There is active debate regarding how GABAergic function changes during seizure initiation and propagation, and whether interneuronal activity drives or impedes the pathophysiology. Here, we track cell-type specific firing during spontaneous human seizures to identify neocortical mechanisms of inhibitory failure. Fast-spiking interneuron activity was maximal over 1 second before equivalent excitatory increases, and showed transitions to out-of-phase firing prior to local tissue becoming incorporated into the seizure-driving territory. Using computational modeling, we linked this observation to transient saturation block as a precursor to seizure invasion, as supported by multiple lines of evidence in the patient data. We propose that transient blocking of inhibitory firing due to selective fast-spiking interneuron saturation - resulting from intense excitatory synaptic drive - is a novel mechanism that contributes to inhibitory failure, allowing seizure propagation.

Objective To determine rates of psychiatric comorbidity in a clinical sample of childhood movement disorders (MDs). Design Cohort study. Setting Tertiary children's hospital MD clinics in Sydney, Australia and London, UK. Patients Cases were children with tic MDs (n=158) and non-tic MDs (n=102), including 66 children with dystonia. Comparison was made with emergency department controls (n=100), neurology controls with peripheral neuropathy or epilepsy (n=37), and community controls (n=10 438). Interventions On-line development and well-being assessment which was additionally clinically rated by experienced child psychiatrists. Main outcome measures Diagnostic schedule and manual of mental disorders-5 criteria for psychiatric diagnoses. Results Psychiatric comorbidity in the non-tic MD cohort (39.2%) was comparable to the tic cohort (41.8%) (not significant). Psychiatric comorbidity in the non-tic MD cohort was greater than the emergency control group (18%, p<0.0001) and the community cohort (9.5%, p<0.00001), but not the neurology controls (29.7%, p=0.31). Almost half of the patients within the tic cohort with psychiatric comorbidity were receiving medical psychiatric treatment (45.5%) or psychology interventions (43.9%), compared with only 22.5% and 15.0%, respectively, of the non-tic MD cohort with psychiatric comorbidity. Conclusions Psychiatric comorbidity is common in non-tic MDs such as dystonia. These psychiatric comorbidities appear to be under-recognised and undertreated.

High frequency oscillations (HFOs) are bursts of neural activity in the range of 80 Hz or higher, recorded from intracranial electrodes during epileptiform discharges. HFOs are a proposed biomarker of epileptic brain tissue and may also be useful for seizure forecasting. Despite such clinical utility of HFOs, the spatial context and neuronal activity underlying these local field potential (LFP) events remains unclear. We sought to further understand the neuronal correlates of ictal high frequency LFPs using multielectrode array recordings in the human neocortex and mesial temporal lobe during rhythmic onset seizures. These multiscale recordings capture single cell, multiunit, and LFP activity from the human brain. We compare features of multiunit firing and high frequency LFP from microelectrodes and macroelectrodes during ictal discharges in both the seizure core and penumbra (spatial seizure domains defined by multiunit activity patterns). We report differences in spectral features, unit-local field potential coupling, and information theoretic characteristics of high frequency LFP before and after local seizure invasion. Furthermore, we tie these time-domain differences to spatial domains of seizures, showing that penumbral discharges are more broadly distributed and less useful for seizure localization. These results describe the neuronal and synaptic correlates of two types of pathological HFOs in humans and have important implications for clinical interpretation of rhythmic onset seizures.

