Effect of RTS,S/AS01E vaccine booster dose on cellular immune responses in African infants and children.

RTS,S/AS01E, the first approved malaria vaccine, demonstrated moderate efficacy during the phase 3 pediatric trial. We previously investigated cell-mediated immune (CMI) responses following the primary 3-dose immunization and now report responses to the booster dose given 18 months later. Thirty CMI markers were measured by Luminex in supernatants of peripheral blood mononuclear cells from 709 children and infants after RTS,S/AS01E antigen stimulation, and their associations with malaria risk and antibodies one month post-booster and one year later were assessed. IL-2, IFN-γ, IL-17, IL-5, and IL-13 were associated with RTS,S/AS01E booster vaccination, and IL-2 responses to the circumsporozoite protein (CSP) remained higher after one year. IL-2 was associated with reduced malaria risk in one site, and IL-10 was associated with increased risk in infants. Anti-CSP IgG and IL-2 were moderately correlated one year after booster. This study highlights the moderate cell-mediated immunogenicity of the RTS,S/AS01E booster dose that aligns with partial recovery of RTS,S/AS01E vaccine efficacy.

The effect of Plasmodium falciparum exposure and maternal anti-circumsporozoite protein antibodies on responses to RTS,S/AS01E vaccination in infants and children: an ancillary observational immunological study to a phase 3, randomised clinical trial.

BACKGROUND: The RTS,S/AS01E malaria vaccine showed lower antibody response and protective efficacy in infants aged 6-12 weeks compared with children aged 5-17 months (for whom this vaccine is recommended). We aimed to study the effect of previous Plasmodium falciparum exposure on the antibody responses to RTS,S/AS01E vaccination in infants and children, and the mediating effect of baseline (including maternal) anti-circumsporozoite protein (CSP) antibodies. METHODS: In this observational study, we included children and infants from six African countries (Burkina Faso, Gabon, Ghana, Kenya, Mozambique, and Tanzania) enrolled in the MAL067 immunology ancillary study of the RTS,S/AS01E phase 3 clinical trial from March 27, 2009, to Jan 21, 2011. We used comparator-vaccinated infants and children to identify antibody-based signatures of previous P falciparum exposure, which were later applied to RTS,S/AS01E-vaccinated infants and children. In these participants, we explored the relationship between vaccine antibody immunoglobulin G (IgG) responses measured by ELISA and pre-vaccination serological markers of malaria exposure by assessing the IgG levels against 1000 P falciparum antigens using partial proteome microarrays. FINDINGS: We included 718 comparator-vaccinated infants (348 [48%]) and children (370 [52%]) and 606 RTS,S/AS01E-vaccinated infants (329 [54%]) and children (277 [46%]). Anti-CSP IgG responses to primary vaccination did not correlate with a baseline signature of previous exposure in children, suggesting that prior P falciparum exposure does not significantly affect antibody immunogenicity in children (Pearson's r=-0·02 [95% CI -0·13 to 0·10]). By contrast, high P falciparum exposure signature levels at the time of vaccination in infants, presumably driven by maternally transferred antibodies and declining within the initial 6-12 months of life, correlated with reduced RTS,S/AS01E responses (r=-0·17 [-0·27 to -0·06]). This negative correlation was stronger for anti-CSP IgG than for the exposure signature or any other more immunogenic blood stage P falciparum antigens (r=-0·42 [-0·50 to -0·33]), persisted after adjustment by baseline levels of the exposure signature (semi-partial correlation r=-0·44 [-0·55 to -0·33]), and involved antibodies to the central NANP region (r=-0·39 [-0·49 to -0·28]) but not the C-terminal region (r=0·02 [-0·10 to 0·15]) of CSP. The negative effect of maternal anti-CSP IgG in infants did not appear to be confounded by other malaria transmission-dependent variables. INTERPRETATION: Interference between passive immunity and vaccine response is clinically significant and might affect the implementation of next-generation CSP-based vaccines for young infants and mothers as well as passive immunisation with human monoclonal antibodies. FUNDING: US National Institutes of Health, National Institute of Allergy and Infectious Diseases; PATH-Malaria Vaccine Initiative; Spanish Ministerio de Economía y Competitividad (Instituto de Salud Carlos III), European Regional Development Fund and European Social Fund; Fundación Ramón Areces; Spanish Ministry of Science and Innovation; and Generalitat de Catalunya (CERCA Program).

