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BackgroundThe 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. MethodsSemi-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.ResultsFour 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 understanding of their pandemic experience”. 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 minimal or positive effects of the pandemic on family wellbeing.ConclusionsThese 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 are 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 identified in this study and implemented across diverse future scenarios to promote coping and positive wellbeing.

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.

Dimensional approaches to psychopathology interrogate the core neurocognitive domains interacting at the individual level to shape diagnostic symptoms. Embedding this approach in prospective longitudinal studies could transform our understanding of the mechanisms underlying neurodevelopmental disorders. Such designs require us to move beyond traditional group comparisons and determine which domain-specific atypicalities apply at the level of the individual, and whether they vary across distinct phenotypic subgroups. As a proof of principle, this study examines how the domain of face processing contributes to a clinical diagnosis of Autism Spectrum Disorder (ASD). We used an event-related potentials (ERPs) task in a cohort of 8-month-old infants with (n=148) and without (n=68) an older sibling with ASD, and combined traditional case-control comparisons with machine-learning techniques like supervised classification for prediction of clinical outcome at 36 months and Bayesian hierarchical clustering for stratification into subgroups. Our findings converge to indicate that a broad profile of alterations in the time-course of neural processing of faces is an early predictor of later ASD diagnosis. Furthermore, we identified two brain response-defined subgroups in ASD that showed distinct alterations in different aspects of face processing compared to siblings without ASD diagnosis, suggesting that individual differences between infants contribute to the diffuse pattern of alterations predictive of ASD in the first year of life. This study shows that moving from group-level comparisons to pattern recognition and stratification can help to understand and reduce heterogeneity in clinical cohorts, and improve our understanding of the mechanisms that lead to later neurodevelopmental outcomes.General Scientific SummaryThis study suggests that neural processing of faces is diffusely atypical in Autism Spectrum Disorder, and that it represents a strong candidate predictor of outcome at an individual level in the first year of life.

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.

Background: The impact of the COVID-19 pandemic on the wellbeing of parents and children in the general population has been well-documented. This study investigated wellbeing in parents of and children with rare neurogenetic conditions, who may have been at greater risk of negative impact on mental health and behavioural challenges during the first UK lockdown. Method: An online survey data was completed by parents of children with a rare neurogenetic condition between May and July 2020 (CoIN sample; N=123) and compared to responses from parents of children in the wider population (Co-SPACE sample; N=2121). Measures of wellbeing included the 21-item Depression, Anxiety and Stress Scale for parents and the Strength and Difficulties Questionnaire for child behaviour. Results: Parent anxiety was significantly higher in CoIN (MedianAnx = 4) than Co-SPACE (MedianAnx = 2). Parent-rated internalising, externalising and impact of child behavioural difficulties were also significantly higher in CoIN (MedianInt = 9.5; MedianExt = 11, MedianImp = 8) than Co-SPACE (MedianInt = 6; MedianExt = 7, MedianImp = 1). Only group differences in child behaviour and impact remained significant when matching for demographic factors and were also larger than previously reported pre-pandemic differences. Discussion: Families of children with rare neurogenetic conditions reported poorer wellbeing during the first lockdown compared to the wider population, affecting both parents and children. This likely reflects pre-existing complex needs, which should be prioritised during future national crises. Investigation of changes in wellbeing in this population over the course of the pandemic is warranted.

To examine the association between perinatal adversities and neurodevelopmental outcome in tuberous sclerosis complex (TSC).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.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.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.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.

