Specialization of amygdala subregions in emotion processing.

The amygdala is important for human fear processing. However, recent research has failed to reveal specificity, with evidence that the amygdala also responds to other emotions. A more nuanced understanding of the amygdala's role in emotion processing, particularly relating to fear, is needed given the importance of effective emotional functioning for everyday function and mental health. We studied 86 healthy participants (44 females), aged 18-49 (mean 26.12 ± 6.6) years, who underwent multiband functional magnetic resonance imaging. We specifically examined the reactivity of four amygdala subregions (using regions of interest analysis) and related brain connectivity networks (using generalized psycho-physiological interaction) to fear, angry, and happy facial stimuli using an emotional face-matching task. All amygdala subregions responded to all stimuli (p-FDR < .05), with this reactivity strongly driven by the superficial and centromedial amygdala (p-FDR < .001). Yet amygdala subregions selectively showed strong functional connectivity with other occipitotemporal and inferior frontal brain regions with particular sensitivity to fear recognition and strongly driven by the basolateral amygdala (p-FDR < .05). These findings suggest that amygdala specialization to fear may not be reflected in its local activity but in its connectivity with other brain regions within a specific face-processing network.

Ten-year follow-up study found that motor-free intelligence quotient declined in children with mild-to-moderate cerebral palsy.

AIM: This 10-year follow-up study examined cognitive change in a cohort of children with cerebral palsy from preschool to adolescence at the group and individual levels. METHODS: The Wechsler Preschool and Primary Scale of Intelligence was administered to 80 children with cerebral palsy (mean = 4 years 6 months, standard deviation = 7 months) at baseline (Time 1). At 10-year follow-up (Time 2), 28 adolescents (mean = 14 years 6 months, standard deviation = 9 months) returned for assessment with the Wechsler Intelligence Scale for Children. Motor-free intelligence quotient (IQ) scores were calculated and paired-samples t-tests and the Reliable Change Index (RCI) were used to investigate change in IQ over time. RESULTS: At the group level, nonverbal IQ scores declined significantly. At the individual level, RCI indicated nine and 11 children showed a clinically significant decline in Full Scale IQ (FSIQ) and nonverbal IQ scores, respectively. Decline in FSIQ was related to a history of seizures whereas decline in nonverbal IQ was associated with higher initial IQ. CONCLUSION: Cognitive abilities in children with cerebral palsy evolve over time and selective deficits may not be observable until a later age, highlighting the importance of repeated cognitive assessment throughout childhood and adolescence.

Feasibility of a virtual reality-based exercise intervention and low-cost motion tracking method for estimation of motor proficiency in youth with autism spectrum disorder.

BACKGROUND: Motor impairment is widely acknowledged as a core feature in children with autism spectrum disorder (ASD), which can affect adaptive behavior and increase severity of symptoms. Low-cost motion capture and virtual reality (VR) game technologies hold a great deal of promise for providing personalized approaches to motor intervention in ASD. The present study explored the feasibility, acceptability and potential efficacy of a custom-designed VR game-based intervention (GaitWayXR™) for improving gross motor skills in youth with ASD. METHODS: Ten children and adolescents (10-17 years) completed six, 20-min VR-based motor training sessions over 2 weeks while whole-body movement was tracked with a low-cost motion capture system. We developed a methodology for using motion tracking data to quantify whole-body movement in terms of efficiency, synchrony and symmetry. We then studied the relationships of the above quantities with standardized measures of motor skill and cognitive flexibility. RESULTS: Our results supported our presumption that the VR intervention is safe, with no adverse events and very few minor to moderate side-effects, while a large proportion of parents said they would use the VR game at home, the most prohibitive reasons for adopting the system for home therapy were cost and space. Although there was little evidence of any benefits of the GaitWayXR™ intervention in improving gross motor skills, we showed several positive correlations between the standardized measures of gross motor skills in ASD and our measures of efficiency, symmetry and synchrony from low-cost motion capture. CONCLUSIONS: These findings, though preliminary and limited by small sample size, suggest that low-cost motion capture of children with ASD is feasible with movement exercises in a VR-based game environment. Based on these preliminary findings, we recommend conducting larger-scale studies with methods for improving adherence to VR gaming interventions over longer periods.

