Mental rotation performance in young adults with and without developmental coordination disorder.

While there have been consistent behavioural reports of atypical hand rotation task (HRT) performance in adults with developmental coordination disorder (DCD), this study aimed to clarify whether this deficit could be attributed to specific difficulties in motor imagery (MI), as opposed to broad deficits in general mental rotation. Participants were 57 young adults aged 18-30 years with (n = 22) and without DCD (n = 35). Participants were compared on the HRT, a measure of MI, and the letter number rotation task (LNRT), a common visual imagery task. Only participants whose behavioural performance on the HRT suggested use of a MI strategy were included in group comparisons. Young adults with DCD were significantly less efficient compared to controls when completing the HRT yet showed comparable performance on the LNRT relative to adults with typical motor ability. Our data are consistent with the view that atypical HRT performance in adults with DCD is likely to be attributed to specific difficulties engaging in MI, as opposed to deficits in general mental rotation. Based on the theory that MI provides insight into the integrity of internal action representations, these findings offer further support for the internal modelling deficit hypothesis of DCD.

Technology-based methods for the assessment of fine and gross motor skill in children: A systematic overview of available solutions and future steps for effective in-field use.

The present review aims at providing researchers and practitioners with a holistic overview of technology-based methods for the assessment of fine and gross motor skill in children. We conducted a search of electronic databases using Web of Science, PubMed and Google Scholar, including studies published up to March 2020, that assessed fine and/or gross motor skills, and utilized technological assessment of varying study design. A total of 739 papers were initially retrieved, and after title/abstract screening, removal of duplicates, and full-text screening, 47 were included. Results suggest that motor skills can be quantitatively estimated using objective methods based on a wearable- and/or laboratory-based technology, for typically developing (TD) and non-TD children. Fine motor skill assessment solutions were; force transducers, instrumented tablets and pens, surface electromyography, and optoelectronic systems. Gross motor skill assessment solutions were; inertial measurements units, optoelectronic systems, baropodometric mats, and force platforms. This review provides a guide in identifying and evaluating the plethora of available technological solutions to motor skill assessment. Although promising, there is still a need for large-scale studies to validate these approaches in terms of accuracy, repeatability, and usability, where interdisciplinary collaborations between researchers and practitioners and transparent reporting practices should be advocated.

Auditory Mapping With MEG: An Update on the Current State of Clinical Research and Practice With Considerations for Clinical Practice Guidelines.

Auditory evoked fields (AEFs) are well suited for studies of auditory processing in patients. Their sources have been localized to Heschl's gyri and to the supratemporal auditory cortices. Auditory evoked fields are known to be modulated by peripheral and central lesions of auditory pathways and to reflect group-level pathophysiology of neurodevelopmental and psychiatric disorders. They are useful in lateralization of language processes for planning neurosurgery and for localization of language-related cortex. The recently developed artifact rejection and movement compensation methods will enhance and extend the use of AEFs in studies of clinical patients and pediatric groups. New pediatric magnetoencephalography systems will facilitate clinical AEF studies of developmental disorders. In addition to their established use in planning neurosurgery, AEF findings in several new clinical patient groups suffering, e.g., from developmental, neurodegenerative, or psychiatric disorders have been reported. Several recent investigations report the correlations with clinical symptoms and sensitivity and specificity profiles of AEFs in studies of these disorders; this development is mandatory in gaining wider clinical approval for the use of AEFs in clinical practice dealing with individual patients. Most promising future research lines of clinical applicability of AEFs focus on developmental and psychiatric disorders.

Basal ganglia and thalamic tract connectivity in very preterm and full-term children; associations with 7-year neurodevelopment.

BACKGROUND: Altered basal ganglia and thalamic connectivity may be critical for cognitive, motor and behavioural impairments common to very preterm (<32 weeks' gestational age) children. This study aims to (1) compare corticostriatal and thalamocortical tract connectivity between very preterm and term-born children at 7 years of age; (2) explore tract connectivity associations with 7-year neurodevelopmental outcomes, and whether these relationships differed between groups. METHODS: Eighty-three very preterm and 19 term-born (≥37 weeks' gestational age) children underwent structural and diffusion magnetic resonance imaging and had a neuropsychological assessment at 7 years. Corticostriatal and thalamocortical tracts were reconstructed and white matter connectivity was estimated with apparent fibre density. RESULTS: Compared with term-born controls, very preterm children had decreased connectivity in tracts linking the caudate to right motor areas (-10%, p = 0.03) and the thalamus with left motor areas (-5.7%, p = 0.03). Reduced connectivity in corticostriatal and thalamocortical tracts was associated with adverse motor functioning in both groups (p = 0.06). Decreased connectivity of the left caudate and putamen with the lateral prefrontal cortex was associated with lower reading performance for controls (p = 0.06). CONCLUSION: Corticostriatal and thalamocortical tracts are vulnerable to very preterm birth. Poorer connectivity in these tracts may underlie the motor impairments observed in very preterm children.

