Scott S. Hall, Ph.D

All Publications

• Evaluating Practical Functional Assessment and Skill-Based Treatment for Severe Challenging Behavior via Telehealth with Novice Dual Parent Implementers: A Pilot Investigation CLINICAL CASE STUDIES Quiroz, L. S., Boyd, J. A., Pollard, J. S., Hall, S. S. 2024

  View details for DOI 10.1177/15346501241297363

  View details for Web of Science ID 001349632200001

• Differential Effects of a Behavioral Treatment Probe on Social Gaze Behavior in Fragile X Syndrome and Non-Syndromic Autism Spectrum Disorder. Journal of autism and developmental disorders Hall, S. S., Britton, T. C. 2023

  Abstract

  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.

  View details for DOI 10.1007/s10803-023-05919-6

  View details for PubMedID 37142899

  View details for PubMedCentralID 3640988

• A Scoping Review of Behavioral Interventions for Promoting Social Gaze in Individuals with Autism Spectrum Disorder and Other Developmental Disabilities. Research in autism spectrum disorders Hustyi, K. M., Ryan, A. H., Hall, S. S. 2023; 100

  Abstract

  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.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.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.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.

  View details for DOI 10.1016/j.rasd.2022.102074

  View details for PubMedID 36843962

  View details for PubMedCentralID PMC9956996

• Brief intensive social gaze training reorganizes functional brain connectivity in boys with fragile X syndrome. Cerebral cortex (New York, N.Y. : 1991) Saggar, M., Bruno, J. L., Hall, S. S. 2022

  Abstract

  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±2.31years) and comparison boys with ASD (mean age 12.15±2.76years) 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

  View details for DOI 10.1093/cercor/bhac411

  View details for PubMedID 36376964

• Examining Phenotypic Differences in Gaze Avoidance Between Autism Spectrum Disorder and Fragile X Syndrome. American journal on intellectual and developmental disabilities Wilkinson, E. H., Britton, T. C., Hall, S. S. 2022; 127 (6): 435-454

  Abstract

  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.

  View details for DOI 10.1352/1944-7558-127.6.435

  View details for PubMedID 36306410

• Long-term follow-up of telehealth-enabled behavioral treatment for challenging behaviors in boys with fragile X syndrome. Journal of neurodevelopmental disorders Hall, S. S., Rodriguez, A. B., Jo, B., Pollard, J. S. 2022; 14 (1): 53

  Abstract

  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.

  View details for DOI 10.1186/s11689-022-09463-9

  View details for PubMedID 36180840

• Brief, Intense Social Gaze Training Normalizes Functional Brain Connectivity in Boys With Fragile X Syndrome Bruno, J., Saggar, M., Hall, S. ELSEVIER SCIENCE INC. 2022: S152

  View details for Web of Science ID 000789022200373

• Implementing Automated Nonparametric Statistical Analysis on Functional Analysis Data: A Guide for Practitioners and Researchers. Perspectives on behavior science Kranak, M. P., Hall, S. S. 2022; 45 (1): 53-75

  Abstract

  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/.The online version contains supplementary material available at 10.1007/s40614-021-00290-2.

  View details for DOI 10.1007/s40614-021-00290-2

  View details for PubMedID 35342875

  View details for PubMedCentralID PMC8894515

• Conducting In-Home Functional Analyses of Aggression and Self-Injury Exhibited by Boys with Fragile X Syndrome. Journal of developmental and behavioral pediatrics : JDBP Monlux, K. D., Pollard, J. S., Bujanda Rodriguez, A. Y., Hall, S. S. 2021

  Abstract

  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 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.

  View details for DOI 10.1097/DBP.0000000000001019

  View details for PubMedID 34711767

• Effects of X Chromosome Monosomy and Genomic Imprinting on Observational Markers of Social Anxiety in Prepubertal Girls with Turner Syndrome. Journal of autism and developmental disorders Hall, S. S., Riley, M. J., Weston, R. N., Lepage, J., Hong, D. S., Jo, B., Hallmayer, J., Reiss, A. L. 2021

  Abstract

  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.

  View details for DOI 10.1007/s10803-021-04896-y

  View details for PubMedID 33751331

• Telehealth-enabled behavioral treatment for problem behaviors in boys with fragile X syndrome: a randomized controlled trial. Journal of neurodevelopmental disorders Hall, S. S., Monlux, K. D., Rodriguez, A. B., Jo, B., Pollard, J. S. 2020; 12 (1): 31

  Abstract

  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 10years, who displayed problem behaviors daily, were randomized to receive FCT via telehealth (n = 30) or treatment as usual (n = 27) over 12weeks. 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.

  View details for DOI 10.1186/s11689-020-09331-4

  View details for PubMedID 33218305

• Examining the Specificity of Forms and Functions of Aggressive Behavior in Boys With Fragile X Syndrome. American journal on intellectual and developmental disabilities Britton, T. C., Wilkinson, E. H., Hall, S. S. 2020; 125 (4): 247–59

  Abstract

  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.

  View details for DOI 10.1352/1944-7558-125.4.247

  View details for PubMedID 32609801

• Interpreting functional analysis outcomes using automated nonparametric statistical analysis. Journal of applied behavior analysis Hall, S. S., Pollard, J. S., Monlux, K. D., Baker, J. M. 2020

  Abstract

  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/.

  View details for DOI 10.1002/jaba.689

  View details for PubMedID 32048279

• Telehealth Delivery of Function-Based Behavioral Treatment for Problem Behaviors Exhibited by Boys with Fragile X Syndrome JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS Monlux, K. D., Pollard, J. S., Rodriguez, A., Hall, S. S. 2019; 49 (6): 2461–75

  View details for DOI 10.1007/s10803-019-03963-9

  View details for Web of Science ID 000470156100021

• Improving social gaze behavior in fragile X syndrome using a behavioral skills training approach: a proof of concept study JOURNAL OF NEURODEVELOPMENTAL DISORDERS Gannon, C. E., Britton, T. C., Wilkinson, E. H., Hall, S. S. 2018; 10: 25

  Abstract

  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.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.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.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.ClinicalTrials.gov, NCT02616796 . Registered 30 November 2015.

  View details for PubMedID 30153790

  View details for PubMedCentralID PMC6114729

• A Screening Tool to Measure Eye Contact Avoidance in Boys with Fragile X Syndrome JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS Hall, S. S., Venema, K. M. 2017; 47 (7): 2254–64

  Abstract

  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.

  View details for PubMedID 28516425

  View details for PubMedCentralID PMC5765981

• Updated report on tools to measure outcomes of clinical trials in fragile X syndrome JOURNAL OF NEURODEVELOPMENTAL DISORDERS Budimirovic, D. B., Berry-Kravis, E., Erickson, C. A., Hall, S. S., Hessl, D., Reiss, A. L., King, M. K., Abbeduto, L., Kaufmann, W. E. 2017; 9: 14

  Abstract

  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.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.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.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.

  View details for PubMedID 28616097

  View details for PubMedCentralID PMC5467057

• Optical-imaging-based neurofeedback to enhance therapeutic intervention in adolescents with autism: methodology and initial data. Neurophotonics Liu, N., Cliffer, S., Pradhan, A. H., Lightbody, A., Hall, S. S., Reiss, A. L. 2017; 4 (1): 011003-?

  Abstract

  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.

  View details for DOI 10.1117/1.NPh.4.1.011003

  View details for PubMedID 27570790

  View details for PubMedCentralID PMC4981748

• The cognitive developmental profile associated with fragile X syndrome: A longitudinal investigation of cognitive strengths and weaknesses through childhood and adolescence. Development and psychopathology Quintin, E., Jo, B., Hall, S. S., Bruno, J. L., Chromik, L. C., Raman, M. M., Lightbody, A. A., Martin, A., Reiss, A. L. 2016; 28 (4): 1457-1469

  Abstract

  Few studies have investigated developmental strengths and weaknesses within the cognitive profile of children and adolescents with fragile X syndrome (FXS), a single-gene cause of inherited intellectual impairment. With a prospective longitudinal design and using normalized raw scores (Z scores) to circumvent floor effects, we measured cognitive functioning of 184 children and adolescents with FXS (ages 6 to 16) using the Wechsler Scale of Intelligence for Children on one to three occasions for each participant. Participants with FXS received lower raw scores relative to the Wechsler Scale of Intelligence for Children normative sample across the developmental period. Verbal comprehension, perceptual organization, and processing speed Z scores were marked by a widening gap from the normative sample, while freedom from distractibility Z scores showed a narrowing gap. Key findings include a relative strength for verbal skills in comparison with visuospatial-constructive skills arising in adolescence and a discrepancy between working memory (weakness) and processing speed (strength) in childhood that diminishes in adolescence. Results suggest that the cognitive profile associated with FXS develops dynamically from childhood to adolescence. Findings are discussed within the context of aberrant brain morphology in childhood and maturation in adolescence. We argue that assessing disorder-specific cognitive developmental profiles will benefit future disorder-specific treatment research.

  View details for PubMedID 26648140

• Problem behaviour in adolescent boys with fragile X syndrome: relative prevalence, frequency and severity. Journal of intellectual disability research Hall, S. S., BARNETT, R. P., Hustyi, K. M. 2016

  Abstract

  A large proportion of boys with fragile X syndrome (FXS), the most common known inherited form of intellectual disability (ID), exhibit problem behaviours (e.g. aggression, self-injury, property destruction and stereotypy) that can negatively impact the health and safety of others as well as the individual concerned. However, data are limited concerning the relative prevalence, frequency and severity of problem behaviours exhibited by boys with FXS compared with those by boys with mixed-aetiology ID who also exhibit problem behaviours.As part of a larger study on problem behaviour, we obtained survey data on 85 adolescent boys with FXS and 155 age-matched boys with mixed-aetiology ID who exhibited at least one form of problem behaviour.For boys with FXS, stereotypy was reported to be more prevalent (χ(2)  = 4.52, P = 0.012), self-injury was reported to more frequent (U = 2525, P = 0.010) and aggression was reported to be less severe (U = 4176, P = 0.029) than for boys with mixed-aetiology ID. Ratings of aggression and property destruction were highly correlated in each group in terms of both frequency and severity (r = 0.60 to 0.71). Examination of the data by age indicated that the relative frequency of self-injury decreased with age in boys with FXS (χ(2)  = 8.29, P = 0.040).Taken together, these results refine and extend previous studies concerning the specificity of the behavioural phenotype in FXS and indicate that specific forms of problem behaviour shown by boys with FXS appear to differ from those exhibited by boys with mixed-aetiology ID in terms of prevalence, frequency and severity. Studies employing more objective measures of frequency and severity, including direct observations, are needed to confirm these findings.

  View details for DOI 10.1111/jir.12341

  View details for PubMedID 27730710

• The Role of Executive Function in Independent Living Skills in Female Adolescents and Young Adults With Fragile X Syndrome. American journal on intellectual and developmental disabilities Martin, A., Quintin, E., Hall, S. S., Reiss, A. L. 2016; 121 (5): 448-460

  Abstract

  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.

  View details for DOI 10.1352/1944-7558-121.5.448

  View details for PubMedID 27611354

• Profiles of aberrant white matter microstructure in fragile X syndrome. NeuroImage. Clinical Hall, S. S., Dougherty, R. F., Reiss, A. L. 2016; 11: 133-138

  Abstract

  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.

  View details for DOI 10.1016/j.nicl.2016.01.013

  View details for PubMedID 26937381

  View details for PubMedCentralID PMC4753809

• Neural Correlates of Self-Injurious Behavior in Prader-Willi Syndrome HUMAN BRAIN MAPPING Klabunde, M., Saggar, M., Hustyi, K. M., Hammond, J. L., Reiss, A. L., Hall, S. S. 2015; 36 (10): 4135-4143

  Abstract

  Individuals with Prader-Willi syndrome (PWS), a genetic disorder caused by mutations to the q11-13 region on chromosome 15, commonly show severe skin-picking behaviors that can cause open wounds and sores on the body. To our knowledge, however, no studies have examined the potential neural mechanisms underlying these behaviors. Seventeen individuals with PWS, aged 6-25 years, who showed severe skin-picking behaviors, were recruited and scanned on a 3T scanner. We used functional magnetic resonance imaging (fMRI) while episodes of skin picking were recorded on an MRI-safe video camera. Three participants displayed skin picking continuously throughout the scan, three participants did not display skin picking, and the data for one participant evidenced significant B0 inhomogeneity that could not be corrected. The data for the remaining 10 participants (six male, four female) who displayed a sufficient number of picking and nonpicking episodes were subjected to fMRI analysis. Results showed that regions involved in interoceptive, motor, attention, and somatosensory processing were activated during episodes of skin-picking behavior compared with nonpicking episodes. Scores obtained on the Self-Injury Trauma scale were significantly negatively correlated with mean activation within the right insula and left precentral gyrus. These data indicate that itch and pain processes appear to underlie skin-picking behaviors in PWS, suggesting that interoceptive disturbance may contribute to the severity and maintenance of abnormal skin-picking behaviors in PWS. Implications for treatments are discussed. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.

