Event-related brain-oscillatory and ex-Gaussian markers of remission and persistence of ADHD.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) often persists into adolescence and adulthood, but the processes underlying persistence and remission remain poorly understood. We previously found that reaction time variability and event-related potentials of preparation-vigilance processes were impaired in ADHD persisters and represented markers of remission, as ADHD remitters were indistinguishable from controls but differed from persisters. Here, we aimed to further clarify the nature of the cognitive-neurophysiological impairments in ADHD and of markers of remission by examining the finer-grained ex-Gaussian reaction-time distribution and electroencephalographic (EEG) brain-oscillatory measures in ADHD persisters, remitters and controls. METHODS: A total of 110 adolescents and young adults with childhood ADHD (87 persisters, 23 remitters) and 169 age-matched controls were compared on ex-Gaussian (mu, sigma, tau) indices and time-frequency EEG measures of power and phase consistency from a reaction-time task with slow-unrewarded baseline and fast-incentive conditions ('Fast task'). RESULTS: Compared to controls, ADHD persisters showed significantly greater mu, sigma, tau, and lower theta power and phase consistency across conditions. Relative to ADHD persisters, remitters showed significantly lower tau and theta power and phase consistency across conditions, as well as lower mu in the fast-incentive condition, with no difference in the baseline condition. Remitters did not significantly differ from controls on any measure. CONCLUSIONS: We found widespread impairments in ADHD persisters in reaction-time distribution and brain-oscillatory measures. Event-related theta power, theta phase consistency and tau across conditions, as well as mu in the more engaging fast-incentive condition, emerged as novel markers of ADHD remission, potentially representing compensatory mechanisms in individuals with remitted ADHD.

Effect of using commercial pre-packaged baby foods on the Fe intake of 7-8 months old infants.

OBJECTIVES: To examine the potential effect on Fe intake of 7-8 months old infants if pre-packaged baby foods (PBF) were used as the sole source of complementary foods. DESIGN: Based on the 7-d recommended feeding plan for 7-8 months old infants in Hong Kong (moderate Fe-fortified rice cereal with home-cooked meals), twenty-four modelling scenarios were created which comprised of two milk use modes (breastmilk v. infant formula), three modes of rice cereal use (no-rice cereal; non-Fe-fortified rice cereal and Fe-fortified rice cereal) and four baby foods usage modes (home-cooked meals; low-Fe PBF only; high-Fe PBF only and mixed PBF). The PBF were randomly selected in each of the models and substituted the original meals/snacks. The average daily Fe intakes of the modelled meal plans were compared with the Chinese estimated average requirement (EAR) and recommended nutrient intake (RNI) for Fe. SETTING: Modelling study. PARTICIPANTS: Not applicable. RESULTS: In general, the infant-formula-based complementary feeding pattern (CFP) had higher average daily Fe intake when compared with breastmilk-based CFP. The Fe intakes of all scenarios under the breastmilk-based CFP were below the RNI and EAR, except for the fortified rice cereal meal plans with high-Fe or mixed PBF. For infant-formula-based CFP, the Fe intakes were close to or above the RNI regardless of types of PBF or rice cereal used. CONCLUSIONS: The inclusion of fortified rice cereal was important in maintaining adequate Fe intake for infants, especially for breast-fed infants. The replacement of home-cooked meals by low-Fe PBF could potentially put infants at risk of Fe deficiency.

Randomised trial of a parent-mediated intervention for infants at high risk for autism: longitudinal outcomes to age 3 years.