Curcumin Prevents Cerebellar Hypoplasia and Restores the Behavior in Hyperbilirubinemic Gunn Rat by a Pleiotropic Effect on the Molecular Effectors of Brain Damage.

Bilirubin toxicity to the central nervous system (CNS) is responsible for severe and permanent neurologic damage, resulting in hearing loss, cognitive, and movement impairment. Timely and effective management of severe neonatal hyperbilirubinemia by phototherapy or exchange transfusion is crucial for avoiding permanent neurological consequences, but these therapies are not always possible, particularly in low-income countries. To explore alternative options, we investigated a pharmaceutical approach focused on protecting the CNS from pigment toxicity, independently from serum bilirubin level. To this goal, we tested the ability of curcumin, a nutraceutical already used with relevant results in animal models as well as in clinics in other diseases, in the Gunn rat, the spontaneous model of neonatal hyperbilirubinemia. Curcumin treatment fully abolished the landmark cerebellar hypoplasia of Gunn rat, restoring the histological features, and reverting the behavioral abnormalities present in the hyperbilirubinemic rat. The protection was mediated by a multi-target action on the main bilirubin-induced pathological mechanism ongoing CNS damage (inflammation, redox imbalance, and glutamate neurotoxicity). If confirmed by independent studies, the result suggests the potential of curcumin as an alternative/complementary approach to bilirubin-induced brain damage in the clinical scenario.

Developmental social vulnerability as the intrinsic origin of psychopathology: A paradigm shift from disease entities to psychiatric derivatives within human diversity.

How a social episode is perceived by a person and how the experience affects her/his subsequent behaviors will inevitably and sometimes accidentally vary in each case on the developmental trajectory from the birth of consciousness to death. Both the preceding developmental conditions and the social impact of the episode become a starting point for the following states of human complex conditions, creating the extraordinary diversity that characterizes our complex society. In this evolutionarily carved landscape, genetic factors including stochastic epistasis, environmental modification, and gene-environment interactions are all active. In these processes, interactions between developmental social vulnerability and environmental influences can lead to the emergence and persistence of some derivative states with social maladaptation. In our model, every psychiatric condition including aberrant paranoid-hallucinatory states is classified as a derivative state. The probability distribution curve for these derivative states has a non-linear relationship with the liability in the population, and there is none with probability 1.0 or zero. Individuals with trivial social vulnerability or high resilience may develop the derivative states in tremendously stressful circumstances, and individuals with huge social vulnerability may not necessarily develop the derivative states in the presence of adequate social supports. Social skillfulness/unskillfulness and behavioral flexibility/inflexibility form the core of the vulnerability-related dimensions. The clinical picture of a derivative manifestation is profiled depending on the individual trait levels in the derivative-related dimensions. Each derivative state has a requisite lineup of dimensions and each dimension can contribute to multiple psychiatric conditions. For example, aberrant paranoid-hallucinatory states and bipolar condition may share some developmental conditions as the derivative-related dimensions. Therefore, multiple derivative states can co-occur or be sequentially comorbid. Although the 'learned strategies' can ostensibly mask the clinical manifestation of developmental deviations, the change of the true dimensional position to the socially skillful direction is efficiently obtained through social experiences in a supportive environment. The liability-probability model makes it impossible to discriminate individuals with psychiatric diagnosis from individuals without the diagnosis and allows all of us to reside in the same human complex diversity.

WNT1-associated osteogenesis imperfecta with atrophic frontal lobes and arachnoid cysts.