  View details for DOI 10.1002/hbm.22903

  View details for Web of Science ID 000364219100031

  View details for PubMedID 26173182

• Quantifying naturalistic social gaze in fragile X syndrome using a novel eye tracking paradigm. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics Hall, S. S., Frank, M. C., Pusiol, G. T., Farzin, F., Lightbody, A. A., Reiss, A. L. 2015; 168 (7): 564-572

  Abstract

  A hallmark behavioral feature of fragile X syndrome (FXS) is the propensity for individuals with the syndrome to exhibit significant impairments in social gaze during interactions with others. However, previous studies employing eye tracking methodology to investigate this phenomenon have been limited to presenting static photographs or videos of social interactions rather than employing a real-life social partner. To improve upon previous studies, we used a customized eye tracking configuration to quantify the social gaze of 51 individuals with FXS and 19 controls, aged 14-28 years, while they engaged in a naturalistic face-to-face social interaction with a female experimenter. Importantly, our control group was matched to the FXS group on age, developmental functioning, and degree of autistic symptomatology. Results showed that participants with FXS spent significantly less time looking at the face and had shorter episodes (and longer inter-episodes) of social gaze than controls. Regression analyses indicated that communication ability predicted higher levels of social gaze in individuals with FXS, but not in controls. Conversely, degree of autistic symptoms predicted lower levels of social gaze in controls, but not in individuals with FXS. Taken together, these data indicate that naturalistic social gaze in FXS can be measured objectively using existing eye tracking technology during face-to-face social interactions. Given that impairments in social gaze were specific to FXS, this paradigm could be employed as an objective and ecologically valid outcome measure in ongoing Phase II/Phase III clinical trials of FXS-specific interventions. © 2015 Wiley Periodicals, Inc.

  View details for DOI 10.1002/ajmg.b.32331

  View details for PubMedID 26079280

• Examining the neural correlates of emergent equivalence relations in fragile X syndrome PSYCHIATRY RESEARCH-NEUROIMAGING Klabunde, M., Saggar, M., Hustyi, K. M., Kelley, R. G., Reiss, A. L., Hall, S. S. 2015; 233 (3): 373-379

  Abstract

  The neural mechanisms underlying the formation of stimulus equivalence relations are poorly understood, particularly in individuals with specific learning impairments. As part of a larger study, we used functional magnetic resonance imaging (fMRI) while participants with fragile X syndrome (FXS), and age- and IQ-matched controls with intellectual disability, were required to form new equivalence relations in the scanner. Following intensive training on matching fractions to pie charts (A=B relations) and pie charts to decimals (B=C relations) outside the scanner over a 2-day period, participants were tested on the trained (A=B, B=C) relations, as well as emergent symmetry (i.e., B=A and C=B) and transitivity/equivalence (i.e., A=C and C=A) relations inside the scanner. Eight participants with FXS (6 female, 2 male) and 10 controls, aged 10-23 years, were able to obtain at least 66.7% correct on the trained relations in the scanner and were included in the fMRI analyses. Across both groups, results showed that the emergence of symmetry relations was correlated with increased brain activation in the left inferior parietal lobule, left postcentral gyrus, and left insula, broadly supporting previous investigations of stimulus equivalence research in neurotypical populations. On the test of emergent transitivity/equivalence relations, activation was significantly greater in individuals with FXS compared with controls in the right middle temporal gyrus, left superior frontal gyrus and left precuneus. These data indicate that neural execution was significantly different in individuals with FXS than in age- and IQ-matched controls during stimulus equivalence formation. Further research concerning how gene-brain-behavior interactions may influence the emergence of stimulus equivalence in individuals with intellectual disabilities is needed.

  View details for DOI 10.1016/j.pscychresns.2015.06.009

  View details for Web of Science ID 000360563800010

• Specific effect of the fragile-X mental retardation-1 gene (FMR1) on white matter microstructure BRITISH JOURNAL OF PSYCHIATRY Green, T., Barnea-Goraly, N., Raman, M., Hall, S. S., Lightbody, A. A., Bruno, J. L., Quintin, E., Reiss, A. L. 2015; 207 (2): 143-148

  Abstract

  Background Fragile-X syndrome (FXS) is a neurodevelopmental disorder associated with intellectual disability and neurobiological abnormalities including white matter microstructural differences. White matter differences have been found relative to neurotypical individuals. Aims To examine whether FXS white matter differences are related specifically to FXS or more generally to the presence of intellectual disability. Method We used voxel-based and tract-based analytic approaches to compare individuals with FXS (n = 40) with gender- and IQ-matched controls (n = 30). Results Individuals with FXS had increased fractional anisotropy and decreased radial diffusivity values compared with IQ-matched controls in the inferior longitudinal, inferior fronto-occipital and uncinate fasciculi. Conclusions The genetic variation associated with FXS affects white matter microstructure independently of overall IQ. White matter differences, found in FXS relative to IQ-matched controls, are distinct from reported differences relative to neurotypical controls. This underscores the need to consider cognitive ability differences when investigating white matter microstructure in neurodevelopmental disorders.

  View details for DOI 10.1192/bjp.bp.114.151654

  View details for Web of Science ID 000359180800009

  View details for PubMedID 25792692

• The Relationship Between Autistic Symptomatology and Independent Living Skills in Adolescents and Young Adults with Fragile X Syndrome JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS Hustyi, K. M., Hall, S. S., Quintin, E., Chromik, L. C., Lightbody, A. A., Reiss, A. L. 2015; 45 (6): 1836-1844

  Abstract

  Few studies have examined the relationship between autistic symptomatology and competence in independent living skills in adolescents and young adults with fragile X syndrome (FXS). In this study, 70 individuals with FXS, aged 15-25 years, and 35 matched controls were administered direct measures of independent living skills and autistic symptomatology. Results showed that higher levels of autistic symptomatology were associated with lower levels of competence in independent living skills in individuals with FXS, but not in controls. These data indicated that the relationship between autistic symptomatology and independent living skills was syndrome-specific. Early intervention strategies that address autistic symptomatology are sorely needed to improve functional outcomes in this population.

  View details for DOI 10.1007/s10803-014-2342-0

  View details for Web of Science ID 000354977700027

  View details for PubMedID 25518824

• Longitudinal trajectories of aberrant behavior in fragile X syndrome. Research in developmental disabilities Hustyi, K. M., Hall, S. S., Jo, B., Lightbody, A. A., Reiss, A. L. 2014; 35 (11): 2691-2701

  Abstract

  The Aberrant Behavior Checklist-Community (ABC-C; Aman et al., 1995) has been increasingly adopted as a primary tool for measuring behavioral change in clinical trials for individuals with fragile X syndrome (FXS). To our knowledge, however, no study has documented the longitudinal trajectory of aberrant behaviors in individuals with FXS using the ABC-C. As part of a larger longitudinal study, we examined scores obtained on the ABC-C subscales for 124 children and adolescents (64 males, 60 females) with FXS who had two or more assessments (average interval between assessments was approximately 4 years). Concomitant changes in age-equivalent scores on the Vineland Adaptive Behavior Scales (VABS) were also examined. As expected for an X-linked genetic disorder, males with FXS obtained significantly higher scores on all subscales of the ABC-C and significantly lower age-equivalent scores on the VABS than females with FXS. In both males and females with FXS, scores on the Irritability/Agitation and Hyperactivity/Noncompliance subscales of the ABC-C decreased significantly with age, with little to no change occurring over time on the Lethargy/Social Withdrawal, Stereotypic Behavior, and Inappropriate Speech subscales. The decrease in scores on the Hyperactivity/Noncompliance domain was significantly greater for males than for females. In both males and females, age-equivalent scores on the VABS increased significantly over this developmental period. These results establish a basis upon which to evaluate long-term outcomes from intervention-based research. However, longitudinal direct observational studies are needed to establish whether the severity of problem behavior actually decreases over time in this population.

  View details for DOI 10.1016/j.ridd.2014.07.003

  View details for PubMedID 25129200

• Experimental functional analysis of severe skin-picking behavior in Prader-Willi syndrome. Research in developmental disabilities Hall, S. S., Hustyi, K. M., Chui, C., Hammond, J. L. 2014; 35 (10): 2284-2292

  Abstract

  Skin picking is an extremely distressing and treatment resistant behavior commonly shown by individuals with Prader-Willi syndrome (PWS). However, with the exception of a limited number of published single-case and survey studies, little is known about the environmental determinants of skin picking in this population. In this study, functional analyses were conducted with thirteen individuals with PWS, aged 6-23 years, who engaged in severe skin-picking behavior. In addition to the conditions typically employed in a functional analysis (i.e., alone, attention, play, demand), we included an ignore condition to examine potential effects of stimulus control by the presence of an adult. Twelve participants engaged in skin picking during the functional analysis, with the highest levels occurring in the alone and ignore conditions for eight participants, suggesting that skin picking in these participants was maintained by automatic reinforcement. For the remaining four participants, an undifferentiated pattern of low-rate skin picking was observed across conditions. These data confirm previous studies indicating that skin picking in PWS may be maintained most often by automatically produced sensory consequences. There were no associations between demographic characteristics of the participants (e.g., sex, age, IQ or BMI) and levels of skin picking observed in the functional analysis. Additional investigations are needed to identify the nature of the sensory consequences produced during episodes of skin picking in PWS. Behavioral interventions designed to extinguish or compete with the potential sensory consequences arising from skin picking in PWS are also warranted.

  View details for DOI 10.1016/j.ridd.2014.05.025

  View details for PubMedID 24952370

• Longitudinal profiles of adaptive behavior in fragile x syndrome. Pediatrics Klaiman, C., Quintin, E., Jo, B., Lightbody, A. A., Hazlett, H. C., Piven, J., Hall, S. S., Reiss, A. L. 2014; 134 (2): 315-324

  Abstract

  To examine longitudinally the adaptive behavior patterns in fragile X syndrome.Caregivers of 275 children and adolescents with fragile X syndrome and 225 typically developing children and adolescents (2-18 years) were interviewed with the Vineland Adaptive Behavior Scales every 2 to 4 years as part of a prospective longitudinal study.Standard scores of adaptive behavior in people with fragile X syndrome are marked by a significant decline over time in all domains for males and in communication for females. Socialization skills are a relative strength as compared with the other domains for males with fragile X syndrome. Females with fragile X syndrome did not show a discernible pattern of developmental strengths and weaknesses.This is the first large-scale longitudinal study to show that the acquisition of adaptive behavior slows as individuals with fragile X syndrome age. It is imperative to ensure that assessments of adaptive behavior skills are part of intervention programs focusing on childhood and adolescence in this condition.

  View details for DOI 10.1542/peds.2013-3990

  View details for PubMedID 25070318

• Using discrete trial training to identify specific learning impairments in boys with fragile x syndrome. Journal of autism and developmental disorders Hall, S. S., Hustyi, K. M., Hammond, J. L., Hirt, M., Reiss, A. L. 2014; 44 (7): 1659-1670

  Abstract

  We examined whether discrete trial training (DTT) could be used to identify learning impairments in mathematical reasoning in boys with fragile X syndrome (FXS). Boys with FXS, aged 10-23 years, and age and IQ-matched controls, were trained to match fractions to pie-charts and pie-charts to decimals either on a computer or with a trained behavior analyst using DTT. Participants with FXS obtained significantly lower learning rates on the fractions to pie-charts task, and were more likely to perseverate on previously reinforced responses during learning compared to controls. These data suggest that DTT can be used to identify specific learning impairments in boys with FXS, as well as other low-functioning individuals with developmental disabilities.

  View details for DOI 10.1007/s10803-014-2037-6

  View details for PubMedID 24452992

• High rates of comorbid depressive and anxiety disorders among women with premutation of the FMR1 gene. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics Kenna, H. A., Tartter, M., Hall, S. S., Lightbody, A. A., Nguyen, Q., de los Angeles, C. P., Reiss, A. L., Rasgon, N. L. 2013; 162 (8): 872-878

  Abstract

  Phenotypic variations are emerging from investigations of carriers of the fragile X mental retardation 1 (FMR1) premutation gene (55 to 200 CGG repeats). Initial studies suggest elevated psychiatric and reproductive system dysfunction, but have largely used self-reports for assessment of psychiatric history. The present study used diagnostic psychiatric interviews and assessed reproductive and menstrual history in women with FMR1 premutation. History of psychiatric diagnoses and data on reproductive functioning were collected in 46 women with FMR1 premutation who were mothers of at least one child with the fragile X full mutation. Results showed a significantly earlier age of menopause (mean age = 45.6 years) relative to the national average age of menopause (mean age = 51 years) and a high rate (76%) of lifetime depressive or anxiety history, with 43% of the overall sample reporting a comorbid history of both diagnoses. Compared to those free of psychiatric history, significantly longer premutation length was observed among women with psychiatric history after adjusting for age, with comorbid women having the highest number of CGG repeats (mean = 95.8) compared to women free of psychiatric history (mean = 79.9). Psychiatric history did not appear significantly related to reproductive system dysfunction, though results may have been obscured by the high rates of psychiatric dysfunction in the sample. These data add to the growing evidence base that women with the FMR1 premutation have an increased risk of psychiatric illness and risk for early menopause. Future investigations may benefit from inclusion of biochemical reproductive markers and longitudinal assessment of psychiatric and reproductive functioning. © 2013 Wiley Periodicals, Inc.

