Predictors of empowerment in parents of children with autism and related neurodevelopmental disorders who are undergoing genetic testing.

BACKGROUND: There is limited empirical data quantifying the utility of genetic testing for families of children with autism spectrum disorder (ASD) or related neurodevelopmental disorders (NDD). We assessed the utility of clinical chromosomal microarray analysis (CMA), defined by diagnostic yield and parental empowerment, in population-based sample of parents of affected children; and explored child, family, and health services factors predictive of empowerment. METHODS: Participants were families of children undergoing diagnostic assessments, between 2016 and 2019. Diagnostic yield of CMA in affected children was determined. Parental empowerment was measured through adapted version of the Genetics Counseling Outcome Scale-24. Parents completed questionnaires to capture child, family, and health service factors. RESULTS: The diagnostic yield of CMA was 2.8% for pathogenic variants. Parental empowerment was significantly correlated with family functioning and aspects of perceived family-centeredness of care. The model accounted for 49.8% of the variation in parental empowerment, F (10,37) = 3.67, p = 0.002. After accounting for other predictors, parental perception of the provision of general information remained significantly associated with empowerment. CONCLUSION: The informational needs of families play an important role in their empowerment during genetic testing. Meeting these needs and monitoring empowerment can aid genomic technologies integration in personalized healthcare for ASD/NDD.

Adaptation and validation of the Genetic Counseling Outcome Scale for autism spectrum disorders and related conditions.

The genetics care pathway experienced by families affected by autism spectrum disorder (ASD) around the time of diagnosis is currently uncharacterized and potentially variable across contexts. The lack of consensus on outcome measures to capture the impact of genetic services for these families shows a gap in understanding and optimizing this genetics care pathway. The Genetic Counseling Outcome Scale (GCOS-24) is a validated outcome measure of clinical genetics services. The current study aims to adapt and validate the GCOS-24 as an outcome measure in the context routine genetic testing in ASD and related conditions. Families seen for their child's developmental evaluation for ASD and related conditions were invited to participate in a genomics cohort between 2016 and 2018. Families (n = 111) completed the mGCOS-24 (modified GCOS-24), adapted from the original GCOS-24 by clinicians working in the target population's routine care pathway. The mGCOS-24 has acceptable internal consistency (Cronbach's α = 0.84) and high test-retest reliability (ICC = 0.88). It also inversely correlates with stress as measured by Perceived Stress Scale (PSS-10) and distress, as measured by the Distress Thermometer, rs ≥ 0.39, ps < 0.001. The mGCOS-24 had adequate readability, as supported by cognitive interviews completed by a sub-sample of five mothers of a child with ASD. Together, our findings show that the mGCOS-24 has good validity for the target population. Preliminary characterization of the genetics care pathway in this population revealed remarkable variability in pre-test counseling and limited post-test counseling. The use of the mGCOS-24 as an outcome measure is useful in filling some of these gaps by offering a way to assess, and in the future, optimize the genetics care pathway for families affected by autism and related neurodevelopmental conditions.

Perceived utility of biological testing for autism spectrum disorder is associated with child and family functioning.

BACKGROUND: The clinical integration of chromosomal microarray testing promises improvements in diagnostic yields in Autism Spectrum Disorder (ASD). While the impact on clinical management is promising for some families, the utility perceived by families, including the majority for whom results are negative, is unclear. With next generation genomic sequencing technologies poised for integration, along with promising ASD biomarkers being developed, there is a need to understand the extent to which genomic and other biological testing would have utility for the target recipients of these tests and their families. The purpose of the present cross-sectional study was to examine the predictors of perceived utility of biological testing among parents of a child with ASD. METHODS: The Perceived Utility of Biotesting (PUB) Questionnaire was developed based on literature review and integrating family review. Following their child's diagnosis, families participating in an ongoing prospective study completed the PUB questionnaire along with self-reported measures of parent stress, child and family functioning, and family-centered care prior to undergoing genetic testing for both clinical and research purposes. RESULTS: Based on n = 85 families, psychometric properties of the Perceived Utility of Biotesting questionnaire suggest a reliable and valid instrument. A stepwise regression analysis reveals that lower levels of child emotional and behavioural functioning and higher levels of family functioning correlated with higher perceived utility for biological testing. LIMITATIONS: A main limitation in the study is the participation rate of 50 %, thus the possibility of self-selection bias cannot be ruled out. We also chose to assess perceived utility among parents rather than the individuals with ASD themselves: modifying the questionnaire to capture perceived utility from autistic individuals across the lifespan would prove essential in future studies. Finally, ongoing validation of the PUB by assessing the PUB's discriminant and convergent validity is still needed. CONCLUSIONS: We conclude that the utility of biological testing perceived by families whose child is undergoing genetic testing around ASD diagnosis depends on their unique child and family characteristics. This signifies that engaging families in biomarker discovery for improving the impact of research and care requires systematic input from a representative sample of families.

Association between distress and knowledge among parents of autistic children.