A rare form of osteogenesis imperfecta (OI) caused by Wingless-type MMTV integration site family 1 (WNT1) mutations combines central nervous system (CNS) anomalies with the characteristic increased susceptibility to fractures. We report an additional case where arachnoid cysts extend the phenotype, and that also confirms the association of intellectual disabilities with asymmetric cerebellar hypoplasia here. Interestingly, if the cerebellum is normal in this disorder, intelligence is as well, analogous to an association with similar delays in a subset of patients with sporadic unilateral cerebellar hypoplasia. Those cases typically appear to represent vascular disruptions, and we suggest that most brain anomalies in WNT1-associated OI have vascular origins related to a role for WNT1 in CNS angiogenesis. This unusual combination of benign cerebellar findings with effects on higher functions in these two situations raises the possibility that WNT1 is involved in the pathogenesis of the associated sporadic cases as well. Finally, our patient reacted poorly to pamidronate, which appears ineffective with this form of OI, so that a lack of improvement is an indication for molecular testing that includes WNT1.

Children who face development risks due to maternal addiction during pregnancy require extra medical and psychosocial resources.

AIM: This study examined medical and psychosocial risk factors in children born to women with addiction problems during pregnancy and the children's needs for extra medical and psychosocial resources. METHODS: Swedish midwives routinely screen pregnant women for drugs and alcohol and refer women with addictions to the Maternity and Child Healthcare Resource Team. We investigated the medical records of 127 children (51% girls) whose mothers were referred to the Resource Team from 2009 to 2015. Additional data were obtained from local child healthcare services (CHS), which provide routine paediatric care. RESULTS: More than three-quarters (76%) of the children had prenatal exposure to alcohol and drugs, and 17% were born with withdrawal symptoms. The mothers had a high rate of psychiatric diagnoses (38%) and were more likely to smoke after delivery and less likely to breastfeed than the general population. However, adherence to the CHS programme was generally high. Additional visits to the nurse, referrals to specialists, collaboration meetings and reports of concerns to social services decreased when the children began attending ordinary CHS centres. CONCLUSION: Children born to women with addictions during pregnancy faced a high risk of developmental problems and should be offered additional CHS resources to minimise negative long-term consequences.

Metabolism of amino acid neurotransmitters: the synaptic disorder underlying inherited metabolic diseases.

Amino acids are involved in various metabolic pathways and some of them also act as neurotransmitters. Since biosynthesis of L-glutamate and γ-aminobutyric acid (GABA) requires 2-oxoglutarate while 3-phosphoglycerate is the precursor of L-glycine and D-serine, evolutionary selection of these amino acid neurotransmitters might have been driven by their capacity to provide important information about the glycolytic pathway and Krebs cycle. Synthesis and recycling of amino acid neurotransmitters as well as composition and function of their receptors are often compromised in inherited metabolic diseases. For instance, increased plasma L-phenylalanine concentrations impair cerebral biosynthesis of protein and bioamines in phenylketonuria, while elevated cerebral L-phenylalanine directly acts via ionotropic glutamate receptors. In succinic semialdehyde dehydrogenase deficiency, the neurotransmitter GABA and neuromodulatory γ-hydroxybutyric acid are elevated. Chronic hyperGABAergic state results in progressive downregulation of GABAA and GABAB receptors and impaired mitophagy. In glycine encephalopathy, the neurological phenotype is precipitated by L-glycine acting both via cortical NMDA receptors and glycine receptors in spinal cord and brain stem neurons. Serine deficiency syndromes are biochemically characterized by decreased biosynthesis of L-serine, an important neurotrophic factor, and the neurotransmitters D-serine and L-glycine. Supplementation with L-serine and L-glycine has a positive effect on seizure frequency and spasticity, while neurocognitive development can only be improved if treatment starts in utero or immediately postnatally. With novel techniques, the study of synaptic dysfunction in inherited metabolic diseases has become an emerging research field. More and better therapies are needed for these difficult-to-treat diseases.

Weird Laughing in Hyperekplexia: A new phenotype associated with a novel mutation in the GLRA1 gene?