Working memory is a core executive function supporting dual-task locomotor performance across childhood and adolescence.

Most daily-life ambulatory tasks involve dual tasking, for example, talking while walking. In children, the evidence supporting the effects of age on dual tasking is confounded by the difficulty of the cognitive task and lack of adjustment to suit individual cognitive abilities. To address this issue, the current study examined the effects of age, cognitive load, and executive functioning on the degree of dual-task gait interference across childhood and adolescence. We tested 120 typically developing children aged 6-11 years, adolescents aged 12-16 years, and young adults aged 18-25 years. Participants were asked to walk while performing a visuospatial working memory task at two levels of cognitive load (easy and difficult) adjusted to suit each participant's cognitive ability. Spatiotemporal characteristics and intra-individual variability of gait were measured using a GAITRite electronic walkway. Irrespective of the cognitive load level, children aged 6 to 11 years showed greater dual-task gait interference for selective spatiotemporal gait characteristics; however, the younger children showed a trade-off pattern in gait variability whereby they prioritized gait stability at the expense of cognitive performance. Our results also showed that age and working memory capacity were significant predictors of dual-task interference for a range of complementary gait parameters in the combined sample. Importantly, working memory capacity was part of a moderating relationship between age and dual-task gait interference. These findings emphasize the importance of dual-task prioritization strategies in younger children and highlight the role of individual differences in working memory capacity in performance in dual-task gait situations.

Do Active Video Games Improve Motor Function in People With Developmental Disabilities? A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To conduct a meta-analysis to examine the effectiveness of active video games (AVGs) interventions on motor function in people with developmental disabilities. DATA SOURCES: An electronic search of 7 databases (PubMed, EbscoHost, Informit, Scopus, ScienceDirect, Proquest, PsychInfo) was conducted for randomized controlled trials (RCTs) evaluating AVGs to improve motor function in people with developmental disability, published through to May 2018. STUDY SELECTION: Only articles in a peer-reviewed journal in English were selected and screened by 2 independent reviewers for RCTs that compared AVGs to conventional therapy. Twelve RCTs involving 370 people with developmental disabilities met the inclusion criteria for quantitative analysis. DATA EXTRACTION: Two independent reviewers assessed risk of bias and study quality using the Egger's R, grading of recommendation, assessment, development and evaluation, and Template for Intervention Description and Replication checklists. DATA SYNTHESIS: Three meta-analyses revealed a large effect size for AVGs to improve gross motor skills (Hedges' g=0.833, 95% confidence interval [95% CI]=0.247-1.420), small to medium effects for balance (g=0.458, 95% CI=0.023-0.948), and a small, nonsignificant effect for functional mobility (g=0.425, 95% CI= -0.03 to 0.881). Training frequency (ie, number of sessions per week) moderated the effect of AVGs on motor function in people with developmental disabilities. CONCLUSION: We conclude that AVGs show task-specific effectiveness for gross motor skills but the effects are moderated by training intensity. However, because of the low number of trials, diverse diagnoses, variable dosage, and multiple outcome measures of the included trials, these results need to be interpreted with caution.

The development of the size-weight illusion in children coincides with the development of nonverbal cognition rather than motor skills.

We examined how the strength of the size-weight illusion develops with age in typically developing children. To this end, we recruited children aged 5-12 years and quantified the degree to which they experienced the illusion. We hypothesized that the strength of the illusion would increase with age. The results supported this hypothesis. We also measured abilities in manual dexterity, receptive language, and abstract reasoning to determine whether changes in illusion strength were associated with these factors. Manual dexterity and receptive language did not correlate with illusion strength. Conversely, illusion strength and abstract reasoning were tightly coupled with each other. Multiple regression further revealed that age, manual dexterity, and receptive language did not contribute more to the variance in illusion strength beyond children's abilities in abstract reasoning. Taken together, the effects of age on the size-weight illusion appear to be explained by the development of nonverbal cognition. These findings not only inform the literature on child development but also have implications for theoretical explanations on the size-weight illusion. We suggest that the illusion has a strong acquired component to it and that it is strengthened by children's reasoning skills and perhaps an understanding of the world that develops with age.

