High-dose vitamin D3 supplementation in pregnancy and risk of neurodevelopmental disorders in the children at age 10: A randomized clinical trial.

BACKGROUND: Vitamin D deficiency in pregnancy may increase the risk of autism and attention deficit hyperactivity disorder (ADHD). OBJECTIVE: The objective of this study was to estimate the effect of vitamin D3 supplementation in pregnancy on risk of autism and ADHD. DESIGN: This randomized clinical trial was part of the COpenhagen Prospective Study on Neuro-PSYCHiatric Development (COPYCH) project nested within the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) cohort comprising a population-based sample of 700 healthy mother-child pairs enrolled at week 24 of pregnancy. Maternal 25-hydroxy-vitamin D (25(OH)D) was measured at inclusion and 623 mothers were randomized 1:1 to either high-dose (2800 IU/d) or standard dose (400 IU/d) vitamin D3 until 1 wk postpartum (315 received high-dose, 308 standard dose). At age 10, diagnoses and symptom load of autism and ADHD, respectively, were established using the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version. RESULTS: The psychopathologic evaluation was completed by 591 children aged 10 y, and 16 children (2.7%) were diagnosed with autism and 65 (11.0%) with ADHD. Hereof, 496 children participated in the vitamin D3 trial (246 received high-dose, 250 standard dose). Of these, 12 children (2.4%) were diagnosed with autism and 58 (11.7%) with ADHD. Higher maternal preintervention 25(OH)D levels were associated with a decreased risk of autism [odd ratio (OR) per 10 nmol/L: 0.76 (0.59,0.97); P = 0.034], lower autistic symptom load [ß per 10 nmol/L: -0.03 (-0.05,0.00); P = 0.024), and decreased risk of ADHD diagnosis (OR per 10 nmol/L: 0.88 (0.78,0.99); P = 0.033]. High-dose vitamin D3 supplementation was not associated with risk of autism or ADHD. CONCLUSIONS: Higher maternal preintervention 25(OH)D was associated with a decreased risk of autism, lower autistic symptom load, and decreased risk of ADHD diagnosis, but high-dose vitamin D3 supplementation in pregnancy had no effect on risk of autism and ADHD. This trial was registered at clinicaltrials.gov as NCT00856947.

Dimensional profiling of psychopathology in children and adolescents based on the K-SADS-PL and an analysis of the construct validity of two ADHD symptom dimensions.

OBJECTIVES: The traditional view on psychiatric disorders as categorical and distinct is being challenged by perspectives emphasizing the relevance of dimensional and transdiagnostic assessment. However, most diagnostic instruments are based on a categorical view with a threshold-approach to disease classification. METHODS: We here describe algorithms for dimensionalizing the psychopathological ratings of the widely used diagnostic interview for children and adolescents, the Kiddie-Schedule for Affective Disorders and Schizophrenia - Present and Lifetime Version (K-SADS-PL). We further evaluate the criterion-related construct validity of the dimensionalized attention-deficit/hyperactivity disorder (ADHD) scales using Rasch models in a sample of 590 children (mean age 10.29 (.36), 49% girls). RESULTS: The algorithms generate scores of current symptom load, i.e., the sum of clinician-rated symptoms within each disorder assessed with the interview. We found support for counting symptoms of inattention and hyperactivity/impulsivity, respectively, but not for a single combined ADHD scale. CONCLUSIONS: The algorithms constitute an initial step in creating a framework for clinician-rated dimensional analyses of symptoms derived from the K-SADS-PL, but future studies are needed to further evaluate the construct validity of the remaining scales and the reliability and clinical utility of the method. We believe that our proposed algorithms offer a novel method of dimensional psychopathological assessment, which can be applied in multiple branches of child and adolescent psychiatry.

COVID-19 lockdown, genetic ADHD susceptibility, and mental health in 10- year-old children.

Previous studies report that the COVID-19 lockdown had an impact on the mental health of the pediatric population. In this study, we harness the deep neuropsychiatric phenotyping of the population-based COPSAC2010 (n = 700) cohort at age 10 to study the impact of the COVID-19 lockdown on mental health outcomes with focus on the role of the genetic vulnerability to attention-deficit/hyperactivity disorder (ADHD), in the form of polygenic risk scores (PRS). A total of 593 children were examined between 2019 and 2021, resulting in two groups of different children, those evaluated before the lockdown (n = 230) and those evaluated after (n = 363). Children assessed after the lockdown presented higher odds of being diagnosed with ADHD and had significantly higher scores in most neuropsychiatric scales, particularly in subscales pertaining to behavior and attention problems. We observed a significant interaction between the lockdown and ADHD PRS on several neuropsychiatric dimensions, with a large post-lockdown increase in children with a high PRS, while there was little to no pre-post difference in children with low PRS. These results indicate mental health consequences of the lockdown in children and suggest that genetically susceptible individuals are more affected by such stressors in childhood.

Exogenous Attention to Emotional Stimuli Presenting Realistic (3D) Looming Motion.