High-resolution kinetics and cellular determinants of SARS-CoV-2 antibody response over two years after COVID-19 vaccination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) studies usually rely on cross-sectional data of large cohorts but limited repeated samples, overlooking significant inter-individual antibody kinetic differences. By combining Luminex, activation-induced marker (AIM) and IFN-γ/IL-2 Fluorospot assays, we characterized the IgM, IgA, and IgG antibody kinetics using 610 samples from 31 healthy adults over two years after COVID-19 vaccination, and the T-cell responses six months post-booster. Antibody trajectories varied among isotypes: IgG decayed slowly, IgA exhibited an initial sharp decline, which gradually slowed down and stabilized above the seropositivity threshold. Contrarily, IgM rapidly dropped to undetectable levels after primary vaccination. Importantly, three vaccine doses induced higher and more durable anti-spike IgG and IgA levels compared to two doses, whereas infection led to the highest antibody peak and slowest antibody decay rate compared to vaccination. Comparing with ancestral virus, antibody levels recognizing Omicron subvariants had a faster antibody decay. Finally, polyfunctional T cells were positively associated with subsequent IgA responses. These results revealed distinctive antibody patterns by isotype and highlight the benefits of booster doses in enhancing and sustaining antibody responses.

RTS,S/AS02A Malaria Vaccine-Induced IgG Responses Equally Recognize Native-Like Fucosylated and Nonfucosylated Plasmodium falciparum Circumsporozoite Proteins.

The RTS,S/AS02A malaria vaccine is based on the Plasmodium falciparum circumsporozoite protein (PfCSP), which is O-fucosylated on the sporozoite surface. We determined whether RTS,S/AS02A-induced immunoglobulin G (IgG) antibodies recognize vaccine-like nonfucosylated PfCSP better than native-like fucosylated PfCSP. Similar to previous vaccine trials, RTS,S/AS02A vaccination induced high anti-PfCSP IgG levels associated with malaria protection. IgG recognition of nonfucosylated and fucosylated PfCSP was equivalent, suggesting that PfCSP fucosylation does not affect antibody recognition. Clinical Trials Registration. NCT00197041.

Neurogenetics of Dynamic Connectivity Patterns Associated With Obsessive-Compulsive Symptoms in Healthy Children.

Background: Obsessive-compulsive symptoms (OCSs) during childhood predispose to obsessive-compulsive disorder and have been associated with changes in brain circuits altered in obsessive-compulsive disorder samples. OCSs may arise from disturbed glutamatergic neurotransmission, impairing cognitive oscillations and promoting overstable functional states. Methods: A total of 227 healthy children completed the Obsessive Compulsive Inventory-Child Version and underwent a resting-state functional magnetic resonance imaging examination. Genome-wide data were obtained from 149 of them. We used a graph theory-based approach and characterized associations between OCSs and dynamic functional connectivity (dFC). dFC evaluates fluctuations over time in FC between brain regions, which allows characterizing regions with stable connectivity patterns (attractors). We then compared the spatial similarity between OCS-dFC correlation maps and mappings of genetic expression across brain regions to identify genes potentially associated with connectivity changes. In post hoc analyses, we investigated which specific single nucleotide polymorphisms of these genes moderated the association between OCSs and patterns of dFC. Results: OCSs correlated with decreased attractor properties in the left ventral putamen and increased attractor properties in (pre)motor areas and the left hippocampus. At the specific symptom level, increased attractor properties in the right superior parietal cortex correlated with ordering symptoms. In the hippocampus, we identified two single nucleotide polymorphisms in glutamatergic neurotransmission genes (GRM7, GNAQ) that moderated the association between OCSs and attractor features. Conclusions: We provide evidence that in healthy children, the association between dFC changes and OCSs may be mapped onto brain circuits predicted by prevailing neurobiological models of obsessive-compulsive disorder. Moreover, our findings support the involvement of glutamatergic neurotransmission in such brain network changes.

