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This study explored whether high autistic traits, high attention deficit hyperactivity disorder (ADHD) traits and their interaction were associated with quality of life (QoL) in a sample of 556 of young-adult twins (Mean age 22 years 5 months, 52% Female). Four participant groups were created: high autistic traits, high ADHD traits, high autistic/ADHD traits, and low ADHD/autistic traits. High autistic traits were associated with lower QoL across domains (physical, psychological, social, and environmental). High ADHD traits associated with lower physical, psychological, and environmental QoL. The interaction of autistic and ADHD traits was not significant in any domain. While mental health difficulties were associated with lower QoL, after accounting for mental health, most relationships between autistic traits, ADHD traits and QoL remained.

Altered power of resting-state neurophysiological activity has been associated with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), which commonly co-occur. We compared resting-state neurophysiological power in children with ASD, ADHD, co-occurring ASD + ADHD, and typically developing controls. Children with ASD (ASD/ASD + ADHD) showed reduced theta and alpha power compared to children without ASD (controls/ADHD). Children with ADHD (ADHD/ASD + ADHD) displayed decreased delta power compared to children without ADHD (ASD/controls). Children with ASD + ADHD largely presented as an additive co-occurrence with deficits of both disorders, although reduced theta compared to ADHD-only and reduced delta compared to controls suggested some unique markers. Identifying specific neurophysiological profiles in ASD and ADHD may assist in characterising more homogeneous subgroups to inform treatment approaches and aetiological investigations.

Aim: To characterize early changes in developmental ability, language, and adaptive behaviour in infants diagnosed with tuberous sclerosis complex (TSC), and determine whether clinical features of epilepsy influence this pathway. Method: Prospective, longitudinal data were collected within the Early Development in Tuberous Sclerosis (EDiTS) Study to track development of infants with TSC (n = 32) and typically developing infants (n = 33) between 3 and 24 months of age. Questionnaire and observational measures were used at up to seven timepoints to assess infants' adaptive behaviour, developmental ability, language, and epilepsy. Results: A significant group by age interaction effect showed that infants with TSC had lower adaptive functioning at 18 to 24 months old (intercept = 88.12, slope estimate = −0.82, p < 0.001) and lower developmental ability scores from 10 months old (intercept = 83.33, slope estimate = −1.44, p < 0.001) compared to typically developing infants. Early epilepsy severity was a significant predictor of these emerging developmental (R2 = 0.35, p = 0.004, 95% confidence interval [CI] –0.08 to −0.01) and adaptive behaviour delays (R2 = 0.34, p = 0.004, 95% CI –0.05 to −0.01]). Lower vocabulary production (intercept = −1.25, slope = −0.12, p < 0.001) and comprehension scores (intercept = 2.39, slope estimate = −0.05, p < 0.001) in infants with TSC at 24 months old were not associated with epilepsy severity. Interpretation: Divergence of developmental ability and adaptive functioning skills occur in infants with TSC from 10 and 18 months, respectively. Associations between early epilepsy severity and impaired development supports the importance of early intervention to reduce seizure severity. This original article is commented on by Jóźwiak on pages 556–557 of this issue. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) often co-occur. Children with ASD and ADHD demonstrate deficits in adaptive functioning, yet pure and comorbid groups have not been directly compared. Vineland Adaptive Behaviour Scales (VABS-II) data were examined in boys with ASD (n = 17), ADHD (n = 31) and ASD + ADHD (n = 38). Results demonstrated lower socialisation and composite scores and greater discrepancy between cognitive and adaptive abilities in the ASD + ADHD group compared to the ADHD-only group. Significant associations were shown between reduced adaptive functioning and autism symptoms, but not ADHD symptoms. Children with ASD + ADHD present with exacerbated impairments in adaptive functioning relative to children with ADHD, associated with ASD symptoms. Disentangling variation in adaptive skills may aid the assessment of complex cases.