BACKGROUND: There has been increasing interest in the potential for pre-emptive interventions in the prodrome of autism, but little investigation as to their effect. METHODS: A two-site, two-arm assessor-blinded randomised controlled trial (RCT) of a 12-session parent-mediated social communication intervention delivered between 9 and 14 months of age (Intervention in the British Autism Study of Infant Siblings-Video Interaction for Promoting Positive Parenting), against no intervention. Fifty-four infants (28 intervention, 26 nonintervention) at familial risk of autism but not otherwise selected for developmental atypicality were assessed at 9-month baseline, 15-month treatment endpoint, and 27- and 39-month follow-up. PRIMARY OUTCOME: severity of autism prodromal symptoms, blind-rated on Autism Observation Schedule for Infants or Autism Diagnostic Observation Schedule 2nd Edition across the four assessment points. SECONDARY OUTCOMES: blind-rated parent-child interaction and child language; nonblind parent-rated communication and socialisation. Prespecified intention-to-treat analysis combined estimates from repeated measures within correlated regressions to estimate the overall effect of the infancy intervention over time. RESULTS: Effect estimates in favour of intervention on autism prodromal symptoms, maximal at 27 months, had confidence intervals (CIs) at each separate time point including the null, but showed a significant overall effect over the course of the intervention and follow-up period (effect size [ES] = 0.32; 95% CI 0.04, 0.60; p = .026). Effects on proximal intervention targets of parent nondirectiveness/synchrony (ES = 0.33; CI 0.04, 0.63; p = .013) and child attentiveness/communication initiation (ES = 0.36; 95% CI 0.04, 0.68; p = .015) showed similar results. There was no effect on categorical diagnostic outcome or formal language measures. CONCLUSIONS: Follow-up to 3 years of the first RCT of a very early social communication intervention for infants at familial risk of developing autism has shown a treatment effect, extending 24 months after intervention end, to reduce the overall severity of autism prodromal symptoms and enhance parent-child dyadic social communication over this period. We highlight the value of extended follow-up and repeat assessment for early intervention trials.

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.

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.

Testing for the mediating role of endophenotypes using molecular genetic data in a twin study of ADHD traits.

Family and twin studies have identified endophenotypes that capture familial and genetic risk in attention-deficit/hyperactivity disorder (ADHD), but it remains unclear if they lie on the causal pathway. Here, we illustrate a stepwise approach to identifying intermediate phenotypes. First, we use previous quantitative genetic findings to delineate the expected pattern of genetically correlated phenotypes. Second, we identify overlapping genetic associations with ADHD-related quantitative traits. Finally, we test for the mediating role of associated endophenotypes. We applied this approach to a sample of 1,312 twins aged 7-10. Based on previous twin model-fitting analyses, we selected hyperactivity-impulsivity, inattention, reading difficulties (RD), reaction time variability (RTV) and commission errors (CE), and tested for association with selected ADHD risk alleles. For nominally significant associations with both a symptom and a cognitive variable, matching the expected pattern based on previous genetic correlations, we performed mediation analysis to distinguish pleiotropic from mediating effects. The strongest association was observed for the rs7984966 SNP in the serotonin receptor gene (HTR2A), and RTV (P = 0.007; unadjusted for multiple testing). Mediation analysis suggested that CE (38%) and RTV (44%) substantially mediated the association between inattention and the T-allele of SNP rs3785157 in the norepinephrine transporter gene (SLC6A2) and the T-allele of SNP rs7984966 in HTR2A, respectively. The SNPs tag risk-haplotypes but are not thought to be functionally significant. While these exploratory findings are preliminary, requiring replication, this study demonstrates the value of this approach that can be adapted to the investigation of multiple genetic markers and polygenic risk scores. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

A Matter of Time: The Influence of Recording Context on EEG Spectral Power in Adolescents and Young Adults with ADHD.