Background: Tuberous Sclerosis Complex (TSC) is a single gene disorder carrying high risk of autism spectrum disorder (ASD). Various neurological complications increase the risk of ASD but the way risk factors operate together is unclear. We aimed to explore risk pathways to ASD by modelling the interplay between genetic mutation (TSC1/TSC2), cortical tuber count, seizure type and severity. Methods: The Tuberous Sclerosis 2000 Study is a UK longitudinal study of the natural history of TSC. We recruited newly diagnosed children (N=125) and collected data on mutation, cortical tuber count (cranial MRI/CT), seizure history, and IQ. ASD and IQ assessments were carried out at 10-year follow up (N=86, M age=13.1 years). Structural equation modelling (SEM) was used to explore pathways that mediate between mutation and ASD symptoms. Results: Risk of ASD was high: 39.5% met research criteria for ASD and a further 41.9% showed autistic traits. SEM resulted in two indirect pathways, with cortical tuber count and occurrence/severity of epileptic spasms in infancy mediating between mutation and ASD (mutation-tubers-spasms-ASD, B=2.08, 95%CI 0.15–8.02; mutation-spasms-ASD, B=2.98, 95%CI 0.04–8.89). Concurrent seizures (B=3.08, 95%CI 0.42–6.18) and IQ (B=-117.10, 95%CI -183.57–-59.16) were also associated with ASD symptoms. Conclusions: There was significantly elevated risk of ASD and subclinical autistic traits. Tuber count and severity of spasms predicted ASD severity, suggesting that prevention/control of seizures in infancy may decrease severity of ASD symptoms. ASD was occasionally reported in the absence of overt seizures in infancy, so their causal role requires further investigation.

This cohort study investigates whether N290 latency to faces vs nonfaces is associated with autism polygenic scores and cross-disorder polygenic scores in infants with and without a family history of autism.

Early difficulties in engaging attentive brain states in social settings could affect learning and have cascading effects on social development. We investigated this possibility using multichannel electroencephalography during a face/non-face paradigm in 8-month-old infants with (FH, n = 91) and without (noFH, n = 40) a family history of autism spectrum disorder (ASD). An event-related potential component reflecting attention engagement, the Nc, was compared between FH infants who received a diagnosis of ASD at 3 years of age (FH-ASD; n = 19), FH infants who did not (FH-noASD; n = 72) and noFH infants (who also did not, hereafter noFH-noASD; n = 40). ‘Prototypical’ microstates during social attention were extracted from the noFH-noASD group and examined in relation to later categorical and dimensional outcome. Machine-learning was used to identify the microstate features that best predicted ASD and social adaptive skills at three years. Results suggested that whilst measures of brain state timing were related to categorical ASD outcome, brain state strength was related to dimensional measures of social functioning. Specifically, the FH-ASD group showed shorter Nc latency relative to other groups, and duration of the attentive microstate responses to faces was informative for categorical outcome prediction. Reduced Nc amplitude difference between faces with direct gaze and a non-social control stimulus and strength of the attentive microstate to faces contributed to the prediction of dimensional variation in social skills. Taken together, this provides consistent evidence that atypical attention engagement precedes the emergence of difficulties in socialization and indicates that using the spatio-temporal characteristics of whole-brain activation to define brain states in infancy provides an important new approach to understanding of the neurodevelopmental mechanisms that lead to ASD.

Contains fulltext : 231789.pdf (Publisher’s version ) (Closed access) 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.

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.

Impaired face processing is proposed to play a key role in the early development of autism spectrum disorder (ASD) and to be an endophenotypic trait which indexes genetic risk for the disorder. However, no published work has examined the development of face processing abilities from infancy into the school-age years and how they relate to ASD symptoms in individuals with or at high-risk for ASD. In this novel study we investigated neural and behavioural measures of face processing at age 7 months and again in mid-childhood (age 7 years) as well as social-communication and sensory symptoms in siblings at high (n = 42) and low (n = 35) familial risk for ASD. In mid-childhood, high-risk siblings showed atypical P1 and N170 event-related potential correlates of face processing and, for high-risk boys only, poorer face and object recognition ability compared to low-risk siblings. These neural and behavioural atypicalities were associated with each other and with higher social-communication and sensory symptoms in mid-childhood. Additionally, more atypical neural correlates of object (but not face) processing in infancy were associated with less right-lateralised (more atypical) N170 amplitudes and greater social-communication problems in mid-childhood. The implications for models of face processing in ASD are discussed.

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.

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.

