Kate Woodcock

Task-switching deficits and repetitive behaviour in genetic neurodevelopmental disorders: Data from children with Prader-Willi syndrome chromosome 15 q11-q13 deletion and boys with Fragile X syndrome

Prader–Willi syndrome (PWS) and Fragile X syndrome (FraX) are associated with distinctive cognitive and behavioural profiles. We examined whether repetitive behaviours in the two syndromes were associated with deficits in specific executive functions. PWS, FraX, and typically developing (TD) children were assessed for executive functioning using the Test of Everyday Attention for Children and an adapted Simon spatial interference task. Relative to the TD children, children with PWS and FraX showed greater costs of attention switching on the Simon task, but after controlling for intellectual ability, these switching deficits were only significant in the PWS group. Children with PWS and FraX also showed significantly increased preference for routine and differing profiles of other specific types of repetitive behaviours. A measure of switch cost from the Simon task was positively correlated to scores on preference for routine questionnaire items and was strongly associated with scores on other items relating to a preference for predictability. It is proposed that a deficit in attention switching is a component of the endophenotypes of both PWS and FraX and is associated with specific behaviours. This proposal is discussed in the context of neurocognitive pathways between genes and behaviour.

The association between repetitive behaviours, impulsivity and hyperactivity in people with intellectual disability.

BACKGROUND There is a need for assessments of psychological difference and disorder in people who have more severe intellectual disability (ID). Hyperactivity and impulsivity are two behavioural domains of importance as they are correlated with self-injury and aggression and this alludes to a shared cognitive correlate of compromised behavioural inhibition. Additionally, compromised behavioural inhibition is demonstrably related to repetitive behaviour and the latter might be expected to be associated with impulsivity and hyperactivity. METHODS The Activity Questionnaire (TAQ) was developed for this study. Three sub-scales with high levels of face validity were supported by factor analysis of the scoring of 755 intellectually disabled participants on the TAQ items. These sub-scales mapped onto the constructs of Overactivity, Impulsivity and Impulsive Speech. Test-retest, inter-rater reliability and internal consistency were robust. TAQ scores and scores on the Repetitive Behaviour Questionnaire (RBQ) were collected for a sample of 136 participants with varying degrees of ID. RESULTS Scores on the TAQ at sub-scale and full-scale level were not related to level of adaptive functioning. There were significant positive associations between overactivity (TAQ) and stereotyped behaviour (RBQ), impulsivity (TAQ) and restricted preferences (RBQ), and impulsive speech (TAQ) and repetitive speech (RBQ). CONCLUSIONS The TAQ is a reliable assessment of hyperactivity and impulsivity for people with ID with robust factor structure. Validity requires evaluation. The relationship between impulsivity and restricted preferences may result from a common cognitive impairment in inhibition, which may underpin these two classes of behaviour.

Associations between Repetitive Questioning, Resistance to Change, Temper Outbursts and Anxiety in Prader-Willi and Fragile-X Syndromes.

BACKGROUND The behavioural phenotypes of Prader-Willi (PWS) and Fragile-X (FraX) syndromes both comprise repetitive behaviours with differences between the profiles. In this study we investigated the context and antecedents to the repetitive behaviours and the association with other behavioural phenotypic characteristics in order to generate testable hypotheses regarding the cause of the behaviours. METHOD The parents or carers of 46 children with PWS (mean age 14.1 years; 20 girls), and 33 boys with FraX (mean age 13.11 years) were interviewed about their childrens repetitive behaviour in a semi-structured format. RESULTS Children showed negative emotional behaviour (PWS: 87.0%; FraX: 79.4%) and repetitive questions (PWS: 78.3%; FraX: 73.5%) following changes in routine or expectations. Significantly more temper outbursts were reported to follow changes in children with PWS (89.1%) compared with boys with FraX (41.2%) (chi(2) = 20.93; P < 0.001). Anxiety that was frequently associated with repetitive and self-injurious behaviours in boys with FraX, followed changes in significantly more boys with FraX (76.5%) compared with children with PWS (6.5%) (chi(2) = 43.19, P < 0.001). DISCUSSION On the basis of these reports and existing literature, we hypothesise that decreases in predictability are aversive to children with PWS and FraX. We also hypothesise that these children have a propensity to show a syndrome-related pattern of behaviour (temper outbursts in PWS and displays of anxiety in FraX) when an event in the environment has this aversive property. We hypothesise that questions may be reinforcing to children in their own right by increasing the predictability of the environment. We outline how a specific cognitive deficit in the endophenotypes associated with both PWS and FraX could be investigated as a potential explanation for the hypothesised aversive properties of decreased predictability.

