Infancy and early childhood maturation of neural auditory change detection and its associations to familial dyslexia risk

Objective: We investigated early maturation of the infant mismatch response MMR, including mismatch negativity (MMN), positive MMR (P-MMR), and late discriminative negativity (LDN), indexing auditory discrimination abilities, and the influence of familial developmental dyslexia risk. Methods: We recorded MMRs to vowel, duration, and frequency deviants in pseudo-words at 0, 6, and 28 months and compared MMRs in subgroups with vs. without dyslexia risk, in a sample overrepresented by risk infants. Results: Neonatal MMN to the duration deviant became larger and earlier by 28 months; MMN was elicited by more deviants only at 28 months. The P-MMR was predominant in infancy; its amplitude increased by 6 and decreased by 28 months; latency decreased with increasing age. An LDN emerged by 6 months and became larger and later by 28 months. Dyslexia risk affected MMRs and their maturation. Conclusions: MMRs demonstrate an expected maturational pattern with 2-3 peaks by 28 months. The effects of dyslexia risk are prominent but not always as expected. Significance: This large-scale longitudinal study shows MMR maturation with three age groups and three deviants. Results illuminate MMR's relation to the adult responses, and hence their cognitive underpinnings, and help in identifying typical/atypical auditory development in early childhood. (c) 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Infant event-related potentials to speech are associated with prelinguistic development

Neural auditory processing and prelinguistic communication build the foundation for later language development, but how these two are associated is not well known. The current study investigated how neural speech processing is associated with the level and development of prelinguistic skills in 102 infants. We recorded event-related potentials (ERPs) in 6-months-olds to assess the neural detection of a pseudoword (obligatory responses), as well as the neural discrimination of changes in the pseudoword (mismatch responses, MMRs). Prelinguistic skills were assessed at 6 and 12 months of age with a parental questionnaire (Infant-Toddler Checklist). The association between the ERPs and prelinguistic skills was examined using latent change score models, a method specifically constructed for longitudinal analyses and explicitly modeling intra-individual change. The results show that a large obligatory P1 at 6 months of age predicted strong improvement in prelinguistic skills between 6 and 12 months of age. The MMR to a frequency change was associated with the concurrent level of prelinguistic skills, but not with the improvement of the skills. Overall, our results highlight the strong association between ERPs and prelinguistic skills, possibly offering opportunities for early detection of atypical linguistic and communicative development.Peer reviewe

Infancy and early childhood maturation of neural auditory change detection and its associations to familial dyslexia risk

ObjectiveWe investigated early maturation of the infant mismatch response MMR, including mismatch negativity (MMN), positive MMR (P-MMR), and late discriminative negativity (LDN), indexing auditory discrimination abilities, and the influence of familial developmental dyslexia risk.MethodsWe recorded MMRs to vowel, duration, and frequency deviants in pseudo-words at 0, 6, and 28 months and compared MMRs in subgroups with vs. without dyslexia risk, in a sample over-represented by risk infants.ResultsNeonatal MMN to the duration deviant became larger and earlier by 28 months; MMN was elicited by more deviants only at 28 months. The P-MMR was predominant in infancy; its amplitude increased by 6 and decreased by 28 months; latency decreased with increasing age. An LDN emerged by 6 months and became larger and later by 28 months. Dyslexia risk affected MMRs and their maturation.ConclusionsMMRs demonstrate an expected maturational pattern with 2–3 peaks by 28 months. The effects of dyslexia risk are prominent but not always as expected.SignificanceThis large-scale longitudinal study shows MMR maturation with three age groups and three deviants. Results illuminate MMR’s relation to the adult responses, and hence their cognitive underpinnings, and help in identifying typical/atypical auditory development in early childhood.</p

Phenotype-genotype correlations in Leigh syndrome : new insights from a multicentre study of 96 patients