Graduate-entry medical students: older and wiser but not less distressed.

OBJECTIVES: Australia has a growing number of graduate-entry medical courses. It is known that undergraduate medical students have high levels of psychological distress; however, little is known about graduate-entry medical students. We examined whether graduate-entry medical students had higher levels of psychological distress than the same-age general population. METHOD: Psychological distress was assessed in 122 graduate-entry medical students in an Australian graduate-entry medical school using the 21-item Depression Anxiety and Stress Scale. Mean scores and the proportion of students with scores in the highly distressed range were compared with non-clinical population norms. Scores were also compared across demographic characteristics. RESULTS: Medical students reported higher mean depression, anxiety and stress scores than the general population and were more likely to score in the moderate to extremely high range for anxiety (45% vs. 13%; p<0.001) and stress (17% vs. 13%; p=0.003). Anxiety and stress were higher in students aged ≥30 years than in younger students. CONCLUSIONS: Despite their maturity, graduate-entry students experienced high psychological distress. Anxiety and stress were higher, not lower, with increasing age. Our results suggest that graduate-entry medical students warrant the same level of concern as their school-leaving counterparts. Further interventions to support these students during medical school are warranted.

Sensitivity of spatiotemporal gait parameters in measuring disease severity in Friedreich ataxia.

Friedreich ataxia (FRDA) is an autosomal recessive disease with gait ataxia being the main source of morbidity. Mobility progressively declines, from initial symptom onset at approximately 10-15 years of age to being unable to ambulate 10-15 years later. Here, we sought to investigate the relationship between spatiotemporal gait parameters and clinical markers of disease severity. Thirteen people with FRDA walked along an 8.3-m GAITRite® mat six times each at their preferred fast and slow speeds. Relationships between spatiotemporal gait parameters and a range of clinical and disease characteristics were examined. Significant correlations were found between spatiotemporal gait characteristics at each of the walking speeds and Friedreich Ataxia Rating Scale (FARS) score and disease duration. During the fast-walking condition, gait speed and cadence decreased with an increase in disease duration and the FARS score. GAA1 repeat expansion negatively correlated with double-support percentage of the gait cycle in all speed conditions demonstrating a relationship between the genetic mutation and compensatory strategies for impaired dynamic balance. In all speed conditions, there were correlations between a range of spatiotemporal gait characteristics and the timed 25-ft walk test, a well-established measure of gait mobility. These findings suggest that spatiotemporal gait parameters are a sensitive measure of gait decline in individuals with FRDA and should be considered for inclusion in intervention studies whilst participants are still ambulant.

Saccade reprogramming in Friedreich ataxia reveals impairments in the cognitive control of saccadic eye movement.

Although cerebellar dysfunction has known effects on motor function in Friedreich ataxia (FRDA), it remains unclear the extent to which the reprogramming of eye movements (saccades) and inhibition of well-learned automatic responses are similarly compromised in affected individuals. Here we examined saccade reprogramming to assess the ability of people with FRDA to respond toward unexpected changes in either the amplitude or direction of an "oddball" target. Thirteen individuals with genetically confirmed FRDA and 12 age-matched controls participated in the study. The saccade reprogramming paradigm was used to examine the effect of an unpredictable "oddball" target on saccade latencies and accuracy when compared to a well-learned sequence of reciprocating movements. Horizontal eye movements were recorded using a scleral search coil eye tracking technique. The results showed a proportionally greater increase in latencies for reprogrammed saccades toward an oddball-direction target in the FRDA group when compared to controls. The FRDA group were also less accurate in primary saccade gain (i.e. ratio of saccade amplitude to target amplitude) when reprogramming saccades toward an unexpected change in direction. No significant group differences were found on any of the oddball-amplitude targets. Significant correlations were revealed between latency and disease severity as measured by the Friedreich Ataxia Rating Scale. These findings provide further support to the view that cognitive changes in FRDA may arise from disruption of cerebellar connections to cortical structures.