Hyperekplexia (HPX) or startle disease is a rare hereditary neurological disorder characterized by generalized stiffness, excessive startle reflex to unexpected stimuli and a short period of generalized stiffness following the startle response, and can be complicated by umbilical or inguinal hernia, developmental delay and apnea spell. HPX is caused mainly by mutations in the GLRA1 gene, and has a good response to clonazepam. In this short communication we describe an 11-year-old girl with excessive startle reflex, weird laughing and developmental delay since early infancy. She also suffered from infantile spasms and generalized tonic-clonic seizures, and became seizure-free with antiepileptic drugs treatment. However, the weird laughing was still present during the treatment. Her mother also appeared excessive startle reflex during early infancy. A novel mutation in GLRA1 was detected in the girl and her mother. Consequently, she was diagnosed with HPX, and clonazepam was added. The weird laughing was dramatic improved, which hasn't been reported in HPX. This is the first report of weird laughing in a hyperekplexia patient carrying a novel GLRA1 mutation, and expanded the phenotype spectrum of HPX.

Multicentre prospective randomised single-blind controlled study protocol of the effect of an additional parent-administered sensorimotor stimulation on neurological development of preterm infants: Primebrain.

INTRODUCTION: Preterm and very low birthweight infants are at increased risk for neurodevelopmental disorders, including cerebral palsy, sensory impairment and intellectual disability. Several early intervention approaches have been designed in the hope of optimising neurological development in this context. It seems important that the intervention takes into account parental mental health, focuses on parent-child interactions and lasts sufficiently long. This study aims to evaluate the effects of a stimulation programme administered by parents until 6 months post-term on motor and neurophysiological development of infants born preterm. METHODS AND ANALYSIS: Participants will be infants born <32 weeks' gestation and/or with a birth weight <1500 g recruited prospectively from two tertiary neonatal intensive care units. They will be randomly assigned to receive nationally recommended follow-up only (control group) or also a stimulation programme between 37 weeks' gestation and 6 months' corrected age. Perinatal, clinical neurodevelopmental, socio-demographic and neuroimaging (ultrasonography or MRI) data will be collected. Bayley Scales of Infant Development will be used up to 24 months' corrected age and Parental Stress Index at 6, 12, 18 and 24 months' corrected age. High-density (64 or 128 electrodes) EEG, visual, somatosensory and long latency auditory evoked potentials will be recorded at term age, 3, 6, 12, 18 and 24 months' corrected age. They will be analysed for spatiotemporal frequency bands contents and source localisation. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committees of the Hôpital Universitaire des Enfants Reine Fabiola and CHU Saint-Pierre. Results dissemination will be made for stakeholders and families, reports will be written for parents, healthcare providers and policymakers, and scientific papers will be published. TRIAL REGISTRATION NUMBER: NCT02159534; Pre-results.

Using Xenopus to understand human disease and developmental disorders.

Model animals are crucial to biomedical research. Among the commonly used model animals, the amphibian, Xenopus, has had tremendous impact because of its unique experimental advantages, cost effectiveness, and close evolutionary relationship with mammals as a tetrapod. Over the past 50 years, the use of Xenopus has made possible many fundamental contributions to biomedicine, and it is a cornerstone of research in cell biology, developmental biology, evolutionary biology, immunology, molecular biology, neurobiology, and physiology. The prospects for Xenopus as an experimental system are excellent: Xenopus is uniquely well-suited for many contemporary approaches used to study fundamental biological and disease mechanisms. Moreover, recent advances in high throughput DNA sequencing, genome editing, proteomics, and pharmacological screening are easily applicable in Xenopus, enabling rapid functional genomics and human disease modeling at a systems level.

Feasibility of a Team Approach to Complex Congenital Heart Defect Neurodevelopmental Follow-Up: Early Experience of a Combined Cardiology/Neonatal Intensive Care Unit Follow-Up Program.

Infants with complex congenital heart disease are at high risk for poor neurodevelopmental outcomes. However, implementation of dedicated congenital heart disease follow-up programs presents important infrastructure, personnel, and resource challenges. We present the development, implementation, and retrospective review of 1- and 2-year outcomes of a Complex Congenital Heart Defect Neurodevelopmental Follow-Up program. This program was a synergistic approach between the Pediatric Cardiology, Cardiothoracic Surgery, Pediatric Intensive Care, and Neonatal Intensive Care Unit Follow-Up teams to provide a feasible and responsible utilization of existing infrastructure and personnel, to develop and implement a program dedicated to children with congenital heart disease. Trained developmental testers administered the Ages and Stages Questionnaire-3 over the phone to the parents of all referred children at least once between 6 and 12 months' corrected age. At 18 months' corrected age, all children were scheduled in the Neonatal Intensive-Care Unit Follow-Up Clinic for a visit with standardized neurological exams, Bayley III, multidisciplinary therapy evaluations and continued follow-up. Of the 132 patients identified in the Cardiothoracic Surgery database and at discharge from the hospital, a total number of 106 infants were reviewed. A genetic syndrome was identified in 23.4% of the population. Neuroimaging abnormalities were identified in 21.7% of the cohort with 12.8% having visibly severe insults. As a result, 23 (26.7%) received first-time referrals for early intervention services, 16 (13.8%) received referrals for new services in addition to their existing ones. We concluded that utilization of existing resources in collaboration with established programs can ensure targeted neurodevelopmental follow-up for all children with complex congenital heart disease.