Purpose – Tuberous sclerosis complex (TSC) is a genetic disorder with a high prevalence of autism spectrum disorder (ASD), yet no single genetic, neurological or neurophysiological risk marker is necessary or sufficient to increase risk for ASD. This paper aims to discuss the utility of adopting a developmental perspective. Design/methodology/approach – The increasing number of TSC infants presenting with abnormalities prenatally provides a unique opportunity to study risk pathways to ASD from birth. Here, the authors review findings to date that support the investigation of infants with TSC to further our understanding of typical and atypical development. Findings – Evidence has accumulated from studies of infants at familial risk for ASD (“baby siblings”) to suggest that early markers of ASD are present in the first year of life. The early waves of prospective studies of infants with TSC indicate dynamic changes in developmental trajectories to ASD and are likely to provide insight into cascading effects of brain “insult” early in development. Emerging evidence of phenotypic and biological homology between syndromic and idiopathic cases of ASD supports the notion of a convergence of risk factors on a final common pathway in ASD. Originality/value – The delineation of brain-based biomarkers of risk, prediction and treatment response in TSC will be critical in aiding the development of targeted intervention and prevention strategies for those infants at high risk of poorer developmental outcomes.

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are common and impairing neurodevelopmental disorders that frequently co-occur. The neurobiological mechanisms involved in ASD and ADHD are not fully understood. However, alterations in large-scale neural networks have been proposed as core deficits in both ASD and ADHD and may help to disentangle the neurobiological basis of these disorders and their co-occurrence. In this study, we examined similarities and differences in large-scale oscillatory neural networks between boys aged 8-13 years with ASD (n = 19), ADHD (n = 18), ASD + ADHD (n = 29) and typical development (Controls, n = 26). Oscillatory neural networks were computed using graph-theoretical methods from electroencephalographic (EEG) data collected during an eyes-open resting-state and attentional control and social cognition tasks in which we previously reported disorder-specific atypicalities in oscillatory power and event-related potentials (ERPs). We found that children with ASD showed significant hypoconnectivity in large-scale networks during all three task conditions compared to children without ASD. In contrast, children with ADHD showed significant hyperconnectivity in large-scale networks during the attentional control and social cognition tasks, but not during the resting-state, compared to children without ADHD. Children with co-occurring ASD + ADHD did not differ from children with ASD when paired with this group and vice versa when paired with the ADHD group, indicating that these children showed both ASD-like hypoconnectivity and ADHD-like hyperconnectivity. Our findings suggest that ASD and ADHD are associated with distinct alterations in large-scale oscillatory networks, and these atypicalities present together in children with both disorders. These alterations appear to be task-independent in ASD but task-related in ADHD, and may underlie other neurocognitive atypicalities in these disorders. [Abstract copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.]

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.

Children with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) demonstrate face processing abnormalities that may underlie social impairment. Despite substantial overlap between ASD and ADHD, ERP markers of face and gaze processing have not been directly compared across pure and comorbid cases. Children with ASD ( n = 19), ADHD ( n = 18), comorbid ASD + ADHD ( n = 29) and typically developing (TD) controls ( n = 26) were presented with upright/inverted faces with direct/averted gaze, with concurrent recording of the P1 and N170 components. While the N170 was predominant in the right hemisphere in TD and ADHD, children with ASD (ASD/ASD + ADHD) showed a bilateral distribution. In addition, children with ASD demonstrated altered response to gaze direction on P1 latency and no sensitivity to gaze direction on midline-N170 amplitude compared to TD and ADHD. In contrast, children with ADHD (ADHD/ASD + ADHD) exhibited a reduced face inversion effect on P1 latency compared to TD and ASD. These findings suggest children with ASD have specific abnormalities in gaze processing and altered neural specialisation, whereas children with ADHD show abnormalities at early visual attention stages. Children with ASD + ADHD are an additive co-occurrence with deficits of both disorders. Elucidating the neural basis of the overlap between ASD and ADHD is likely to inform aetiological investigation and clinical assessment.

BackgroundRecent studies point to overlap between neuropsychiatric disorders in symptomatology and genetic aetiology.AimsTo systematically investigate genomics overlap between childhood and adult attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and major depressive disorder (MDD).MethodAnalysis 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).ResultsWeighted 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.ConclusionsOur 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.