Previous research shows that dynamic stimuli, on the one hand, and emotional stimuli, on the other, capture exogenous attention due to their biological relevance. Through neural (ERPs) and behavioral measures (reaction times and errors), the present study explored the combined effect of looming motion and emotional content on attentional capture. To this end, 3D-recreated static and dynamic animals assessed as emotional (positive or negative) or neutral were presented as distractors while 71 volunteers performed a line orientation task. We observed a two-phase effect: firstly (before 300 ms), early components of ERPs (P1p and N2po) showed enhanced exogenous attentional capture by looming positive distractors and static threatening animals. Thereafter, dynamic and static threatening distractors received enhanced endogenous attention as revealed by both late ERP activity (LPC) and behavioral (errors) responses. These effects are likely explained by both the emotional valence and the distance of the stimulus at each moment.

Realistic (3D) looming of emotional visual stimuli: Attentional effects at neural and behavioral levels.

Previous research shows that endogenous attention (the controlled selection of certain aspects of our environment) is enhanced toward emotional stimuli due to its biological relevance. Although looming affective stimuli such as threat seem even more critical for survival, little is known about their effect on endogenous attention. Here, we recorded neural (event-related potentials, ERPs) and behavioral responses (errors and reaction times) to explore the combined effect of emotion and looming motion. 3D-recreated static and moving animals assessed as emotionally positive, negative, and neutral, were presented to participants (n = 71), who performed an indirect categorization task (vertebrate vs. invertebrate). Behavioral results showed better task performance, as reflected by lower number of errors and reaction times, in response to threatening stimuli. Neural indices revealed significant early (P1p, 150 milliseconds), intermediate (P2p, 240), and late (LPP, 450) effects, the latter being more intensely associated with behavior, as revealed by regression analyses. In general, neural indexes of attention to both static and dynamic stimuli showed a positivity offset in early stages and a negativity bias in subsequent phases. However, and importantly, the progressive inclusion of negative stimuli in the attentional focus is produced earlier in the case of dynamic (at P2p latency) than in static versions (at LPP). These results point to an enhancement of attention, particularly in temporal terms, toward stimuli combining motion and biological significance.

Enhanced N170 to outgroup faces: Perceptual novelty or prejudice?

Habituation to ethnic ingroup members has been reported to be greater than to ethnic outgroup members. This pattern could be due to the lack of perceptive experience (familiarity) with outgroup facial morphs or, alternatively, to the prejudice held toward that outgroup. We explored this disjunctive in 71 participants, all Spanish, who were experimentally habituated to faces from their Ingroup and to faces from two unfamiliar outgroups, one for which there is low probability of prejudice in this population (Non-prejudiced Outgroup), and one for which the probability of prejudice is higher (Prejudiced Outgroup). We indexed habituation through event-related potentials, concretely as the differential amplitude of the face-sensitive N170 component from Initial to Final trials of each group. Afterward, participants completed several prejudice measures. N170 showed significant habituation to all faces, though it did not differ among groups. However, a regression analysis revealed that individual habituation to the Outgroup faces was inversely related to implicit prejudice scores. Importantly, N170 amplitudes were maximal for the Prejudiced Outgroup in both Initial and Final trials. We conclude that these effects are explained by the prejudice held toward a specific outgroup rather than perceptive experience.

Retinotopy of emotion: Perception of negatively valenced stimuli presented at different spatial locations as revealed by event-related potentials.

Scarce previous data on how the location where an emotional stimulus appears in the visual scene modulates its perception suggest that, for functional reasons, a perceptual advantage may exist, vertically, for stimuli presented at the lower visual field (LoVF) and, horizontally, for stimuli presented at the left visual field (LeVF). However, this issue has been explored through a limited number of spatial locations, usually in a single spatial dimension (e.g., horizontal) and invariant eccentricities. Event-related potentials (ERPs) were recorded from 39 participants perceiving brief neutral (wheels) and emotional stimuli (spiders) presented at 17 different locations, one foveal and 16 at different peripheral coordinates. As a secondary scope, we explored the role of the magnocellular (M) and the parvocellular (P) visual pathways by presenting an isoluminant/heterochromatic (P-biased) and a heteroluminant/isochromatic version (M-biased) of each stimulus. Emo > Neu effects were observed in PN1 (120 ms) for stimuli located at fovea, and in PN2 (215 ms) for stimuli located both at fovea and diverse peripheral regions. A factorial approach to these effects further revealed that: (a) emotional stimuli presented in the periphery are efficiently perceived, without evident decrease from para- to perifovea; (b) peripheral Emo > Neu effects are reflected 95 ms later than foveal Emo > Neu effects in ERPs; (c) LoVF is more involved than UVF in these effects; (d) our data fail to support the LeVF advantage previously reported, and (e) Emo > Neu effects were significant for both M and P stimuli.

Binocular rivalry and emotion: Implications for neural correlates of consciousness and emotional biases in conscious perception.

