Maternal childhood maltreatment: associations to offspring brain volume and white matter connectivity.

The deleterious effects of adversity are likely intergenerational, such that one generation's adverse experiences can affect the next. Epidemiological studies link maternal adversity to offspring depression and anxiety, possibly via transmission mechanisms that influence offspring fronto-limbic connectivity. However, studies have not thoroughly disassociated postnatal exposure effects nor considered the role of offspring sex. We utilized infant neuroimaging to test the hypothesis that maternal childhood maltreatment (CM) would be associated with increased fronto-limbic connectivity in infancy and tested brain-behavior associations in childhood. Ninety-two dyads participated (32 mothers with CM, 60 without; 52 infant females, 40 infant males). Women reported on their experiences of CM and non-sedated sleeping infants underwent MRIs at 2.44 ± 2.74 weeks. Brain volumes were estimated via structural MRI and white matter structural connectivity (fiber counts) via diffusion MRI with probabilistic tractography. A subset of parents (n = 36) reported on children's behaviors at age 5.17 ± 1.73 years. Males in the maltreatment group demonstrated greater intra-hemispheric fronto-limbic connectivity (b = 0.96, p= 0.008, [95%CI 0.25, 1.66]), no differences emerged for females. Fronto-limbic connectivity was related to somatic complaints in childhood only for males (r = 0.673, p = 0.006). Our findings suggest that CM could have intergenerational associations to offspring brain development, yet mechanistic studies are needed.

The association between duration of breastfeeding and the trajectory of brain development from childhood to young adulthood: an 8-year longitudinal study.

Breastfeeding has been associated with several short- and long-term health benefits, including positive cognitive and behavioral outcomes. However, the impact of breastfeeding on structural brain development over time remains unclear. We aimed to assess the association between breastfeeding duration in childhood and the developmental trajectory of overall cortical thickness, cortical area, and total intracranial volume during the transition from childhood to early adulthood. Participants included 670 children and adolescents with 1326 MRI scans acquired over 8 years from the Brazilian High-Risk Cohort for Mental Conditions (BHRCS). Breastfeeding was assessed using a questionnaire answered by the parents. Brain measures were estimated using MRI T1-weighted images at three time points, with 3-year intervals. Data were evaluated using generalized additive models adjusted for multiple confounders. We found that a longer breastfeeding duration was directly associated with higher global cortical thickness in the left (edf = 1.0, F = 6.07, p = 0.01) and right (edf = 1.0, F = 4.70, p = 0.03) hemispheres. For the total intracranial volume, we found an interaction between duration of breastfeeding and developmental stage (edf = 1.0, F = 6.81, p = 0.009). No association was found between breastfeeding duration and brain area. Our study suggests that the duration of breastfeeding impacts overall cortical thickness and the development of total brain volume, but not area. This study adds to the evidence on the potential impact of breastfeeding on brain development and provides relevant insights into the mechanisms by which breastfeeding might confer cognitive and mental health benefits.

Country-level gender inequality is associated with structural differences in the brains of women and men.

Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women's worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women's brains and provide initial evidence for neuroscience-informed policies for gender equality.

Generalizability of 3D CNN models for age estimation in diverse youth populations using structural MRI.

Recently, several studies have investigated the neurodevelopment of psychiatric disorders using brain data acquired via structural magnetic resonance imaging (sMRI). These analyses have shown the potential of sMRI data to provide a relatively precise characterization of brain structural biomarkers. Despite these advances, a relatively unexplored question is how reliable and consistent a model is when assessing subjects from other independent datasets. In this study, we investigate the performance and generalizability of the same model architecture trained from distinct datasets comprising youths in diverse stages of neurodevelopment and with different mental health conditions. We employed models with the same 3D convolutional neural network (CNN) architecture to assess autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), brain age, and a measure of dimensional psychopathology, the Child Behavior Checklist (CBCL) total score. The investigated datasets include the Autism Brain Imaging Data Exchange II (ABIDE-II, N = 580), Attention Deficit Hyperactivity Disorder (ADHD-200, N = 922), Brazilian High-Risk Cohort Study (BHRCS, N = 737), and Adolescent Brain Cognitive Development (ABCD, N = 11,031). Models' performance and interpretability were assessed within each dataset (for diagnosis tasks) and inter-datasets (for age estimation). Despite the demographic and phenotypic differences of the subjects, all models presented significant estimations for age (p value < 0.001) within and between datasets. In addition, most models showed a moderate to high correlation in age estimation. The results, including the models' brain regions of interest (ROI), were analyzed and discussed in light of the youth neurodevelopmental structural changes. Among other interesting discoveries, we found that less confounded training datasets produce models with higher generalization capacity.