Sustained seropositivity up to 20.5 months after COVID-19.

This study evaluated the persistence of IgM, IgA, and IgG to SARS-CoV-2 spike and nucleocapsid antigens up to 616 days since the onset of symptoms in a longitudinal cohort of 247 primary health care workers from Barcelona, Spain, followed up since the start of the pandemic. The study also assesses factors affecting antibody levels, including comorbidities and the responses to variants of concern as well as the frequency of reinfections. Despite a gradual and significant decline in antibody levels with time, seropositivity to five SARS-CoV-2 antigens combined was always higher than 90% over the whole study period. In a subset of 23 participants who had not yet been vaccinated by November 2021, seropositivity remained at 95.65% (47.83% IgM, 95.65% IgA, 95.65% IgG). IgG seropositivity against Alpha and Delta predominant variants was comparable to that against the Wuhan variant, while it was lower for Gamma and Beta (minority) variants and for IgA and IgM. Antibody levels at the time point closest to infection were associated with age, smoking, obesity, hospitalization, fever, anosmia/hypogeusia, chest pain, and hypertension in multivariable regression models. Up to 1 year later, just before the massive roll out of vaccination, antibody levels were associated with age, occupation, hospitalization, duration of symptoms, anosmia/hypogeusia, fever, and headache. In addition, tachycardia and cutaneous symptoms associated with slower antibody decay, and oxygen supply with faster antibody decay. Eight reinfections (3.23%) were detected in low responders, which is consistent with a sustained protective role for anti-spike naturally acquired antibodies. Stable persistence of IgG and IgA responses and cross-recognition of the predominant variants circulating in the 2020-2021 period indicate long-lasting and largely variant-transcending humoral immunity in the initial 20.5 months of the pandemic, in the absence of vaccination.

Strong off-target antibody reactivity to malarial antigens induced by RTS,S/AS01E vaccination is associated with protection.

The RTS,S/AS01E vaccine targets the circumsporozoite protein (CSP) of the Plasmodium falciparum (P. falciparum) parasite. Protein microarrays were used to measure levels of IgG against 1000 P. falciparum antigens in 2138 infants (age 6-12 weeks) and children (age 5-17 months) from 6 African sites of the phase III trial, sampled before and at 4 longitudinal visits after vaccination. One month postvaccination, IgG responses to 17% of all probed antigens showed differences between RTS,S/AS01E and comparator vaccination groups, whereas no prevaccination differences were found. A small subset of antigens presented IgG levels reaching 4- to 8-fold increases in the RTS,S/AS01E group, comparable in magnitude to anti-CSP IgG levels (~11-fold increase). They were strongly cross-correlated and correlated with anti-CSP levels, waning similarly over time and reincreasing with the booster dose. Such an intriguing phenomenon may be due to cross-reactivity of anti-CSP antibodies with these antigens. RTS,S/AS01E vaccinees with strong off-target IgG responses had an estimated lower clinical malaria incidence after adjusting for age group, site, and postvaccination anti-CSP levels. RTS,S/AS01E-induced IgG may bind strongly not only to CSP, but also to unrelated malaria antigens, and this seems to either confer, or at least be a marker of, increased protection from clinical malaria.

No Association Between Loneliness, Episodic Memory and Hippocampal Volume Change in Young and Healthy Older Adults: A Longitudinal European Multicenter Study.

Background: Loneliness is most prevalent during adolescence and late life and has been associated with mental health disorders as well as with cognitive decline during aging. Associations between longitudinal measures of loneliness and verbal episodic memory and brain structure should thus be investigated. Methods: We sought to determine associations between loneliness and verbal episodic memory as well as loneliness and hippocampal volume trajectories across three longitudinal cohorts within the Lifebrain Consortium, including children, adolescents (N = 69, age range 10-15 at baseline examination) and older adults (N = 1468 over 60). We also explored putative loneliness correlates of cortical thinning across the entire cortical mantle. Results: Loneliness was associated with worsening of verbal episodic memory in one cohort of older adults. Specifically, reporting medium to high levels of loneliness over time was related to significantly increased memory loss at follow-up examinations. The significance of the loneliness-memory change association was lost when eight participants were excluded after having developed dementia in any of the subsequent follow-up assessments. No significant structural brain correlates of loneliness were found, neither hippocampal volume change nor cortical thinning. Conclusion: In the present longitudinal European multicenter study, the association between loneliness and episodic memory was mainly driven by individuals exhibiting progressive cognitive decline, which reinforces previous findings associating loneliness with cognitive impairment and dementia.