  View details for DOI 10.1002/ajmg.b.32196

  View details for PubMedID 24003006

• Examining the Relationship Between Heart Rate and Problem Behavior: A Case Study of Severe Skin Picking in Prader-Willi Syndrome AJIDD-AMERICAN JOURNAL ON INTELLECTUAL AND DEVELOPMENTAL DISABILITIES Hall, S. S., Hammond, J. L., Hustyi, K. M. 2013; 118 (6): 460-474

  Abstract

  Abstract Few studies have examined the relationship between heart rate and self-injurious behavior (SIB) shown by individuals with IDD (intellectual and developmental disabilities). In this single-case study, we simultaneously monitored heart rate and activity levels during a functional analysis of severe skin picking behavior exhibited by a young man with Prader-Willi syndrome (PWS). Results of the functional analysis indicated that the participant's skin picking was maintained by automatic reinforcement. A within-session analysis of the data indicated that skin picking bouts resulted in an increase in heart rate, suggesting a positive- automatic reinforcement function. These data indicate that inclusion of heart rate and activity-level monitoring during a functional analysis may provide important additional information concerning the determinants of SIB.

  View details for DOI 10.1352/1944.7558-118.6.460

  View details for Web of Science ID 000330185500007

  View details for PubMedID 24432859

• Examining the relationship between heart rate and problem behavior: a case study of severe skin picking in Prader-Willi syndrome. American journal on intellectual and developmental disabilities Hall, S. S., Hammond, J. L., Hustyi, K. M. 2013; 118 (6): 460-474

  Abstract

  Abstract Few studies have examined the relationship between heart rate and self-injurious behavior (SIB) shown by individuals with IDD (intellectual and developmental disabilities). In this single-case study, we simultaneously monitored heart rate and activity levels during a functional analysis of severe skin picking behavior exhibited by a young man with Prader-Willi syndrome (PWS). Results of the functional analysis indicated that the participant's skin picking was maintained by automatic reinforcement. A within-session analysis of the data indicated that skin picking bouts resulted in an increase in heart rate, suggesting a positive- automatic reinforcement function. These data indicate that inclusion of heart rate and activity-level monitoring during a functional analysis may provide important additional information concerning the determinants of SIB.

  View details for DOI 10.1352/1944.7558-118.6.460

  View details for PubMedID 24432859

• Identifying large-scale brain networks in fragile x syndrome. JAMA psychiatry Hall, S. S., Jiang, H., Reiss, A. L., Greicius, M. D. 2013; 70 (11): 1215-1223

  Abstract

  Fragile X syndrome (FXS) is an X-linked neurogenetic disorder characterized by a cognitive and behavioral phenotype resembling features of autism spectrum disorder. Until now, research has focused largely on identifying regional differences in brain structure and function between individuals with FXS and various control groups. Very little is known about the large-scale brain networks that may underlie the cognitive and behavioral symptoms of FXS.To identify large-scale, resting-state networks in FXS that differ from control individuals matched on age, IQ, and severity of behavioral and cognitive symptoms.Cross-sectional, in vivo neuroimaging study conducted in an academic medical center. Participants (aged 10-23 years) included 17 males and females with FXS and 16 males and females serving as controls.Univariate voxel-based morphometric analyses, fractional amplitude of low-frequency fluctuations (fALFF) analysis, and group-independent component analysis with dual regression.Patients with FXS showed decreased functional connectivity in the salience, precuneus, left executive control, language, and visuospatial networks compared with controls. Decreased fALFF in the bilateral insular, precuneus, and anterior cingulate cortices also was found in patients with FXS compared with control participants. Furthermore, fALFF in the left insular cortex was significantly positively correlated with IQ in patients with FXS. Decreased gray matter density, resting-state connectivity, and fALFF converged in the left insular cortex in patients with FXS.Fragile X syndrome results in widespread reductions in functional connectivity across multiple cognitive and affective brain networks. Converging structural and functional abnormalities in the left insular cortex, a region also implicated in individuals diagnosed with autism spectrum disorder, suggests that insula integrity and connectivity may be compromised in FXS. This method could prove useful in establishing an imaging biomarker for FXS.

  View details for DOI 10.1001/jamapsychiatry.2013.247

  View details for PubMedID 24068330

• An analysis of the topography, severity, potential sources of reinforcement, and treatments utilized for skin picking in Prader-Willi syndrome RESEARCH IN DEVELOPMENTAL DISABILITIES Hustyi, K. M., Hammond, J. L., Rezvani, A. B., Hall, S. S. 2013; 34 (9): 2890-2899

  Abstract

  We examined the topography, severity, potential sources of reinforcement, and treatments utilized for skin-picking behavior shown by individuals with Prader-Willi syndrome (PWS). The parents of 55 individuals with PWS, aged 6-25 years, were interviewed about their child's skin-picking behavior using the Self-Injury Trauma Scale (SIT; Iwata, Pace, Kissel, Nau, & Farber, 1990) and the Functional Analysis Screening Tool (FAST; Iwata, DeLeon, & Roscoe, 2013). Results showed that skin picking in PWS occurred on the extremities (i.e., arms, legs, hands, and feet) for 75% of cases and resulted in bodily injury for 83.7% cases. Skin picking posed a high risk to the individual concerned in 41.8% of cases. Automatic sensory stimulation was identified as a potential source of reinforcement in the majority of cases (52.7%) followed by access to social attention or preferred items (36.4%). Treatments utilized by parents were primarily behavioral strategies (56.3%) followed by basic first aid (54.5%). There were no differences in the topography, severity or potential source of reinforcement between those with the deletion (DEL) subtype and those with the uniparental disomy (UPD) subtype. Taken together, these data indicate that skin picking shown by individuals with PWS is a particularly severe and intractable behavioral issue that may be maintained by (as yet unknown) sensory consequences. Further studies to identify the determinants of skin picking in PWS are therefore needed. The implications for interventions are discussed.

  View details for DOI 10.1016/j.ridd.2013.06.014

  View details for Web of Science ID 000322423200049

  View details for PubMedID 23810929

• Outcome Measures for Clinical Trials in Fragile X Syndrome JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS Berry-Kravis, E., Hessl, D., Abbeduto, L., Reiss, A. L., Beckel-Mitchener, A., Urv, T. K. 2013; 34 (7): 508-522

  Abstract

  Progress in basic neuroscience has led to identification of molecular targets for treatment in fragile X syndrome (FXS) and other neurodevelopmental disorders; however, there is a gap in translation to targeted therapies in humans. One major obstacle to the demonstration of efficacy in human trials has been the lack of generally accepted endpoints to assess improvement in function in individuals with FXS. To address this problem, the National Institutes of Health convened a meeting of leading scientists and clinicians with the goal of identifying and standardizing outcome measures for use as potential endpoints in clinical trials in FXS.Participants in the meeting included FXS experts, experts in the design and implementation of clinical trials and measure development, and representatives from advocacy groups, industry, and federal agencies.The group generated recommendations for optimal outcome measures in cognitive, behavioral, and biomarker/medical domains, including additional testing and validation of existing measures and development of new measures in areas of need. Although no one endpoint or set of endpoints could be identified that met all criteria as an optimal measure, recommendations are presented in this report.The report is expected to guide the selection of measures in clinical trials and lead to the use of a more consistent battery of measures across trials. Furthermore, this will help to direct research toward gaps in the development of validated FXS-specific outcome measures and to assist with interpretation of clinical trial data by creating templates for measurement of treatment efficacy.

  View details for Web of Science ID 000330359000008

  View details for PubMedID 24042082

• Delineating the Profile of Autism Spectrum Disorder Characteristics in Cornelia de Lange and Fragile X Syndromes AJIDD-AMERICAN JOURNAL ON INTELLECTUAL AND DEVELOPMENTAL DISABILITIES Moss, J., Oliver, C., Nelson, L., Richards, C., Hall, S. 2013; 118 (1): 55-73

  Abstract

  An atypical presentation of autism spectrum disorder is noted in Cornelia de Lange and Fragile X syndromes, but there are few detailed empirical descriptions. Participants in this study were individuals with Cornelia de Lange syndrome (n  =  130, M age  =  17.19), Fragile X syndrome (n  =  182, M age  =  16.94), and autism spectrum disorder (n  =  142, M age  =  15.19), who were comparable on chronological age. Using the Social Communication Questionnaire, the proportion meeting cutoff for autism spectrum disorder and autism was 78.6%, and 45.6%, respectively, in Cornelia de Lange syndrome and 83.6% and 48.6% in Fragile X syndrome. Domain and item analyses indicate differing, atypical autism spectrum disorder profiles in Fragile X and Cornelia de Lange syndromes. A limited association between adaptive behavior and autism spectrum disorder was identified in all groups. The findings have implications for intervention in genetic syndromes and conceptualization of autism spectrum disorder in the wider population.

  View details for DOI 10.1352/1944-7558-118.1.55

  View details for Web of Science ID 000317912500006

  View details for PubMedID 23301903

• COGNITIVE TRAJECTORY IN MALES AND FEMALES WITH FRAGILE X SYNDROME 20th Annual Meeting of the Cognitive-Neuroscience-Society Quintin, E., Hall, S., Jo, B., Bruno, J., Chromik, L., Raman, M., Linghtbody, A., Reiss, A. MIT PRESS. 2013: 251–251

  View details for Web of Science ID 000317030501371

• A 'learning platform' approach to outcome measurement in fragile X syndrome: a preliminary psychometric study JOURNAL OF INTELLECTUAL DISABILITY RESEARCH Hall, S. S., Hammond, J. L., Hirt, M., Reiss, A. L. 2012; 56 (10): 947-960

  Abstract

  Clinical trials of medications to alleviate the cognitive and behavioural symptoms of individuals with fragile X syndrome (FXS) are now underway. However, there are few reliable, valid and/or sensitive outcome measures available that can be directly administered to individuals with FXS. The majority of assessments employed in clinical trials may be suboptimal for individuals with intellectual disability (ID) because they require face-to-face interaction with an examiner, taxing administration periods, and do not provide reinforcement and/or feedback during the test. We therefore examined the psychometric properties of a new computerised 'learning platform' approach to outcome measurement in FXS.A brief computerised test, incorporated into the Discrete Trial Trainer©- a commercially available software program designed for children with ID - was administered to 13 girls with FXS, 12 boys with FXS and 15 matched ID controls aged 10 to 23 years (mental age = 4 to 12 years). The software delivered automated contingent access to reinforcement, feedback, token delivery and prompting procedures (if necessary) on each trial to facilitate responding. The primary outcome measure was the participant's learning rate, derived from the participant's cumulative record of correct responses.All participants were able to complete the test and floor effects appeared to be minimal. Learning rates averaged approximately five correct responses per minute, ranging from one to eight correct responses per minute in each group. Test-retest reliability of the learning rates was 0.77 for girls with FXS, 0.90 for boys with FXS and 0.90 for matched ID controls. Concurrent validity with raw scores obtained on the Arithmetic subtest of the Wechsler Intelligence Scale for Children-III was 0.35 for girls with FXS, 0.80 for boys with FXS and 0.56 for matched ID controls. The learning rates were also highly sensitive to change, with effect sizes of 1.21, 0.89 and 1.47 in each group respectively following 15 to 20, 15-min sessions of intensive discrete trial training conducted over 1.5 days.These results suggest that a learning platform approach to outcome measurement could provide investigators with a reliable, valid and highly sensitive measure to evaluate treatment efficacy, not only for individuals with FXS but also for individuals with other ID.

  View details for DOI 10.1111/j.1365-2788.2012.01560.x

  View details for Web of Science ID 000308872200003

  View details for PubMedID 22533667

  View details for PubMedCentralID PMC3417081

• Psychometric Study of the Aberrant Behavior Checklist in Fragile X Syndrome and Implications for Targeted Treatment JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS Sansone, S. M., Widaman, K. F., Hall, S. S., Reiss, A. L., Lightbody, A., Kaufmann, W. E., Berry-Kravis, E., Lachiewicz, A., Brown, E. C., Hessl, D. 2012; 42 (7): 1377-1392

  Abstract

  Animal studies elucidating the neurobiology of fragile X syndrome (FXS) have led to multiple controlled trials in humans, with the Aberrant Behavior Checklist-Community (ABC-C) commonly adopted as a primary outcome measure. A multi-site collaboration examined the psychometric properties of the ABC-C in 630 individuals (ages 3-25) with FXS using exploratory and confirmatory factor analysis. Results support a six-factor structure, with one factor unchanged (Inappropriate Speech), four modified (Irritability, Hyperactivity, Lethargy/Withdrawal, and Stereotypy), and a new Social Avoidance factor. A comparison with ABC-C data from individuals with general intellectual disability and a list of commonly endorsed items are also reported. Reformulated ABC-C scores based on this FXS-specific factor structure may provide added outcome measure specificity and sensitivity in FXS clinical trials.