Objective High frequency oscillations (HFOs) recorded from intracranial electrodes during epileptiform discharges have been proposed as a biomarker of epileptic brain sites and may also be a useful feature for seizure forecasting, with mixed results. Currently, pathological subclasses of HFOs have been defined primarily by frequency characteristics. Despite this, there has been limited investigation into the spatial context of HFOs with recruitment of local cortex into seizure discharging. We sought to further understand the biophysical underpinnings of ictal HFOs. Methods Here we examine ictal HFOs from multi-scale electrophysiological recordings during spontaneous human rhythmic onset seizures. We compare features of ictal discharges in both the seizure core and penumbra, as defined by multiunit activity patterns. Results We show marked differences in spectral features, unit coupling, and information theoretic characteristics of HFOs during ictal discharges before and after local seizure invasion. Furthermore, we tie these timing-related differences to different spatial domains of seizures, showing that eccentric, penumbral discharges are widely distributed and less useful for seizure localization, which may explain the variable utility of HFOs in seizure localization and forecasting. Interpretation We thus identify two distinct classes of ictal HFOs, implying two different mechanisms underlying pathological HFOs with contrasting significance for seizure localization. ### Competing Interest Statement Dr. Rolston reports personal fees from Medtronic, personal fees from NeuroPace, Dr. Friedman reports grants, non-financial support and other from Epilepsy Study Consortium, personal fees and other from Eisai, personal fees from Penumbra, grants, personal fees and other from Neuropace, grants from Epitel, grants and other from Empatica, grants and personal fees from UCB, Inc, other from Acorda Pharmaceuticals, grants and other from Adamas Pharmaceuticals, other from Alexza, other from Axcella, other from Biogen, other from Biopharm, other from CuroNZ, other from Engage, other from GW Pharma, other from Pfizer, other from Pfizer-Neusentis, other from Marinus, other from SK Life Sciences, other from Upsher Smith, other from Zogenix, other from Zynerba, other from Neuroview Technology, other from Receptor Life Sciences, other from Medtronic, Inc, other from Xenon pharmaceuticals, outside the submitted work; and Dr. Friedman serves on the editorial board of epilepsy.com and is a member of the executive committee of the physician advisory board of the Epilepsy Foundation of America. Dr. McKhann reports personal fees from Koh Young Inc. Dr. Doyle reports non-financial support and other from Neuroview Technology. ### Funding Statement This work was supported by NIH S10 OD018211 (CAS), NIH R01 NS084142 (CAS), NIH R01 NS095368 (CAS), NIH R21 NS113031 (JDR), and NIH KL2 TR002539 (JDR). ### Author Declarations All relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript. Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All analyses code are publicly available and data may be shared with the approval of the Columbia University Medical Center Institutional Review Board

The Galilee Study is the first large epidemiological study to compare correlates of mental disorders between two Arab Palestinian minority groups of adolescents in Israel. A two-stage cross-sectional study, carried out between 2012 and 2014, included all 9th grade students from 5 Arab localities, representative of 77% of the Muslim and 100% of Druze citizens in Israel. During the screening stage, 1639 students completed the Strengths and Difficulties Questionnaire in the classroom (response rate = 69.3%). During the follow-up stage, 704 adolescent-mother dyads were interviewed at home; using the Development and Well-Being Assessment, the General Health Questionnaire (GHQ)-12, the Subjective Feeling of Discrimination Index (FDI), and socio-demographic questions (response rate = 84.4%). Prevalence of any disorder, internalizing or externalizing disorders among Muslim adolescents were 19.2, 15.8 and 4.2%, respectively and among Druze adolescents 10.9, 5.9 and 5.5%, respectively. Muslim adolescents were 3.2 times more likely than Druze adolescents to have an internalizing disorder, while Druze were 2 times more likely than Muslim to have an externalizing disorder. Males were at higher risk than females for externalizing disorders in both populations, though among Druze the risk was more striking. Learning disabilities increased the likelihood of having an externalizing disorder in both populations. Risk factors for internalizing disorders among Muslim adolescents were female gender, a very low socio-economic level, few siblings, LD, high maternal GHQ-12 score and high FDI; and for externalizing disorders, male gender, a relatively low socio-economic level but not the lowest, learning disability and high maternal GHQ-12 score. We found an association between religion/ethnicity and internalizing and externalizing disorders as well as a strong correlation between religion/ethnicity and socio-economic variables. Therefore, we tend to conclude that not religion per se but the multifaceted socio-cultural and economic factors that characterize religious groups are associated with mental disorders. Very low socio-economic level and feeling discriminated which were traits connected only to Muslim adolescents, were associated with internalizing disorders. When preparing preventive measures aimed at furthering mental health among minority adolescents, authorities should focus on improving the socio-economic status of minorities and reducing institutional and personal discrimination. The educational and mental health establishments could undertake measures to improve resilience and coping strategies of Muslim families living in the most adverse conditions, such as providing special support through the school counseling services and coordinating, at the ministerial levels, school and community health services in order to carry out joint preventive programs and referrals to specialist services when needed.