Exploring inhibitory deficits in female premutation carriers of fragile X syndrome: through eye movements.

There is evidence which demonstrates that a subset of males with a premutation CGG repeat expansion (between 55 and 200 repeats) of the fragile X mental retardation 1 gene exhibit subtle deficits of executive function that progressively deteriorate with increasing age and CGG repeat length. However, it remains unclear whether similar deficits, which may indicate the onset of more severe degeneration, are evident in female PM-carriers. In the present study we explore whether female PM-carriers exhibit deficits of executive function which parallel those of male PM-carriers. Fourteen female fragile X premutation carriers without fragile X-associated tremor/ataxia syndrome and fourteen age, sex, and IQ matched controls underwent ocular motor and neuropsychological tests of select executive processes, specifically of response inhibition and working memory. Group comparisons revealed poorer inhibitory control for female premutation carriers on ocular motor tasks, in addition to demonstrating some difficulties in behaviour self-regulation, when compared to controls. A negative correlation between CGG repeat length and antisaccade error rates for premutation carriers was also found. Our preliminary findings indicate that impaired inhibitory control may represent a phenotype characteristic which may be a sensitive risk biomarker within this female fragile X premutation population.

Movement planning and online control in multiple sclerosis: assessment using a Fitts law reciprocal aiming task.

OBJECTIVE: We sought to quantify subtle changes in motor control in multiple sclerosis (MS) using a Fitts law reciprocal aiming task presented on a computer touchscreen. BACKGROUND: Upper-limb motor control is impaired in MS. However, many commonly used motor assessments do not detect subtle changes in motor function or differentiate between aspects of movement such as planning and online control. Fitts law states that movement time varies as a function of task difficulty, with smaller targets and greater distances making the task more difficult. METHODS: We gave a Fitts aiming task to 22 patients with MS and 22 matched controls. We manipulated movement difficulty by changing the targets' size and distance apart. RESULTS: The patients spent a significantly longer time than the controls stationary in each target before starting the next movement, and had a lower peak velocity, suggesting deficits in movement planning. The patients also spent longer in the deceleration phase of each movement, indicating deficits in the online control of movement. CONCLUSIONS: The computerized Fitts task allows quick, easy, and sensitive measurement of subtle aspects of movement. This task should be useful in clinical and research settings for assessing MS motor symptoms, disease progression, and treatment efficacy.

Impaired response inhibition is associated with self-reported symptoms of depression, anxiety, and ADHD in female FMR1 premutation carriers.

Fragile X Mental Retardation 1 (FMR1) premutation carriers (PM-carriers) have a defective trinucleotide expansion on the FMR1 gene that is associated with continuum of neuropsychological and mental disorders. Currently, little is known about the distinct subcomponents of executive function potentially impaired in female PM-carriers, and there have been no investigations into associations between executive function and incidences of mental disorders. A total of 35 female PM-carriers confirmed by Asuragen triple primed PCR DNA testing and 35 age- and intelligence-matched controls completed tests of executive function (i.e., response inhibition and working memory) and self-reported on social anxiety, depression, and ADHD predominantly inattentive (ADHD-PI) symptoms. Compared to controls, PM-carriers were significantly elevated on self-reported social anxiety and ADHD-PI symptoms. Irrespective of mental symptoms, female PM-carries performed significantly worse than controls on a response inhibition test, and further investigations revealed significant correlations between executive function performance and self-reported symptoms of anxiety, depression and ADHD-PI. Critically, among PM-carriers with good executive function performance, no women exceeded threshold markers for probable caseness of mental disorder. However, rates of probable caseness were elevated in those with average performance (response inhibition: social anxiety: 41.7%; depression: 20%; ADHD: 44.4%; working memory: social anxiety: 27.3%; depression: 9.1%; ADHD: 18.2%) and highly elevated for those with poor executive function performance (response inhibition: social anxiety: 58.3%; depression: 80%; ADHD: 55.6%; working memory: social anxiety: 100%; depression: 50%; ADHD: 83.3%). These data suggest that subtle executive dysfunction may be a useful neuropsychological indicator for a range of mental disorders previously reported in female PM-carriers.