  View details for DOI 10.1007/s10803-011-1370-2

  View details for Web of Science ID 000305231000009

  View details for PubMedID 21972117

  View details for PubMedCentralID PMC3290710

• Effects of intranasal oxytocin on social anxiety in males with fragile X syndrome PSYCHONEUROENDOCRINOLOGY Hall, S. S., Lightbody, A. A., McCarthy, B. E., Parker, K. J., Reiss, A. L. 2012; 37 (4): 509-518

  Abstract

  Fragile X syndrome (FXS) is a rare inherited genetic disorder causing severe intellectual disability and autistic-like symptoms. Individuals with FXS, males in particular, often exhibit extreme eye gaze avoidance and hyperarousal when they encounter stressful social situations. We investigated whether oxytocin (OT), a hormone with prosocial and anxiolytic effects, could alleviate symptoms of social anxiety in this population. A randomized double-blind placebo-controlled single-dose trial was performed with intranasal administration of placebo, 24 IU OT and 48 IU OT. Measures of eye gaze frequency, heart rate, respiratory sinus arrhythmia (RSA), heart rate variability (HRV) and salivary cortisol were obtained during a structured social challenge conducted 50 min following OT administration. Ten low-functioning males with FXS (aged 13-28 years) traveled to Stanford for the initial visit: 8 completed the study. Eye gaze frequency improved significantly in response to the 24 IU OT dose and salivary cortisol levels decreased significantly in response to the 48 IU OT dose. There was no effect of OT on heart rate, RSA or HRV although individual plots of the heart rate data suggested that OT increased heart rate in some participants and decreased heart rate in others. These findings suggest that intranasal administration of OT may ameliorate some symptoms of social anxiety in patients with FXS. Further double-blind placebo-controlled studies of OT, conducted in combination with behavioral treatment programs, may be warranted.

  View details for DOI 10.1016/j.psyneuen.2011.07.020

  View details for Web of Science ID 000302044800007

  View details for PubMedID 21862226

  View details for PubMedCentralID PMC3353652

• Effects of computerized match-to-sample training on emergent fraction-decimal relations in individuals with fragile X syndrome RESEARCH IN DEVELOPMENTAL DISABILITIES Hammond, J. L., Hirt, M., Hall, S. S. 2012; 33 (1): 1-11

  Abstract

  Individuals diagnosed with fragile X syndrome (FXS), the most common known form of inherited intellectual disability, are reported to exhibit considerable deficits in mathematical skills that are often attributed to brain-based abnormalities associated with the syndrome. We examined whether participants with FXS would display emergent fraction-decimal relations following brief, intensive match-to-sample training on baseline relations. The performance profiles on tests of symmetry and transitivity/equivalence of 11 participants with FXS, aged 10-23 years, following baseline match-to-sample training were compared to those of 11 age- and IQ-matched controls with idiopathic developmental disability. The results showed that both groups of participants showed significant improvements in the baseline (trained) relations, as expected. However, participants with FXS failed to show significant improvements in the (untrained) symmetry and transitivity/equivalence relations compared to those in the control group. A categorical analysis of the data indicated that five participants with FXS and eight controls showed at least "intermediate" emergence of symmetry relations, whereas one individual with FXS and three controls showed at least intermediate emergence of transitivity/equivalence relations. A correlation analysis of the data indicated that improvements in the symmetry relations were significantly associated with improvements in the transitivity/equivalence relations in the control group (r=.69, p=.018), but this was not the case in the FXS group (r=.34, p>.05). Participant IQ was significantly associated with improvements in the symmetry relations in individuals with FXS (r=.60, p=.049), but not in controls (r=.21, p>.05). Taken together, these results suggest that brief, computerized match-to-sample training may produce emergent mathematical relations for a subset of children with FXS and developmental disabilities. However, the ability of individuals with FXS to form transitivity/equivalence relations may be impaired relative to those with idiopathic developmental disabilities, which may be attributed to neurodevelopmental variables associated with the syndrome.

  View details for DOI 10.1016/j.ridd.2011.08.021

  View details for Web of Science ID 000297661500001

  View details for PubMedID 22093642

  View details for PubMedCentralID PMC3352237

• Aberrant Frontal Lobe Maturation in Adolescents with Fragile X Syndrome is Related to Delayed Cognitive Maturation BIOLOGICAL PSYCHIATRY Bray, S., Hirt, M., Jo, B., Hall, S. S., Lightbody, A. A., Walter, E., Chen, K., Patnaik, S., Reiss, A. L. 2011; 70 (9): 852-858

  Abstract

  Fragile X syndrome (FXS) is the most common known heritable cause of intellectual disability. Prior studies in FXS have observed a plateau in cognitive and adaptive behavioral development in early adolescence, suggesting that brain development in FXS may diverge from typical development during this period.In this study, we examined adolescent brain development using structural magnetic resonance imaging data acquired from 59 individuals with FXS and 83 typically developing control subjects aged 9 to 22, a subset of whom were followed up longitudinally (1-5 years; typically developing: 17, FXS: 19). Regional volumes were modeled to obtain estimates of age-related change.We found that while structures such as the caudate showed consistent volume differences from control subjects across adolescence, prefrontal cortex (PFC) gyri showed significantly aberrant maturation. Furthermore, we found that PFC-related measures of cognitive functioning followed a similarly aberrant developmental trajectory in FXS.Our findings suggest that aberrant maturation of the PFC during adolescence may contribute to persistent or increasing intellectual deficits in FXS.

  View details for DOI 10.1016/j.biopsych.2011.05.038

  View details for Web of Science ID 000296228000012

  View details for PubMedID 21802660

  View details for PubMedCentralID PMC3191299

• Insular volume reduction in fragile X syndrome INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE Cohen, J. D., Nichols, T., Brignone, L., Hall, S. S., Reiss, A. L. 2011; 29 (4): 489-494

  Abstract

  Fragile X syndrome (FraX) is the most common form of inherited mental deficit and is caused by mutations of the Fragile X Mental Retardation 1 (FMR1) gene on the X chromosome. While males and females with the full FMR1 mutation are affected differently because the disorder is X-linked, both suffer from varying degrees of cognitive impairment, attention deficits and social anxiety. The insula is a sensory integrative region that has been increasingly suggested as a critical area involved in anxiety manifestation. The current study was designed to examine possible changes in insular volume in FraX compared to age- and gender-matched typically developing healthy controls (HC) as well as age-, gender-, and intelligence-matched developmentally delayed controls (DD). An established native-space, manual morphometry method was utilized to quantify total and regional insular volumes using structural magnetic resonance imaging. Total, anterior and posterior insular volumes were found to be reduced in FraX compared to both HC and DD. The current data add to a growing literature concerning brain abnormalities in FraX and suggests that significant volume reduction of the insula is a component of the FraX neuroanatomical phenotype. This finding also provides an intriguing potential neural correlate for hyperarousal and gaze aversion, which are prominent behavioral symptoms of FraX.

  View details for DOI 10.1016/j.ijdevneu.2011.01.003

  View details for Web of Science ID 000291506000016

  View details for PubMedID 21291994

  View details for PubMedCentralID PMC3095676

• Behavioural Excesses and Deficits Associated with Dementia in Adults who have Down Syndrome JOURNAL OF APPLIED RESEARCH IN INTELLECTUAL DISABILITIES Oliver, C., Kalsy, S., McQuillan, S., Hall, S. 2011; 24 (3): 208-216

  View details for DOI 10.1111/j.1468-3148.2010.00604.x

  View details for Web of Science ID 000289470000003

• Functional analysis and treatment of aggressive behavior following resection of a craniopharyngioma DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY Hammond, J. L., Hall, S. S. 2011; 53 (4): 369-374

  Abstract

  Craniopharyngioma is a relatively rare, benign tumor that most often affects pre-adolescent children. Surgical resection is a common form of treatment, which may result in adverse physical, neurological, and behavioral effects, most notably, aggressive behavior. In this case study we describe a typically developing 6 year old female who had resection of a craniopharyngioma and subsequently developed severe aggressive behavior that interfered significantly with her recovery and functioning. Results of a functional analysis indicated that her aggression was maintained by contingent escape from task demands and access to preferred food items. A highly structured behavioral intervention, consisting of differential reinforcement of alternative behaviors, together with extinction targeted to each function of the behavior, was effective in reducing her aggression to below 88% of baseline levels. Her adaptive behaviors also increased significantly. These results suggest that assessment and treatment utilizing principles of applied behavior analysis can ameliorate the occurrence of problem behavior following craniopharyngioma resection.

  View details for DOI 10.1111/j.1469-8749.2010.03887.x

  View details for Web of Science ID 000288380600019

  View details for PubMedID 21232057

• Autism in Fragile X Syndrome: A Category Mistake? JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Hall, S. S., Lightbody, A. A., Hirt, M., Rezvani, A., Reiss, A. L. 2010; 49 (9): 921-933

  Abstract

  Many investigators now routinely classify children with fragile X syndrome (FXS) according to whether or not they also meet diagnostic criteria for autism. To determine whether this classification is appropriate, we examined the profiles of autistic behaviors shown by boys and girls with FXS.Individuals with FXS, aged 5 to 25 years, were assessed on two established measures of autism, the Social Communication Questionnaire (SCQ) and the Autism Diagnostic Observation Schedule (ADOS).We found that 35.1% of boys and 4.3% of girls with FXS scored in the "autism" category on both instruments. Analysis of the symptom profile indicated that both boys and girls with FXS showed lower rates of impairment on communication and reciprocal social interaction items than the reference autism samples on the measures. Furthermore, a regression model showed that IQ was significantly negatively associated with the SCQ total score in both boys and girls with FXS, when controlling for age, medication use, and FMRP levels.These data suggest that there are significant differences in the profile of social and communicative symptomatology in FXS compared with individuals diagnosed with idiopathic autism. Given these differences, the implementation of standard autism interventions for individuals with FXS may not be optimal. Maintaining the conceptual distinction between FXS (an established biological disease) and idiopathic autism (a phenomenologically defined behavioral disorder) may also facilitate the development of more targeted and thus effective interventions for individuals with FXS in the future.

  View details for DOI 10.1016/j.jaac.2010.07.001

  View details for Web of Science ID 000281331400006

  View details for PubMedID 20732628

  View details for PubMedCentralID PMC2943372

• Self-injurious behaviour in Cornelia de Lange syndrome: 2. association with environmental events JOURNAL OF INTELLECTUAL DISABILITY RESEARCH Sloneem, J., Arron, K., Hall, S. S., Oliver, C. 2009; 53: 590-603

  Abstract

  Self-injurious behaviour is commonly seen in Cornelia de Lange syndrome (CdLS). However, there has been limited research into the aetiology of self-injury in CdLS and whether environmental factors influence the behaviour.We observed the self-injury of 27 individuals with CdLS and 17 participants who did not have CdLS matched for age, gender, level of intellectual disability and mobility. Descriptive analyses were used to determine the extent to which environmental events were associated with self-injury.Lag sequential analysis of the association between self-injurious behaviour and environmental events revealed no differences between the two groups in terms of either the number or degree of environmental associations.The results suggest that the associations between the environment and self-injury in CdLS do not differ from those seen in the broader population of people with intellectual disability. By implication the social reinforcement hypothesis is equally applicable to both groups.

  View details for DOI 10.1111/j.1365-2788.2009.01183.x

  View details for Web of Science ID 000266923600002

  View details for PubMedID 19533839

• Self-injurious behaviour in Cornelia de Lange syndrome: 1. Prevalence and phenomenology JOURNAL OF INTELLECTUAL DISABILITY RESEARCH Oliver, C., Sloneem, J., Hall, S., Arron, K. 2009; 53: 575-589

  Abstract

  Self-injurious behaviour is frequently identified as part of the behavioural phenotype of Cornelia de Lange syndrome (CdLS). We conducted a case-control study of the prevalence and phenomenology of self-injurious behaviour (SIB) in CdLS.A total of 54 participants with CdLS were compared with 46 individuals who were comparable on key variables including age, degree of intellectual disability and wheelchair use, using questionnaire and observational measures.Clinically significant self-injury was not more prevalent in the CdLS group (55.6%), nor was it different in presentation from that seen in the comparison group. Hyperactivity, stereotyped and compulsive behaviours predicted clinically significant self-injury in all participants. Hand directed, mild self-injury was more prevalent in CdLS.The results show that clinically significant self-injury may not be part of the behavioural phenotype of CdLS but a specific body target for proto-SIB is more common.

  View details for DOI 10.1111/j.1365-2788.2009.01179.x

  View details for Web of Science ID 000266923600001

  View details for PubMedID 19522788

• USING PERCENTILE SCHEDULES TO INCREASE EYE CONTACT IN CHILDREN WITH FRAGILE X SYNDROME JOURNAL OF APPLIED BEHAVIOR ANALYSIS Hall, S. S., Maynes, N. P., Reiss, A. L. 2009; 42 (1): 171-176

  Abstract

  Aversion to eye contact is a common behavior of individuals diagnosed with Fragile X syndrome (FXS); however, no studies to date have attempted to increase eye-contact duration in these individuals. In this study, we employed a percentile reinforcement schedule with and without overcorrection to shape eye-contact duration of 6 boys with FXS. Results showed that although aversion to eye contact is often thought to be unamenable to change in FXS, it can be shaped in some individuals using percentile schedules either alone or in combination with overcorrection.