tDCS-Induced Memory Reconsolidation Effects and Its Associations With Structural and Functional MRI Substrates in Subjective Cognitive Decline.

Previous evidence suggests that transcranial direct current stimulation (tDCS) to the left dorsolateral prefrontal cortex (l-DLPFC) can enhance episodic memory in subjects with subjective cognitive decline (SCD), known to be at risk of dementia. Our main goal was to replicate such findings in an independent sample and elucidate if baseline magnetic resonance imaging (MRI) characteristics predicted putative memory improvement. Thirty-eight participants with SCD (aged: 60-65 years) were randomly assigned to receive active (N = 19) or sham (N = 19) tDCS in a double-blind design. They underwent a verbal learning task with 15 words (DAY-1), and 24 h later (DAY-2) stimulation was applied for 15 min at 1.5 mA targeting the l-DLPFC after offering a contextual reminder. Delayed recall and recognition were measured 1 day after the stimulation session (DAY-3), and at 1-month follow-up (DAY-30). Before the experimental session, structural and functional MRI were acquired. We identified a group∗time interaction in recognition memory, being the active tDCS group able to maintain stable memory performance between DAY-3 and DAY-30. MRI results revealed that individuals with superior tDCS-induced effects on memory reconsolidation exhibited higher left temporal lobe thickness and greater intrinsic FC within the default-mode network. Present findings confirm that tDCS, through the modulation of memory reconsolidation, is capable of enhancing performance in people with self-perceived cognitive complaints. Results suggest that SCD subjects with more preserved structural and functional integrity might benefit from these interventions, promoting maintenance of cognitive function in a population at risk to develop dementia.

The genetic organization of longitudinal subcortical volumetric change is stable throughout the lifespan.

Development and aging of the cerebral cortex show similar topographic organization and are governed by the same genes. It is unclear whether the same is true for subcortical regions, which follow fundamentally different ontogenetic and phylogenetic principles. We tested the hypothesis that genetically governed neurodevelopmental processes can be traced throughout life by assessing to which degree brain regions that develop together continue to change together through life. Analyzing over 6000 longitudinal MRIs of the brain, we used graph theory to identify five clusters of coordinated development, indexed as patterns of correlated volumetric change in brain structures. The clusters tended to follow placement along the cranial axis in embryonic brain development, suggesting continuity from prenatal stages, and correlated with cognition. Across independent longitudinal datasets, we demonstrated that developmental clusters were conserved through life. Twin-based genetic correlations revealed distinct sets of genes governing change in each cluster. Single-nucleotide polymorphisms-based analyses of 38,127 cross-sectional MRIs showed a similar pattern of genetic volume-volume correlations. In conclusion, coordination of subcortical change adheres to fundamental principles of lifespan continuity and genetic organization.

Differences between the child and adult brain in the local functional structure of the cerebral cortex.

Imaging studies on neuronal network formation provide relevant information as to how the brain matures during adolescence. We used a novel imaging approach combining well-established MRI measures of local functional connectivity that jointly provide qualitatively different information relating to the functional structure of the cerebral cortex. To investigate the adolescent transition into adulthood, we comparatively assessed 169 preadolescents aged 8-12 years and 121 healthy adults. Whole-brain functional connectivity maps were generated using multi-distance measures of intracortical neural activity coupling defined within iso-distant local areas. Such Iso-Distant Average Correlation (IDAC) measures therefore represent the average temporal correlation of a given brain unit, or voxel, with other units situated at increasingly separated iso-distant intervals. The results indicated that between-group differences in the functional structure of the cerebral cortex are extensive and implicate part of the lateral prefrontal cortex, a medial frontal/anterior cingulate region, the superior parietal lobe extending to the somatosensory strip and posterior cingulate cortex, and local connections within the visual cortex, hippocampus, amygdala and insula. We thus provided detail of the cerebral cortex functional structure maturation during the transition to adulthood, which may serve to establish more accurate links between adolescent performance gains and cerebral cortex maturation. Remarkably, our study provides new information as to the cortical maturation processes in prefrontal areas relevant to executive functioning and rational learning, medial frontal areas playing an active role in the cognitive appraisal of emotion and anxiety, and superior parietal cortices strongly associated with bodily self-consciousness in the context of body image formation.