Background: Attention deficit hyperactivity disorder (ADHD) is a common and highly heritable neurodevelopmental disorder with a complex aetiology. The identification of candidate intermediate phenotypes that are both heritable and genetically linked to ADHD may facilitate the detection of susceptibility genes and elucidate aetiological pathways. Very low-frequency (VLF; less than 0.5 Hz) electroencephalographic (EEG) activity represents a promising indicator of risk for ADHD, but it currently remains unclear as to whether it is heritable or genetically linked to the disorder. Methods: Direct-current (DC)-EEG was recorded during a cognitive activation condition in 30 monozygotic and dizygotic adolescent twin pairs concordant or discordant for high ADHD symptom scores, and 37 monozygotic and dizygotic matched-control twin pairs with low ADHD symptom scores. Structural equation modelling was used to quantify the genetic and environmental contributions to the phenotypic covariance between ADHD and VLF activity. Results: Attention deficit hyperactivity disorder was significantly associated with reduced VLF power during cognitive activation, which suggests reduced synchronization of widespread neuronal activity. Very low-frequency power demonstrated modest heritability (0.31), and the genetic correlation (-0.80) indicated a substantial degree of overlap in genetic influences on ADHD and VLF activity. Conclusions: Altered VLF activity is a potential candidate intermediate phenotype of ADHD, which warrants further investigation of underlying neurobiological and genetic mechanisms.

Background: The Coronavirus disease 2019 (COVID-19) pandemic has impacted parental and child mental health and wellbeing in the UK. This study aimed to explore the experiences of parents of children with rare neurological and neurodevelopmental conditions with a known or suspected genetic cause (neurogenetic) across the first year of the pandemic in the UK. Methods: Semi-structured interviews were conducted with 11 parents of children with rare neurogenetic conditions. Parents were recruited via opportunity sampling from the CoIN Study, a longitudinal quantitative study exploring the impact of the pandemic on the mental health and wellbeing of families with rare neurogenetic conditions. Interviews were analysed using Interpretative Phenomenological Analysis. Results: Four main themes were identified: (1) "A varied impact on child wellbeing: from detrimental to 'no big drama'"; (2) "Parental mental health and wellbeing: impact, changes, and coping"; (3) "'The world had shut its doors and that was that': care and social services during the pandemic"; and (4) "Time and luck: abstract concepts central to parents' perspectives of how they coped during the pandemic". The majority of parents described experiencing an exacerbation of pre-pandemic challenges due to increased uncertainty and a lack of support, with a minority reporting positive effects of the pandemic on family wellbeing. Conclusions: These findings offer a unique insight into the experiences parents of children with rare neurogenetic conditions across the first year of the pandemic in the UK. They highlight that the experiences of parents were not pandemic-specific, and will continue to be highly relevant in a non-pandemic context. Future support should to be tailored to the needs of families and implemented across diverse future scenarios to promote coping and positive wellbeing. [ABSTRACT FROM AUTHOR]

Background: Atypicalities in perception and interpretation of faces and emotional facial expressions have been reported in both autism and attention-deficit/hyperactivity disorder (ADHD) during childhood and adulthood. Investigation of face processing during young adulthood (18 to 25 years), a transition period to full-fledged adulthood, could provide important information on the adult outcomes of autism and ADHD. Methods: In this study, we investigated event-related potentials (ERPs) related to visual face processing in autism, ADHD, and co-occurring autism and ADHD in a large sample of young adults (N = 566). The groups were based on the Diagnostic Interview for ADHD in Adults 2.0 (DIVA-2) and the Autism Diagnostic Observation Schedule-2 (ADOS-2). We analyzed ERPs from two passive viewing tasks previously used in childhood investigations: (1) upright and inverted faces with direct or averted gaze; (2) faces expressing different emotions. Results: Across both tasks, we consistently found lower amplitude and longer latency of N170 in participants with autism compared to those without. Longer P1 latencies and smaller P3 amplitudes in response to emotional expressions and longer P3 latencies for upright faces were also characteristic to the autistic group. Those with ADHD had longer N170 latencies, specific to the face-gaze task. Individuals with both autism and ADHD showed additional alterations in gaze modulation and a lack of the face inversion effect indexed by a delayed N170. Conclusion: Alterations in N170 for autistic young adults is largely consistent with studies on autistic adults, and some studies in autistic children. These findings suggest that there are identifiable and measurable socio-functional atypicalities in young adults with autism. [ABSTRACT FROM AUTHOR]

