Keeping Things Positive: Affect as a Mediator between Physical Activity and Psychological Functioning.

Higher physical activity is generally associated with more favorable psychological functioning. However, the role of positive and negative affect in such associations is unclear. Accordingly, this cross-sectional study explored whether affect mediated the relationship of physical activity with psychological well-being (PWB) and psychological dysfunctioning (PD). Young Iranian adults (N = 200) completed self-rating questionnaires covering physical activity, positive and negative affect, and proxies of PWB and PD. Regression analyses indicated that higher physical activity levels and higher positive and lower negative affect predicted proxies of PWB. The same (albeit in the opposite direction) applied to proxies of PD. Structural equation modeling indicated that positive and negative affect mediated the relationship between physical activity and PWB/PD. Accordingly, change in affect might be an important mechanism behind the association of physical activity and PWB/PD. Future research should further explore this across target populations and cultural contexts. Longitudinal and/or experimental studies are needed to disentangle causality.

Differential Effects of a Behavioral Treatment Probe on Social Gaze Behavior in Fragile X Syndrome and Non-Syndromic Autism Spectrum Disorder.

The purpose of this study was to examine potential differences in social learning between individuals with fragile X syndrome (FXS), the leading known inherited cause of intellectual disability, and individuals with non-syndromic autism spectrum disorder (ASD). Thirty school-aged males with FXS and 26 age and symptom-matched males with non-syndromic ASD, were administered a behavioral treatment probe designed to improve levels of social gaze during interactions with others. The treatment probe was administered by a trained behavior therapist over two days in our laboratory and included reinforcement of social gaze in two alternating training conditions - looking while listening and looking while speaking. Prior to each session, children in each group were taught progressive muscle relaxation and breathing techniques to counteract potential increased hyperarousal. Measures included the rate of learning in each group during treatment, in addition to levels of social gaze and heart rate obtained during administration of a standardized social conversation task administered prior to and following the treatment probe. Results showed that learning rates obtained during administration of the treatment probe were significantly less steep and less variable for males with FXS compared to males with non-syndromic ASD. Significant improvements in social gaze were also observed for males with FXS during the social conversation task. There was no effect of the treatment probe on heart rate in either group. These data reveal important differences in social learning between the two groups and have implications for early interventions in the two conditions.

A Scoping Review of Behavioral Interventions for Promoting Social Gaze in Individuals with Autism Spectrum Disorder and Other Developmental Disabilities.

Background: Individuals diagnosed with autism spectrum disorder (ASD) commonly experience difficulties maintaining social gaze with others during interactions. Although behavioral interventions targeted to promote social gaze in ASD are evident in the literature, to our knowledge, no review of the literature has been conducted to summarize and evaluate the evidence for these interventions. Methods: We reviewed and summarized behavioral intervention studies designed to promote social gaze in individuals diagnosed with ASD and other developmental disabilities published in English between 1977 and January 2022 using PsychINFO and PubMed databases. Results: 41 studies met the inclusion criteria describing interventions conducted on 608 individuals. A variety of intervention strategies were employed to promote social gaze in these individuals including discrete trial instruction, prompting, modeling, and imitation. Most studies employed single-case research designs and reported successful outcomes, but limited data were available concerning the generalization, maintenance and social validity of these interventions. An increasing number of studies utilized technology-based procedures including computer application gameplay, gaze-contingent eye tracking devices and humanoid robots. Conclusions: The present review indicates that behavioral interventions can be successfully employed to promote social gaze in individuals with ASD and other developmental disabilities. However, future research is needed to establish the generalization, maintenance and social validity of these interventions. There are also important ethical issues to be addressed given the increasing divide between treatment advocates and proponents of the neurodiversity movement.

Brief intensive social gaze training reorganizes functional brain connectivity in boys with fragile X syndrome.