Youths with attention-deficit/hyperactivity disorder symptomatology often exhibit residual inattention and/or hyperactivity in adulthood; however, this is not true for all individuals. We recently reported that dimensional, multi-informant ratings of hyperactive/inattentive symptoms are associated with ventromedial prefrontal cortex (vmPFC) structure. Herein, we investigate the degree to which vmPFC structure during adolescence predicts hyperactive/inattentive symptomatology at 5-year follow-up. Structural equation modeling was used to test the extent to which adolescent vmPFC volume predicts hyperactive/inattentive symptomatology 5 years later in early adulthood. 1104 participants (M = 14.52 years, standard deviation = 0.42; 583 females) possessed hyperactive/inattentive symptom data at 5-year follow-up, as well as quality controlled neuroimaging data and complete psychometric data at baseline. Self-reports of hyperactive/inattentive symptomatology were obtained during adolescence and at 5-year follow-up using the Strengths and Difficulties Questionnaire (SDQ). At baseline and 5-year follow-up, a hyperactive/inattentive latent variable was derived from items on the SDQ. Baseline vmPFC volume predicted adult hyperactive/inattentive symptomatology (standardized coefficient = -0.274, P < 0.001) while controlling for baseline hyperactive/inattentive symptomatology. These results are the first to reveal relations between adolescent brain structure and adult hyperactive/inattentive symptomatology, and suggest that early structural development of the vmPFC may be consequential for the subsequent expression of hyperactive/inattentive symptoms.

Heavy drinker adolescents: altered brainstem microstructure.

Compassion has been directly trained for over 2500 years alongside loving-kindness, sympathetic joy, and equanimity, which together represent the four brahmavihāras, also known as the divine or immeasurable abodes. The present chapter describes the four brahmavihāras as they are conceptualized in Early Buddhist canonical literature. We explore how the overlapping theoretical components of the brahmavihāras may shed light on conceptual/psychological similarities and differences among them. Next, the brahmavihāras are compared and contrasted with other foundational contemplative practices, such as sustained attention and open monitoring. Following this conceptual exploration of contemplative practices, we explore the extant neuroscience literature on sustained attention and open monitoring to shed light on how these foundational practices influence a variety of neural markers, such as attention, emotion, and self-referential processing. Finally, we review the emerging neuroscience literature that examines how deliberate training of the brahmavihāras may influence the brain. Weaving together Early Buddhist scholarship with modern neuroscience, changes in neural activity that result from the deliberate cultivation of loving-kindness and compassion are identified and differentiated from their contemplative cousins.

AimValid instruments for the early identification of psychotic experiences (PE) and symptoms in youths are urgently needed for large‐scale preventive interventions. A new section of The‐Development‐and‐Well‐Being Assessment (DAWBA) measuring child self‐reported PE has yet to be validated. The current study aimed to investigate the concurrent validity of DAWBA‐based self‐reported PE (PE‐S) with regard to interview‐based measures of PE (PE‐I).MethodsParticipants were 1571 (47.8% male) children of age 11 to 12 years from the Copenhagen Child Cohort 2000 (CCC2000) with complete data from both the online PE‐section of DAWBA and the following face‐to‐face interview and assessment of PE. The DAWBA‐PE‐section asks the child 10 questions covering auditory and visual hallucinations, delusional ideas and subjective thought disturbances ever in life; and attributions to sleep, fever, illness or drug intake. The interview‐based assessment of PE was performed by trained professionals using 22 items from The Schedule for Affective Disorders and Schizophrenia for School Aged Children‐Present and Lifetime Version (KSADS‐PL). The two assessments were completed independently.ResultsThe prevalence of PE‐S was 28.1% (24.3% for PE‐S with no frequent attributions), compared with 10.2% for PE‐I. The predictive values of PE‐S for any PE‐I were: sensitivity = 73.8%, specificity = 77.1%, positive predictive value (PPV) = 26.8% and negative predictive value (NPV) = 96.3%. Self‐reported visual hallucinations had the best overall predictive values with a sensitivity of 43.1%, specificity of 94.0%, PPV of 44.8% and a NPV of 93.6% for any PE‐I.ConclusionThe DAWBA‐section proved valuable as a screening tool for PE in the youth general population.

Parents and teachers often disagree on the presence of Oppositional Defiant Disorder (ODD) in children. It has been argued that ODD should be treated as an informant-specific disorder. This study compared the characteristics of children identified with ODD by parent- and teacher report. We used the 1999 British Child and Adolescent Mental Health Survey, including more than 10,000 observations aged 5–15 years, to investigate symptom profiles, risk factors, comorbidities and three-year outcomes of parent- and teacher-reported ODD. Parents and teachers poorly agreed on ODD diagnosis. Parent-reported ODD was more strongly associated with a concurrent anxiety disorder at time 1 and a successive diagnosis of ODD at time 2 . Beyond these differences, parent- and teacher- reported ODD showed similar symptom profiles, risk factors, comorbidities, and outcomes. Children identified by parent report and teacher report share more similarities than differences in the characteristics of their disorder. This does not support the formation of informant-specific ODD disorders.