Understanding the overall utility of biological testing for autism spectrum disorder (ASD) is essential for the development and integration of biomarkers into routine care. One measure related to the overall utility of biological testing is the knowledge that a person has about the condition he/she suffers from. However, a major gap towards understanding the role of knowledge in overall utility is the absence of studies that have assessed knowledge of autism along with its predictors within a representative sample of families within the context of routine care. The objective of this study was to measure knowledge of ASD among families within the routine care pathway for biological testing in ASD by examining the association between knowledge with potential correlates of knowledge namely sociodemographic factors, parental stress and distress, and time since diagnosis among parents whose child with ASD is undergoing clinical genetic testing. Parents of a child diagnosed with ASD (n = 85, Mage = 39.0, SD = 7.7) participating in an ongoing prospective genomics study completed the ASD Quiz prior to undergoing genetic testing for clinical and research purposes. Parents also completed self-reported measures of stress and distress. Parent stress and distress was each independently correlated with knowledge of ASD, rs ≥ 0.26, ps < 0.05. Stepwise regression analysis revealed a significant model accounting for 7.8% of the variance in knowledge, F (1, 82) = 8.02, p = 0.006. The only factor significantly associated with knowledge was parental distress, ß = 0.30, p = 0.006. Parental stress, time since diagnosis, and sociodemographic factors were not significant predictors in this model. We concluded that families require tailored support prior to undergoing genetic testing to address either knowledge gaps or high distress. Ongoing appraisal of the testing process among families of diverse backgrounds is essential in offering optimal care for families undergoing genetic testing.

Assuming ability of youth with autism: Synthesis of methods capturing the first-person perspectives of children and youth with disabilities.

Most research regarding youth with autism spectrum disorder has not focused on their first-person perspectives providing limited insight into methodologies best suited to eliciting their voices. We conducted a synthesis of methods previously used to obtain the first-person perspectives of youth with various disabilities, which may be applicable to youth with autism spectrum disorder. Two-hundred and eighty-four articles met the inclusion criteria of our scoping review. We identified six distinct primary methods (questionnaires, interviews, group discussion, narratives, diaries, and art) expressed through four communication output modalities (language, sign language and gestures, writing, and images). A group of parents who have children with autism spectrum disorder were then presented with a synthesis of results. This parent consultation was used to build on approaches identified in the literature. Parents identified barriers that may be encountered during participant engagement and provided insights on how best to conduct first-person research with youth with autism spectrum disorder. Based on our findings, we present a novel methodological framework to capture the perspectives of youth with various communication and cognitive abilities, while highlighting family, youth, and expert contributions.

The effect of practice pattern on the acquisition, consolidation, and transfer of visual-motor sequences.

The contextual interference hypothesis proposes that when learning multiple skills, massing practice leads to better within-day acquisition, whereas random practice leads to better retention and transfer. In this experiment, we examined the effect of practice pattern on the learning, consolidation (retention), and transfer of visual-motor sequences. On Day 1, participants were randomly assigned to the Massed, Alternating, or Random condition. On Day 2, all participants were tested for consolidation and transfer. Learning was assessed through changes in accuracy and response synchronization. We found that massed practice led to enhanced sensorimotor integration and timing (as measured by response synchronization), whereas random practice led to better stimulus-response association (as measured by accuracy). On day 2, all groups showed consolidation for both measures, as well as transfer for accuracy but not response synchronization. Overall, this pattern of results provides limited support for the contextual interference hypothesis. Our findings are consistent with differential encoding of specific domains of motor performance. We propose that learning of the more explicit stimulus-response association is a fast process that benefits from random practice because it requires the acquisition of this association in multiple contexts. Once the association is learned, it seems resistant to interference and transferrable to a novel sequence. In contrast, learning of the sensorimotor integration and timing is a slower process that benefits from blocked training because practice in a single context allows fine-tuning of the response. Given that all groups showed consolidation, we postulate that learning that occurs in the context of interference can show consolidation.

Developmental contributions to motor sequence learning.

Little is known about how children acquire new motor sequences. In particular, it is not clear if the same learning progression observed in adults is also present in childhood nor whether motor skills are acquired in a similar fashion across development. In the present study we used the multi-finger sequencing task (MFST), a variant of the serial reaction time (SRT) task, to study motor sequence learning, across two consecutive days, in three cross-sectional samples of children aged 6, 8, and 10 years, and a control sample of adults. In the MFST, participants reproduced 10-element sequences of key presses on an electronic keyboard, using four fingers of the right hand. Each block of practice included 10 intermixed trials of a Repeated (REP) sequence and four trials of Random (RAN) sequences. Performance was assessed by examining changes in accuracy, a component of the task that requires the association of the visual stimulus with the motor response, and response synchronization, a component that requires fine-grained sensorimotor integration and timing. Additionally, participants completed Recognition and Recall tests, to assess explicit knowledge of the repeated sequence. Overall, results showed a developmental progression in motor sequence learning within and across days of practice. Interestingly, the two behavioral measures showed different developmental trajectories. For accuracy, differences were greatest for the two youngest groups early in learning, and these groups also showed the greatest rate of improvement. However, by the end of Day 2, only the 6-year-olds still lagged behind all other groups. For response synchronization, all child groups differed from adults early in learning, but both child and adult groups showed similar rates of improvement across blocks of practice. By the end of Day 2, 10-year-olds reached adult levels of performance, whereas 6- and 8-year-olds did not. Taken together, the dissociation observed with our two behavioral measures of sequence learning is consistent with the hypothesis that accuracy or finger-stimulus association may rely on cortical pathways that show the greatest maturation between ages 6 and 10; whereas motor timing and sensorimotor integration may rely on subcortical pathways that continue to develop into young adulthood. Despite developmental differences across blocks of practice on both behavioral measures, there were no significant group differences for either the Recognition or Recall tests. We suggest that explicit knowledge of the MFST is not directly linked to task performance, thus challenging the implicit-explicit distinction in pediatric SRT studies assessing the developmental invariance model.