Boys with fragile X syndrome (FXS), the leading known genetic cause of autism spectrum disorder (ASD), demonstrate significant impairments in social gaze and associated weaknesses in communication, social interaction, and other areas of adaptive functioning. Little is known, however, concerning the impact of behavioral treatments for these behaviors on functional brain connectivity in this population. As part of a larger study, boys with FXS (mean age 13.23 ± 2.31 years) and comparison boys with ASD (mean age 12.15 ± 2.76 years) received resting-state functional magnetic resonance imaging scans prior to and following social gaze training administered by a trained behavior therapist in our laboratory. Network-agnostic connectome-based predictive modeling of pretreatment resting-state functional connectivity data revealed a set of positive (FXS > ASD) and negative (FXS < ASD) edges that differentiated the groups significantly and consistently across all folds of cross-validation. Following administration of the brief training, the FXS and ASD groups demonstrated reorganization of connectivity differences. The divergence in the spatial pattern of reorganization response, based on functional connectivity differences pretreatment, suggests a unique pattern of response to treatment in the FXS and ASD groups. These results provide further support for implementing targeted behavioral treatments to ameliorate syndrome-specific behavioral features in FXS.

Examining Phenotypic Differences in Gaze Avoidance Between Autism Spectrum Disorder and Fragile X Syndrome.

We examined potential phenotypic differences in eye gaze avoidance exhibited by boys with autism spectrum disorder (ASD) and boys with fragile X syndrome (FXS). In Study 1, the Eye Contact Avoidance Scale (ECAS) was administered to caregivers of boys aged 7-18 years with FXS (n = 148), ASD (n = 168), and mixed developmental disabilities (MDD; n = 128). In Study 2, subsets of boys with FXS (n = 31) and boys with ASD (n = 25) received a brief behavioral treatment probe to improve eye contact. Results showed that boys with FXS obtained significantly higher scores on the ECAS compared to boys with ASD and MDD. Exposure to the brief behavioral treatment probe resulted in significant decreases in scores for boys with FXS, but not for boys with ASD.

Long-term follow-up of telehealth-enabled behavioral treatment for challenging behaviors in boys with fragile X syndrome.

BACKGROUND: A significant proportion of boys with fragile X syndrome (FXS), the most common known genetic cause of intellectual disability, exhibit challenging behaviors such as aggression and self-injury that can cause significant distress to families. Recent evidence suggests that coaching caregivers to implement functional communication training (FCT) with their child via telehealth can help to ameliorate these behaviors in FXS. In the present study, we followed families who had participated in our previous randomized controlled trial of FCT to evaluate the longer-term effects of FCT on challenging behaviors in this population. METHODS: In study 1, follow-up emails, phone calls, text messages, and letters were sent to caregivers of 48 boys with FXS who had completed our previous study conducted between 2016 and 2019. The main outcome measures administered at follow-up were the Aberrant Behavior Checklist-Community (ABC-C) and the Parenting Stress Index, 4th Edition (PSI-4). In study 2, families who had received FCT treatment but whose child exhibited challenging behaviors daily at follow-up received a 1-h parent training booster session to determine whether the intervention effect could be recovered. RESULTS: Sixteen (66.7%) of 24 families who had received FCT treatment and 18 (75.0%) of 24 families who had received treatment as usual were traced and consented between March and August 2021. The mean follow-up time was 3.1 years (range, 1.4 to 4.2 years). Longitudinal mixed effects analyses indicated that boys who had received FCT were more likely to show improvements on the irritability and lethargy/social withdrawal subscales of the ABC-C over the follow-up interval compared to boys who had continued with treatment as usual. Four of the six boys who had received the booster parent training session via telehealth were reported to exhibit fewer forms of challenging behavior at a 4-week follow-up. CONCLUSIONS: Empowering parents to implement behavior analytic treatments with their child in their own home can have durable effects on maintaining low levels of challenging behaviors in boys with FXS. These data further support the need to implement parent-mediated interventions for challenging behaviors in this population at an early age. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03510156 . Registered 27 April 2018.

Implementing Automated Nonparametric Statistical Analysis on Functional Analysis Data: A Guide for Practitioners and Researchers.

Functional analysis (FA) is an integral component of behavioral assessment and treatment given that clinicians design behavioral treatments based on FA results. Unfortunately, the interrater reliability of FA data interpretation by visual analysis can be inconsistent, potentially leading to ineffective treatment implementation. Hall et al. (2020) recently developed automated nonparametric statistical analysis (ANSA) to facilitate the interpretation of FA data and Kranak et al. (2021) subsequently extended and validated ANSA by applying it to unpublished clinical data. The results of both Hall et al. and Kranak et al. support ANSA as an emerging statistical supplement for interpreting FA data. In the present article, we show how ANSA can be applied to interpret FA data collected in clinical settings in multielement and pairwise designs. We provide a detailed overview of the calculations involved, how to use ANSA in practice, and recommendations for its implementation. A free web-based application is available at https://ansa.shinyapps.io/ansa/. Supplementary Information: The online version contains supplementary material available at 10.1007/s40614-021-00290-2.

