Celeste H.M. Cheung

Neural signatures of autism

Functional magnetic resonance imaging of brain responses to biological motion in children with autism spectrum disorder (ASD), unaffected siblings (US) of children with ASD, and typically developing (TD) children has revealed three types of neural signatures: (i) state activity, related to the state of having ASD that characterizes the nature of disruption in brain circuitry; (ii) trait activity, reflecting shared areas of dysfunction in US and children with ASD, thereby providing a promising neuroendophenotype to facilitate efforts to bridge genomic complexity and disorder heterogeneity; and (iii) compensatory activity, unique to US, suggesting a neural system–level mechanism by which US might compensate for an increased genetic risk for developing ASD. The distinct brain responses to biological motion exhibited by TD children and US are striking given the identical behavioral profile of these two groups. These findings offer far-reaching implications for our understanding of the neural systems underlying autism.

Childhood predictors of adolescent and young adult outcome in ADHD

BACKGROUND Attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood, but it remains unclear which childhood factors predict future outcome. AIM To identify childhood predictors of ADHD outcome using both dimensional and categorical approaches. METHODS 116 adolescents and young adults with childhood ADHD were followed up on average 6.6 years later. ADHD outcome variables were interview-based parent-reported ADHD symptoms and impairment. Childhood predictors included parent- and teacher-rated ADHD symptoms and co-occurring behaviours; actigraph measures of activity level; socio-economic status (SES); and cognitive measures previously associated with ADHD. RESULTS Of the sample, 79% continued to meet clinical criteria of ADHD in adolescence and young adulthood. Higher parent-rated ADHD symptoms and movement intensity in childhood, but not teacher-rated symptoms, predicted ADHD symptoms at follow up. Co-occurring symptoms of oppositional behaviours, anxiety, social and emotional problems were also significant predictors, but these effects disappeared after controlling for ADHD symptoms. IQ and SES were significant predictors of both ADHD symptoms and impairment at follow up, but no other cognitive measures significantly predicted outcome. CONCLUSIONS SES and IQ emerge as potential moderators for the prognosis of ADHD. Childhood severity of ADHD symptoms, as measured by parent ratings and actigraph movement intensity, also predicts later ADHD outcome. These factors should be considered when identifying ADHD children at most risk of poor long-term outcomes and for the development of interventions to improve prognosis.

Cognitive and neurophysiological markers of ADHD persistence and remission

BACKGROUND Attention-deficit hyperactivity disorder (ADHD) persists in around two-thirds of individuals in adolescence and early adulthood. AIMS To examine the cognitive and neurophysiological processes underlying the persistence or remission of ADHD. METHOD Follow-up data were obtained from 110 young people with childhood ADHD and 169 controls on cognitive, electroencephalogram frequency, event-related potential (ERP) and actigraph movement measures after 6 years. RESULTS ADHD persisters differed from remitters on preparation-vigilance measures (contingent negative variation, delta activity, reaction time variability and omission errors), IQ and actigraph count, but not on executive control measures of inhibition or working memory (nogo-P3 amplitudes, commission errors and digit span backwards). CONCLUSIONS Preparation-vigilance measures were markers of remission, improving concurrently with ADHD symptoms, whereas executive control measures were not sensitive to ADHD persistence/remission. For IQ, the present and previous results combined suggest a role in moderating ADHD outcome. These findings fit with previously identified aetiological separation of the cognitive impairments in ADHD. The strongest candidates for the development of non-pharmacological interventions involving cognitive training and neurofeedback are the preparation-vigilance processes that were markers of ADHD remission.

Face-related ERPs are modulated by point of gaze

This study examined the influence of gaze fixation on face-sensitive ERPs. A fixation crosshair presented prior to face onset directed visual attention to upper, central, or lower face regions while ERPs were recorded. This manipulation modulated a face-sensitive component (N170) but not an early sensory component (P1). Upper and lower face fixations elicited enhanced N170 amplitude and longer N170 latency. Results expand upon extant hemodynamic research by demonstrating early effects at basic stages of face processing. These findings distinguish attention to facial features in context from attention to isolated features, and they inform electrophysiological studies of face processing in clinical populations.