The association between attention‐deficit/hyperactivity disorder (ADHD) and tuberous sclerosis complex (TSC) is widely reported, with support for the role of epilepsy, yet the mechanisms underlying the association across development are unclear. The Tuberous Sclerosis 2000 Study is a prospective longitudinal study of TSC. In Phase 1 of the study, baseline measures of epilepsy, cortical tuber load, and mutation were obtained with 125 children ages 0–16 years. In Phase 2, at an average of 8 years later, ADHD symptoms were measured for 81 of the participants. Structural equation modeling revealed an indirect pathway from genetic mutation, to cortical tuber load, to epileptic spasm severity in infancy, to ADHD symptoms in middle childhood and adolescence, in addition to a pathway linking current seizure severity to ADHD symptoms. Findings were retained when intelligence quotient (IQ) was entered as a correlated factor. The findings support a cascading developmental pathway to ADHD symptoms mediated by early‐onset and severe epilepsy in the first 2 years of life. This warrants detailed investigation of seizure characteristics and cognitive and behavioral sequelae associated with ADHD from early in life, to further the understanding of the association between ADHD and early‐onset epilepsy across syndromic and non‐syndromic populations. [ABSTRACT FROM AUTHOR]

Aim: To examine the association between perinatal adversities and neurodevelopmental outcome in tuberous sclerosis complex (TSC). Method: The Tuberous Sclerosis 2000 study is a prospective, longitudinal UK study of TSC. In phase 1, mutation type, TSC family history, tuber characteristics, presence of cardiac rhabdomyomas, seizure characteristics, and intellectual ability were assessed in 125 children affected with TSC (64 females, 61 males; median age 39mo, range 4–254). In phase 2, 88 participants (49 females, 39 males; median age 148mo, range 93–323) were assessed for neurodevelopmental outcomes including intellectual ability, autism spectrum disorder, and attention‐deficit/hyperactivity disorder. Perinatal histories of 88 participants with TSC and 80 unaffected siblings were collected retrospectively using the Obstetric Enquiry Schedule and coded with a modified Gillberg Optimality Scale to measure levels of perinatal adversity. Data were analysed using Mann–Whitney U tests, Spearman's rank correlation, and linear regression with robust standard errors. Results: Children with familial TSC experienced significantly greater perinatal adversity than unaffected siblings. Perinatal adversity was higher in children with TSC‐affected mothers than those with unaffected mothers. There was no significant association between perinatal adversities and neurodevelopmental outcomes after controlling for confounders. Interpretation: Maternal TSC is a significant marker of elevated perinatal risk in addition to risks incurred by fetal genotype. Pregnancies complicated by maternal or fetal TSC require higher vigilance, and mechanisms underlying increased perinatal adversity require further research. What this paper adds: Higher perinatal adversity is associated with familial tuberous sclerosis complex (TSC).Maternal TSC was associated with higher frequencies of several perinatal risk markers.Paternal TSC was not associated with higher levels of perinatal adversity.Perinatal adversity levels in TSC1 and TSC2 subgroups did not differ significantly.Perinatal adversities were not associated with neurodevelopmental outcomes. What this paper adds: Higher perinatal adversity is associated with familial tuberous sclerosis complex (TSC).Maternal TSC was associated with higher frequencies of several perinatal risk markers.Paternal TSC was not associated with higher levels of perinatal adversity.Perinatal adversity levels in TSC1 and TSC2 subgroups did not differ significantly.Perinatal adversities were not associated with neurodevelopmental outcomes. This original article is commented on by Franz on pages 1184–1185 of this issue. [ABSTRACT FROM AUTHOR]