Elevated theta or theta/beta ratio is often reported in attention deficit hyperactivity disorder (ADHD), but the consistency across studies and the relation to hypoarousal are increasingly questioned. Reports of elevated delta related to maturational lag and of attenuated beta activity are less well replicated. Some critical inconsistencies could relate to differences in recording context. We examined if resting-state EEG power or global field synchronization (GFS) differed between recordings made at the beginning and end of a 1.5 h testing session in 76 adolescents and young adults with ADHD, and 85 controls. In addition, we aimed to examine the effect of IQ on any potential group differences. Both regional and midline electrodes yielded group main effects for delta, trends in theta, but no differences in alpha or theta/beta ratio. An additional group difference in beta was detected when using regions. Group by time interactions in delta and theta became significant when controlling for IQ. The ADHD group had higher delta and theta power at time-1, but not at time-2, whereas beta power was elevated only at time-2. GFS did not differ between groups or condition. We show some ADHD-control differences on EEG spectral power varied with recording time within a single recording session, with both IQ and electrode selection having a small but significant influence on observed differences. Our findings demonstrate the effect of recording context on resting-state EEG, and highlight the importance of accounting for these variables to ensure consistency of results in future studies.

IRF-1 regulates alternative mRNA splicing of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in breast epithelial cells generating an immunoreceptor tyrosine-based inhibition motif (ITIM) containing isoform.

BACKGROUND: Interferon regulatory factor-1 (IRF-1) is a master regulator of IFN-γ induced gene transcription. Previously we have shown that IRF-1 transcriptionally induces CEACAM1 via an ISRE (Interferon-Stimulated Response Element) in its promoter. CEACAM1 pre-mRNA undergoes extensive alternative splicing (AS) generating isoforms to produce either a short (S) cytoplasmic domain expressed primarily in epithelial cells or as an ITIM-containing long (L) isoform in immune cells. METHODS: The transcriptional and molecular mechanism of CEACAM1 minigenes AS containing promoter ISREs mutations in the breast epithelial, MDA-MB-468, cell line was detected using flow cytometry. In addition, transcriptome sequencing was utilized to determine whether IRF-1 could direct the AS of other genes as well. Tumor xenografts were used to evaluate CEACAM1 isoform expression on the leading edge of breast tumor cells. RESULTS: In the present study, we provide evidence that CEACAM1's promoter and variable exon 7 cross-talk allowing IRF-1 to direct AS events. Transcriptome sequencing shows that IRF-1 can also induce the global AS of genes involved in regulation of growth and differentiation as well as genes of the cytokine family. Furthermore, MDA-MB-468 cells grown as tumor xenografts exhibit an AS switch to the L-isoform of CEACAM1, demonstrating that an in vivo inflammatory milieu is also capable of generating the AS switch, similar to that found in human breast cancers Mol Cancer 7:46, 2008. CONCLUSIONS: The novel AS regulatory activities attributed to IRF-1 indicate that the IFN-γ response involves a global change in both gene transcription and AS in breast epithelial cells.

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.

The Etiological and Predictive Association Between ADHD and Cognitive Performance From Childhood to Young Adulthood.

OBJECTIVE: Evidence about the etiology of the predictive associations between a diagnosis of ADHD and cognitive performance over time is scarce. Here, we examine these predictive and etiological patterns using a cross-lagged model design in a sample of 404 participants (74% males) from ADHD and control sibling pairs aged 6 to 17 years at baseline and 12 to 24 years at follow-up. METHODS: Data included IQ, short-term and working memory measures, and response speed and variability from a four-choice reaction-time task. RESULTS: ADHD and IQ predicted each other over time. ADHD at baseline predicted lower working memory performance at follow-up. Stable etiological influences emerged in the association between ADHD and cognitive variables across time. CONCLUSION: Whether early interventions can reduce negative interference with learning at school requires further study.

Sucrose-induced hyperglycemia dysregulates intestinal zinc metabolism and integrity: risk factors for chronic diseases.