An explanation of the pathophysiology of adverse neurodevelopmental outcomes in iron deficiency.

Iron deficiency (ID) is a major public health problem worldwide among children aged 0-12 months. Several factors seem to contribute to the iron-deficient state in infancy, including insufficient antenatal and neonatal iron supplementation, exclusive breastfeeding, and early umbilical cord clamping after birth. The most concerning complications of ID, except for anemia, are related to altered long-term neurodevelopment. Clinical studies have shown a negative impact of ID anemia on fetal and neonatal behavior including impairments of motor maturity, autonomic response, memory/learning, and mood. ID-induced defects during infancy seem to persist later in life, even after ID treatment. The underlying mechanisms involve dysfunctional myelination, neurotransmission alterations, and altered synaptogenesis and/or dendritogenesis. The purpose of the present review is to summarize these mechanisms and to provide recommendations for future clinical research in the field.

The birth and future health of DOHaD.

Professor David Barker, CBE, FRS, made an enormous contribution to biomedical research, which helped to change its direction and assisted translation to clinical medicine in the area of non-communicable disease (NCD). In this paper, I briefly note some of the studies, which led to his work, and describe how the underlying mechanisms came to be investigated by fetal physiologists. This is a unique aspect of the change in scientific emphasis, from a gene-centric and adult lifestyle view of NCD to a more holistic perspective, which placed emphasis on the importance of development that took place in the late 20th century. Early this century, the DOHaD Society was formed: I discuss some aspects of the formation of the Society and note the important role it is now playing in addressing the need to find early-life interventions to reduce NCD. This forms part of the unique legacy that David Barker has left to science and medicine.

Broccoli sprout supplementation during pregnancy prevents brain injury in the newborn rat following placental insufficiency.

Chronic placental insufficiency and subsequent intrauterine growth restriction (IUGR) increase the risk of hypoxic-ischemic encephalopathy in the newborn by 40 fold. The latter, in turn, increases the risk of cerebral palsy and developmental disabilities. This study seeks to determine the effectiveness of broccoli sprouts (BrSp), a rich source of the isothiocyanate sulforaphane, as a neuroprotectant in a rat model of chronic placental insufficiency and IUGR. Placental insufficiency and IUGR was induced by bilateral uterine artery ligation (BUAL) on day E20 of gestation. Dams were fed standard chow or chow supplemented with 200mg of dried BrSp from E15 - postnatal day 14 (PD14). Controls received Sham surgery and the same dietary regime. Pups underwent neurologic reflex testing and open field testing, following which they were euthanized and their brains frozen for neuropathologic assessment. Compared to Sham, IUGR pups were delayed in attaining early reflexes and performed worse in the open field, both of which were significantly improved by maternal supplementation of BrSp (p<0.05). Neuropathology revealed diminished white matter, ventricular dilation, astrogliosis and reduction in hippocampal neurons in IUGR animals compared to Sham, whereas broccoli sprout supplementation improved outcome in all histological assessments (p<0.05). Maternal dietary supplementation with BrSp prevented the detrimental neurocognitive and neuropathologic effects of chronic intrauterine ischemia. These findings suggest a novel approach for prevention of cerebral palsy and/or developmental disabilities associated with placental insufficiency.

fMRI assessment of neuroplasticity in youths with neurodevelopmental-associated motor disorders after piano training.