Background: Autism Spectrum Disorder (ASD) and Attention‐Deficit/Hyperactivity Disorder (ADHD) share impairments in top‐down and bottom‐up modulation of attention. However, it is not yet well understood if co‐occurrence of ASD and ADHD reflects a distinct or additive profile of attention deficits. We aimed to characterise alpha oscillatory activity (stimulus‐locked alpha desynchronisation and prestimulus alpha) as an index of integration of top‐down and bottom‐up attentional processes in ASD and ADHD. Methods: Children with ASD, ADHD, comorbid ASD+ADHD, and typically‐developing children completed a fixed‐choice reaction‐time task ('Fast task') while neurophysiological activity was recorded. Outcome measures were derived from source‐decomposed neurophysiological data. Main measures of interest were prestimulus alpha power and alpha desynchronisation (difference between poststimulus and prestimulus alpha). Poststimulus activity linked to attention allocation (P1, P3), attentional control (N2), and cognitive control (theta synchronisation, 100–600 ms) was also examined. ANOVA was used to test differences across diagnostics groups on these measures. Spearman's correlations were used to investigate the relationship between attentional control processes (alpha oscillations), central executive functions (theta synchronisation), early visual processing (P1), and behavioural performance. Results: Children with ADHD (ADHD and ASD+ADHD) showed attenuated alpha desynchronisation, indicating poor integration of top‐down and bottom‐up attentional processes. Children with ADHD showed reduced N2 and P3 amplitudes, while children with ASD (ASD and ASD+ADHD) showed greater N2 amplitude, indicating atypical attentional control and attention allocation across ASD and ADHD. In the ASD group, prestimulus alpha and theta synchronisation were negatively correlated, and alpha desynchronisation and theta synchronisation were positively correlated, suggesting an atypical association between attentional control processes and executive functions. Conclusions: ASD and ADHD are associated with disorder‐specific impairments, while children with ASD+ADHD overall presented an additive profile with attentional deficits of both disorders. Importantly, these findings may inform the improvement of transdiagnostic procedures and optimisation of personalised intervention approaches. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD) is highly heterogeneous in its etiology and manifestation. The neurobiological processes underlying ASD development are reflected in multiple features, from behaviour and cognition to brain functioning. An integrated analysis of these features may optimize the identification of these processes. Methods: We examined cognitive and adaptive functioning and ASD symptoms between 8 and 36 months in 161 infants at familial high risk for ASD and 71 low-risk controls; we also examined neural sensitivity to eye gaze at 8 months in a subsample of 140 high-risk and 61 low-risk infants. We used linked independent component analysis to extract patterns of variation across domains and development, and we selected the patterns significantly associated with clinical classification at 36 months. Results: An early process at 8 months, indicating high levels of functioning and low levels of symptoms linked to higher attention to gaze shifts, was reduced in infants who developed ASD. A longitudinal process of increasing functioning and low levels of symptoms was reduced in infants who developed ASD, and another process suggesting a stagnation in cognitive functioning at 24 months was increased in infants who developed ASD. Limitations: Although the results showed a clear significant trend relating to clinical classification, we found substantial overlap between groups. Conclusion: We uncovered underlying processes that acted together early in development and were associated with clinical outcomes. Our results highlighted the complexity of emerging ASD, which goes beyond the borders of clinical categories. Future work should integrate genetic data to investigate the specific genetic risks linked to these processes. [ABSTRACT FROM AUTHOR]

Aim: To investigate the interdependence between risk factors associated with long-term intellectual development in individuals with tuberous sclerosis complex (TSC).Method: The Tuberous Sclerosis 2000 Study is a prospective longitudinal study of individuals with TSC. In phase 1 of the study, baseline measures of intellectual ability, epilepsy, cortical tuber load, and mutation were obtained for 125 children (63 females, 62 males; median age=39mo). In phase 2, at an average of 8 years later, intellectual abilities were estimated for 88 participants with TSC and 35 unaffected siblings. Structural equation modelling was used to determine the risk pathways from genetic mutation through to IQ at phase 2.Results: Intellectual disability was present in 57% of individuals with TSC. Individuals without intellectual disability had significantly lower mean IQ compared to unaffected siblings, supporting specific genetic factors associated with intellectual impairment. Individuals with TSC who had a slower gain in IQ from infancy to middle childhood were younger at seizure onset and had increased infant seizure severity. Structural equation modelling indicated indirect pathways from genetic mutation, to tuber count, to seizure severity in infancy, through to IQ in middle childhood and adolescence.Interpretation: Early-onset and severe epilepsy in the first 2 years of life are associated with increased risk of long-term intellectual disability in individuals with TSC, emphasizing the importance of early and effective treatment or prevention of epilepsy.What This Paper Adds: Intellectual disability was present in 57% of individuals with tuberous sclerosis complex (TSC). Those with TSC without intellectual disability had significantly lower mean IQ compared to unaffected siblings. Earlier onset and greater severity of seizures in the first 2 years were observed in individuals with a slower gain in intellectual ability. Risk pathways through seizures in the first 2 years predict long-term cognitive outcomes in individuals with TSC. [ABSTRACT FROM AUTHOR]