Objective: Zinc is an essential micronutrient that is critical for many physiological processes, including glucose metabolism, regulation of inflammation, and intestinal barrier function. Further, zinc dysregulation is associated with an increased risk of chronic inflammatory diseases such as type II diabetes, obesity, and inflammatory bowel disease. However, whether altered zinc status is a symptom or cause of disease onset remains unclear. Common symptoms of these three chronic diseases include the onset of increased intestinal permeability and zinc dyshomeostasis. The specific focus of this work is to investigate how dietary sources of intestinal permeability, such as high sucrose consumption, impact transporter-mediated zinc homeostasis and subsequent zinc-dependent physiology contributing to disease development. Method: We used in vivo subchronic sucrose treatment, ex vivo intestinal organoid culture, and in vitro cell systems. We analyze the alterations in zinc metabolism and intestinal permeability and metabolic outcomes. Results: We found that subchronic sucrose treatment resulted in systemic changes in steady-state zinc distribution and increased 65Zn transport (blood-to-intestine) along with greater ZIP14 expression at the basolateral membrane of the intestine. Further, sucrose treatment enhanced cell survival of intestinal epithelial cells, activation of the EGFR-AKT-STAT3 pathway, and intestinal permeability. Conclusion: Our work suggests that subchronic high sucrose consumption alters systemic and intestinal zinc homeostasis linking diet-induced changes in zinc homeostasis to the intestinal permeability and onset of precursors for chronic disease.

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.

Longitudinal touchscreen use across early development is associated with faster exogenous and reduced endogenous attention control.

Childhood screen time is associated with both attentional difficulties (for television viewing) and benefits (in action video gamers), but few studies have investigated today's pervasive touchscreen devices (e.g. smartphones and tablets), which combine salient features, interactive content, and accessibility from toddlerhood (a peak period of cognitive development). We tested exogenous and endogenous attention, following forty children who were stable high (HU) or low (LU) touchscreen users from toddlerhood to pre-school. HUs were slower to disengage attention, relative to their faster baseline orienting ability. In an infant anti-saccade task, HUs displayed more of a corrective strategy of orienting faster to distractors before anticipating the target. Results suggest that long-term high exposure to touchscreen devices is associated with faster exogenous attention and concomitant decreases in endogenous attention control. Future work is required to demonstrate causality, dissociate variants of use, and investigate how attention behaviours found in screen-based contexts translate to real-world settings.

Iron content and fortification status of a sample of local and imported pre-packaged baby foods available in Hong Kong.

AIM: To examine the iron content and fortification status of pre-packaged baby foods in Hong Kong. METHODS: Data of 472 pre-packaged baby foods were collected from various distribution points in Hong Kong in July-August 2018. Item descriptors, iron content, ingredients list, country of origin, organic status and iron-related guidelines displayed on the package were recorded. Between group differences in the median (IQR) iron content were compared by the Mann-Whitney U test; and by Pearson's χ2 test for the proportion of pre-packaged baby foods that were iron-fortified or displaying iron-related guidelines, stratified by country of origin and organic status where appropriate. RESULTS: Only 79 out of 472 pre-packaged baby foods displayed iron content on their labels, and their median iron content was 6.80 (1.3-20.0) mg/100 g. Of these, cereals [14.0 (12.0-32.0)] and snacks and finger foods [12.6 (1.4-21.3)] had significantly higher iron content than other pre-packaged baby foods. Less than 20% of pre-packaged baby foods in Hong Kong were iron-fortified. North American pre-packaged baby foods (49.2%) were more likely than those from other places of origin (all P < .001) to be iron-fortified, and marginally more non-organic pre-packaged baby foods were iron-fortified products than organic (23.6% vs 16.2%, P = .043). Only 17.2% of products included iron-related guidelines/cautions on their packaging. CONCLUSIONS: The majority of pre-packaged baby foods available in Hong Kong lacked iron fortification, and did not display iron-related guidelines/cautions or their iron content on the package. Given the inconsistent fortification practices by manufacturers, labelling of iron content should be mandatory to assist parents in identifying iron-rich pre-packaged baby foods.

Does Co-Occurring Anxiety Modulate ADHD-Related Cognitive and Neurophysiological Impairments?