The interplay between executive control and motor functioning in Williams syndrome.

Previous studies suggest that individuals with Williams syndrome (WS), a rare genetically based neurodevelopmental disorder, show specific weaknesses in visual attention and response inhibition within the visuospatial domain. Here we examine the extent to which impairments in attentional control extend to the visuomotor domain using a well-validated measure of choice stepping reaction time (CSRT) in individuals with WS. We examined the interaction between executive control and visually guided stepping using a verbal fluency dual-task or Go/NoGo paradigm during CSRT performance. Relationships between dual-task and inhibitory stepping and behavioural inattention and hyperactivity were also examined. Our results showed clear dual-task costs in stepping response times when performing a concurrent cognitive task in the WS group when compared to spatial and verbal ability matched typically developing controls. Although no group differences in stepping accuracy were observed between the WS and typically developing control groups, the WS group showed progressive slowing and more variable response times across the duration of the Go/NoGo task. These results suggest dysfunction in circuits involved in top-down attentional control processes in WS. These findings provide novel evidence that core executive control deficits in WS extend to the visuomotor domain, and impact on ADHD-related inattentive symptoms.

Delineating Visual Habituation Profiles in Preschoolers with Neurofibromatosis Type 1 and Autism Spectrum Disorder: A Cross-Syndrome Study.

Atypical habituation to repetitive information has been commonly reported in Autism Spectrum Disorder (ASD) but it is not yet clear whether similar abnormalities are present in Neurofibromatosis Type 1 (NF1). We employed a cross-syndrome design using a novel eye tracking paradigm to measure habituation in preschoolers with NF1, children with idiopathic ASD and typically developing (TD) children. Eye movements were recorded to examine fixation duration to simultaneously presented repeating and novel stimuli. Children with NF1 showed a bias for longer look durations to repeating stimuli at the expense of novel stimuli, and slower habituation in NF1 was associated with elevated ASD traits. These findings could indicate aberrant modulation of bottom-up attentional networks that interact with the emergence of ASD phenotypes.

Selective spatial processing deficits in an at-risk subgroup of the fragile X premutation.

Until a decade ago, it was assumed that males with the fragile X premutation were unaffected by any cognitive phenotype. Here we examined the extent to which CGG repeat toxicity extends to visuospatial functioning in male fragile X premutation carriers who are asymptomatic for a late-onset neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS). Thirty-three premutation males aged 20-68 years [divided into two groups: 16 low-repeat carriers (CGG ≥ 55 ≤ 100) and 17 high-repeat carriers (CGG>100)] with a family history of fragile X syndrome and 62 non-affected adult males with normal FMR1 alleles were recruited. Subjects underwent neuropsychological tests of visuospatial and visual working memory functioning and visuoperceptual processing. On measures of visuospatial processing, the high-repeat carriers performed significantly worse than the normal allele group when age and IQ were covaried out. With increasing age and only in carriers of a larger (>100 repeats) premutation allele was there a greater decrement in visuospatial working memory functioning. Performance on spatial and perceptual judgement tasks failed to show similar specificity in males within the upper premutation range. We conclude that identification of selective visuospatial impairments in carriers of a larger premutation allele indicates greater CGG repeat toxicity in specific neural regions. Longitudinal follow-up studies will be needed to determine whether subtle decline in visuospatial functioning is associated with the later onset of motor symptoms of FXTAS.