  View details for DOI 10.1901/jaba.2009.42-171

  View details for Web of Science ID 000263982700013

  View details for PubMedID 19721738

  View details for PubMedCentralID PMC2649838

• Physiological Correlates of Social Avoidance Behavior in Children and Adolescents With Fragile X Syndrome JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Hall, S. S., Lightbody, A. A., Huffman, L. C., Lazzeroni, L. C., Reiss, A. L. 2009; 48 (3): 320-329

  Abstract

  To investigate whether eye-gaze avoidance, a striking phenotypic feature in fragile X syndrome (FXS), is associated with high levels of "hyperarousal" during social interactions with others. To date, almost all studies in this area have been confounded by inclusion of task demands in addition to social demands.We monitored the cardiovascular activity and eye-gaze avoidance of 50 boys and girls with FXS aged 5 to 20 years during a 25-minute intensive social interaction session with an unfamiliar experimenter. To control for possible family and genetic factors in cardiovascular activity, we compared each child with FXS with their same-sex typically developing biological sibling.Participants with FXS obtained significantly higher heart rates, lower vagal tone, and lower heart rate variability estimates both at baseline and during the social interaction session compared with their typically developing siblings. Although eye-gaze avoidance occurred at significantly higher levels in the children with FXS, this behavior decreased slightly over the course of the session (a "warm-up" effect) and did not seem to be associated with cardiovascular activity. In the girls with FXS, higher levels of the fragile X mental retardation protein were associated with higher (and more typical) heart rate variability.These data suggest that both sympathetic and parasympathetic nervous systems are dysregulated in FXS. However, given that prolonged exposure to social demands does not inevitably lead to increased anxiety or "hyperarousal," professionals should not be deterred from providing much needed social skills interventions for individuals with FXS.

  View details for DOI 10.1097/CHI.0b013e318195bd15

  View details for PubMedID 19182690

• A solution to limitations of cognitive testing in children with intellectual disabilities: the case of fragile X syndrome JOURNAL OF NEURODEVELOPMENTAL DISORDERS Hessl, D., Nguyen, D. V., Green, C., Chavez, A., Tassone, F., Hagerman, R. J., Senturk, D., Schneider, A., Lightbody, A., Reiss, A. L., Hall, S. 2009; 1 (1): 33-45

  Abstract

  Intelligence testing in children with intellectual disabilities (ID) has significant limitations. The normative samples of widely used intelligence tests, such as the Wechsler Intelligence Scales, rarely include an adequate number of subjects with ID needed to provide sensitive measurement in the very low ability range, and they are highly subject to floor effects. The IQ measurement problems in these children prevent characterization of strengths and weaknesses, poorer estimates of cognitive abilities in research applications, and in clinical settings, limited utility for assessment, prognosis estimation, and planning intervention. Here, we examined the sensitivity of the Wechsler Intelligence Scale for Children (WISC-III) in a large sample of children with fragile X syndrome (FXS), the most common cause of inherited ID. The WISC-III was administered to 217 children with FXS (age 6-17 years, 83 girls and 134 boys). Using raw norms data obtained with permission from the Psychological Corporation, we calculated normalized scores representing each participant's actual deviation from the standardization sample using a z-score transformation. To validate this approach, we compared correlations between the new normalized scores versus the usual standard scores with a measure of adaptive behavior (Vineland Adaptive Behavior Scales) and with a genetic measure specific to FXS (FMR1 protein or FMRP). The distribution of WISC-III standard scores showed significant skewing with floor effects in a high proportion of participants, especially males (64.9%-94.0% across subtests). With the z-score normalization, the flooring problems were eliminated and scores were normally distributed. Furthermore, we found correlations between cognitive performance and adaptive behavior, and between cognition and FMRP that were very much improved when using these normalized scores in contrast to the usual standardized scores. The results of this study show that meaningful variation in intellectual ability in children with FXS, and probably other populations of children with neurodevelopmental disorders, is obscured by the usual translation of raw scores into standardized scores. A method of raw score transformation may improve the characterization of cognitive functioning in ID populations, especially for research applications.

  View details for DOI 10.1007/s11689-008-9001-8

  View details for Web of Science ID 000274727000004

  View details for PubMedID 19865612

  View details for PubMedCentralID PMC2768415

• The neural basis of auditory temporal discrimination in girls with fragile X syndrome JOURNAL OF NEURODEVELOPMENTAL DISORDERS Hall, S. S., Walter, E., Sherman, E., Hoeft, F., Reiss, A. L. 2009; 1 (1): 91-99

  Abstract

  Fragile X syndrome (FXS) is a common genetic disorder in which temporal processing may be impaired. To our knowledge however, no studies have examined the neural basis of temporal discrimination in individuals with FXS using functional magnetic resonance imaging (fMRI). Ten girls with fragile X syndrome and ten developmental age-matched typically developing controls performed an auditory temporal discrimination task in a 3T scanner. Girls with FXS showed significantly greater brain activation in a left-lateralized network, comprising left medial frontal gyrus, left superior and middle temporal gyrus, left cerebellum, and left brainstem (pons), when compared to a developmental age-matched typically developing group of subjects who had similar in-scanner task performance. There were no regions that showed significantly greater brain activation in the control group compared to individuals with FXS. These data indicate that networks of brain regions involved in auditory temporal processing may be dysfunctional in FXS. In particular, it is possible that girls with FXS employ left hemispheric resources to overcompensate for relative right hemispheric dysfunction.

  View details for DOI 10.1007/s11689-009-9007-x

  View details for Web of Science ID 000274727000008

  View details for PubMedID 19890439

  View details for PubMedCentralID PMC2772079

• TREATMENTS FOR FRAGILE X SYNDROME: A CLOSER LOOK AT THE DATA DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS Hall, S. S. 2009; 15 (4): 353-360

  Abstract

  Research into the determinants and developmental course of fragile X syndrome (FXS) has made remarkable progress over the last 25 years. However, treatments to ameliorate the symptoms of FXS have been less forthcoming. While there is optimism in the field that the pace of intervention research is quickening, there has been a bias toward psychopharmacological approaches to treatment. A closer look at the data from those investigations reveals a paucity of evidence that medications can improve intellectual and adaptive functioning in FXS, or decrease associated behavioral and/or emotional issues. Work in other related disorders (e.g., autism) has shown that dramatic improvements in intellectual and adaptive functioning, as well as behavioral and emotional problems, can occur if intensive behavioral treatment is begun early in the child's life. It is hoped that future research efforts will evaluate these intensive early intervention strategies in children with FXS, perhaps in combination with pharmacological approaches.

  View details for DOI 10.1002/ddrr.78

  View details for Web of Science ID 000273207500011

  View details for PubMedID 20014373

  View details for PubMedCentralID PMC2898566

• Behavioural phenotype of Cornelia de Lange syndrome: case-control study BRITISH JOURNAL OF PSYCHIATRY Oliver, C., Arron, K., Sloneem, J., Hall, S. 2008; 193 (6): 466-470

  Abstract

  Cornelia de Lange syndrome is associated with abnormalities on chromosomes 5, 10 and X.To delineate the behavioural phenotype of Cornelia de Lange syndrome with specific reference to autistic-spectrum disorder.A total of 54 individuals with Cornelia de Lange syndrome (mean age 13.88 years; s.d.=8.58) and 46 comparable individuals with intellectual disability (mean age 13.74 years; s.d.=7.99) were assessed on measures of autistic-spectrum disorder, and adaptive, compulsive and disordered behaviour.There was no difference between the groups in global behaviour disorder. Severe autism was significantly more prevalent in the syndrome group (32.1%) than the comparison group (7.1%). In addition, the syndrome group also evidenced significantly higher levels of compulsive behaviour.These data suggest that autistic-spectrum disorder is part of the behavioural phenotype of Cornelia de Lange syndrome and that compulsive behaviours are evident. Future research should investigate this behavioural phenotype using contemporary diagnostic algorithms for autism with detailed examination of the phenomenology of compulsive behaviours.

  View details for DOI 10.1192/bjp.bp.107.044370

  View details for Web of Science ID 000261574600008

  View details for PubMedID 19043149

• Aberrant Brain Activation During Gaze Processing in Boys With Fragile X Syndrome ARCHIVES OF GENERAL PSYCHIATRY Watson, C., Hoeft, F., Garrett, A. S., Hall, S. S., Reiss, A. L. 2008; 65 (11): 1315-1323

  Abstract

  Eye contact is a fundamental component of human social behavior. Individuals with fragile X syndrome (fraX), particularly male subjects, avoid eye contact and display other social deficits. To date (to our knowledge), this behavior in fraX has been studied only in female subjects, who show lesser degrees of gaze aversion.To determine the neural correlates of the perception of direct eye gaze in adolescent boys with fraX using functional magnetic resonance imaging.Cross-sectional study.Academic medical center.Thirteen adolescent boys with fraX, 10 boys with developmental delay, and 13 typically developing control subjects.Behavioral performance and brain activation during functional magnetic resonance imaging were evaluated during the presentation of faces with eye gaze directed to or averted away from subjects and during successive presentations of stimuli with eye gaze directed toward the subject. Whole-brain and region of interest analyses and regression analyses with task performance were performed.Significantly greater activation was observed in prefrontal cortices in controls compared with boys having fraX, who (in contrast) demonstrated elevated left insula activation to direct eye gaze stimuli. Furthermore, compared with controls, boys with fraX showed greater sensitization in the left amygdala with successive exposure to direct gaze.Compared with controls, boys with fraX display distinct patterns of brain activation in response to direct eye gaze. These results suggest that aberrant neural processing of direct eye gaze in subjects with fraX may be related to the associated avoidant response.

  View details for Web of Science ID 000260600300009

  View details for PubMedID 18981343

• Longitudinal changes in intellectual development in children with Fragile X syndrome JOURNAL OF ABNORMAL CHILD PSYCHOLOGY Hall, S. S., Burns, D. D., Lightbody, A. A., Reiss, A. L. 2008; 36 (6): 927-939

  Abstract

  Structural equation modeling (SEM) was used to examine the development of intellectual functioning in 145 school-age pairs of siblings. Each pair included one child with Fragile X syndrome (FXS) and one unaffected sibling. All pairs of children were evaluated on the Wechsler Intelligence Scale for Children-Third Edition (WISC-III) at time 1 and 80 pairs of children received a second evaluation at time 2 approximately 4 years later. Compared to their unaffected siblings, children with FXS obtained significantly lower percentage correct scores on all subtests of the WISC at both time points. During the time between the first and second assessments, the annual rate of intellectual development was approximately 2.2 times faster in the unaffected children compared to the children with FXS. Levels of the fragile X mental retardation protein (FMRP) were highly associated with intellectual ability scores of the children with FXS at both time points (r=0.55 and 0.64 respectively). However, when gender, age, and the time between assessments were included as covariates in the structural equation model, FMRP accounted for only 5% of the variance in intellectual ability scores at time 1 and 13% of the variance at time 2. The results of this study suggest that slower learning contributes to the low and declining standardized IQ scores observed in children with FXS.

  View details for DOI 10.1007/s10802-008-9223-y

  View details for Web of Science ID 000257726600010

  View details for PubMedID 18347972

• Health and sleep problems in Cornelia de Lange Syndrome: a case control study JOURNAL OF INTELLECTUAL DISABILITY RESEARCH Hall, S. S., Arron, K., Sloneem, J., Oliver, C. 2008; 52: 458-468

  Abstract

  Self-injury, sleep problems and health problems are commonly reported in Cornelia de Lange Syndrome (CdLS) but there are no comparisons with appropriately matched participants. The relationship between these areas and comparison to a control group is warranted.54 individuals with CdLS were compared with 46 participants with intellectual disability (ID) of mixed aetiology who were similar in terms of degree of ID, mobility, age and gender using informant-based measures of health problems, sleep and self-injury.Participants with CdLS experienced significantly more current and lifetime health problems with eye problems and gastrointestinal disorders prominent. Although 55% of those with CdLS experienced sleep problems this prevalence was not different from the comparison group. Sleep disorder was not associated with self-injury in the CdLS group, skin problems were associated with severity of self-injury but not presence.People with CdLS experience a range of significant health problems and have more health concerns than others with the same degree of ID. Although this has been well documented in the past, the current high prevalence of health concerns indicates the need for regular health assessment and appropriate intervention.

  View details for DOI 10.1111/j.1365-2788.2008.01047.x

  View details for Web of Science ID 000254990800009

  View details for PubMedID 18341525

• Compulsive, self-injurious, and autistic behavior in children and adolescents with fragile X syndrome AMERICAN JOURNAL ON MENTAL RETARDATION Hall, S. S., Lightbody, A. A., Reiss, A. L. 2008; 113 (1): 44-53

  Abstract

  Compulsive, self-injurious, and autistic behaviors were examined in 31 boys and 29 girls with fragile X syndrome aged 5 to 20 years. Self-injurious behavior occurred in 58% of boys and 17% of girls, whereas compulsive behavior occurred in 72% of boys and 55% of girls and did not appear to be associated with self-injurious behavior. Fifty percent of boys and 20% of girls met diagnostic criteria for autism on the ADOS-G. Girls who showed compulsive behavior had lower levels of FMRP than girls who did not show compulsive behavior, and boys with autistic symptoms had lowered levels of cortisol. Taken together, these data suggest that autistic and compulsive behaviors are highly prevalent in fragile X syndrome and that lowered levels of FMRP and cortisol may be biological markers for these behaviors.

