20 HR infants and 20 LR controls matched on sex and chronological age were followed over 18 months. At entry to the study, when infants were 18 months old, sensory responsiveness was measured using the Sensory Processing Assessment and the Sensory Experiences Questionnaire, and a number of putative neural signatures of early sensory differences were measured via resting state EEG. When infants were 24 and 36 months of age, ASD and related symptomatology was evaluated in a comprehensive diagnostic evaluation. RESULTS/ANTICIPATED RESULTS: Results: HR infants trended towards increased hyporesponsiveness and hyperresponsiveness and showed significantly elevated levels of sensory seeking relative to LR controls at 18 months of age. Both groups, furthermore, displayed a high degree of heterogeneity in sensory responsiveness. Atypical sensory responsiveness (increased hyperresponsiveness and/or hyporesponsiveness, as well as sensory seeking behavior) predicted several aspects of ASD and related symptomatology, including social, communication, and play skill, and was associated with differences in resting brain state, including metrics of oscillatory power, complexity, and connectivity, as well as hemispheric asymmetry. Moderation analyses revealed that several relations varied according to risk group, such that associations were stronger in magnitude in the HR Versus LR group. DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusion: Findings provide empirical support for the notion that early sensory responsiveness may produce cascading effects on development in infants at heightened risk for ASD. Differences in resting brain states may underlie atypical behavioral patterns of sensory responsiveness. From a clinical standpoint, results suggest that early sensory differences may be useful for predicting developmental trajectories, and be potentially important targets for early preventive intervention, in infants at risk for autism.