The effect of early musical training on adult motor performance: evidence for a sensitive period in motor learning.

Developmental changes in the human brain coincide with and underlie changes in a wide range of motor and cognitive abilities. Neuroimaging studies have shown that musical training can result in structural and functional plasticity in the brains of musicians, and that this plasticity is greater for those who begin training early in life. However, previous studies have not controlled for differences between early-trained (ET) and late-trained (LT) musicians in the total number of years of musical training and experience. In the present experiment, we tested musicians who began training before and after the age of 7 on learning of a timed motor sequence task. The groups were matched for years of musical experience, years of formal training and hours of current practice. Results showed that ET musicians performed better than LT musicians, and that this performance advantage persisted after 5 days of practice. Performance differences were greatest for a measure of response synchronization, suggesting that early training has its greatest effect on neural systems involved in sensorimotor integration and timing. These findings support the idea that there may be a sensitive period in childhood where enriched motor training through musical practice results in long-lasting benefits for performance later in life. These results are also consistent with the results of studies showing structural changes in motor-related regions of the brain in musicians that are specifically related to training early in life.

Executive functions and methylphenidate response in subtypes of attention-deficit/hyperactivity disorder.

BACKGROUND: Oculomotor tasks are a well-established means of studying executive functions and frontal-striatal functioning in both nonhuman primates and humans. Attention-deficit/hyperactivity disorder (ADHD) is thought to implicate frontal-striatal circuitry. We used oculomotor tests to investigate executive functions and methylphenidate response in two subtypes of ADHD. METHODS: Subjects were boys, aged 11.5-14 years, with ADHD-combined (n = 10), ADHD-inattentive (n = 12), and control subjects (n = 10). Executive functions assessed were motor planning (tapped with predictive saccades), response inhibition (antisaccades), and task switching (saccades-antisaccades mixed). RESULTS: The ADHD-combined boys were impaired relative to control subjects in motor planning (p < .003) and response inhibition (p < .007) but not in task switching (p > .92). They were also significantly impaired relative to ADHD-inattentive boys, making fewer predictive saccades (p < .03) and having more subjects with antisaccade performance in the impaired range (p < .04). Methylphenidate significantly improved motor planning and response inhibition in both subtypes. CONCLUSIONS: ADHD-combined but not ADHD-inattentive boys showed impairments on motor planning and response inhibition. These deficits might be mediated by brain structures implicated specifically in the hyperactive/impulsive symptoms. Methylphenidate improved oculomotor performance in both subtypes; thus, it was effective even when initial performance was not impaired.

The effect of early musical training on adult motor performance: evidence for a sensitive period in motor learning.

This experiment demonstrates that musicians who began training before age seven perform better on a rhythmic tapping task than musicians who began after the age of seven, when the two groups are matched for years of experience. These results support the idea that there may be a sensitive period in childhood for motor training, similar to that observed for language learning.

The effects of practice and delay on motor skill learning and retention.

The present study assessed the effects of amount of practice and length of delay on the learning and retention of a timed motor sequence task. Participants learned to reproduce ten-element visual sequences by tapping in synchrony with the stimulus. Participants were randomly assigned to a varied-practice condition or a varied-delay condition. In the varied-practice condition, participants received either one, three, or six blocks of practice followed by a fixed 4-week delayed-recall. In the varied-delay condition, participants received three blocks of practice followed by a varied delay of either 3 days, or 2, 4, or 8 weeks. Learning was assessed by changes in accuracy, response variance, and percent response asynchrony. Our results showed that amount of practice per se did not affect learning and retention of the task. Rather, distribution of practice over several days was the most important factor affecting learning and retention. We hypothesize that passage of time is essential for a maximum benefit of practice to be gained, as the time delay may allow for consolidation of learning, possibly reflecting plastic changes in motor cortical representations of the skill. With regards to delay, our findings suggest that explicit and motoric components of a motor sequence are likely to be learned and maintained in separate but interacting systems. First, only the longest delay group showed decrements in percent correct, indicating that longer lengths of delay might hinder retrieval of explicit aspects of the task. Second, all groups showed a decrement in percent response asynchrony, suggesting that synchronization may be a more difficult parameter to maintain because it relies heavily on sensorimotor integration.