Efficacy and safety of ketamine for the treatment of depressive symptoms in palliative care: a systematic review

Objectives: Ketamine has a fast onset of action that may offer a paradigm change for depression management at the end of life. We aimed to synthesize evidence regarding the safety and efficacy of ketamine in depression treatment within a broad palliative care concept. Methods: We searched seven databases and included studies on the safety and efficacy of ketamine for depression treatment in patients diagnosed with any life-threatening disease. We also conducted a narrative review of the evidence. Results: Among 2,252 screened titles and abstracts, we included 32 studies in our final synthesis: 14 case reports, two case series, two quasi-experimental studies, and seven randomized clinical trials (RCTs), as well as data from three unpublished clinical trials and seven cases from four larger case series. Most case reports reported a robust effect; however, the larger studies reported conflicting findings. Five RCTs reported positive outcomes; however, four of them were focused on a perioperative setting. Two negative studies did not primarily focus on depression and did not apply severity cutoffs. Conclusion: Although ketamine is generally safe and potentially useful, its efficacy in palliative care settings remains unclear. It may be a reasonable alternative for perioperative depression in oncological patients.

Polygenic risk score for attention-deficit/hyperactivity disorder and brain functional networks segregation in a community-based sample.

Neuroimaging studies suggest that brain development mechanisms might explain at least some behavioural and cognitive attention-deficit/hyperactivity disorder (ADHD) symptoms. However, the putative mechanisms by which genetic susceptibility factors influence clinical features via alterations of brain development remain largely unknown. Here, we set out to integrate genomics and connectomics tools by investigating the associations between an ADHD polygenic risk score (ADHD-PRS) and functional segregation of large-scale brain networks. With this aim, ADHD symptoms score, genetic and rs-fMRI (resting-state functional magnetic resonance image) data obtained in a longitudinal community-based cohort of 227 children and adolescents were analysed. A follow-up was conducted approximately 3 years after the baseline, with rs-fMRI scanning and ADHD likelihood assessment in both stages. We hypothesised a negative correlation between probable ADHD and the segregation of networks involved in executive functions, and a positive correlation with the default-mode network (DMN). Our findings suggest that ADHD-PRS is correlated with ADHD at baseline, but not at follow-up. Despite not surviving for multiple comparison correction, we found significant correlations between ADHD-PRS and segregation of cingulo-opercular networks and DMN at baseline. ADHD-PRS was negatively correlated with the segregation level of cingulo-opercular networks but positively correlated with the DMN segregation. These directions of associations corroborate the proposed counter-balanced role of attentional networks and DMN in attentional processes. However, the association between ADHD-PRS and brain networks functional segregation was not found at follow-up. Our results provide evidence for specific influences of genetic factors on development of attentional networks and DMN. We found significant correlations between polygenic risk score for ADHD (ADHD-PRS) and segregation of cingulo-opercular networks and default-mode network (DMN) at baseline. ADHD-PRS was negatively correlated with the segregation level of cingulo-opercular networks but positively correlated with the DMN segregation.

Volume of subcortical brain regions in social anxiety disorder: mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group.

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, pFWE = 0.037; right: d = -0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, pFWE < 0.001; right: d = -0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood.

Efficacy and safety of ketamine for the treatment of depressive symptoms in palliative care: A systematic review.