  View details for Web of Science ID 000252702800004

  View details for PubMedID 18173299

• Neuroanatomy of fragile X syndrome is associated with aberrant behavior and the fragile X mental retardation protein (FMRP) ANNALS OF NEUROLOGY Gothelf, D., Furfaro, J. A., Hoeft, F., Eckert, M. A., Hall, S. S., O'Hara, R., Erba, H. W., Ringel, J., Hayashi, K. M., Patnaik, S., Golianu, B., Kraemer, H. C., Thompson, P. M., Piven, J., Reiss, A. L. 2008; 63 (1): 40-51

  Abstract

  To determine how neuroanatomic variation in children and adolescents with fragile X syndrome is linked to reduced levels of the fragile X mental retardation-1 protein and to aberrant cognition and behavior.This study included 84 children and adolescents with the fragile X full mutation and 72 typically developing control subjects matched for age and sex. Brain morphology was assessed with volumetric, voxel-based, and surface-based modeling approaches. Intelligence quotient was evaluated with standard cognitive testing, whereas abnormal behaviors were measured with the Autism Behavior Checklist and the Aberrant Behavior Checklist.Significantly increased size of the caudate nucleus and decreased size of the posterior cerebellar vermis, amygdala, and superior temporal gyrus were present in the fragile X group. Subjects with fragile X also demonstrated an abnormal profile of cortical lobe volumes. A receiver operating characteristic analysis identified the combination of a large caudate with small posterior cerebellar vermis, amygdala, and superior temporal gyrus as distinguishing children with fragile X from control subjects with a high level of sensitivity and specificity. Large caudate and small posterior cerebellar vermis were associated with lower fragile X mental retardation protein levels and more pronounced cognitive deficits and aberrant behaviors.Abnormal development of specific brain regions characterizes a neuroanatomic phenotype associated with fragile X syndrome and may mediate the effects of FMR1 gene mutations on the cognitive and behavioral features of the disorder. Fragile X syndrome provides a model for elucidating critical linkages among gene, brain, and cognition in children with serious neurodevelopmental disorders.

  View details for DOI 10.1002/ana.21243

  View details for Web of Science ID 000253008700007

  View details for PubMedID 17932962

  View details for PubMedCentralID PMC2773141

• Fragile X syndrome: Assessment and treatment implications CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA Reiss, A. L., Hall, S. S. 2007; 16 (3): 663-?

  Abstract

  Fragile X syndrome (FraX) is the most common known cause of inherited mental impairment. FMR1 gene mutations, the cause of FraX, lead to reduced expression of FMR1 protein and an increased risk for a particular profile of cognitive, behavioral, and emotional dysfunction. The study of individuals with FraX provides a unique window of understanding into important disorders such as autism, social phobia, cognitive disability, and depression. This review highlights the typical phenotypic features of individuals with FraX, discussing the apparent strengths and weaknesses in intellectual functioning, as evidenced from longitudinal follow-up studies. It also discusses recent neuroanatomic findings that may pave the way for more focused disease-specific pharmacologic and behavioral interventions. This article describes the results of recent medication trials designed to target symptoms associated with FraX. It also describes some recent behavioral interventions that were conducted in our laboratory.

  View details for DOI 10.1016/j.chc.2007.03.001

  View details for Web of Science ID 000247944400010

  View details for PubMedID 17562585

• Fronto-striatal dysfunction and potential compensatory mechanisms in male adolescents with fragile X syndrome HUMAN BRAIN MAPPING Hoeft, F., Hernandez, A., Parthasarathy, S., Watson, C. L., Hall, S. S., Reiss, A. L. 2007; 28 (6): 543-554

  Abstract

  Response inhibition is an important facet of executive function. Fragile X syndrome (FraX), with a known genetic etiology (fragile X mental retardation-1 (FMR1) mutation) and deficits in response inhibition, may be an ideal condition for elucidating interactions among gene-brain-behavior relationships. Functional magnetic resonance imaging (fMRI) studies have shown evidence of aberrant neural activity when individuals with FraX perform executive function tasks, though the specific nature of this altered activity or possible compensatory processes has yet to be elucidated. To address this question, we examined brain activation patterns using fMRI during a go/nogo task in adolescent males with FraX and in controls. The critical comparison was made between FraX individuals and age, gender, and intelligent quotient (IQ)-matched developmentally delayed controls; in addition to a control group of age and gender-matched typically developing individuals. The FraX group showed reduced activation in the right ventrolateral prefrontal cortex (VLPFC) and right caudate head, and increased contralateral (left) VLPFC activation compared with both control groups. Individuals with FraX, but not controls, showed a significant positive correlation between task performance and activation in the left VLPFC. This potential compensatory activation was predicted by the interaction between FMR1 protein (FMRP) levels and right striatal dysfunction. These results suggest that right fronto-striatal dysfunction is likely an identifiable neuro-phenotypic feature of FraX and that activation of the left VLPFC during successful response inhibition may reflect compensatory processes. We further show that these putative compensatory processes can be predicted by a complex interaction between genetic risk and neural function.

  View details for DOI 10.1002/hbm.20406

  View details for Web of Science ID 000246628900009

  View details for PubMedID 17437282

• Modeling family dynamics in children with fragile X syndrome JOURNAL OF ABNORMAL CHILD PSYCHOLOGY Hall, S. S., Burns, D. D., Reiss, A. L. 2007; 35 (1): 29-42

  Abstract

  Few studies have examined the impact of children with genetic disorders and their unaffected siblings on family functioning. In this study, the reciprocal causal links between problem behaviors and maternal distress were investigated in 150 families containing a child with fragile X syndrome (FXS) and an unaffected sibling. Both children's behavior problems appeared to have strong, direct effects on maternal distress, but maternal distress did not appear to have any reciprocal causal effects on either child's behavior problems. Surprisingly, there were no significant differences in the effects of the two children's behavior problems on maternal distress. These data suggest that the problem behaviors of children with FXS, as well as their unaffected siblings, can have a substantial and additive impact on maternal depression and anxiety. Future research efforts should employ longitudinal research designs to confirm these findings.

  View details for DOI 10.1007/s10802-006-9081-4

  View details for Web of Science ID 000244835500003

  View details for PubMedID 17165142

• 3D pattern of brain abnormalities in Fragile X syndrome visualized using tensor-based morphometry NEUROIMAGE Lee, A. D., Leow, A. D., Lu, A., Reiss, A. L., Hall, S., Chiang, M., Toga, A. W., Thompson, P. M. 2007; 34 (3): 924-938

  Abstract

  Fragile X syndrome (FraX), a genetic neurodevelopmental disorder, results in impaired cognition with particular deficits in executive function and visuo-spatial skills. Here we report the first detailed 3D maps of the effects of the Fragile X mutation on brain structure, using tensor-based morphometry. TBM visualizes structural brain deficits automatically, without time-consuming specification of regions-of-interest. We compared 36 subjects with FraX (age: 14.66+/-1.58 S.D., 18 females/18 males), and 33 age-matched healthy controls (age: 14.67+/-2.2 S.D., 17 females/16 males), using high-dimensional elastic image registration. All 69 subjects' 3D T1-weighted brain MRIs were spatially deformed to match a high-resolution single-subject average MRI scan in ICBM space, whose geometry was optimized to produce a minimal deformation target. Maps of the local Jacobian determinant (expansion factor) were computed from the deformation fields. Statistical maps showed increased caudate (10% higher; p = 0.001) and lateral ventricle volumes (19% higher; p = 0.003), and trend-level parietal and temporal white matter excesses (10% higher locally; p = 0.04). In affected females, volume abnormalities correlated with reduction in systemically measured levels of the Fragile X mental retardation protein (FMRP; Spearman's r < -0.5 locally). Decreased FMRP correlated with ventricular expansion (p = 0.042; permutation test), and anterior cingulate tissue reductions (p = 0.0026; permutation test) supporting theories that FMRP is required for normal dendritic pruning in fronto-striatal-limbic pathways. No sex differences were found; findings were confirmed using traditional volumetric measures in regions of interest. Deficit patterns were replicated by performing statistics after logarithmic transformation, which may be more appropriate for tensor-valued data. Investigation of how these anomalies emerge over time will accelerate our understanding of FraX and its treatment.

  View details for DOI 10.1016/j.neuroimage.2006.09.043

  View details for Web of Science ID 000243758700007

  View details for PubMedID 17161622

  View details for PubMedCentralID PMC1995408

• Social escape behaviors in children with fragile X syndrome 30th Annual Meeting of the Association-for-Behavior-Analysis Hall, S., DeBernardis, M., Reiss, A. SPRINGER/PLENUM PUBLISHERS. 2006: 935–47

  Abstract

  Social escape behavior is a common behavioral feature of individuals with fragile X syndrome (fraX). In this observational study, we examined the effect of antecedent social and performance demands on problem behaviors in four conditions: face-to-face interview, silent reading, oral reading and a singing task. Results showed that problem behaviors were significantly more likely to occur during the interview and singing conditions. Higher levels of salivary cortisol were predictive of higher levels of fidgeting behavior and lower levels of eye contact in male participants. There were no associations between level of FMRP expression and social escape behaviors. These data suggest that specific antecedent biological and environmental factors evoke social escape behaviors in fragile X syndrome.

  View details for DOI 10.1007/s10803-006-0132-z

  View details for Web of Science ID 000241171600011

  View details for PubMedID 16897394

• The acquisition of stimulus equivalence in individuals with fragile X syndrome JOURNAL OF INTELLECTUAL DISABILITY RESEARCH Hall, S. S., DeBernardis, G. M., Reiss, A. L. 2006; 50: 643-651

  Abstract

  Few studies have employed stimulus equivalence procedures to teach individuals with intellectual disabilities (IDs) new skills. To date, no studies of stimulus equivalence have been conducted in individuals with fragile X syndrome (FXS), the most common known cause of inherited ID.Five adolescents with FXS were taught basic math and geography skills by using a computerized stimulus equivalence training programme administered over 2 days in 2-h sessions.Four of the five participants learned the math relations, with one participant demonstrating stimulus equivalence at post-test. Three of the five participants learned the geography relations, with all three of these participants demonstrating stimulus equivalence at post-test.These data indicate that computerized stimulus equivalence procedures, conducted in time-limited sessions, may help individuals with FXS learn new skills. Hypotheses concerning the failure of some participants to learn the training relations and to demonstrate stimulus equivalence at post-test are discussed.

  View details for DOI 10.1111/j.1365-2788.2006.00814.x

  View details for Web of Science ID 000239258100003

  View details for PubMedID 16901291

• Chronological age, but not FMRP levels, predicts neuropsychological performance in girls with fragile X syndrome AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS Lightbody, A. A., Hall, S. S., Reiss, A. L. 2006; 141B (5): 468-472

  Abstract

  The effect of FMRP levels and chronological age on executive functioning, visual-spatial abilities ,and verbal fluency tasks were examined in 46 school-age girls with fragile X syndrome (FXS). Results indicated that FMRP levels were not predictive of outcome on the neuropsychological tests but that performance on the executive functioning task tended to worsen with chronological age. This age effect was not observed on the tests of visual-spatial abilities or verbal fluency. These data indicate that relative deficits in executive functioning in girls with FXS become more pronounced with age. In contrast, the relative deficits in spatial and verbal abilities of these girls did not appear to increase with age, suggesting that these abilities may be spared.

  View details for DOI 10.1002/ajmg.b.30307

  View details for Web of Science ID 000238622300006

  View details for PubMedID 16741913

  View details for PubMedCentralID PMC2663575

• Effects of social context on social interaction and self-injurious behavior in Cornelia de Lange syndrome AMERICAN JOURNAL ON MENTAL RETARDATION Oliver, C., Arron, K., Hall, S., Sloneem, J., Forman, D., McClintock, K. 2006; 111 (3): 184-192

  Abstract

  Cornelia de Lange syndrome is reported to be associated with self-injurious behavior (SIB) and social avoidance. We used analog methodology to examine the effect of manipulating adult social contact on social communicative behaviors and SIB in 16 children with this syndrome. For 9 participants engagement behavior was related to levels of adult attention, and SIB showed significant variability across conditions for 3 participants. These findings indicate that SIB can be affected by environmental factors, even though it is thought to be part of the behavioral phenotype of Cornelia de Lange syndrome and suggest that individuals with this syndrome show socially motivated attention-soliciting behaviors. The implications for gene-environment interactions are discussed.

  View details for Web of Science ID 000237836200003

  View details for PubMedID 16597185

• Comparing descriptive, experimental and informant-based assessments of problem behaviors 29th Annual Meeting of the Association-for-Behavior-Analysis Hall, S. S. PERGAMON-ELSEVIER SCIENCE LTD. 2005: 514–26

  Abstract

  In this study, the outcomes of descriptive, experimental and informant-based methods of functional assessment were compared in four individuals with developmental disabilities who showed problem behaviors. Results indicated that the descriptive and experimental assessments were concordant in only one of the four cases whilst informant-based and experimental assessments were concordant in three of the four cases. The descriptive assessment identified thin schedules of attention in all cases. These results appear to question the usefulness of employing descriptive assessments for problem behaviors either as an adjunct or replacement for experimental assessments, particularly given their time-consuming nature.