Mapping the Synchronization Effect of Gamma-Aminobutyric Acid Inhibition on the Cerebral Cortex Using Magnetic Resonance Imaging.

Background: Functional magnetic resonance imaging (fMRI) of spontaneous brain activity permits the identification of functional networks on the basis of region synchrony. The functional coupling between the elements of a neural system increases during brain activation. However, neural synchronization may also be the effect of inhibitory gamma-aminobutyric acid (GABA) neurons in states of brain inhibition such as sleep or pharmacological sedation. We investigated the effects of an oral dose of alprazolam, a classical benzodiazepine known to enhance inhibitory neurotransmission, using recently developed measures of local functional connectivity. Methods: In a randomized, double-blind, placebo-controlled, crossover design, 32 non-treatment-seeking individuals with social anxiety underwent two identical resting-state fMRI sessions on separate days after receiving 0.75 mg of alprazolam and placebo. Functional connectivity maps of the cerebral cortex were generated by using multidistance functional connectivity measures defined within iso-distant local areas. Results: Relative to placebo, increased intracortical functional connectivity was observed in the alprazolam condition in visual, auditory, and sensorimotor cortices, and in areas of sensory integration such as the posterior insula and orbitofrontal cortex (OFC). Alprazolam significantly reduced subjective arousal compared with placebo, and the change was associated with variations in multidistance functional connectivity measures in the OFC. Discussion: In conclusion, we report evidence that alprazolam significantly modifies neural activity coupling at rest in the form of functional connectivity enhancement within the cerebral cortex. The effect of alprazolam was particularly evident in the cortical sensory system, which would further suggest a differentiated effect of GABA inhibition on sensory processing.

Meaning in Life: A Major Predictive Factor for Loneliness Comparable to Health Status and Social Connectedness.

Objective: Loneliness is the subjective distress of feeling alone and has a strong impact on wellbeing and health. In addition to well-known predictors like isolation and poor health, a better understanding of the psychological determinants of loneliness would offer effective targets for future complementary interventions. Methods: In this cross-sectional observational study (N = 2,240), we compared the explanatory power of several important risk factors of loneliness with the affective, motivational, and cognitive aspects of the Meaning in Life (MiL) construct. Different nested linear models were compared including socio-demographic, lifestyles, social-connectedness, and self-rated health variables, to assess the overlapping and non-overlapping explanatory power of each of them. Results: Health status and MiL were found to be the most important predictors of loneliness, followed by social connectedness and, with a much lower weight, lifestyles, and socio-demographic factors. Within the MiL factor, the most cognitive component, sense of coherence, had a greater explanatory power than the more affective and motivational ones. Conclusion: Reduced MiL, the capacity of an individual to attach "value and significance" to life, is a crucial predictor to the feeling of loneliness. These results suggest that programs aiming to combat loneliness should go well beyond situational interventions and include more cognitive, value-centered interventions that enable individuals to define and pursue a meaningful vital plan.

The paradoxical effect of COVID-19 outbreak on loneliness.