Relationships of Motor Changes with Cognitive and Neuropsychiatric Features in FMR1 Male Carriers Affected with Fragile X-Associated Tremor/Ataxia Syndrome.

The premutation expansion of the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene on the X chromosome has been linked to a range of clinical and subclinical features. Nearly half of men with FMR1 premutation develop a neurodegenerative disorder; Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS). In this syndrome, cognitive executive decline and psychiatric changes may co-occur with major motor features, and in this study, we explored the interrelationships between these three domains in a sample of adult males affected with FXTAS. A sample of 23 adult males aged between 48 and 80 years (mean = 62.3; SD = 8.8), carrying premutation expansions between 45 and 118 CGG repeats, and affected with FXTAS, were included in this study. We employed a battery of cognitive assessments, two standard motor rating scales, and two self-reported measures of psychiatric symptoms. When controlling for age and/or educational level, where appropriate, there were highly significant correlations between motor rating score for ICARS gait domain, and the scores representing global cognitive decline (ACE-III), processing speed (SDMT), immediate memory (Digit Span), and depression and anxiety scores derived from both SCL90 and DASS instruments. Remarkably, close relationships of UPDRS scores, representing the contribution of Parkinsonism to FXTAS phenotypes, were exclusive to psychiatric scores. Highly significant relationships between CGG repeat size and most scores for three phenotypic domains suggest a close tracking with genetic liability. These findings of relationships between a constellation of phenotypic domains in male PM carriers with FXTAS are reminiscent of other conditions associated with disruption to cerebro-cerebellar circuits.

Assessing IQ in adolescents with mild to moderate cerebral palsy using the WISC-V.

Objective: To examine the influence of subtests that require fine motor responses on measures of intellectual ability, and compare three approaches to minimizing motor demands while assessing cognitive abilities in adolescents with cerebral palsy (CP) to the traditional method of the Wechsler Intelligence Scale for Children - Fifth edition (WISC-V). Method: Seventy adolescents with CP (M = 14 years 6 months, SD = 10 months) who were able to provide either a verbal or point response were assessed using the WISC-V administered via Q-interactive. The pencil-to-paper version of Coding was also administered. Performance on Block Design and pencil-to-paper Coding was compared to Visual Puzzles and Coding on Q-interactive, respectively. Full Scale IQ (FSIQ) scores derived according to the Traditional method of the WISC-V were compared to alternative estimates of FSIQ derived according to the Q-interactive, Nonmotor, and Motor-free methods, which minimized motor demands. Results: An additional 7-12% of participants were able to respond to Visual puzzles and Coding on Q-interactive compared to Block Design and pencil-to-paper Coding, respectively, and performance was marginally but significantly better. For 54 adolescents (Gross Motor Function Classification System (GMFCS) Level I-III) who were able to obtain FSIQ scores, the Traditional method underestimated FSIQ by 3-6 points compared to the alternative methods and the difference was most pronounced for those with more severe CP as measured by the GMFCS. Conclusion: Adolescents with CP are at an inherent disadvantage when cognitive ability is assessed using the Traditional method of the WISC-V. Findings suggest clinicians should employ the Nonmotor or Motor-free methods when assessing IQ in adolescents with CP.

Association of the DAT1 genotype with inattentive behavior is mediated by reading ability in a general population sample.

Attention deficit hyperactivity disorder (ADHD) and reading disability (RD) frequently co-occur in the child population and therefore raise the possibility of shared genetic etiology. We used a quantitative trait loci (QTL) approach to assess the involvement of the dopamine transporter (DAT1) gene polymorphism in mediating reading disability and poor attention in a general population sample of primary school children aged 6-11 years in the UK. The potential confounding effects of IQ and chronological age were also investigated. We found an independent association between the homozygous DAT1 10/10 repeat genotype and RD that was not accounted for by the level of ADHD symptoms. This finding suggests that the DAT1 gene polymorphism may influence a common neural mechanism underlying both reading acquisition and ADHD symptoms.