OBJECTIVES: Ketamine has a fast onset of action that may offer a paradigm change for depression management at the end of life. We aimed to synthesize evidence regarding the safety and efficacy of ketamine in depression treatment within a broad palliative care concept. METHODS: We searched seven databases and included studies on the safety and efficacy of ketamine for depression treatment in patients diagnosed with any life-threatening disease. We also conducted a narrative review of the evidence. RESULTS: Among 2,252 screened titles and abstracts, we included 32 studies in our final synthesis: 14 case reports, two case series, two quasi-experimental studies, and seven randomized clinical trials (RCTs), as well as data from three unpublished clinical trials and seven cases from four larger case series. Most case reports reported a robust effect; however, the larger studies reported conflicting findings. Five RCTs reported positive outcomes; however, four of them were focused on a perioperative setting. Two negative studies did not primarily focus on depression and did not apply severity cutoffs. CONCLUSIONS: Although ketamine is generally safe and potentially useful, its efficacy in palliative care settings remains unclear. It may be a reasonable alternative for perioperative depression in oncological patients.

Deviations from a typical development of the cerebellum in youth are associated with psychopathology, executive functions and educational outcomes.

BACKGROUND: Understanding deviations from typical brain development is a promising approach to comprehend pathophysiology in childhood and adolescence. We investigated if cerebellar volumes different than expected for age and sex could predict psychopathology, executive functions and academic achievement. METHODS: Children and adolescents aged 6-17 years from the Brazilian High-Risk Cohort Study for Mental Conditions had their cerebellar volume estimated using Multiple Automatically Generated Templates from T1-weighted images at baseline (n = 677) and at 3-year follow-up (n = 447). Outcomes were assessed using the Child Behavior Checklist and standardized measures of executive functions and school achievement. Models of typically developing cerebellum were based on a subsample not exposed to risk factors and without mental-health conditions (n = 216). Deviations from this model were constructed for the remaining individuals (n = 461) and standardized variation from age and sex trajectory model was used to predict outcomes in cross-sectional, longitudinal and mediation analyses. RESULTS: Cerebellar volumes higher than expected for age and sex were associated with lower externalizing specific factor and higher executive functions. In a longitudinal analysis, deviations from typical development at baseline predicted inhibitory control at follow-up, and cerebellar deviation changes from baseline to follow-up predicted changes in reading and writing abilities. The association between deviations in cerebellar volume and academic achievement was mediated by inhibitory control. CONCLUSIONS: Deviations in the cerebellar typical development are associated with outcomes in youth that have long-lasting consequences. This study highlights both the potential of typical developing models and the important role of the cerebellum in mental health, cognition and education.

Relationships Between Telomere Length, Plasma Glucagon-like Peptide 1, and Insulin in Early-Life Stress-Exposed Nonhuman Primates.

Background: Early-life stress is associated with alterations in telomere length, a marker of accumulated stress and aging, and a risk factor for psychiatric disorders. Nonhuman primate maternal variable foraging demand (VFD) is a validated early-life stress model, resulting in anxiety- and depressive-like symptoms in offspring. Previous studies reported increased plasma glucagon-like peptide 1 (pGLP-1) along with insulin resistance in this model. We investigated whether VFD rearing related to adult telomere length and to these neuroendocrine markers. Methods: Adult leukocyte telomere length was measured in VFD-reared (12 males, 13 females) and non-VFD-reared (9 males, 26 females) bonnet macaques. Associations between adult telomere length and adolescent fasting pGLP-1 or insulin resistance in VFD-reared versus non-VFD-reared groups were examined using regression modeling, controlling for sex, weight, and age. Results: VFD subjects had relatively longer telomeres than non-VFD subjects (p = .017), and females relatively longer than males (p = .0004). Telomere length was positively associated with pGLP-1 (p = .0009) and with reduced insulin sensitivity (p < .0001) in both sexes, but not as a function of rearing group. Conclusions: Unexpectedly, VFD was associated with longer adult telomere length. Insulin resistance may lead to higher pGLP-1 levels in adolescence, which could protect telomere length in VFD offspring as adults. Associations between adult telomere length and adolescent insulin resistance and high pGLP-1 may reflect an adaptive, compensatory response after early-life stress exposure.