As in previous periods of quarantine, lockdown confinement measures dictated to control SARS-CoV-2 would be expected to negatively affect mental health. We investigated the immediate effects (over a 10 day period) of a strict nationwide stay-at-home order imposed in Spain, one of the countries most affected by the COVID-19 pandemic. Focusing our analysis on the feelings of loneliness, we obtained our measures within a social context characterised by strong and continuous public and governmental support for increasing social bonds and cooperation in order to face the common public threat. Leveraging data from the Barcelona Brain Health Initiative, a prospective population-based study cohort, the short UCLA Loneliness Scale was administered to 1604 participants 2 years and 1 year before the stay-at-home lockdown and repeated, on average, 10 days after the official confinement order issued by the Spanish government. Ratings of loneliness remained stable during the 2 years before lockdown; however, they decreased significantly during the early stages of home confinement. This effect was particularly significant for the item 'feeling excluded from others' and was also observed among individuals who were confined alone. Overall, the results suggest that gestures and manifestations of appreciation by people for the labour and efforts of certain individuals, along with official campaigns designed to promote feelings of inclusion and belonging, may have beneficial effects on feelings of loneliness, a negative emotional state strongly regarded as a risk factor for impaired mental and general health status. Further assessments during the later stages of home confinement are now warranted.

Meta-analysis of generalized additive models in neuroimaging studies.

Analyzing data from multiple neuroimaging studies has great potential in terms of increasing statistical power, enabling detection of effects of smaller magnitude than would be possible when analyzing each study separately and also allowing to systematically investigate between-study differences. Restrictions due to privacy or proprietary data as well as more practical concerns can make it hard to share neuroimaging datasets, such that analyzing all data in a common location might be impractical or impossible. Meta-analytic methods provide a way to overcome this issue, by combining aggregated quantities like model parameters or risk ratios. Most meta-analytic tools focus on parametric statistical models, and methods for meta-analyzing semi-parametric models like generalized additive models have not been well developed. Parametric models are often not appropriate in neuroimaging, where for instance age-brain relationships may take forms that are difficult to accurately describe using such models. In this paper we introduce meta-GAM, a method for meta-analysis of generalized additive models which does not require individual participant data, and hence is suitable for increasing statistical power while upholding privacy and other regulatory concerns. We extend previous works by enabling the analysis of multiple model terms as well as multivariate smooth functions. In addition, we show how meta-analytic p-values can be computed for smooth terms. The proposed methods are shown to perform well in simulation experiments, and are demonstrated in a real data analysis on hippocampal volume and self-reported sleep quality data from the Lifebrain consortium. We argue that application of meta-GAM is especially beneficial in lifespan neuroscience and imaging genetics. The methods are implemented in an accompanying R package metagam, which is also demonstrated.

Brain Functional Connectivity Correlates of Subclinical Obsessive-Compulsive Symptoms in Healthy Children.

OBJECTIVE: Commonly observed subclinical obsessive-compulsive symptoms in healthy children may predispose to obsessive-compulsive disorder (OCD). Therefore, investigating the underlying neurobiology may be relevant to identify alterations in specific brain circuits potentially accounting for clinical heterogeneity in OCD without the confounding effects of clinical samples. We analyzed the brain correlates of different obsessive-compulsive symptoms in a large group of healthy children using functional connectivity measures. METHOD: We evaluated 227 healthy children (52% girls; mean [SD] age 9.71 [0.86] years; range, 8-12.1 years). Participants underwent clinical assessment with the Obsessive-Compulsive Inventory-Child Version and a resting-state functional magnetic resonance imaging examination. Total and symptom-specific severity were correlated with voxelwise global functional connectivity degree values. Significant clusters were then used as seeds of interest in seed-to-voxel analyses. Modulating effects of age and sex were also assessed. RESULTS: Global functional connectivity of the left ventral putamen and medial dorsal thalamus correlated negatively with total obsessive-compulsive symptom severity. Seed-to-voxel analyses revealed specific negative correlations from these clusters with limbic, sensorimotor, and insular regions in association with obsessing, ordering, and doubt-checking symptoms, respectively. Hoarding symptoms were associated with negative correlations between the left medial dorsal thalamus and a widespread pattern of regions, with such associations modulated by sex and age. CONCLUSION: Our findings concur with prevailing neurobiological models of OCD on the importance of cortico-striato-thalamo-cortical dysfunction to account for symptom severity. Notably, we showed that changes in cortico-striato-thalamo-cortical connectivity are present at subclinical stages, which may result in an increased vulnerability for OCD. Moreover, we mapped different symptom dimensions onto specific cortico-striato-thalamo-cortical circuit attributes.