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

There are high rates of overlap between autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Emotional impairment in the two disorders, however, has not been directly compared using event-related potentials (ERPs) that are able to measure distinct temporal stages in emotional processing. The N170 and N400 ERP components were measured during presentation of emotional face stimuli to boys with ASD (n=19), ADHD (n=18), comorbid ASD+ADHD (n=29) and typically developing controls (n=26). Subjects with ASD (ASD/ASD+ADHD) displayed reduced N170 amplitude across all stimuli, particularly for fearful versus neutral facial expressions. Conversely, subjects with ADHD (ADHD/ASD+ADHD) demonstrated reduced modulation of N400 amplitude by fearful expressions in parietal scalp regions and happy facial expressions in central scalp regions. These findings indicate a dissociation between disorders on the basis of distinct stages of emotion processing; while children with ASD show alterations at the structural encoding stage, children with ADHD display abnormality at the contextual processing stage. The comorbid ASD+ADHD group presents as an additive condition with the unique deficits of both disorders. This supports the use of objective neural measurement of emotional processing to delineate pathophysiological mechanisms in complex overlapping disorders.

Attention deficit hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder with complex genetic aetiology. The identification of candidate intermediate phenotypes may facilitate the detection of susceptibility genes and neurobiological mechanisms underlying the disorder. Electroencephalography (EEG) is an ideal neuroscientific approach, providing a direct measurement of neural activity that demonstrates reliability, developmental stability and high heritability. This systematic review evaluates the utility of a subset of electrophysiological measures as potential intermediate phenotypes for ADHD: quantitative EEG indices of arousal and intraindividual variability, and functional investigations of attention, inhibition and performance monitoring using the event-related potential (ERP) technique. Each measure demonstrates consistent and meaningful associations with ADHD, a degree of genetic overlap with ADHD and potential links to specific genetic variants. Investigations of the genetic and environmental contributions to EEG/ERP and shared genetic overlap with ADHD might enhance molecular genetic studies and provide novel insights into aetiology. Such research will aid in the precise characterisation of the clinical deficits seen in ADHD and guide the development of novel intervention and prevention strategies for those at risk.

Graph theory has been recently introduced to characterize complex brain networks, making it highly suitable to investigate altered connectivity in neurologic disorders. A current model proposes autism spectrum disorder (ASD) as a developmental disconnection syndrome, supported by converging evidence in both non-syndromic and syndromic ASD. However, the effects of abnormal connectivity on network properties have not been well studied, particularly in syndromic ASD. To close this gap, brain functional networks of electroencephalographic (EEG) connectivity were studied through graph measures in patients with Tuberous Sclerosis Complex (TSC), a disorder with a high prevalence of ASD, as well as in patients with non-syndromic ASD.EEG data were collected from TSC patients with ASD (n = 14) and without ASD (n = 29), from patients with non-syndromic ASD (n = 16), and from controls (n = 46). First, EEG connectivity was characterized by the mean coherence, the ratio of inter- over intra-hemispheric coherence and the ratio of long- over short-range coherence. Next, graph measures of the functional networks were computed and a resilience analysis was conducted. To distinguish effects related to ASD from those related to TSC, a two-way analysis of covariance (ANCOVA) was applied, using age as a covariate.Analysis of network properties revealed differences specific to TSC and ASD, and these differences were very consistent across subgroups. In TSC, both with and without a concurrent diagnosis of ASD, mean coherence, global efficiency, and clustering coefficient were decreased and the average path length was increased. These findings indicate an altered network topology. In ASD, both with and without a concurrent diagnosis of TSC, decreased long- over short-range coherence and markedly increased network resilience were found.The altered network topology in TSC represents a functional correlate of structural abnormalities and may play a role in the pathogenesis of neurological deficits. The increased resilience in ASD may reflect an excessively degenerate network with local overconnection and decreased functional specialization. This joint study of TSC and ASD networks provides a unique window to common neurobiological mechanisms in autism.