Background Leigh syndrome is a phenotypically and genetically heterogeneous mitochondrial disorder. While some genetic defects are associated with well-described phenotypes, phenotype-genotype correlations in Leigh syndrome are not fully explored. Objective We aimed to identify phenotype-genotype correlations in Leigh syndrome in a large cohort of systematically evaluated patients. Methods We studied 96 patients with genetically confirmed Leigh syndrome diagnosed and followed in eight European centres specialising in mitochondrial diseases. Results We found that ataxia, ophthalmoplegia and cardiomyopathy were more prevalent among patients with mitochondrial DNA defects. Patients with mutations in MT-ND and NDUF genes with complex I deficiency shared common phenotypic features, such as early development of central nervous system disease, followed by high occurrence of cardiac and ocular manifestations. The cerebral cortex was affected in patients with NDUF mutations significantly more often than the rest of the cohort. Patients with the m. 8993T> G mutation in MT-ATP6 gene had more severe clinical and radiological manifestations and poorer disease outcome compared with patients with the m. 8993T> C mutation. Conclusion Our study provides new insights into phenotype-genotype correlations in Leigh syndrome and particularly in patients with complex I deficiency and with defects in the mitochondrial ATP synthase.Peer reviewe

How young adults with autism spectrum disorder watch and interpret pragmatically complex scenes

The aim of the current study was to investigate subtle characteristics of social perception and interpretation in high-functioning individuals with autism spectrum disorders (ASDs), and to study the relation between watching and interpreting. As a novelty, we used an approach that combined moment-by-moment eye tracking and verbal assessment. Sixteen young adults with ASD and 16 neurotypical control participants watched a video depicting a complex communication situation while their eye movements were tracked. The participants also completed a verbal task with questions related to the pragmatic content of the video. We compared verbal task scores and eye movements between groups, and assessed correlations between task performance and eye movements. Individuals with ASD had more difficulty than the controls in interpreting the video and during two short moments there were significant group differences in eye movements. Additionally, we found significant correlations between verbal task scores and moment-level eye movement in the ASD group, but not among the controls. We concluded that participants with ASD had slight difficulties in understanding the pragmatic content of the video stimulus and attending to social cues, and that the connection between pragmatic understanding and eye movements was more pronounced for participants with ASD than for neurotypical participants.Our Research Report for 2000-2002 reflects an outstanding level of achievement throughout the institution and demonstrates once again our high level of commitment to strategic and applied research particularly in areas that enhance the quality of life.casl70pub4526pub1

A multicenter study on Leigh syndrome: Disease course and predictors of survival

Background: Leigh syndrome is a progressive neurodegenerative disorder, associated with primary or secondary dysfunction of the mitochondrial oxidative phosphorylation. Despite the fact that Leigh syndrome is the most common phenotype of mitochondrial disorders in children, longitudinal natural history data is missing. This study was undertaken to assess the phenotypic and genotypic spectrum of patients with Leigh syndrome, characterise the clinical course and identify predictors of survival in a large cohort of patients. Methods. This is a retrospective study of patients with Leigh syndrome that have been followed at eight centers specialising in mitochondrial diseases in Europe; Gothenburg, Rotterdam, Helsinki, Copenhagen, Stockholm, Brussels, Bergen and Oulu. Results: A total of 130 patients were included (78 males; 52 females), of whom 77 patients had identified pathogenic mutations. The median age of disease onset was 7 months, w

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

How do first-time mother´s experience the first meeting with the personnel at the delivery ward? An interviewstudy.

Att kvinnor ska få en positiv upplevelse av förlossningen är ett mål inom förlossningsvården i Sverige. Barnmorskans bemötande präglar till stor del kvinnans förlossningsupplevelse. Det finns inte mycket forskat tidigare om just det första mötet och vad det har för betydelse för den fortsatta förlossningen. Syftet med vår studie var därför att undersöka hur förstföderskor upplevde det första mötet med personalen på förlossningsavdelningen. Intervjuer genomfördes med 30 kvinnor. En kvalitativ innehållsanalys utkristalliserades i tre kategorier, få lämna över sig till professionell personal, ha en konversation och få upplysning samt känna sig alldeles speciell, och åtta underkategorier. Resultatet visar på att förstföderskor upplever en trygghet vid det första mötet med personalen. De känner förtroende för personalen och de blir bekräftade och sedda som en unik människa. Oro och nervositet dämpas då tryggheten infinner sig. Mödrarna känner att de har en bra dialog med personalen och att informationen de får oftast är tillräcklig

Civil society in reconciliation : beyond the 'Cyprus problem'

Linda Lönnqvis