  View details for DOI 10.1016/j.ridd.2004.11.004

  View details for Web of Science ID 000234062600002

  View details for PubMedID 16303582

• Effects of increasing task load on memory impairment in adults with Down syndrome AMERICAN JOURNAL ON MENTAL RETARDATION Oliver, C., Holland, T., Hall, S., Crayton, L. 2005; 110 (5): 339-345

  Abstract

  The effect of increasing the number of stimuli to be recalled was investigated to evaluate whether sensitivity for memory impairment was enhanced in adults with Down syndrome when using higher task load. Three levels of load were compared across three groups of adults: those with cognitive deterioration, no cognitive deterioration over age 40, and no cognitive-deterioration under 40. The cognitive-deterioration group showed impaired performance in comparison to the no cognitive-deterioration-40+ group at all levels of task load, with performance declining over 4 years. The no cognitive-deterioration-40+ group showed no impairment in performance compared to no cognitive-deterioration-under 40 group, except when task load was high. Implications for identification of dementia and age-related cognitive change are discussed.

  View details for Web of Science ID 000231766200002

  View details for PubMedID 16080772

• The early development of self-injurious behaviour: evaluating the role of social reinforcement JOURNAL OF INTELLECTUAL DISABILITY RESEARCH Oliver, C., Hall, S., Murphy, G. 2005; 49: 591-599

  Abstract

  The potential role of social reinforcement in the development of self-injury has not yet been subjected to empirical analysis. In this 2-year prospective study, the pattern of social interactions related to the early presentation of self-injury were examined to identify a potential association with an increase in self-injury.The self-injurious behaviour and social contact with adults of 16 children with intellectual disability (ID) with self-injury of recent onset were observed at 3-month intervals over 2 years.Increase in self-injury over a 2-year period was positively correlated with a distribution of social contact relative to episodes of self-injury that is consistent with a mutual social reinforcement paradigm. When this paradigm was operative, self-injury was evoked under stable antecedent conditions over time but tended to evoke increasing levels of social interaction.These results support the hypothesis that increases in the frequency of early self-injury in children with ID may be determined by social reinforcement with implications for early intervention and proactive identification of children at risk for increases in self-injury.

  View details for DOI 10.1111/j.1365-2788.2005.00694.x

  View details for Web of Science ID 000230290100002

  View details for PubMedID 16011552

• The association between environmental events and self-injurious behaviour in Cornelia de Lange syndrome JOURNAL OF INTELLECTUAL DISABILITY RESEARCH Moss, J., Oliver, C., Hall, S., Arron, K., Sloneem, J., Petty, J. 2005; 49: 269-277

  Abstract

  There has been limited empirical research into the environmental causes of self-injury in Cornelia de Lange syndrome. The present study examined the variability of self-injurious behaviour in Cornelia de Lange syndrome across environmental setting events. Additionally, the association between setting events and more specific environmental events was examined.A descriptive analysis of observational data on eight children with Cornelia de Lange syndrome aged between 4 and 14 years was carried out. The association between self-injurious behaviour and four environmental setting events and between specific environmental events and setting events was examined using established statistical methods for observational data.Seven out of eight of the participants showed at least one form of self-injurious behaviour that was associated with a particular setting event. The study also demonstrated that the relationship between setting events and environmental events is extremely variable across individuals.Self-injurious behaviour in some individuals with Cornelia de Lange syndrome is associated with environmental events although the precise nature of the association warrants clarification. Using broad setting events as a methodological tool in isolation provides some insight into the role of specific environmental factors in maintaining self-injurious behaviour but the integrity of setting events must be established.

  View details for Web of Science ID 000227721500006

  View details for PubMedID 15816814

• A reply to Uttal (2004) BEHAVIOR ANALYST Mobbs, D., Hall, S. 2005; 28 (1): 77-79

  View details for DOI 10.1007/BF03392106

  View details for Web of Science ID 000229603900007

  View details for PubMedID 22478442

  View details for PubMedCentralID PMC2755349

• Structural and environmental characteristics of stereotyped behaviors AMERICAN JOURNAL ON MENTAL RETARDATION Hall, S., Thorns, T., Oliver, C. 2003; 108 (6): 391-402

  Abstract

  Structural and environmental characteristics of multiple topographies of stereotypic behaviors shown by 8 individuals with developmental disabilities are described. Analysis of structural characteristics show that the parameters of stereotyped behavior (percentage of time, bout length, and bout length variability) were highly correlated. Analysis of the influence of environmental variables indicated that topographies of stereotyped behaviors were more likely to occur under conditions of low stimulation and less likely during conditions involving social contact. Individuals whose stereotyped behaviors were less influenced by environmental factors were more likely to engage in them for greater periods of time. Results suggest that an examination of individual topographies of stereotyped behaviors and their structural and environmental characteristics may provide useful insights for understanding the origins of these behaviors.

  View details for Web of Science ID 000186297000003

  View details for PubMedID 14561109

• Descriptive functional analysis of behavioral excesses shown by adults with Down syndrome and dementia INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY Millichap, D., Oliver, C., McQuillan, S., Kalsy, S., Lloyd, V., Hall, S. 2003; 18 (9): 844-854

  Abstract

  The study examined the hypothesis that a functional relationship exists between social environmental events and behavioral excesses in individuals with Down syndrome and dementia.A case-series design was employed (n = 4) using an direct observation-based descriptive functional assessment procedure.Observations were conducted in the natural environments of four participants over periods ranging from 11 to 15.4 hours. Data were collected on non-verbal and verbal behavioral excesses, appropriate engagement and verbal interaction with others. Social environmental events observed including both staff and peer behavior.Analysis of co-occurrence for behavioral excesses and social environmental events indicated significant relationships for some behaviours consistent with operant reinforcement processes. Sequential analysis showed that changes in the probability of social contact occurred in the period directly preceding and following verbal behaviors.Results support the hypothesis that, consistent with literature for older adults with dementia in the general population, some behavioral excesses were functional in nature and not randomly occurring events. No relationship was found between appropriate engagement and staff contact. Evidence of the functional nature of target behavioral excesses indicates that behavioral interventions have potential for this client group.

  View details for DOI 10.1002/gps.930

  View details for Web of Science ID 000185363100011

  View details for PubMedID 12949853

• Risk markers associated with challenging behaviours in people with intellectual disabilities: a meta-analytic study JOURNAL OF INTELLECTUAL DISABILITY RESEARCH McClintock, K., Hall, S., Oliver, C. 2003; 47: 405-416

  Abstract

  A meta-analysis of prevalence and cohort studies conducted over the last 30 years was carried out to identify risk markers for challenging behaviour shown by individuals with intellectual disabilities (IDs). A total of 86 potential studies was identified from the review, with 22 (25.6%) containing sufficient data to enable a statistical analysis to be conducted. Results indicated that males were significantly more likely to show aggression than females, and that individuals with a severe/profound degree of ID were significantly more likely to show self-injury and stereotypy than individuals with a mild/moderate degree of ID. Individuals with a diagnosis of autism were significantly more likely to show self-injury, aggression and disruption to the environment whilst individuals with deficits in receptive and expressive communication were significantly more likely to show self-injury. In most cases, tests for heterogeneity were statistically significant, as expected. The meta-analysis highlighted the paucity of methodologically robust studies of risk markers for challenging behaviours and the lack of data on incidence, prevalence and chronicity of challenging behaviour in this population.

  View details for Web of Science ID 000185203500001

  View details for PubMedID 12919191

• Phenomenology of self-restraint AMERICAN JOURNAL ON MENTAL RETARDATION Oliver, C., Murphy, G., Hall, S., Arron, K., Leggett, J. 2003; 108 (2): 71-81

  Abstract

  Self-restraint is often reported in individuals with mental retardation who show self-injurious behavior (SIB). In this study, the phenomenology and prevalence of self-restraint in individuals showing self-injury and wearing protective devices and those showing self-injury but not wearing protective devices were compared. A high prevalence of self-restraint in the whole sample of individuals showing self-injury was identified (67/88, 76.1%), and self-restraint was more prevalent in a group showing self-injury but not wearing protective devices (43/47, 91.5%) than in a group showing self-injury and wearing protective devices (24/41, 58.5%). Individuals not wearing protective devices showed a greater number of topographies of self-restraint than those who did wear them. Results are discussed with reference to the purely topographical definition of self-restraint employed and the potential equivalence of protective devices and self-restraint.

  View details for Web of Science ID 000181562900001

  View details for PubMedID 12564940

• Assessing the severity of challenging behaviour: Psychometric properties of the challenging behaviour interview JOURNAL OF APPLIED RESEARCH IN INTELLECTUAL DISABILITIES Oliver, C., McClintock, K., Hall, S., Smith, M., Dagnan, D., Stenfert-Kroese, B. 2003; 16 (1): 53-61

  View details for Web of Science ID 000181055200005

• Transitions between cooperative and non-cooperative responding in the 'Pigeon's Dilemma' Behavioural processes Hall, S. S. 2003; 60 (3): 199-208

  Abstract

  Two pigeons played Iterated Prisoner's Dilemma (IPD) against a simulated opponent pre-programmed to play 'Tit-For-Tat' (TFT) and 'Random' (RND) strategies. Each pigeon received differential amounts of access to food following choices of either 'cooperate' or 'defect' on a trial. After 1000 trials against TFT and 500 trials against RND, results indicated that choice allocation was optimal when the birds played against RND but was sub-optimal when the birds played against TFT. In order to determine why the pigeons responded suboptimally against TFT, a trial-by-trial analysis of the data was conducted. The analysis revealed that once a pigeon had received the 'Sucker's' payoff (S), it was more likely to defect and receive the 'Temptation' payoff (T) than to cooperate and receive the 'Reward' (R) payoff. Local reinforcement contingencies appear to determine suboptimal responding against TFT in the iterated Pigeon's Dilemma.

  View details for PubMedID 12505173

• Molecular analyses of the principal components of response strength JOURNAL OF THE EXPERIMENTAL ANALYSIS OF BEHAVIOR Killeen, P. R., Hall, S. S., Reilly, M. P., Kettle, L. C. 2002; 78 (2): 127-160

  Abstract

  Killeen and Hall (2001) showed that a common factor called strength underlies the key dependent variables of response probability, latency, and rate, and that overall response rate is a good predictor of strength. In a search for the mechanisms that underlie those correlations, this article shows that (a) the probability of responding on a trial is a two-state Markov process; (b) latency and rate of responding can be described in terms of the probability and period of stochastic machines called clocked Bernoulli modules, and (c) one such machine, the refractory Poisson process, provides a functional relation between the probability of observing a response during any epoch and the rate of responding. This relation is one of proportionality at low rates and curvilinearity at higher rates.

  View details for Web of Science ID 000177850900001

  View details for PubMedID 12216975

• Effects of environmental events on smiling and laughing behavior in Angelman syndrome AMERICAN JOURNAL ON MENTAL RETARDATION Oliver, C., Demetriades, L., Hall, S. 2002; 107 (3): 194-200

  Abstract

  Angelman syndrome is a neurogenetic disorder associated with unique behaviors and characteristics, including an unusually happy expression, inability to speak, ataxia, mental retardation, and abnormal EEG. Previous research has suggested that smiling and laughing behaviors in Angelman syndrome are inappropriate, excessive, and dissociated from contextual events. In the present study, the variability of smiling and laughing behaviors of 3 individuals with Angelman syndrome was examined across typical social contexts. Results indicate that laughing and smiling increased during social situations and occurred at low levels during non-social situations. The behaviors, therefore, did not occur totally inappropriately, as has been suggested. The findings illustrate the need to divert attention to the examination of environmental influences on purported phenotypic behavior in genetic syndromes.

  View details for Web of Science ID 000175518200004

  View details for PubMedID 11966332

• Self-injurious behavior, self-restraint, and compulsive Behaviors in Cornelia de Lange syndrome AMERICAN JOURNAL ON MENTAL RETARDATION Hyman, P., Oliver, C., Hall, S. 2002; 107 (2): 146-154

  Abstract

  Researchers have argued that individuals who show self-restraint are more likely to show self-injurious behavior (SIB) that is compulsive. Self-injurious behavior, self-restraint, and compulsive behaviors have been described as features of Cornelia de Lange syndrome. We examined whether individuals with this syndrome displaying SIB and self-restraint exhibit more compulsive behaviors than do those without SIB and self-restraint. Main caregivers of individuals with the syndrome completed questionnaires. A significant association was found between SIB and self-restraint, and those displaying both behaviors displayed significantly more compulsions than did those not exhibiting them. Findings extend the compulsive behavior theory and highlight areas for further research.