Objective: This study investigates whether anxiety modulates cognitive-performance, electrophysiological and electrodermal processes that we previously found impaired in individuals with ADHD. Method: Self-reported anxiety symptoms, cognitive-electrophysiological measures of response inhibition, working memory, attention, conflict monitoring, error processing, and peripheral arousal during three cognitive tasks were obtained from 87 adolescents and young adults with ADHD and 169 controls. We tested the association of anxiety symptoms with each measure and whether controlling for anxiety symptoms attenuates the ADHD-control difference for each measure. Results: Individuals with ADHD showed significantly elevated anxiety symptoms compared with controls. Only commission errors on a Continuous Performance Test (measuring response inhibition) were significantly associated with anxiety symptoms and only among controls, with the ADHD-control difference in this measure remaining significant. Conclusion: Using a wide range of cognitive, electrophysiological, and electrodermal measures, our investigation suggests, overall, limited malleability of these impairments in individuals with ADHD irrespective of their levels of anxiety.

The Etiological Structure of Cognitive-Neurophysiological Impairments in ADHD in Adolescence and Young Adulthood.

Objective: Previous studies in children with ADHD identified two partially separable familial factors underlying cognitive dysfunction, but evidence in adolescents and adults is lacking. Here, we investigate the etiological structure of cognitive-neurophysiological impairments in ADHD in adolescents and young adults. Method: Factor analyses and multivariate familial models were run in 356 participants from ADHD and control sibling pairs aged 11 to 27 years on data on IQ, digit span forward (DSF) and backward (DSB), and cognitive-performance and event-related potential (ERP) measures from three cognitive tasks. Results: Three familial factors (cF1-3), showing substantial familial overlap with ADHD, captured the familial covariation of ADHD with nine cognitive-ERP measures. cF1 loaded on IQ, mean reaction time (MRT), and reaction-time variability (RTV); cF2 on DSF and DSB; and cF3 on number of errors and ERPs of inhibition and error processing. Conclusion: These results identify three partially separable etiological pathways leading to cognitive-neurophysiological impairments in adolescent and adult ADHD.

Peripheral Hypoarousal but Not Preparation-Vigilance Impairment Endures in ADHD Remission.

Objective: This study investigates whether impairments associated with persistent ADHD-impaired attention allocation (P3 amplitude), peripheral hypoarousal (skin conductance level [SCL]), and adjustment in preparatory state (contingent negative variation [CNV])-reflect enduring deficits unrelated to ADHD outcome or are markers of ADHD remission. Method: Young people with childhood ADHD (73 persisters and 18 remitters) and 144 controls were compared on neurophysiological measures during two conditions (baseline and fast-incentive) of a four-choice reaction time task. Results: ADHD remitters differed from persisters, and were indistinguishable from controls, on baseline P3 amplitude and fast-incentive CNV amplitude (p ≤ .05). ADHD remitters differed from controls (p ≤ .01), and were indistinguishable from persisters (p > .05), on baseline SCL. Conclusion: Preparation-vigilance measures were markers of ADHD remission, confirming previous findings with other measures. Yet, SCL-measured peripheral hypoarousal emerges as an enduring deficit unrelated to ADHD improvement. Future studies should explore potential compensatory mechanisms that enable efficient preparation-vigilance processes in ADHD remitters.

Atypical functional connectivity in adolescents and adults with persistent and remitted ADHD during a cognitive control task.