We investigated key event-related brain potential markers (ERPs) derived from a flanked continuous performance task (CPT) and whether these would show phenotypic associations with ADHD (attention-deficit/hyperactivity disorder) in a population-based sample. We further explored whether there was preliminary evidence that such ERPs could also index genetic risk for ADHD (depending on finding phenotypic associations). Sixty-seven male-only twin pairs (N = 134; aged 12–15) from a subsample of the Twins’ Early Development Study, concordant and discordant for ADHD symptoms, performed the flanked CPT (or CPT-OX) while electroencephalography (EEG) was recorded. ERPs were obtained for cue (P3, CNV or contingency negative variation), go (P3, N2) and nogo trials (P3, N2). We found no phenotypic associations between CPT-derived ERPs and ADHD—the sizes of the estimated phenotypic correlations were nonsignificant and very small (r’s = -.11 to .04). Twin-model fitting analyses using structural equation modelling provided preliminary evidence that some of the ERPs were heritable (with the most robust effect for go-P3 latency), but there was limited evidence of any genetic associations between ERPs and ADHD, although with the caveat that our sample was small and hence had limited power. Overall, unlike in previous research, there was no evidence of phenotypic (nor preliminary evidence for genetic) associations between ADHD and CPT-derived ERPs in this study. Hence, it may be currently premature for genetic analyses of ADHD to be guided by CPT-derived ERP parameters (unlike alternative cognitive-neurophysiological approaches which may be more promising). Further research with better-powered, population-based, genetically-informative and cross-disorder samples are required, which could be facilitated by emerging mobile EEG technologies. [ABSTRACT FROM AUTHOR]

Co-occurring medical disorders and associated physiological abnormalities in individuals with autism spectrum disorder (ASD) may provide insight into causal pathways or underlying biological mechanisms. Here, we review medical conditions that have been repeatedly highlighted as sharing the strongest associations with ASD—epilepsy, sleep, as well as gastrointestinal and immune functioning. We describe within each condition their prevalence, associations with behavior, and evidence for successful treatment. We additionally discuss research aiming to uncover potential aetiological mechanisms. We then consider the potential interaction between each group of conditions and ASD and, based on the available evidence, propose a model that integrates these medical comorbidities in relation to potential shared aetiological mechanisms. Future research should aim to systematically examine the interactions between these physiological systems, rather than considering these in isolation, using robust and sensitive biomarkers across an individual's development. A consideration of the overlap between medical conditions and ASD may aid in defining biological subtypes within ASD and in the development of specific targeted interventions. [ABSTRACT FROM AUTHOR]

Summary: Tuberous sclerosis complex (TSC) is a multisystem genetic disorder caused by mutations in TSC1 or TSC2. Epilepsy occurs in 80%‐90% of affected individuals during their lifetime, and up to one‐third of children with TSC will develop epileptic (infantile) spasms, for which vigabatrin has been shown to be particularly effective. Epilepsy severity and epileptic spasms are consistent markers of risk for the development of intellectual impairment in TSC. Although previous studies demonstrate a bimodal distribution of intellectual ability in TSC, recent findings suggest a unimodal distribution, which may reflect a change in IQ distribution over time. We compared 3 large historical UK cohorts of TSC (n = 331) that show varied distributions of intellectual ability, first ruling out differences in study methodology. Later‐born individuals had a higher frequency of reported spasms and higher likelihood of vigabatrin administration, but were less likely to have profound intellectual impairment, compared to the earlier‐born individuals. Our findings suggest that epileptic spasms went undetected in the older patients and therefore were not treated, leading to a higher occurrence of profound impairment, whereas the later born cohort had better access to treatment. These findings support the importance of early identification and treatment of seizures in TSC. [ABSTRACT FROM AUTHOR]