Effects of X Chromosome Monosomy and Genomic Imprinting on Observational Markers of Social Anxiety in Prepubertal Girls with Turner Syndrome.

Previous studies have suggested that girls with Turner syndrome (TS) exhibit symptoms of social anxiety during interactions with others. However, few studies have quantified these behaviors during naturalistic face-to-face social encounters. In this study, we coded observational markers of social anxiety in prepubertal girls with TS and age-matched controls during a 10-min social encounter with an unfamiliar examiner. Results showed that girls with TS exhibited significantly higher levels of gaze avoidance compared to controls. Impairments in social gaze were particularly increased in girls with a maternally retained X chromosome (Xm), suggesting a genomic imprinting effect. These data indicate that social gaze avoidance may be a critical behavioral marker for identifying early social dysfunction in young girls with TS.

Conducting In-Home Functional Analyses of Aggression and Self-Injury Exhibited by Boys with Fragile X Syndrome.

OBJECTIVE: Boys with fragile X syndrome (FXS) are at increased risk for exhibiting aggression and self-injury that can be extremely disruptive to families. Few studies, however, have examined the extent to which social-environmental factors can influence these behaviors, particularly in home settings. METHODS: Caregivers of 32 boys with FXS, aged 3 to 10 years, were coached by a board-certified behavior analyst to implement a functional analysis (FA) with their child in their home over 2 days. The functions identified in the FAs were validated by behavioral interventions conducted through telehealth over 12 weeks. RESULTS: Social functions for aggression and self-injury were identified in 29 (90.6%) cases, with the most common functions identified being escape from demands/transitions and/or tangible reinforcement. Subsequent function-based behavioral interventions (i.e., functional communication training) implemented for 22 cases by telehealth resulted in decreased rates of aggression and self-injury by 74% to 100%. CONCLUSION: These data underscore the significant impact that social-environmental factors can have on the development and maintenance of aggression and self-injury in FXS. Conducting early home-based behavioral interventions designed to increase functional communication skills may therefore be an effective solution for the treatment of aggression and self-injury in FXS in the long term.

Dislocated College Students and the Pandemic: Back Home Under Extraordinary Circumstances.

OBJECTIVE: This research examines college students' experiences of dislocation during the COVID-19 pandemic. BACKGROUND: Due to governmental stay-at-home orders during the pandemic, families with "dislocated" (compelled to return home) college students would likely encounter unique stressors while also being limited in their normal ways of coping. METHODS: Using an online survey, the current study sought to discover how diverse individual characteristics and family living situations of 323 dislocated students associated with varying homelife experiences (e.g., intrusive parenting, students making an extra effort to spend time with family), and how such experiences associated with relationship changes during the quarantine. RESULTS: Analyses detected some differences in the students' homelife experiences based on background and living situations, especially related to being a first-year student, having been excited about returning home, and feeling accepted by parents about being home. Negative family relationship quality during the quarantine was most predicted by negative attitudes from students and parents about students being home, the student feeling less adultlike (based on treatment and own identity conception), and having low autonomy. CONCLUSION: Returning home for quarantine was challenging for most students, and circumstances and attitudes appeared to contribute to how such challenges associated with family relationship changes. IMPLICATIONS: Implications for practitioners and universities are discussed in regard to preparing college students and their families for similar conditions.

Telehealth-enabled behavioral treatment for problem behaviors in boys with fragile X syndrome: a randomized controlled trial.