We previously provided initial evidence for cognitive and event-related potential markers of persistence/remission of attention-deficit/hyperactivity disorder (ADHD) from childhood to adolescence and adulthood. Here, using a novel brain-network connectivity approach, we aimed to examine whether task-based functional connectivity reflects a marker of ADHD remission or an enduring deficit unrelated to ADHD outcome. High-density EEG was recorded in a follow-up of 110 adolescents and young adults with childhood ADHD (87 persisters, 23 remitters) and 169 typically developing individuals during an arrow-flanker task, eliciting cognitive control. Functional connectivity was quantified with network-based graph-theory metrics before incongruent (high-conflict) target onset (pre-stimulus), during target processing (post-stimulus) and in the degree of change between pre-stimulus/post-stimulus. ADHD outcome was examined with parent-reported symptoms and impairment using both a categorical (DSM-IV) and a dimensional approach. Graph-theory measures converged in indicating that, compared to controls, ADHD persisters showed increased connectivity in pre-stimulus theta, alpha, and beta and in post-stimulus beta (all p < .01) and reduced pre-stimulus/post-stimulus change in theta connectivity (p < .01). In the majority of indices showing ADHD persister-control differences, ADHD remitters differed from controls (all p < .05) but not from persisters. Similarly, connectivity measures were unrelated to continuous outcome measures of ADHD symptoms and impairment in participants with childhood ADHD. These findings indicate that adolescents and young adults with persistent and remitted ADHD share atypical over-connectivity profiles and reduced ability to modulate connectivity patterns with task demands, compared to controls. Task-based functional connectivity impairments may represent enduring deficits in individuals with childhood ADHD irrespective of diagnostic status in adolescence/young adulthood.

Daily touchscreen use in infants and toddlers is associated with reduced sleep and delayed sleep onset.

Traditional screen time (e.g. TV and videogaming) has been linked to sleep problems and poorer developmental outcomes in children. With the advent of portable touchscreen devices, this association may be extending down in age to disrupt the sleep of infants and toddlers, an age when sleep is essential for cognitive development. However, this association has not been demonstrated empirically. This study aims to examine whether frequency of touchscreen use is associated with sleep in infants and toddlers between 6 and 36 months of age. An online survey was administered to 715 parents reporting on child media use (daily exposure to TV and use of touchscreens), sleep patterns (night-time and daytime sleep duration, sleep onset - time to fall asleep, and frequencies of night awakenings). Structural equation models controlling for age, sex, TV exposure and maternal education indicated a significant association between touchscreen use and night-time sleep, daytime sleep and sleep onset. No significant effect was observed for the number of night awakenings. To our knowledge, this is the first report linking the use of touchscreen with sleep problems in infants and toddlers. Future longitudinal studies are needed to clarify the direction of effects and the mechanisms underlying these associations using detailed sleep tracking.

Modifiable Arousal in Attention-Deficit/Hyperactivity Disorder and Its Etiological Association With Fluctuating Reaction Times.

BACKGROUND: Cognitive theories of attention-deficit/hyperactivity disorder (ADHD) propose that high within-subject fluctuations of cognitive performance in ADHD, particularly reaction time (RT) variability (RTV), may reflect arousal dysregulation. However, direct evidence of arousal dysregulation and how it may account for fluctuating RTs in ADHD is limited. We used skin conductance (SC) as a measure of peripheral arousal and aimed to investigate its phenotypic and familial association with RTV in a large sample of ADHD and control sibling pairs. METHODS: Adolescents and young adults (N = 292), consisting of 73 participants with ADHD and their 75 siblings, and 72 controls and their 72 siblings, completed the baseline (slow, unrewarded) and fast-incentive conditions of a RT task, while SC was simultaneously recorded. RESULTS: A significant group-by-condition interaction emerged for SC level (SCL). Participants with ADHD had decreased SCL, compared with controls, in the baseline condition but not the fast-incentive condition. Baseline SCL was negatively associated with RTV, and multivariate model fitting demonstrated that the covariance of SCL with RTV, and of SCL with ADHD, was mostly explained by shared familial effects. CONCLUSIONS: ADHD is associated with decreased, but modifiable, tonic peripheral arousal. A shared familial cause underlies the relationship between arousal and RTV and between arousal and ADHD. Given the malleability of SCL, if our findings are replicated, it warrants further exploration as a potential treatment target for ADHD.