From the public health perspective, epidemiological data of child mental health and psychosocial correlates were necessary and very lacking in Lithuanian society that has been undergoing rapid socio-economic change since the past decades. Together with determining the prevalence rates of disorders and assessing the needs for the services, this study has also shifted attention from the highly selective samples of children attending children and adolescent mental health services towards less severe cases of psychopathology as well as different attitudes of parents and teachers. The aim of the first epidemiological study in Lithuania was to identify the prevalence of psychiatric disorders in the community sample of children.

Background. There is limited research that explores the association between exclusion from school and mental health, but it seems intuitively plausible that the recognition of mental difficulties by key teachers and parents would influence the likelihood of exclusion from school. Methods. A secondary analysis of the British Child and Adolescent Mental Health survey 2004, (n = 7997) and the 2007 follow-up (n = 5326) was conducted. Recognition of difficulty was assessed via a derived variable that combined the first item of the Impact supplement of the Strengths and Difficulties Questionnaire which asked parents and teachers if they thought that the child has difficulties with emotions, behaviour and concentration, and the presence/ absence of psychiatric disorder measured by the Development and Well-being Assessment. Results. Adjusted logistic regression models demonstrated that children with recognised difficulties were more likely to be excluded [adjusted odds ratio (OR) 5.78, confidence interval 3.45-9.64, p < 0.001], but children with unrecognised difficulties [adjusted OR 3.58 (1.46-8.81) p < 0.005] or recognised subclinical difficulties [adjusted OR 3.42 (2.04-5.73) p< 0.001] were also more likely to be excluded than children with no difficulties. Children with conduct disorder and attention deficit hyperactivity disorder were most likely to be excluded compared with other types of disorder. Conclusion. Exclusion from school may result from a failure to provide timely and effective support rather than a failure to recognise psychopathology.

Body Dysmorphic Disorder (BDD) is a distressing disorder that is widely underdetected in youth. This study aimed to examine the potential utility of the Development and Well-Being Assessment (DAWBA) as a tool to improve recognition of BDD in routine clinical practice . One hundred and sixty-one patients assessed across two national and specialist child and adolescent mental health services, one specialising in mood disorders and one specialising in obsessive compulsive disorder and BDD, were included in this study. Results from the DAWBA were compared with clinical diagnosis to examine the utility of the DAWBA in detecting BDD. Only 27% of participants who received a diagnosis of BDD at assessment had been referred with concerns about appearance anxiety suggesting significant under detection in youth mental health services. Using the single-screener question on the DAWBA, it was possible to correctly identify 97% of cases with BDD. Body dysmorphic disorder often goes undetected in routine clinical practice. The DAWBA shows promise as a tool for helping clinicians to accurately detect BDD in routine clinical practice.

BackgroundBody Dysmorphic Disorder (BDD) is a distressing disorder that is widely underdetected in youth. This study aimed to examine the potential utility of the Development and Well-Being Assessment (DAWBA) as a tool to improve recognition of BDD in routine clinical practice. MethodsOne hundred and sixty-one patients assessed across two national and specialist child and adolescent mental health services, one specialising in mood disorders and one specialising in obsessive compulsive disorder and BDD, were included in this study. Results from the DAWBA were compared with clinical diagnosis to examine the utility of the DAWBA in detecting BDD. ResultsOnly 27% of participants who received a diagnosis of BDD at assessment had been referred with concerns about appearance anxiety suggesting significant under detection in youth mental health services. Using the single-screener question on the DAWBA, it was possible to correctly identify 97% of cases with BDD. ConclusionsBody dysmorphic disorder often goes undetected in routine clinical practice. The DAWBA shows promise as a tool for helping clinicians to accurately detect BDD in routine clinical practice.

Objective: White matter microstructure alterations have recently been associated with depressive episodes during adolescence, but it is unknown whether they predate depression. The authors investigated whether subthreshold depression in adolescence is associated with white matter microstructure variations and whether they relate to depression outcome. Method: Adolescents with subthreshold depression (N=96) and healthy control subjects (N=336) drawn from a community-based cohort were compared using diffusion tensor imaging and whole brain tract-based spatial statistics (TBSS) at age 14 to assess white matter microstructure. They were followed up at age 16 to assess depression. Probabilistic tractography was used to reconstruct white matter streamlines spreading from the regions identified in the TBSS analysis and along bundles implicated in emotion regulation, the uncinate fasciculus and the cingulum. The authors searched for mediating effects of white matter microstructure on the relationship between baseline subthreshold depression and depression at follow-up, and then explored the specificity of the findings. Results: Lower fractional anisotropy (FA) and higher radial diffusivity were found in the anterior corpus callosum in the adolescents with subthreshold depression. Tractography analysis showed that they also had lower FA in the right cingulum streamlines, along with lower FA and higher mean diffusivity in tracts connecting the corpus callosum to the anterior cingulate cortex. The relation between subthreshold depression at baseline and depression at follow-up was mediated by FA values in the latter tracts, and lower FA values in those tracts distinctively predicted higher individual risk for depression. Conclusions: Early FA variations in tracts projecting from the corpus callosum to the anterior cingulate cortex may denote a higher risk of transition to depression in adolescents.