BACKGROUND: Children with fragile X syndrome (FXS) are at increased risk for exhibiting problem behaviors such as aggression and self-injury. However, many children with FXS have limited access to behavioral treatments that have known efficacy due to the low availability of treatment providers and the wide geographical dispersion of families with FXS across the country. Telehealth may offer a cost-effective and practical solution to overcome these significant barriers. We examined the effect of administering an established behavior analytic intervention called functional communication training (FCT) via telehealth on levels of problem behaviors exhibited by boys with FXS. We also examined treatment acceptability, as well as the effect of the treatment on levels of parenting stress. METHODS: Boys with FXS, aged 3 to 10 years, who displayed problem behaviors daily, were randomized to receive FCT via telehealth (n = 30) or treatment as usual (n = 27) over 12 weeks. Outcome measures included in-session observations of problem behavior, the Aberrant Behavior Checklist-Community (ABC-C), the Treatment Acceptability Rating Form-Revised (TARF-R), and the Parenting Stress Index, 4th edition (PSI-4). RESULTS: Intention-to-treat analyses indicated that scores on the irritability subscale of the ABC-C, our primary outcome measure, decreased significantly for boys who received FCT via telehealth compared to boys who received treatment as usual (p < .001, Cohen's d = 0.65). In-session observations conducted for those who received treatment showed that levels of problem behavior decreased by 91% from baseline. Levels of parenting stress related to child behavioral problems were also lower following FCT treatment, and caregivers reported that the intervention was acceptable. CONCLUSIONS: These findings support telehealth-enabled FCT as a framework for expanding access to behavioral treatments for problem behaviors in children with FXS. Expanded delivery of behavior analytic treatment via telehealth also has the potential to lower healthcare costs, improve child and family quality of life, and lead to advances in the treatment of problem behavior in the broader population of individuals with neurodevelopmental disorders. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03510156 . Registered 27 April 2018.

Examining the Specificity of Forms and Functions of Aggressive Behavior in Boys With Fragile X Syndrome.

Limited information is available concerning the specificity of the forms and functions of aggressive behavior exhibited by boys with fragile X syndrome (FXS). To investigate these relationships, we conducted indirect functional assessments of aggressive behavior exhibited by 41 adolescent boys with FXS and 59 age and symptom-matched controls with intellectual and developmental disability (IDD) and compared the data between groups. Results showed that boys with FXS were more likely to exhibit specific forms of aggressive behavior (i.e., scratching others and biting others) compared to controls, but the sources of reinforcement identified for aggression were similar across groups. Boys with FXS who were prescribed psychotropic medications were more likely to be older and to exhibit more forms of aggression. The implications for the treatment of aggressive behavior during this critical developmental period in FXS are discussed.

Interpreting functional analysis outcomes using automated nonparametric statistical analysis.

Current methods employed to interpret functional analysis data include visual analysis and post-hoc visual inspection (PHVI). However, these methods may be biased by dataset complexity, hand calculations, and rater experience. We examined whether an automated approach using nonparametric rank-based statistics could increase the accuracy and efficiency of functional analysis data interpretation. We applied Automated Nonparametric Statistical Analysis (ANSA) to a sample of 65 published functional analyses for which additional experimental evidence was available to verify behavior function. Results showed that exact behavior function agreement between ANSA and the publications authors was 83.1%, exact agreement between ANSA and PHVI was 75.4%, and exact agreement across all 3 methods was 64.6%. These preliminary findings suggest that ANSA has the potential to support the data interpretation process. A web application that incorporates the calculations and rules utilized by ANSA is accessible at https://ansa.shinyapps.io/ansa/.

Telehealth Delivery of Function-Based Behavioral Treatment for Problem Behaviors Exhibited by Boys with Fragile X Syndrome.

Telehealth is increasingly being employed to extend the reach of behavior analytic interventions to families of children with developmental disorders who exhibit problem behaviors. In this preliminary study, we examined whether function-based behavior analytic interventions could be delivered via telehealth over 12 weeks to decrease problem behaviors exhibited by ten boys with fragile X syndrome (FXS), aged 3- to 10-years. Results showed that for eight children who completed treatment, rates of problem behavior decreased from baseline by 78.8-95.3%. Parent procedural integrity and acceptability ratings remained high throughout the treatment. These data indicate that implementing function-based behavioral treatment via telehealth can be a feasible, acceptable and potentially cost-effective approach for decreasing problem behaviors exhibited by boys with FXS.

Improving social gaze behavior in fragile X syndrome using a behavioral skills training approach: a proof of concept study.