Poor Self-Reported Sleep is Related to Regional Cortical Thinning in Aging but not Memory Decline-Results From the Lifebrain Consortium.

We examined whether sleep quality and quantity are associated with cortical and memory changes in cognitively healthy participants across the adult lifespan. Associations between self-reported sleep parameters (Pittsburgh Sleep Quality Index, PSQI) and longitudinal cortical change were tested using five samples from the Lifebrain consortium (n = 2205, 4363 MRIs, 18-92 years). In additional analyses, we tested coherence with cell-specific gene expression maps from the Allen Human Brain Atlas, and relations to changes in memory performance. "PSQI # 1 Subjective sleep quality" and "PSQI #5 Sleep disturbances" were related to thinning of the right lateral temporal cortex, with lower quality and more disturbances being associated with faster thinning. The association with "PSQI #5 Sleep disturbances" emerged after 60 years, especially in regions with high expression of genes related to oligodendrocytes and S1 pyramidal neurons. None of the sleep scales were related to a longitudinal change in episodic memory function, suggesting that sleep-related cortical changes were independent of cognitive decline. The relationship to cortical brain change suggests that self-reported sleep parameters are relevant in lifespan studies, but small effect sizes indicate that self-reported sleep is not a good biomarker of general cortical degeneration in healthy older adults.

The Barcelona Brain Health Initiative: Cohort description and first follow-up.

The Barcelona Brain Health Initiative is a longitudinal cohort study that began in 2017 and aims to understand and characterize the determinants of brain health maintenance in middle aged adults. A cohort of 4686 individuals between the ages of 40 and 65 years free from any neurological or psychiatric diseases was established, and we collected extensive demographic, socio-economic information along with measures of self-perceived health and lifestyles (general health, physical activity, cognitive activity, socialization, sleep, nutrition and vital plan). Here we report on the baseline characteristics of the participants, and the results of the one-year follow-up evaluation. Participants were mainly women, highly educated, and with better lifestyles compared with the general population. After one year 60% of participants completed the one-year follow-up, and these were older, with higher educational level and with better lifestyles in some domains. In the absence of any specific interventions to-date, these participants showed small improvements in physical activity and sleep, but decreased adherence to a Mediterranean diet. These changes were negatively associated with baseline scores, and poorer habits at baseline were predictive of an improvement in lifestyle domains. Of the 2353 participants who completed the one-year follow-up, 73 had been diagnosed with new neurological and neuropsychiatric diseases. Changes in vital plan at follow-up, as well as gender, sleep quality and sense of coherence at baseline were shown to be significant risk factors for the onset of these diagnoses. Notably, gender risk factor decreased in importance as we adjusted by sleep habits, suggesting its potential mediator effects. These findings stress the importance of healthy lifestyles in sustaining brain health, and illustrate the individual benefit that can be derived from participation in longitudinal observational studies. Modifiable lifestyles, specifically quality of sleep, may partially mediate the effect of other risk factors in the development of some neuropsychiatric conditions.

Mapping Alterations of the Functional Structure of the Cerebral Cortex in Obsessive-Compulsive Disorder.

We mapped alterations of the functional structure of the cerebral cortex using a novel imaging approach in a sample of 160 obsessive-compulsive disorder (OCD) patients. Whole-brain functional connectivity maps were generated using multidistance measures of intracortical neural activity coupling defined within isodistant local areas. OCD patients demonstrated neural activity desynchronization within the orbitofrontal cortex and in primary somatosensory, auditory, visual, gustatory, and olfactory areas. Symptom severity was significantly associated with the degree of functional structure alteration in OCD-relevant brain regions. By means of a novel imaging perspective, we once again identified brain alterations in the orbitofrontal cortex, involving areas purportedly implicated in the pathophysiology of OCD. However, our results also indicated that weaker intracortical activity coupling is also present in each primary sensory area. On the basis of previous neurophysiological studies, such cortical activity desynchronization may best be interpreted as reflecting deficient inhibitory neuron activity and altered sensory filtering.