Structural Brain Correlates of Childhood Inhibited Temperament: An ENIGMA-Anxiety Mega-analysis.

Temperament involves stable behavioral and emotional tendencies that differ between individuals, which can be first observed in infancy or early childhood and relate to behavior in many contexts and over many years.1 One of the most rigorously characterized temperament classifications relates to the tendency of individuals to avoid the unfamiliar and to withdraw from unfamiliar people, objects, and unexpected events. This temperament is referred to as behavioral inhibition or inhibited temperament (IT).2 IT is a moderately heritable trait1 that can be measured in multiple species.3 In humans, levels of IT can be quantified from the first year of life through direct behavioral observations or reports by caregivers or teachers. Similar approaches as well as self-report questionnaires on current and/or retrospective levels of IT1 can be used later in life.

The relationship between recent PTSD secondary to sexual assault, hippocampal volume and resting state functional connectivity in adolescent girls.

Objective: Improved understanding of the time course of neural changes associated with adolescent PTSD would elucidate the development of the disorder and could inform approaches to treatment. We compared hippocampal volumes and resting state functional connectivity (RSFC) in adolescent girls with post-traumatic stress disorder (PTSD) secondary to sexual assault, within six months of onset and age- and gender-matched, non-trauma exposed healthy controls (HCs) in São Paulo, Brazil. We also examined the relationship between pre- and post-treatment PTSD symptoms and RSFC. Method: We collected brain structure, RSFC, and PTSD symptoms in 30 adolescents with PTSD (mean age: 15.7 ± 1.04 years) and 21 HCs (mean age: 16.2 ± 1.21 years) at baseline. We collected repeated measures in 21 participants with PTSD following treatment; 9 participants dropped out. Hippocampal volume and RSFC from hippocampal and default mode network (DMN) seeds were compared between participants with PTSD and HCs. We examined associations between within-subject changes in RSFC and PTSD symptoms following treatment. Results: No hippocampal volumetric differences between groups were found. Compared to HCs, adolescents with recent PTSD had reduced RSFC between hippocampus and the lateral parietal node of the DMN, encompassing the angular gyrus, peak coordinates: -38, -54, 16; 116 voxels; peak F 1,47 = 31.76; FDR corrected p = 0.038. Improvements in PTSD symptoms were associated with increased RSFC between hippocampus and part of the lateral parietal node of the DMN, peak coordinates: -38, -84, 38; 316 voxels; peak F 1,47 = 40.28; FDR corrected p < 0.001. Conclusion: Adolescents with recent PTSD had reduced hippocampal-DMN RSFC, while no group differences in hippocampal volume were found, suggesting that hippocampal function, but not structure, is altered early in the course of PSTD. Following treatment, hippocampal-DMN RSFC increased with symptom improvement and may indicate an important neural mechanism related to successful PTSD treatment.

Mega-analysis methods in ENIGMA: The experience of the generalized anxiety disorder working group.

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as the approach taken to implement them. The goal is to document the approach and help guide other research groups working with large brain imaging data sets as they develop their own analytic pipelines for mega-analyses.

The probability of response after each subcutaneous injection of esketamine in treatment-resistant depression.

INTRODUCTION: The administration of multiple esketamine doses has shown efficacy for unipolar and bipolar treatment-resistant depression (TRD). Nevertheless, the probability of responding or not after each dose in the real-world remains unknown. This study aimed to estimate it throughout four doses of esketamine, administrated via subcutaneous (SC). MATERIAL AND METHODS: We conducted a retrospective analysis of a case series of 70 patients with TRD who received treatment from the esketamine assistance program at Federal University of Sao Paulo, between April 2017 and December 2018. The SC injections were administrated weekly at a dose of 0.5-1.0mg/kg, in conjunction with patients' psychotropic drugs. Response was defined as a decrease of at least 50% in the Montgomery-Åsberg Depression Rating Scale between baseline and 24h after dose. We used hidden Markov modeling in order to estimate de probability of response after each esketamine injection. RESULTS: The probability of a patient that was a "non-responder" to become a "responder" following a SC injection of esketamine was 17.30% and the probability that this patient remains a "non-responder" was 82.70%. The probability of a patient that was a "responder" to remain as a "responder" was 95%. CONCLUSIONS: Patients with TRD who had not responded after the first dose of esketamine, still had a chance of responding after the subsequent dose administrated via SC.