Studies of the neural correlates of consciousness (NCCs) combining MEG/EEG with behavioral data have described two main time ranges relating to conscious perception: 130-320 (the visual awareness negativity; VAN) and 300-500 (P3a) ms after stimulus onset. At the same time, two event-related potential (ERP) peaks have shown an emotional modulation of endogenous attention: the early posterior negativity (EPN; peaking around 250 msec) and the late positive potential (LPP, peaking around 600 msec). Furthermore, an emotional bias on conscious perception has been reported in Binocular Rivalry (BR) studies. Here, we combined an intermittent BR paradigm with neutral and emotional stimuli while recording the behavioral subjective perception and ERPs with two aims: i) to explore the NCCs of emotional content in the time ranges previously described, and ii) to study the emotional bias in conscious perception as first percept when neutral and emotional images rival against each other. First, results revealed a specific ERP emotional modulation (emotional content awareness modulation; ECAM) at the VAN time range. This was the first time window sensitive to the emotional information and showing the strongest modulation in conscious emotional content. Second, results revealed an emotional bias in conscious perception towards the positive valence. This work shows how conscious perception pertaining to emotional content relates to perceptual areas at the VAN latency, which supports the claim of the 130-320 msec time window as the earliest NCC and extends the claim to apply to more than visual perceptual features. Additionally, our findings show that positive and negative content modulates the conscious perception differently.

Aging Modulates the Resting Brain after a Memory Task: A Validation Study from Multivariate Models.

Recent work has demonstrated that aging modulates the resting brain. However, the study of these modulations after cognitive practice, resulting from a memory task, has been scarce. This work aims at examining age-related changes in the functional reorganization of the resting brain after cognitive training, namely, neuroplasticity, by means of the most innovative tools for data analysis. To this end, electroencephalographic activity was recorded in 34 young and 38 older participants. Different methods for data analyses, including frequency, time-frequency and machine learning-based prediction models were conducted. Results showed reductions in Alpha power in old compared to young adults in electrodes placed over posterior and anterior areas of the brain. Moreover, young participants showed Alpha power increases after task performance, while their older counterparts exhibited a more invariant pattern of results. These results were significant in the 140-160 s time window in electrodes placed over anterior regions of the brain. Machine learning analyses were able to accurately classify participants by age, but failed to predict whether resting state scans took place before or after the memory task. These findings greatly contribute to the development of multivariate tools for electroencephalogram (EEG) data analysis and improve our understanding of age-related changes in the functional reorganization of the resting brain.

Magnocellular Bias in Exogenous Attention to Biologically Salient Stimuli as Revealed by Manipulating Their Luminosity and Color.

Exogenous attention is a set of mechanisms that allow us to detect and reorient toward salient events-such as appetitive or aversive-that appear out of the current focus of attention. The nature of these mechanisms, particularly the involvement of the parvocellular and magnocellular visual processing systems, was explored. Thirty-four participants performed a demanding digit categorization task while salient (spiders or S) and neutral (wheels or W) stimuli were presented as distractors under two figure-ground formats: heterochromatic/isoluminant (exclusively processed by the parvocellular system, Par trials) and isochromatic/heteroluminant (preferentially processed by the magnocellular system, Mag trials). This resulted in four conditions: SPar, SMag, WPar, and WMag. Behavioral (RTs and error rates in the task) and electrophysiological (ERPs) indices of exogenous attention were analyzed. Behavior showed greater attentional capture by SMag than by SPar distractors and enhanced modulation of SMag capture as fear of spiders reported by participants increased. ERPs reflected a sequence from magnocellular dominant (P1p, ≃120 msec) to both magnocellular and parvocellular processing (N2p and P2a, ≃200 msec). Importantly, amplitudes in one N2p subcomponent were greater to SMag than to SPar and WMag distractors, indicating greater magnocellular sensitivity to saliency. Taking together, results support a magnocellular bias in exogenous attention toward distractors of any nature during initial processing, a bias that remains in later stages when biologically salient distractors are present.

Exogenous attention to fear: Differential behavioral and neural responses to snakes and spiders.

Research has consistently shown that threat stimuli automatically attract attention in order to activate the defensive response systems. Recent findings have provided evidence that snakes tuned the visual system of evolving primates for their astute detection, particularly under challenging perceptual conditions. The goal of the present study was to measure behavioral and electrophysiological indices of exogenous attention to snakes, compared with spiders - matched for rated fear levels but for which sources of natural selection are less well grounded, and to innocuous animals (birds), which were presented as distracters, while participants were engaged in a letter discrimination task. Duration of stimuli, consisting in a letter string and a concurrent distracter, was either presented for 180 or 360ms to explore if the stimulus duration was a modulating effect of snakes in capturing attention. Results showed a specific early (P1) exogenous attention-related brain potential with maximal amplitude to snakes in both durations, which was followed by an enhanced late attention-related potential (LPP) showing enhanced amplitudes to spiders, particularly under the longer exposure durations. These results suggest that exogenous attention to different classes of threat stimuli follows a gradual process, with the most evolutionary-driven stimulus, i.e., snakes, being more efficient at attracting early exogenous attention, thus more dependent on bottom-up processes.