Corticostriatal connectivity mediates the reciprocal relationship between parent-reported sleep duration and impulsivity in early adolescents.

BACKGROUND: Adolescence, a developmental period characterized by significant changes in sleep, is associated with normative increases in impulsivity. While short sleep duration has been linked to elevated impulsivity, the neural mechanism underlying the relationship between short sleep duration and elevated impulsivity remains poorly understood. METHODS: We analyzed a dataset of 7,884 drug-naive 9-10 year-olds from the Adolescent Brain Cognitive Development (ABCD) study. Among them, 5,166 have two-year follow-up neuroimaging data. Linear mixed-effects models, mediation analyses, and longitudinal mediation analyses were used to investigate the relationship between parent-reported sleep duration, impulsivity, and functional and structural connectivity between the cortex and the striatum. RESULTS: We found that less sleep duration is significantly associated with higher positive and negative urgency, which are two affect-related components of impulsivity. In addition, we observed a link between short sleep duration and reduced corticostriatal connectivity. Neural pathways associated with short sleep duration-functional connectivity between the cingulo-opercular network and the left caudate, and between the cingulo-parietal network and the right pallidum-mediated the association between sleep duration and positive urgency both at baseline and two-year follow-up. Longitudinal mediation analyses further revealed that short sleep duration and elevated positive urgency exacerbated each other through these two corticostriatal connectivities. CONCLUSIONS: These findings highlight the key role of corticostriatal connectivities in the reciprocal relationship between short sleep duration and elevated impulsivity. Given the increasing prevalence of short sleep duration in adolescents, the link between sleep duration, impulsivity, and corticostriatal connectivities has important implications for timely interventions to address impulsive problems in early adolescents.

Efficacy of a bivalent (D614 + B.1.351) SARS-CoV-2 Protein Vaccine

Background COVID-19 vaccines with alternative strain compositions are needed to provide broad protection against newly emergent SARS-CoV-2 variants of concern. Methods We conducted a global Phase 3, multi-stage efficacy study (NCT04904549) among adults aged [≥]18 years. Participants were randomized 1:1 to receive two intramuscular injections 21 days apart of a bivalent SARS-CoV-2 recombinant protein vaccine with AS03-adjuvant (5 g of ancestral (D614) and 5 g of B.1.351 [beta] variant spike protein) or placebo. Symptomatic COVID-19 was defined as laboratory-confirmed COVID-19 with COVID-19-like illness (CLI) symptoms. The primary efficacy endpoint was the prevention of symptomatic COVID-19 [≥]14 days after the second injection. Results Between 19 Oct 2021 and 15 Feb 2022, 12,924 participants received [≥]1 study injection. 75% of participants were SARS-CoV-2 non-naive. 11,416 participants received both study injections (efficacy-evaluable population [vaccine, n=5,736; placebo, n=5,680]). Up to 15 March 2022, 121 symptomatic COVID-19 cases were reported (32 in the vaccine group and 89 in the placebo group) [≥]14 days after the second injection with a vaccine efficacy (VE) of 64.7% (95% confidence interval [CI] 46.6; 77.2%). VE was 75.1% (95% CI 56.3; 86.6%) in non-naive and 30.9% (95% CI -39.3; 66.7%) in naive participants. Viral genome sequencing identified the infecting strain in 68 cases (Omicron [BA.1 and BA.2 subvariants]: 63; Delta: 4; Omicron and Delta: 1). The vaccine was well-tolerated and had an acceptable safety profile. Conclusions A bivalent vaccine conferred heterologous protection against symptomatic infection with newly emergent Omicron (BA.1 and BA.2) in non-naive adults 18-59 years of age. ClinicalTrials.gov: NCT04904549

Functional connectome mediates the association between sleep disturbance and mental health in preadolescence: A longitudinal mediation study.