Background: Recent studies point to overlap between neuropsychiatric disorders in symptomatology and genetic aetiology.Aims: To systematically investigate genomics overlap between childhood and adult attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and major depressive disorder (MDD).Method: Analysis of whole-genome blood gene expression and genetic risk scores of 318 individuals. Participants included individuals affected with adult ADHD (n = 93), childhood ADHD (n = 17), MDD (n = 63), ASD (n = 51), childhood dual diagnosis of ADHD-ASD (n = 16) and healthy controls (n = 78).Results: Weighted gene co-expression analysis results reveal disorder-specific signatures for childhood ADHD and MDD, and also highlight two immune-related gene co-expression modules correlating inversely with MDD and adult ADHD disease status. We find no significant relationship between polygenic risk scores and gene expression signatures.Conclusions: Our results reveal disorder overlap and specificity at the genetic and gene expression level. They suggest new pathways contributing to distinct pathophysiology in psychiatric disorders and shed light on potential shared genomic risk factors. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD) is a common and highly heritable neurodevelopmental disorder that is likely to be the outcome of complex aetiological mechanisms. One strategy to provide insight is to study ASD within tuberous sclerosis complex (TSC), a rare disorder with a high incidence of ASD, but for which the genetic cause is determined. Individuals with ASD consistently demonstrate face processing impairments, but these have not been examined in adults with TSC using event-related potentials (ERPs) that are able to capture distinct temporal stages of processing. Methods: For adults with TSC ( n = 14), 6 of which had a diagnosis of ASD, and control adults ( n = 13) passively viewed upright and inverted human faces with direct or averted gaze, with concurrent EEG recording. Amplitude and latency of the P1 and N170 ERPs were measured. Results: Individuals with TSC + ASD exhibited longer N170 latencies to faces compared to typical adults. Typical adults and adults with TSC-only exhibited longer N170 latency to inverted versus upright faces, whereas individuals with TSC + ASD did not show latency differences according to face orientation. In addition, individuals with TSC + ASD showed increased N170 latency to averted compared to direct gaze, which was not demonstrated in typical adults. A reduced lateralization was shown for the TSC + ASD groups on P1 and N170 amplitude. Conclusions: The findings suggest that individuals with TSC + ASD may have similar electrophysiological abnormalities to idiopathic ASD and are suggestive of developmental delay. Identifying brain-based markers of ASD that are similar in TSC and idiopathic cases is likely to help elucidate the risk pathways to ASD. [ABSTRACT FROM AUTHOR]

Background: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are promoted as cognitive enhancers with consumption recommended in the general population and those with neurocognitive deficits such as attention deficit hyperactivity disorder (ADHD). However, evidence from randomised placebo-controlled trials is inconclusive. Aims: This study aimed to conduct a systematic review and meta-analysis examining the effect of n-3 PUFA supplementation on cognition in healthy populations and those with ADHD and related disorders (RDs). Methods: Databases were searched for randomised controlled trials (RCTs) in adults and school-aged children (who were healthy and typically developing (TD) or had ADHD or a related-neurodevelopmental disorder (ADHD+RD) which assessed the effects of n-3 PUFA on cognition. Results: In the 24 included studies n-3 PUFA supplementation, in the whole sample and the TD and ADHD+RD subgroup, did not show improvements in any of the cognitive performance measures. In those with low n-3 PUFA status, supplementation improved short-term memory. Conclusions: There is marginal evidence that n-3 PUFA supplementation effects cognition in those who are n-3 PUFA deficient. However, there is no evidence of an effect in the general population or those with neurodevelopmental disorders. This has important implications given the widespread advertisement and consumption of n-3 PUFA; claims of cognitive benefit should be narrowed. [ABSTRACT FROM PUBLISHER]

Autism Spectrum Disorder (ASD) is a behavioral syndrome caused by complex genetic and non-genetic risk factors. It has been proposed that these risk factors lead to alterations in the development and 'wiring' of brain circuits and hence, the emergence of ASD. Although several lines of research lend support to this theory, etiological and clinical heterogeneity, methodological issues and inconsistent findings have led to significant doubts. One of the best established, albeit rare, causes of ASD is the genetic condition Tuberous Sclerosis Complex (TSC), where 40% of individuals develop ASD. A recent study by Peters and Taquet et al. analyzed electroencephalography (EEG) data using graph theory to model neural 'connectivity' in individuals with TSC with and without ASD and cases with 'idiopathic' ASD. TSC cases exhibited global under-connectivity and abnormal network topology, whereas individuals with TSC + ASD demonstrated similar connectivity patterns to those seen in individuals with idiopathic ASD: decreased long- over short-range connectivity. The similarity in connectivity abnormalities in TSC + ASD and ASD suggest a common final pathway and provide further support for 'mis-wired' neural circuitry in ASD. The origins of the connectivity changes, and their role in mediating between the neural and the cognitive/behavioral manifestations, will require further study. Please see related research article here http://www. biomedcentral.com/1741-7015/11/54 [ABSTRACT FROM AUTHOR]