Aetiology for the covariation between combined type ADHD and reading difficulties in a family study: the role of IQ

BACKGROUND Twin studies using both clinical and population-based samples suggest that the frequent co-occurrence of attention deficit hyperactivity disorder (ADHD) and reading ability/disability (RD) is largely driven by shared genetic influences. While both disorders are associated with lower IQ, recent twin data suggest that the shared genetic variability between reading difficulties and ADHD inattention symptoms is largely independent from genetic influences contributing to general cognitive ability. The current study aimed to extend the previous findings that were based on rating scale measures in a population sample by examining the generalisability of the findings to a clinical population, and by measuring reading difficulties both with a rating scale and with an objective task. This study investigated the familial relationships between ADHD, reading difficulties and IQ in a sample of individuals diagnosed with ADHD combined type, their siblings and control sibling pairs. METHODS Multivariate familial models were run on data from 1,789 individuals at ages 6-19. Reading difficulties were measured with both rating scale and an objective task. IQ was obtained using the Wechsler Intelligence Scales (WISC-III/WAIS-III). RESULTS Significant phenotypic (.2-.4) and familial (.3-.5) correlations were observed among ADHD, reading difficulties and IQ. Yet, 53%-72% of the overlapping familial influences between ADHD and reading difficulties were not shared with IQ. CONCLUSIONS Our finding that familial influences shared with general cognitive ability, although present, do not account for the majority of the overlapping familial influences on ADHD and reading difficulties extends previous findings from a population-based study to a clinically ascertained sample with combined type ADHD.

Neural responses to faces reflect social personality traits

Faces are a developmentally primary and critically important source of social information, and they are processed differently from most other visual percepts. Studies of brain electrophysiology reveal a face-sensitive component, the N170, which is typically enhanced to faces relative to other stimuli. Research in social disabilities suggests that an atypical N170 response in this population may stem from decreased developmental exposure to faces secondary to reduced social interest. Here we examined the relationship between neural responses to faces and social personality characteristics in a normative sample. Participants were pre-screened to identify individuals scoring high on extraversion or introversion. Both groups were presented with upright and inverted face stimuli. An inversion effect, a marker of expertise for faces, was observed in people with high extraversion but not in those with high introversion. These findings suggest that, within typically developing populations, social attitudes are reflected in the neural correlates of face perception.

Attention-Deficit/Hyperactivity Disorder Remission Is Linked to Better Neurophysiological Error Detection and Attention-Vigilance Processes

Background The processes underlying persistence and remission of attention-deficit/hyperactivity disorder (ADHD) are poorly understood. We examined whether cognitive and neurophysiological impairments on a performance-monitoring task distinguish between ADHD persisters and remitters. Methods On average 6 years after initial assessment, 110 adolescents and young adults with childhood ADHD (87 persisters, 23 remitters) and 169 age-matched control participants were compared on cognitive-performance measures and event-related potentials of conflict monitoring (N2) and error processing (error-related negativity and positivity) from an arrow flanker task with low-conflict and high-conflict conditions. ADHD outcome was examined with parent-reported symptoms and functional impairment measures using a categorical (DSM-IV) and a dimensional approach. Results ADHD persisters were impaired compared with controls on all cognitive-performance and event-related potential measures (all p < .05). ADHD remitters differed from persisters and were indistinguishable from control participants on the number of congruent (low-conflict) errors, reaction time variability, error-related negativity, and error-related positivity (all p ≤ .05). Remitters did not differ significantly from the other groups on incongruent (high-conflict) errors, mean reaction time, and N2. In dimensional analyses on all participants with childhood ADHD, ADHD symptoms and functional impairment at follow-up were significantly correlated with congruent errors, reaction time variability, and error-related positivity (r = .19–.23, p ≤ .05). Conclusions Cognitive and neurophysiological measures of attention-vigilance and error detection distinguished ADHD remitters from persisters. These results extend our previous findings with other tasks and indicate that such measures are markers of remission and candidates for the development of nonpharmacological interventions.

Shared cognitive impairments and aetiology in ADHD symptoms and reading difficulties.