Sleep disturbance is known to be associated with various mental disorders and often precedes the onset of mental disorders in youth. Given the increasingly acknowledged bidirectional influence between sleep disturbance and mental disorders, we aim to identify a shared neural mechanism that underlies sleep disturbance and mental disorders in preadolescents. We analyzed a dataset of 9,350 9-10 year-old children, among whom 8,845 had 1-year follow-up data, from the Adolescent Brain Cognitive Development (ABCD) study. Linear mixed-effects models, mediation analysis, and longitudinal mediation analysis were used to investigate the relationship between sleep disturbance, mental disorders, and resting-state network connectivity. Out of 186 unique connectivities, the effect of total sleep disturbance (TSP, from Sleep Disturbance Scale) and mental problems (MP, from Child Behavior Checklist) converged in the default mode network (DMN) and the dorsal attention network (DAN). Within- and between-network connectivities (DMN-DAN, DMN-DMN, DAN-DAN) mediated the relationship between baseline TSD and MP at 1-year follow-up and the relationship between baseline MP and TSD at 1-year follow-up. The pathway model in which sleep disturbance and mental problems affect each other through two anticorrelated brain networks (DMN and DAN) suggests a common neural mechanism between them. Longitudinally, a less segregated DMN and DAN is associated with negative outcomes on mental well-being and sleep disturbance a year later. These findings have important implications for the design of prevention and neurofeedback intervention for mental disorders and sleep problems.

Safety and immunogenicity of a SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in healthy adults: interim findings from a phase 2, randomised, dose-finding, multi-centre study

BackgroundThis study evaluated the safety and immunogenicity of an AS03-adjuvanted SARS-CoV-2 recombinant protein candidate vaccine, CoV2 preS dTM. MethodsThis Phase 2, modified double-blind, parallel-group study (NCT04762680) was conducted in adults, including those at increased risk of severe COVID-19. Participants were randomised 1:1:1, stratified by age (18-59/[≥]60 years), rapid serodiagnostic test (positive/negative) and high-risk medical conditions (yes/no), to receive two injections (day [D]1 and D22) of 5g, 10g or 15g of CoV2 preS dTM antigen with fixed AS03 content. Interim safety and reactogenicity results (to D43) and neutralising antibodies (NAbs) against the D614G variant are presented (primary objectives). FindingsOf 722 participants enrolled and randomised between 24 February and 8 March 2021, 721 received [≥]1 injections (5g, n=240; 10g, n=239; 15g, n=242). Four participants reported unsolicited immediate adverse events (AEs), two were vaccine-related (investigator assessment). Five participants reported seven vaccine-related medically-attended AEs. No vaccine-related serious AEs and no AEs of special interest were reported. Solicited reactions (local and systemic) were reported at similar frequencies between study groups; these were mostly mild to moderate and transient, with higher frequency and intensity post-injection 2 than post-injection 1. In SARS-CoV-2 naive participants at D36, 96{middle dot}9%, 97.0% and 97{middle dot}6% of participants had [≥]4-fold-rise in NAb titres from baseline in the 5g-, 10g- and 15g-dose groups, respectively. NAb titres increased with antigen dose in younger (GMTs: 2954, 3951 and 5142 for 5g-, 10g- and 15g-dose groups) but not older adults (GMTs: 1628, 1393 and 1736, respectively). NAb titres in non-naive adults after one injection were higher than titres after two injections in naive adults. InterpretationTwo injections of CoV2 preS dTM-AS03 demonstrated acceptable safety and reactogenicity, and robust immunogenicity in SARS-CoV-2 naive and non-naive adults. These results informed antigen dose selection for progression to Phase 3 evaluation of primary and booster vaccination.

Effects of unilateral cortical resection of the visual cortex on bilateral human white matter.

Children with unilateral resections of ventral occipito-temporal cortex (VOTC) typically do not evince visual perceptual impairments, even when relatively large swathes of VOTC are resected. In search of possible explanations for this behavioral competence, we evaluated white matter microstructure and connectivity in eight pediatric epilepsy patients following unilateral cortical resection and 15 age-matched controls. To uncover both local and broader resection-induced effects, we analyzed tractography data using two complementary approaches. First, the microstructural properties were measured in the inferior longitudinal and the inferior fronto-occipital fasciculi, the major VOTC association tracts. Group differences were only evident in the ipsilesional, and not in the contralesional, hemisphere, and single-subject analyses revealed that these differences were limited to the site of the resection. Second, graph theory was used to characterize the connectivity of the contralesional occipito-temporal regions. There were no changes to the network properties in patients with left VOTC resections nor in patients with resections outside the VOTC, but altered network efficiency was observed in two cases with right VOTC resections. These results suggest that, in many, although perhaps not all, cases of unilateral VOTC resections in childhood, the white matter profile in the preserved contralesional hemisphere along with residual neural activity might be sufficient for normal visual perception.