BACKGROUND: Individuals diagnosed with fragile X syndrome (FXS), the most common known inherited form of intellectual disability, commonly exhibit significant impairments in social gaze behavior during interactions with others. Although this behavior can restrict social development and limit educational opportunities, behavioral interventions designed to improve social gaze behavior have not been developed for this population. In this proof of concept (PoC) study, we examined whether administering a behavioral skills training package-discrete trial instruction (DTI) plus relaxation training-could increase social gaze duration in males with FXS. METHODS: As part of a larger clinical trial, 20 boys with FXS, aged 8 to 18 years, were randomized to receive DTI plus relaxation training administered at one of two prescribed doses over a 2-day period at our research center. Potential improvements in social gaze behavior were evaluated by direct observations conducted across trials during the training, and generalization effects were examined by administering a social challenge before and after the treatment. During the social challenge, social gaze behavior was recorded using an eye tracker and physiological arousal levels were simultaneously recorded by monitoring the child's heart rate. RESULTS: Levels of social gaze behavior increased significantly across blocks of training trials for six (60%) boys who received the high-dose behavioral treatment and for three (30%) boys who received the low-dose behavioral treatment. Boys who received the high-dose treatment also showed greater improvements in social gaze behavior during the social challenge compared to boys who received the low-dose treatment. There was no effect of the treatment on physiological arousal levels recorded on the heart rate monitor at either dose. CONCLUSIONS: These results suggest that appropriate social gaze behavior can be successfully taught to boys with FXS using a standardized behavioral skills training approach. Future studies will need to evaluate whether younger children with FXS might benefit from this treatment, and/or whether more naturalistic forms of behavioral skills training might be beneficial, before social gaze avoidance becomes established in the child's repertoire. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02616796 . Registered 30 November 2015.

Updated report on tools to measure outcomes of clinical trials in fragile X syndrome.

OBJECTIVE: Fragile X syndrome (FXS) has been the neurodevelopmental disorder with the most active translation of preclinical breakthroughs into clinical trials. This process has led to a critical assessment of outcome measures, which resulted in a comprehensive review published in 2013. Nevertheless, the disappointing outcome of several recent phase III drug trials in FXS, and parallel efforts at evaluating behavioral endpoints for trials in autism spectrum disorder (ASD), has emphasized the need for re-assessing outcome measures and revising recommendations for FXS. METHODS: After performing an extensive database search (PubMed, Food and Drug Administration (FDA)/National Institutes of Health (NIH)'s www.ClinicalTrials.gov, etc.) to determine progress since 2013, members of the Working Groups who published the 2013 Report evaluated the available outcome measures for FXS and related neurodevelopmental disorders using the COSMIN grading system of levels of evidence. The latter has also been applied to a British survey of endpoints for ASD. In addition, we also generated an informal classification of outcome measures for use in FXS intervention studies as instruments appropriate to detect shorter- or longer-term changes. RESULTS: To date, a total of 22 double-blind controlled clinical trials in FXS have been identified through www.ClinicalTrials.gov and an extensive literature search. The vast majority of these FDA/NIH-registered clinical trials has been completed between 2008 and 2015 and has targeted the core excitatory/inhibitory imbalance present in FXS and other neurodevelopmental disorders. Limited data exist on reliability and validity for most tools used to measure cognitive, behavioral, and other problems in FXS in these trials and other studies. Overall, evidence for most tools supports a moderate tool quality grading. Data on sensitivity to treatment, currently under evaluation, could improve ratings for some cognitive and behavioral tools. Some progress has also been made at identifying promising biomarkers, mainly on blood-based and neurophysiological measures. CONCLUSION: Despite the tangible progress in implementing clinical trials in FXS, the increasing data on measurement properties of endpoints, and the ongoing process of new tool development, the vast majority of outcome measures are at the moderate quality level with limited information on reliability, validity, and sensitivity to treatment. This situation is not unique to FXS, since reviews of endpoints for ASD have arrived at similar conclusions. These findings, in conjunction with the predominance of parent-based measures particularly in the behavioral domain, indicate that endpoint development in FXS needs to continue with an emphasis on more objective measures (observational, direct testing, biomarkers) that reflect meaningful improvements in quality of life. A major continuous challenge is the development of measurement tools concurrently with testing drug safety and efficacy in clinical trials.