  View details for Web of Science ID 000174135100008

  View details for PubMedID 11853532

• Descriptive analysis of self-injurious behaviour and self-restraint JOURNAL OF APPLIED RESEARCH IN INTELLECTUAL DISABILITIES Forman, D., Hall, S., Oliver, C. 2002; 15 (1): 1-7

  View details for Web of Science ID 000174486000001

• Self-injurious behaviour in young children with Lesch-Nyhan syndrome DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY Hall, S., Oliver, C., Murphy, G. 2001; 43 (11): 745-749

  Abstract

  The early development of self-injurious behaviour in three young boys (aged 17, 25, and 30 months at start of study) with Lesch-Nyhan syndrome was examined by means of parental interviews and by direct observations completed at 3 to 4 monthly intervals over an 18-month period. Results suggest that the self-injury began in a different way from that of other young children with autism and/or developmental disabilities in that, from the start, self-injurious responses were sudden and violent, rather than emerging gradually over time. Drastic measures, such as removal of the teeth or provision of tooth guards, were often taken to prevent further tissue damage. Direct observations showed that the boys' self-injury occurred at lower rates, but their carers were highly concerned about the behaviour. Sequential analysis of the observational data indicated that on some occasions the children were more likely to self-injure during periods of low social interaction, suggesting that their self-injury may have been influenced by environmental factors. The theoretical and practical implications of these findings are discussed.

  View details for Web of Science ID 000172366500005

  View details for PubMedID 11730148

• Effects of social proximity on multiple aggressive behaviors JOURNAL OF APPLIED BEHAVIOR ANALYSIS Oliver, C., Oxener, G., Hearn, M., Hall, S. 2001; 34 (1): 85-88

  Abstract

  We systematically manipulated social proximity to examine its influence on multiple topographies of aggression. Aggression occurred at high levels during close-proximity sessions and at low levels during distant-proximity sessions even though social contact was presented continuously during both conditions. Topographies of aggression emerged sequentially across the close-proximity sessions, and all topographies were reduced to zero following extended sessions of this condition.

  View details for Web of Science ID 000167649500011

  View details for PubMedID 11317994

• The principal components of response strength JOURNAL OF THE EXPERIMENTAL ANALYSIS OF BEHAVIOR Killeen, P. R., Hall, S. S. 2001; 75 (2): 111-134

  Abstract

  As Skinner (1938) described it, response strength is the "state of the reflex with respect to all its static properties" (p. 15), which include response rate, latency, probability, and persistence. The relations of those measures to one another was analyzed by probabilistically reinforcing, satiating, and extinguishing pigeons' key pecking in a trials paradigm. Reinforcement was scheduled according to variable-interval, variable-ratio, and fixed-interval contingencies. Principal components analysis permitted description in terms of a single latent variable, strength, and this was validated with confirmatory factor analyses. Overall response rate was an excellent predictor of this state variable.

  View details for Web of Science ID 000168966500001

  View details for PubMedID 11394483

• Early development of self-injurious behavior: An empirical study AMERICAN JOURNAL ON MENTAL RETARDATION Hall, S., Oliver, C., Murphy, G. 2001; 106 (2): 189-199

  Abstract

  The early development of SIB in young children with developmental disabilities was examined by tracking over an 18-month period 16 school-age children who had recently started to show early SIB. Naturalistic observations were conducted in each child's classroom every 3 months, and the association between early SIB and environmental events was examined. Results showed that for the 4 children whose early SIB had escalated over this period, there was a significant association between early SIB and low levels of social contact across observation points, supporting models of the development of SIB. This association might be considered as a risk marker for the exacerbation of SIB. Implications of this finding for targeting early interventions for SIB are discussed.

  View details for Web of Science ID 000167861400008

  View details for PubMedID 11321609

• Cognitive deterioration in adults with Down syndrome: Effects on the individual, caregivers, and service use AMERICAN JOURNAL ON MENTAL RETARDATION Oliver, C., Crayton, L., Holland, A., Hall, S. 2000; 105 (6): 455-465

  Abstract

  Individuals with Down syndrome (N = 49) who had participated in serial neuropsychological assessments were assigned to one of three groups comparable in level of premorbid mental retardation: those showing cognitive deterioration, those comparable in age but not showing cognitive deterioration, and those not showing cognitive deterioration but younger. Those experiencing cognitive deterioration were less likely to receive day services, had more impoverished life experiences, and required more support compared to groups without cognitive deterioration. When age was controlled for, cognitive deterioration was significantly positively associated with caregiver difficulties and service use and negatively associated with life experiences for the individual. Results suggest a potential role for caregiver difficulties in influencing life experiences of adults with Down syndrome showing cognitive decline.

  View details for Web of Science ID 000165585400002

  View details for PubMedID 11958199

• Aggression and the termination of "rituals": a new variant of the escape function for challenging behavior? RESEARCH IN DEVELOPMENTAL DISABILITIES Murphy, G., MacDonald, S., Hall, S., Oliver, C. 2000; 21 (1): 43-59

  Abstract

  Aggression and stereotyped behaviors are not uncommon among people with intellectual disabilities and they are often treated separately as operant behaviors. In this single case study, it is argued that the function of a young woman's aggressive behavior appeared to be that of avoiding or escaping the termination of a chain of complex stereotyped behavior (or "ritual"). She became aggressive only when this chain of stereotyped behavior was terminated and the aggression appeared to extinguish when it no longer led to escape from the termination of the "ritual". It is suggested that this is an example of a complex interaction between two behaviors and that it illustrates the need for very careful analysis of the functions of challenging behavior. Furthermore, it is proposed that the lengthening list of variables already documented as determinants of challenging behavior (provision of attention (verbal and physical), mechanical restraint, sensory or tangible events, escape from demands or from social attention, denials, escape from intrusive medical procedures, escape from task difficulty) be lengthened to include the possibility of escape from (or avoidance of) the interruption of a chain of complex stereotyped behavior or "ritual".

  View details for Web of Science ID 000086123500004

  View details for PubMedID 10750165

• Identification of early self-injurious behaviour in young children with intellectual disability JOURNAL OF INTELLECTUAL DISABILITY RESEARCH Murphy, G., Hall, S., Oliver, C., Kissi-Debra, R. 1999; 43: 149-163

  Abstract

  Very little is known about the early stages of self-injurious behaviour (SIB) in young children with developmental disabilities, even though there has been a great deal of research into the prevalence, assessment and treatment of well-established SIB in older individuals. In the present initial study, teachers in special schools for children under II years of age with severe intellectual disability and/or autism were asked to identify children who were beginning to show early self-injury (the index group). These children were then matched to classroom controls (of the same ability level and mobility), and teachers were interviewed about the children's behaviours and skills. The index children showed significantly more potential SIB than the control group children, but there was overlap between the groups in terms of percentage duration of potential SIB, suggesting that teachers do not find it easy to identify children with 'early' SIB. The index children's skills and problem behaviours, their sensory impairments and degree of autism did not differ significantly from those of the control group. When all the children showing any potential SIB were pooled together, it transpired that developmental age and degree of mobility were significantly correlated with percentage duration of SIB, suggesting that these characteristics may be important risk markers. The index children were also observed at 3-month intervals at school over the following 18 months and self-injury clearly escalated for some of the index children, while it did not do so for others. Using regression analysis, increases in SIB were shown to be associated only with the degree of concern expressed about the child's behaviour at time I by the teacher, no other variables predicting increases in SIB.

  View details for Web of Science ID 000081098200002

  View details for PubMedID 10392602

• A molecular to molar analysis of communicative and problem behaviors RESEARCH IN DEVELOPMENTAL DISABILITIES Oliver, C., Hall, S., Nixon, L. 1999; 20 (3): 197-213

  Abstract

  Few studies have examined the relationship between communicative and problem behaviors that are already present in a behavioral repertoire. In this study, a detailed microanalysis of the antecedents and consequences of aggressive and communicative behavior of a 7-year-old boy was conducted. By using both descriptive and experimental methodologies, the data suggested that problem and communicative behavior were maintained on thin concurrent schedules of social negative reinforcement. A molar analysis of the descriptive data showed that the relative amount of time allocated to each behavior was a function of the relative amount of reinforcement that each behavior accrued. The implications of these findings are discussed in terms of conducting descriptive analyses and for enhancing the efficacy of interventions for problem behavior.

  View details for Web of Science ID 000080741800002

  View details for PubMedID 10372412

• A clock not wound runs down BEHAVIOURAL PROCESSES Killeen, P. R., Hall, S., Bizo, L. A. 1999; 45 (1-3): 129-139

  View details for Web of Science ID 000079593700010

• Watching the clock BEHAVIOURAL PROCESSES Fetterman, J. G., Killeen, P. R., Hall, S. 1998; 44 (2): 211-224

  View details for Web of Science ID 000078204000010

• A four year prospective study of age-related cognitive change in adults with Down's syndrome PSYCHOLOGICAL MEDICINE Oliver, C., Crayton, L., Holland, A., Hall, S., Bradbury, J. 1998; 28 (6): 1365-1377

  Abstract

  While neuropathological studies indicate a high risk for Alzheimer's disease in adults with Down's syndrome, neuropsychological studies suggest a lower prevalence of dementia. In this study, cognitive deterioration in adults with Down's syndrome was examined prospectively over 4 years to establish rates and profiles of cognitive deterioration.Fifty-seven people with Down's syndrome aged 30 years or older were assessed using a battery of neuropsychological tests on five occasions across 50 months. Assessments of domains of cognitive function known to change with the onset of Alzheimer related dementia were employed. These included tests of learning, memory, orientation, agnosia, apraxia and aphasia. The individual growth trajectory methodology was used to analyse change over time.Severe cognitive deterioration, such as acquired, apraxia and agnosia, was evident in 28.3% of those aged over 30 and a higher prevalence of these impairments was associated with older age. The rate of cognitive deterioration also increased with age and degree of pre-existing cognitive impairment. Additionally, deterioration in memory, learning and orientation preceded the acquisition of aphasia, agnosia and apraxia.The prevalence of cognitive impairments consistent with the presence of Alzheimer's disease is lower than that suggested by neuropathological studies. The pattern of the acquisition of cognitive impairments in adults with Down's syndrome is similar to that seen in individuals with Alzheimer's disease who do not have Down's syndrome.

  View details for Web of Science ID 000077362600012

  View details for PubMedID 9854278

• The treatment of severe self-injurious behavior by the systematic fading of restraints: Effects on self-injury, self-restraint, adaptive behavior, and behavioral correlates of affect RESEARCH IN DEVELOPMENTAL DISABILITIES Oliver, C., Hall, S., Hales, J., Murphy, G., WATTS, D. 1998; 19 (2): 143-165

  Abstract

  Severe self-injurious behavior (SIB) in people with mental retardation is difficult to treat when dangerously frequent or intense responding rules out functional analysis and interventions that permit free responding. This situation is common when restrictive devices, such as straight arm splints, are used. In this study, the effects of introducing flexion into a straight-arm splint, on SIB, self-restraint, adaptive behavior, and behavioral correlates of affect were examined for three individuals with severe mental retardation. Using single-case design methodology, for two individuals self-injury was reduced to zero, while the overall level of restriction was also significantly reduced. From the observed behavioral correlates of affect, there was no evidence of an increase in negative affect with the introduction of the new splint and the fading procedure, but there was evidence of an increase in positive vocalizations. Engagement in activities and social contact were not affected by the introduction of the new splint. The reasons for a decrease in SIB with a corresponding decrease in restriction in the absence of any manipulation of contingencies for SIB are discussed, with particular reference to stimulus control.

  View details for Web of Science ID 000072502600004

  View details for PubMedID 9547526

• The neuropsychological assessment of age related cognitive deficits in adults with Down's syndrome JOURNAL OF APPLIED RESEARCH IN INTELLECTUAL DISABILITIES Crayton, L., Oliver, C., Holland, A., Bradbury, J., Hall, S. 1998; 11 (3): 255-272

  View details for Web of Science ID 000076253300007

• A graphical method to aid the sequential analysis of observational data BEHAVIOR RESEARCH METHODS INSTRUMENTS & COMPUTERS Hall, S., Oliver, C. 1997; 29 (4): 563-573

  View details for Web of Science ID 000071076900011

• Self-injurious behaviour and people with intellectual disabilities: Assessing the behavioural knowledge and causal explanations of care staff JOURNAL OF APPLIED RESEARCH IN INTELLECTUAL DISABILITIES Oliver, C., Hall, S., Hales, J., Head, D. 1996; 9 (3): 229-239

  View details for Web of Science ID A1996VZ77600006

• EPIDEMIOLOGY OF SELF-INJURY, CHARACTERISTICS OF PEOPLE WITH SEVERE SELF-INJURY AND INITIAL TREATMENT OUTCOME Conference on Research to Practice: Implications of Research on the Challenging Behaviour of People with Learning Disability Murphy, G. H., Oliver, C., Corbett, J., Crayton, L., Hales, J., Head, D., Hall, S. BILD PUBLICATIONS. 1993: 1–35

  View details for Web of Science ID A1993BA33T00001

• DIFFERENTIAL-EFFECTS OF SEVERE SELF-INJURIOUS-BEHAVIOR ON THE BEHAVIOR OF OTHERS BEHAVIOURAL PSYCHOTHERAPY Hall, S., Oliver, C. 1992; 20 (4): 355-365

  View details for Web of Science ID A1992JT97300003