Background Twin studies indicate that the frequent co-occurrence of attention deficit hyperactivity disorder (ADHD) symptoms and reading difficulties (RD) is largely due to shared genetic influences. Both disorders are associated with multiple cognitive impairments, but it remains unclear which cognitive impairments share the aetiological pathway, underlying the co-occurrence of the symptoms. We address this question using a sample of twins aged 7–10 and a range of cognitive measures previously associated with ADHD symptoms or RD. Methods We performed multivariate structural equation modelling analyses on parent and teacher ratings on the ADHD symptom domains of inattention and hyperactivity, parent ratings on RD, and cognitive data on response inhibition (commission errors, CE), reaction time variability (RTV), verbal short-term memory (STM), working memory (WM) and choice impulsivity, from a population sample of 1312 twins aged 7–10 years. Results Three cognitive processes showed significant phenotypic and genetic associations with both inattention symptoms and RD: RTV, verbal WM and STM. While STM captured only 11% of the shared genetic risk between inattention and RD, the estimates increased somewhat for WM (21%) and RTV (28%); yet most of the genetic sharing between inattention and RD remained unaccounted for in each case. Conclusion While response inhibition and choice impulsivity did not emerge as important cognitive processes underlying the co-occurrence between ADHD symptoms and RD, RTV and verbal memory processes separately showed significant phenotypic and genetic associations with both inattention symptoms and RD. Future studies employing longitudinal designs will be required to investigate the developmental pathways and direction of causality further.

Neurophysiological Correlates of Attentional Fluctuation in Attention-Deficit/Hyperactivity Disorder

Cognitive performance in attention-deficit/hyperactivity disorder (ADHD) is characterised, in part, by frequent fluctuations in response speed, resulting in high reaction time variability (RTV). RTV captures a large proportion of the genetic risk in ADHD but, importantly, is malleable, improving significantly in a fast-paced, rewarded task condition. Using the temporal precision offered by event-related potentials (ERPs), we aimed to examine the neurophysiological measures of attention allocation (P3 amplitudes) and preparation (contingent negative variation, CNV), and their associations with the fluctuating RT performance and its improvement in ADHD. 93 participants with ADHD and 174 controls completed the baseline and fast-incentive conditions of a four-choice reaction time task, while EEG was simultaneously recorded. Compared to controls, individuals with ADHD showed both increased RTV and reduced P3 amplitudes during performance on the RT task. In the participants with ADHD, attenuated P3 amplitudes were significantly associated with high RTV, and the increase in P3 amplitudes from a slow baseline to a fast-paced, rewarded condition was significantly associated with the RTV decrease. Yet, the individuals with ADHD did not show the same increase in CNV from baseline to fast-incentive condition as observed in controls. ADHD is associated both with a neurophysiological impairment of attention allocation (P3 amplitudes) and an inability to adjust the preparatory state (CNV) in a changed context. Our findings suggest that both neurophysiological and cognitive performance measures of attention are malleable in ADHD, which are potential targets for non-pharmacological interventions.

Six-year follow-up study of combined type ADHD from childhood to young adulthood: Predictors of functional impairment and comorbid symptoms.

BACKGROUND ADHD in childhood is associated with development of negative psychosocial and behavioural outcomes in adults. Yet, relatively little is known about which childhood and adulthood factors are predictive of these outcomes and could be targets for effective interventions. To date follow-up studies have largely used clinical samples from the United States with children ascertained at baseline using broad criteria for ADHD including all clinical subtypes or the use of DSM III criteria. AIMS To identify child and adult predictors of comorbid and psychosocial comorbid outcomes in ADHD in a UK sample of children with DSM-IV combined type ADHD. METHOD One hundred and eighteen adolescents and young adults diagnosed with DSM-IV combined type ADHD in childhood were followed for an average of 6years. Comorbid mental health problems, drug and alcohol use and police contact were compared for those with persistent ADHD, sub-threshold ADHD and population norms taken from the Adult Psychiatric Morbidity Study 2007. Predictors included ADHD symptomology and gender. RESULTS Persistent ADHD was associated with greater levels of anger, fatigue, sleep problems and anxiety compared to sub-threshold ADHD. Comorbid mental health problems were predicted by current symptoms of hyperactivity-impulsivity, but not by childhood ADHD severity. Both persistent and sub-threshold ADHD was associated with higher levels of drug use and police contact compared to population norms. CONCLUSIONS Young adults with a childhood diagnosis of ADHD showed increased rates of comorbid mental health problems, which were predicted by current levels of ADHD symptoms. This suggests the importance of the continuing treatment of ADHD throughout the transitional years and into adulthood. Drug use and police contact were more common in ADHD but were not predicted by ADHD severity in this sample.