Youth- and parent-rated screening measures derived from the Strengths and Difficulties Questionnaire (SDQ) and Development and Well-Being Assessment (DAWBA) were compared on their psychometric properties as predictors of caseness in adolescence (mean age 14). Successful screening was judged firstly against the likelihood of having an ICD-10 psychiatric diagnosis and secondly by the ability to discriminate between community (N = 252) and clinical (N = 86) samples (sample status). Both, SDQ and DAWBA measures adequately predicted the presence of an ICD-10 disorder as well as sample status. The hypothesis that there was an informant gradient was confirmed: youth self-reports were less discriminating than parent reports, whereas combined parent and youth reports were more discriminating-a finding replicated across a diversity of measures. When practical constraints only permit screening for caseness using either a parent or an adolescent informant, parents are the better source of information.

Background: Discrepancies between multiple informants often create considerable uncertainties in delivering services to youth. The present study assessed the ability of the parent and youth scales of the Strength and Difficulties Questionnaire (SDQ) to predict mental health problems/disorders across several mental health domains as validated against two contrasting indices of validity for psychopathology derived from the Development and Well Being Assessment (DAWBA): (1) an empirically derived computer algorithm and (2) expert based ICD-10 diagnoses. Methods: Ordinal and logistic regressions were used to predict any problems/disorders, emotional problems/disorders and behavioural problems/disorders in a community sample (n = 252) and in a clinic sample (n = 95). Results: The findings were strikingly similar in both samples. Parent and youth SDQ scales were related to any problem/disorder. Youth SDQ symptom and impact had the strongest association with emotional problems/disorder and parent SDQ symptom score were most strongly related to behavioural problems/disorders. Both the SDQ total and the impact scores significantly predicted emotional problems/disorders in males whereas this was the case only for the total SDQ score in females. Conclusion: The present study confirms and expands previous findings on parent and youth informant validity. Clinicians should include both parent and youth for identifying any mental health problems/disorders, youth information for detecting emotional problems/disorders, and parent information to detect behavioural problems/disorders. Not only symptom scores but also impact measures may be useful to detect emotional problems/disorders, particularly in male youth.

Small-scale neuronal networks may impose widespread effects on large network dynamics. To unravel this relationship, we analyzed eight multiscale recordings of spontaneous seizures from four patients with epilepsy. During seizures, multiunit spike activity organizes into a submillimeter-sized wavefront, and this activity correlates significantly with low-frequency rhythms from electrocorticographic recordings across a 10-cm-sized neocortical network. Notably, this correlation effect is specific to the ictal wavefront and is absent interictally or from action potential activity outside the wavefront territory. To examine the multiscale interactions, we created a model using a multiscale, nonlinear system and found evidence for a dual role for feedforward inhibition in seizures: while inhibition at the wavefront fails, allowing seizure propagation, feedforward inhibition of the surrounding centimeter-scale networks is activated via long-range excitatory connections. Bifurcation analysis revealed that distinct dynamical pathways for seizure termination depend on the surrounding inhibition strength. Using our model, we found that the mesoscopic, local wavefront acts as the forcing term of the ictal process, while the macroscopic, centimeter-sized network modulates the oscillatory seizure activity.

It has been suggested that the structure of psychiatric phenomena can be reduced to a few symptom dimensions. These proposals, mainly based on epidemiological samples, may not apply to clinical populations. We tested the structure of psychiatric symptoms across two pediatric clinical samples from England (N = 8434) and Norway (N = 5866). Confirmatory factor analyses of the parent-reported Strengths and Difficulties Questionnaire (SDQ) evaluated the relative fit of several models, including a first-order model, a second-order model with the widely-established broad symptom dimensions of internalizing-externalizing, and two bi-factor models capturing a general psychopathology factor. Predictive value of the SDQ subscales for psychiatric disorders was examined. A first-order five-factor solution better fit the data. The expected SDQ subscale(s) related best to the corresponding psychiatric diagnosis. In pediatric clinical samples, a granular approach to psychiatric symptoms where several dimensions are considered seems to fit the data better than models based on lumping symptoms into internalizing/externalizing dimensions.