Actigraphy, an objective measure of motor activity, reliably indexes increased movement levels in attention-deficit/hyperactivity disorder (ADHD) and may be useful for diagnosis and treatment-monitoring. However, actigraphy has not been examined in complex neurodevelopmental conditions. This study used actigraphy to objectively measure movement levels in individuals with a complex neurodevelopmental genetic disorder, tuberous sclerosis (TSC). Thirty participants with TSC (11–21 years, 20 females, IQ = 35–108) underwent brief (approximately 1 h) daytime actigraph assessment during two settings: movie viewing and cognitive testing. Multiple linear regressions were used to test associations between movement measurements and parent-rated ADHD symptoms. Correlations were used to examine associations between actigraph measures and parent-rated ADHD symptoms and other characteristics of TSC (symptoms of autism spectrum disorder (ASD), intellectual ability (IQ), epilepsy severity, cortical tuber count). Higher movement levels during movies were associated with higher parent-rated ADHD symptoms. Higher ADHD symptoms and actigraph-measured movement levels during movies were positively associated with ASD symptoms and negatively associated with IQ. Inter-individual variability of movement during movies was not associated with parent-rated hyperactivity or IQ but was negatively associated with ASD symptoms. There were no associations with tuber count or epilepsy. Our findings suggest that actigraph-measured movement provides a useful correlate of ADHD in TSC. [ABSTRACT FROM AUTHOR]

Introduction and objective: Increased reaction-time variability (RTV) in ADHD may arise from the inability to appropriately modulate very low-frequency oscillations (VLFOs; <0.05 Hz) of the brain that are observed when the brain is in ‘default-mode’. A lack of sufficient VLFO attenuation or ‘default-mode interference’ during cognitive activity may play a role in attentional lapses that contribute to RTV [3]. Recent studies using EEG to investigate this hypothesis have reported an association between reduced VLFO power and inattention symptom scores and that less rest-to-task VLFO attenuation is associated with ADHD [1]. State-related conditions can affect the transition; if the individual is experiencing little extrinsic motivation, VLFO attenuation would require a larger investment of energetic resources [3]. Therefore it can be hypothesised that default-mode interference in ADHD would decrease when the individual is offered a reward, as extrinsic motivation increases and arousal is optimised. EEG frequency bands consistently demonstrate high heritability, an important criterion for its acceptance as a marker of a disorder, yet this has not yet been investigated in VLFOs. An additional aim of the study is to investigate heritability and genetic overlap between ADHD and VLFOs. Methods: 68 twin pairs were recruited from the twins early development study (TEDS) based on a trajectory analysis of consistently high or low ADHD scores. The fast task [2], a four-choice reaction time task, was administered to measure the effects of arousal consisting of a baseline and a fast-incentive condition combining a fast event rate and rewards. VLFO activity was measured using DC-EEG. Mean absolute power was calculated using fast-Fourier transform (FFT) analysis across sub-delta very low-frequency bands Slow-4 (S4; 0.02–0.06 Hz), Slow-3 (S3; 0.06–0.2 Hz), Slow-2 (S2; 0.2– 0.5 Hz) and Slow-1 (S1; 0.5–1.5 Hz). We will apply structural equation model-fitting using monozygotic (MZ) and dizygotic (DZ) twin pairs ascertained on ADHD scores. The program Mx will be used for maximum likelihood genetic model fitting, using an applied bivariate model, to directly estimate model parameters [additive genetic (A); common environmental (C); and unique environmental effects (E)] from the observed data. Results: Based on previous research (Helps et al. 2010), we combined S4 + S3 and S2 + S1. Preliminary analysis of 60 twin pairs during the completion of the baseline condition of the Fast task suggests significantly higher S3 + S4 power in those with high symptoms scores (M = 0.7140, SD = 1.90) compared to those with low symptom scores (M = -0.3275, SD = 1.74; t = -2.12, p < 0.05). Additionally, significant associations were found between S3 + S4 and mean reaction-time (MRT; r = 0.307, p\0.05) and reaction-time standard deviation (RTSD; r = 0.397, p < 0.01), and between S1 + S2 and MRT (r = 0.376, p < 0.01) and RTSD (r = 0.283, p < 0.05). We will report VLFO patterns during the fast-incentive and rest conditions to assess the effect of arousal on default-mode interference. We will further describe the genetic models for VLFOs based on model-fitting analyses. Discussion: The findings support previous studies reporting increased VLFO power during cognitive activity in ADHD, suggesting that during task completion those with ADHD have increased default-mode interference. Moreover, decreased attenuation of VLFOs during cognitive activity is associated with poor task performance. The implications of heritability will be discussed. Conclusion: These findings strengthen the association between nonoptimal arousal and inattention, and warrant further investigation of the state-related factors that may improve task performance and EEG-indexed arousal using genetically sensitive designs. [ABSTRACT FROM AUTHOR]