BACKGROUND: Damage to the developing brain may lead to lifelong motor impairments namely of the hand function. Playing an instrument combines the execution of gross and fine motor movements with direct auditory feedback of performance and with emotional value. This motor-associated sensory information may work as a self-control of motor performance in therapeutic settings. AIMS: The current study examined the occurrence of neuronal changes associated to piano training in youths with neurodevelopmental-associated hand motor deficits. METHODS: Functional magnetic resonance imaging responses evoked during a finger tapping task in a group of ten youths with neuromotor impairments that received individualized piano lessons for eighteen months were analyzed. Functional imaging data obtained before and after the piano training was compared to that obtained from a similar group of six youths who received no training during the same period of time. RESULTS: Dynamic causal modeling of functional data indicated an increase in positive connectivity from the left primary motor cortical area to the right cerebellum from before to after the piano training. CONCLUSIONS: A wide variability across patients was observed and further studies remain necessary to clarify the neurophysiological basis of the effects of piano training in hand motor function of patients with neurodevelopmental motor disorders.

How child's play impacts executive function--related behaviors.

Executive functions refer to an array of organizing and self-regulating behaviors often associated with maturation of the prefrontal cortex. In fact, young children with rudimentary neurodevelopment of the prefrontal cortex develop ways to inhibit impulses and regulate behavior from a very early age. Can executive functioning be impacted by intervention, practice, or training? What interventions impact development of executive function in childhood, and how can these be studied? Several programs are reviewed that propose to positively impact executive/self-regulation skills. Evidence-based programs are contrasted with popular programs that have little empirical basis but have apparent wide acceptance by educators and families. As self-regulation has critical implications for later school and life success, interventions may well attenuate the negative consequences of attention-deficit hyperactivity disorder, brain injury, and social stressors. Programs with active play components may be more successful in eliciting improved executive function (defined here as self-regulation) because of the importance of motor learning early on and because of the social motivation aspects of learning. Caution is advised in the recommendation of programs where there is little empirical basis to support program claims. Carefully planned outcome studies can help bring the most effective components of programs to the mainstream.

Creatine deficiency syndrome. A treatable myopathy due to arginine-glycine amidinotransferase (AGAT) deficiency.

We report two sisters, aged 11 and 6years, with AGAT deficiency syndrome (OMIM 612718) which is the least common creatine deficiency syndrome. They were born full-term to consanguineous parents and had moderate developmental delay. Examination showed an important language delay, a progressive proximal muscular weakness in the lower limbs with Gowers sign and myopathic electromyography. Investigations revealed undetectable guanidinoacetate and low level of creatine in plasma and urine, characteristic findings of AGAT deficiency syndrome. Brain magnetic resonance spectroscopy showed a markedly reduced level of creatine. Guanidinoacetate methyltransferase (GATM) gene sequencing revealed a homozygous missense mutation in exon 4:c.608A>C, (p.Tyr203Ser). Thirteen months after beginning the treatment with oral creatine monohydrate 200mg/kg/day, then 400mg/kg/day, there was a dramatic improvement in muscle strength with Gowers sign disappearance in both patients, and a mild improvement in language and cognitive functions. AGAT deficiency syndrome should be considered in all patients with language retardation and cognitive impairment associated to a myopathy of unknown etiology such that early diagnosis must lead to creatine supplementation to cure the myopathy and improve language and cognitive function.

Mismatch negativity (MMN) and sensory auditory processing in children aged 9-12 years presenting with putative antecedents of schizophrenia.

Identification of markers of abnormal brain function in children at-risk of schizophrenia may inform early intervention and prevention programs. Individuals with schizophrenia are characterised by attenuation of MMN amplitude, which indexes automatic auditory sensory processing. The current aim was to examine whether children who may be at increased risk of schizophrenia due to their presenting multiple putative antecedents of schizophrenia (ASz) are similarly characterised by MMN amplitude reductions, relative to typically developing (TD) children. EEG was recorded from 22 ASz and 24 TD children aged 9 to 12 years (matched on age, sex, and IQ) during a passive auditory oddball task (15% duration deviant). ASz children were those presenting: (1) speech and/or motor development lags/problems; (2) social, emotional, or behavioural problems in the clinical range; and (3) psychotic-like experiences. TD children presented no antecedents, and had no family history of a schizophrenia spectrum disorder. MMN amplitude, but not latency, was significantly greater at frontal sites in the ASz group than in the TD group. Although the MMN exhibited by the children at risk of schizophrenia was unlike that of their typically developing peers, it also differed from the reduced MMN amplitude observed in adults with schizophrenia. This may reflect developmental and disease effects in a pre-prodromal phase of psychosis onset. Longitudinal follow-up is necessary to establish the developmental trajectory of MMN in at-risk children.