Prevalence, Phenomenology, Aetiology and Predictors of Challenging Behaviour in Smith-Magenis Syndrome.

BACKGROUND The prevalence, phenomenology aetiology and correlates of four forms of challenging behaviour in 32 children and adults with Smith-Magenis syndrome (SMS) were investigated. METHODS Cognitive assessments, questionnaires and semi-structured interviews were used to gather data on intellectual disability, verbal and physical aggression, destructive behaviour and self-injury and on characteristics known to be associated with aggression. RESULTS Aggression in SMS was more prevalent (87%), but not more severe than aggression in contrast groups. Aggressive behaviour was more frequently associated with environmental contingencies (e.g. attention, escape and access to tangibles) than self-injury and destructive behaviours. Severity of challenging behaviours was associated with high impulsivity. CONCLUSION Aggression is seen in the majority of people with SMS. Results suggest that behavioural disinhibition and operant social reinforcement are associated with the manifestation of aggression.

Neural correlates of task switching in paternal 15q11-q13 deletion Prader-Willi syndrome.

We report a first study of brain activity linked to task switching in individuals with Prader-Willi syndrome (PWS). PWS individuals show a specific cognitive deficit in task switching which may be associated with the display of temper outbursts and repetitive questioning. The performance of participants with PWS and typically developing controls was matched in a cued task switching procedure, and brain activity was contrasted on switching and non-switching blocks using fMRI. Individuals with PWS did not show the typical frontal-parietal pattern of neural activity associated with switching blocks, with significantly reduced activation in regions of the posterior parietal and ventromedial prefrontal cortices. We suggest that this is linked to a difficulty in PWS in setting appropriate attentional weights to enable task-set reconfiguration. In addition to this, PWS individuals did not show the typical pattern of deactivation, with significantly less deactivation in an anterior region of the ventromedial prefrontal cortex. One plausible explanation for this is that individuals with PWS show dysfunction within the default mode network, which has been linked to attentional control. The data point to functional changes in the neural circuitry supporting task switching in PWS even when behavioural performance is matched to controls and thus highlight neural mechanisms that may be involved in a specific pathway between genes, cognition and behaviour.

Oxytocin effects on neural correlates of self-referential processing

Oxytocin (OT) influences how humans process information about others. Whether OT affects the processing of information about oneself remains unknown. Using a double-blind, placebo-controlled within-subject design, we recorded event-related potentials (ERPs) from adults during trait judgments about oneself and a celebrity and during judgments on word valence, after intranasal OT or placebo administration. We found that OT vs. placebo treatment reduced the differential amplitudes of a fronto-central positivity at 220-280 ms (P2) during self- vs. valence-judgments. OT vs. placebo treatment tended to reduce the differential amplitude of a late positive potential at 520-1000 ms (LPP) during self-judgments but to increase the differential LPP amplitude during other-judgments. OT effects on the differential P2 and LPP amplitudes to self- vs. celebrity-judgments were positively correlated with a measure of interdependence of self-construals. Thus OT modulates the neural correlates of self-referential processing and this effect varies as a function of interdependence.

Dorsal and ventral stream mediated visual processing in genetic subtypes of Prader–Willi syndrome

Previous work has suggested that there are specific deficits in dorsal stream processing in a variety of developmental disorders. Prader-Willi syndrome (PWS) is associated with two main genetic subtypes, deletion and disomy. Relative strengths in visual processing are shown in PWS, although these strengths may be specific to the deletion subtype. We investigated visual processing in PWS using an adapted Simon task which contrasted location (dorsal stream) and shape identity (ventral stream) tasks. Compared to a group of typically developing children, children with PWS deletion showed a greater degree of impairment in the dorsal stream task than in the ventral stream task, a pattern similar to that shown in a group of boys with Fragile-X syndrome. When matched on a measure of non-verbal ability, children with PWS disomy showed the opposite pattern with better performance in the location compared to the shape task, although these task performance asymmetries may have been linked to executive control processes. It is proposed that children with PWS deletion show a relative strength in visual processing in the ventral stream along with a specific deficit in dorsal stream processing. In contrast, children with PWS disomy show neither effect.