Ecological Momentary Assessment using smartphone technology (smart EMA) has grown substantially over the last decade. However, little is known about the factors associated with completion rates in populations who have a higher likelihood of cognitive impairment. A systematic review of Smart EMA studies in populations who have a higher likelihood of cognitive impairment was carried out (PROSPERO; ref no CRD42022375829). Smartphone EMA studies in neurological, neurodevelopmental and neurogenetic conditions were included. Six databases were searched, and bias was assessed using Egger’s test. Completion rates and moderators were analyzed using meta-regression. Fifty-five cohorts were included with 18 cohorts reporting confirmed cognitive impairment. In the overall cohort, the completion rate was 74.4% and EMA protocol characteristics moderated completion rates. Participants with cognitive impairment had significantly lower completion rates compared with those without (p = .021). There were no significant moderators in the cognitive impairment group. Limitations included significant methodological issues in reporting of completion rates, sample characteristics, and associations with completion and dropout rates. These findings conclude that smart EMA is feasible for people with cognitive impairment. Future research should focus on the efficacy of using smart EMA within populations with cognitive impairment to develop an appropriate methodological evidence base. [ABSTRACT FROM AUTHOR]

• Altered performance monitoring has been implicated in OCD, Gilles de la Tourette syndrome (GTS), ADHD and autism. • We conducted a meta-analysis of electrophysiological correlates of performance monitoring in OCD, GTS, ADHD and autism. • OCD and GTS showed increased electrophysiological correlates of performance monitoring. • ADHD and autism showed reduced electrophysiological correlates of performance monitoring. • Findings suggest overlap in neural markers of performance monitoring alterations in four common developmental conditions. Altered performance monitoring is implicated in obsessive-compulsive disorder (OCD), Gilles de la Tourette syndrome (GTS), attention-deficit/hyperactivity disorder (ADHD) and autism. We conducted a systematic review and meta-analysis of electrophysiological correlates of performance monitoring (error-related negativity, ERN; error positivity, Pe; feedback-related negativity, FRN; feedback-P3) in individuals with OCD, GTS, ADHD or autism compared to control participants, or associations between correlates and symptoms/traits of these conditions. Meta-analyses on 97 studies (5890 participants) showed increased ERN in OCD (Hedge's g = 0.54[CIs:0.44,0.65]) and GTS (g = 0.99[CIs:0.05,1.93]). OCD also showed increased Pe (g = 0.51[CIs:0.21,0.81]) and FRN (g = 0.50[CIs:0.26,0.73]). ADHD and autism showed reduced ERN (ADHD: g=-0.47[CIs:-0.67,-0.26]; autism: g=-0.61[CIs:-1.10,-0.13]). ADHD also showed reduced Pe (g=-0.50[CIs:-0.69,-0.32]). These findings suggest overlap in electrophysiological markers of performance monitoring alterations in four common neurodevelopmental conditions, with increased amplitudes of the markers in OCD and GTS and decreased amplitudes in ADHD and autism. Implications of these findings in terms of shared and distinct performance monitoring alterations across these neurodevelopmental conditions are discussed. PROSPERO pre-registration code: CRD42019134612. [ABSTRACT FROM AUTHOR]