A Screening Tool to Measure Eye Contact Avoidance in Boys with Fragile X Syndrome.

We examined the reliability, validity and factor structure of the Eye Contact Avoidance Scale (ECAS), a new 15-item screening tool designed to measure eye contact avoidance in individuals with fragile X syndrome (FXS). Internal consistency of the scale was acceptable to excellent and convergent validity with the Social Responsiveness Scale, Second Edition (SRS-2) and the Anxiety, Depression, and Mood Scale (ADAMS) was good. Boys with a comorbid ASD diagnosis obtained significantly higher scores on the ECAS compared to boys without ASD, when controlling for communication ability. A confirmatory factor analysis indicated that a two-factor model (avoidance and aversion) provided an excellent fit to the data. The ECAS appears to be a promising reliable and valid tool that could be employed as an outcome measure in future pharmacological/behavioral treatment trials for FXS.

Optical-imaging-based neurofeedback to enhance therapeutic intervention in adolescents with autism: methodology and initial data.

Impaired facial processing may contribute to social dysfunction in certain individuals with autism spectrum disorder (ASD). Prior studies show that electroencephalogram-based and functional magnetic resonance imaging-based neurofeedback might help some individuals with ASD learn to modulate regional brain activity and thus reduce symptoms. Here, we report for the first time the feasibility of employing functional near-infrared spectroscopy (fNIRS)-based neurofeedback training in children with ASD. We developed a method to study physiological self-regulation of oxy-hemoglobin using real-time feedback. The paradigm is illustrated with initial data from four subjects who engaged in a facial-identity recognition training program during which an implicit reinforcement was given based on the participant's brain activity and behavioral performance. Two participants had a confirmed diagnosis of ASD, and the other two were typically developing (TD). One participant with ASD and one TD participant received real-feedback (real-FB) during the training, whereas the other two received sham-feedback (sham-FB). After five training sessions, the subjects who received real-FB showed more improvement in facial recognition performance compared with those receiving sham-FB, particularly in the participant with ASD. These results suggest fNIRS-based neurofeedback could enhance therapeutic intervention in children with ASD.

The Role of Executive Function in Independent Living Skills in Female Adolescents and Young Adults With Fragile X Syndrome.

Fragile X syndrome (FXS) is associated with executive function (EF) and independent living skills (ILS) deficits. We examined the role of childhood EF in ILS during adolescence/early adulthood in females with FXS and two comparison groups in the same age range (matched for IQ [IQ/Age group] and with another genetic condition, Turner syndrome [TS group]). EF and ILS were significantly higher for the FXS group than the IQ/Age group but did not differ from the TS group. For the FXS group, age and EF were significant predictors of ILS during adolescence/early adulthood, but there were no statistically significant longitudinal associations between EF and ILS. Our findings suggest that impairments in EF may have a significant effect on ILS in FXS.

Profiles of aberrant white matter microstructure in fragile X syndrome.

Previous studies attempting to quantify white matter (WM) microstructure in individuals with fragile X syndrome (FXS) have produced inconsistent findings, most likely due to the various control groups employed, differing analysis methods, and failure to examine for potential motion artifact. In addition, analyses have heretofore lacked sufficient specificity to provide regional information. In this study, we used Automated Fiber-tract Quantification (AFQ) to identify specific regions of aberrant WM microstructure along WM tracts in patients with FXS that differed from controls who were matched on age, IQ and degree of autistic symptoms. Participants were 20 patients with FXS, aged 10 to 23 years, and 20 matched controls. Using Automated Fiber-tract Quantification (AFQ), we created Tract Profiles of fractional anisotropy and mean diffusivity along 18 major WM fascicles. We found that fractional anisotropy was significantly increased in the left and right inferior longitudinal fasciculus (ILF), right uncinate fasciculus, and left cingulum hippocampus in individuals with FXS compared to controls. Conversely, mean diffusivity was significantly decreased in the right ILF in patients with FXS compared to controls. Age was significantly negatively associated with MD values across both groups in 11 tracts. Taken together, these findings indicate that FXS results in abnormal WM microstructure in specific regions of the ILF and uncinate fasciculus, most likely caused by inefficient synaptic pruning as a result of decreased or absent Fragile X Mental Retardation Protein (FMRP). Longitudinal studies are needed to confirm these findings.