Temper outbursts in Prader–Willi syndrome: causes, behavioural and emotional sequence and responses by carers

BACKGROUND Temper outbursts are common in Prader-Willi syndrome but rarely described in detail. This study investigated the phenomenology of temper outbursts in terms of antecedents, sequence of behaviours and emotions and intervention strategies used. METHOD A semi-structured interview about temper outbursts was conducted with the main carers of seven children (9.5 to 16.7 years) and seven adults (24.7 to 47.10 years) with Prader-Willi syndrome (10 male, 4 female). Reliability and validity of the interview results was established. RESULTS Various setting events increased and reduced the likelihood of temper outbursts. The most common antecedent was a change to routine or expectation. There were marked similarities in the sequence of behaviours and emotions during temper outbursts, with anger rising quickly followed by expressions of remorse and distress at the end of an outburst. DISCUSSION The sequence of behaviours and emotions within outbursts was similar to that described in temper tantrums in typical development. Cognitive and emotional processes are likely to be important in the understanding of temper outbursts with implications for early intervention.

Integrating levels of explanation in behavioural phenotype research.

The abstracts for the papers presented at this year’s meeting of the Society for the Study of Behavioural Phenotypes (SSBP) are published in this edition of the Journal of Intellectual Disability Research (JIDR). This is the 21st meeting of the Society and the content reflects the diversity of disciplines, methods and phenomenology that characterize research in this field. Describing and understanding behavioural phenotypes inevitably entails crossing the boundaries of traditional disciplines and this in turn means addressing two long-standing problems in the intellectual disability field.These are: (1) single discipline approaches cannot find routes from biological cause to brain to cognition to behaviour to environment and back to behaviour and cognition; and (2) researchers schooled in one discipline are unlikely to have expertise in each of the other disciplines necessary to trace these routes.The significance of these problems is that research that cannot generate multilevel models is less likely to be successful in leading to effective interventions for problems that have complex causes. Some of the most obvious examples of problems that warrant this kind of approach are sleep disorders, enuresis and encopresis, eating disorders and repetitive and selfinjurious behaviours. Many of these behaviours are prominent in the SSBP abstracts published in this edition. The designs of studies that characterize behavioural phenotypes are increasingly required to protect against threats to internal, external and construct validity by using appropriate contrast groups, methods of assessment and sampling. For each genetic disorder, there appears to be a gradual evolution in the literature from case study to cohort description to matched comparison. More refined designs then follow with the outcome of variations in genotype featuring as the independent variable and longitudinal designs being employed to examine developmental trajectories. Neuroimaging studies are then undertaken with brain–cognition– behaviour correlations being explored. Finally, studies of gene environment interactions emerge and these provide a dynamic context for behaviour that may contribute to understanding within syndrome variation and change over time. This sequence of development for the characterization of a phenotype shows the gradual spread of interest in a genetic disorder across disciplines with the creation of datasets relevant to biological, psychological and social factors. As these data are produced, models of the determinants of a behavioural phenotype must be able to incorporate the more robust findings. There is widespread rhetorical support for the assertion that biopsychosocial models of cognitive, emotional and behavioural difference and disorder provide a more complete account for the available empirical data than, for example, purely biological or social constructionist perspectives. However, it is not clear whether this rhetoric is being readily translated into practice. These impressions of trends in the research literature are worth evaluating to see if biopsychosocial models are emerging as evidenced by multilevel Journal of Intellectual Disability Research doi: 10.1111/j.1365-2788.2008.01117.x

Informing the structure of executive function in children: a meta-analysis of functional neuroimaging data

The structure of executive function (EF) has been the focus of much debate for decades. What is more, the complexity and diversity provided by the developmental period only adds to this contention. The development of executive function plays an integral part in the expression of childrens behavioral, cognitive, social, and emotional capabilities. Understanding how these processes are constructed during development allows for effective measurement of EF in this population. This meta-analysis aims to contribute to a better understanding of the structure of executive function in children. A coordinate-based meta-analysis was conducted (using BrainMap GingerALE 2.3), which incorporated studies administering functional magnetic resonance imaging (fMRI) during inhibition, switching, and working memory updating tasks in typical children (aged 6–18 years). The neural activation common across all executive tasks was compared to that shared by tasks pertaining only to inhibition, switching or updating, which are commonly considered to be fundamental executive processes. Results support the existence of partially separable but partially overlapping inhibition, switching, and updating executive processes at a neural level, in children over 6 years. Further, the shared neural activation across all tasks (associated with a proposed “unitary” component of executive function) overlapped to different degrees with the activation associated with each individual executive process. These findings provide evidence to support the suggestion that one of the most influential structural models of executive functioning in adults can also be applied to children of this age. However, the findings also call for careful consideration and measurement of both specific executive processes, and unitary executive function in this population. Furthermore, a need is highlighted for a new systematic developmental model, which captures the integrative nature of executive function in children.