The probability of response after each subcutaneous injection of esketamine in treatment-resistant depression / Probabilidad de respuesta tras cada inyección subcutánea de esketamina en la depresión resistente al tratamiento

Introduction The administration of multiple esketamine doses has shown efficacy for unipolar and bipolar treatment-resistant depression (TRD). Nevertheless, the probability of responding or not after each dose in the real-world remains unknown. This study aimed to estimate it throughout four doses of esketamine, administrated via subcutaneous (SC). Material and methods We conducted a retrospective analysis of a case series of 70 patients with TRD who received treatment from the esketamine assistance program at Federal University of Sao Paulo, between April 2017 and December 2018. The SC injections were administrated weekly at a dose of 0.5–1.0mg/kg, in conjunction with patients’ psychotropic drugs. Response was defined as a decrease of at least 50% in the Montgomery-Åsberg Depression Rating Scale between baseline and 24h after dose. We used hidden Markov modeling in order to estimate de probability of response after each esketamine injection. Results The probability of a patient that was a “non-responder” to become a “responder” following a SC injection of esketamine was 17.30% and the probability that this patient remains a “non-responder” was 82.70%. The probability of a patient that was a “responder” to remain as a “responder” was 95%. Conclusions Patients with TRD who had not responded after the first dose of esketamine, still had a chance of responding after the subsequent dose administrated via SC. (AU)

Introducción La administración de dosis múltiples de esketamina ha demostrado su eficacia para el tratamiento de la depresión unipolar y bipolar resistente al tratamiento (TRD). Sin embargo, sigue siendo una incógnita la probabilidad de responder o no tras cada dosis en el mundo real. El objetivo de este estudio fue calcular dicha probabilidad durante la administración vía subcutánea (SC) de cuatro dosis de esketamina. Material y métodos Realizamos un análisis retrospectivo de una serie de casos de 70 pacientes con TRD, que recibieron tratamiento a través del programa de asistencia con esketamina en la Universidad Federal University de Sao Paulo, entre abril de 2017 y diciembre de 2018. Las inyecciones SC se administraron semanalmente, a dosis de 0,5-1mg/kg, junto con los medicamentos psicotrópicos de los pacientes. Se definió la respuesta como una reducción de al menos el 50% en la Escala de Calificación de la Depresión de Montgomery-Åsberg entre el valor basal y las 24 horas posteriores a la administración de la dosis. Utilizamos el modelo oculto de Markov para calcular la probabilidad de respuesta tras cada inyección de esketamina. Resultados La probabilidad de que un paciente que fuera «no respondedor» se convirtiera en «respondedor», tras una inyección SC de esketamina fue del 17,3%, y la probabilidad de que este paciente siguiera siendo «no respondedor» fue del 82,7%. La probabilidad de que un paciente que fuera «respondedor» lo siguiera siendo fue del 95%. Conclusiones Los pacientes con TRD que no han respondido a la primera dosis de esketamina, tienen probabilidad de respuesta tras la administración de las siguientes dosis por vía SC. (AU)

Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the ENIGMA-Anxiety Working Group.

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5-90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology.

Cortical surface abnormalities are different depending on the stage of schizophrenia: A cross-sectional vertexwise mega-analysis of thickness, area and gyrification.

BACKGROUND: Brain magnetic resonance imaging studies have not investigated the cortical surface comprehensively in schizophrenia subjects by assessing thickness, surface area and gyrification separately during the first-episode of psychosis (FEP) or chronic schizophrenia (ChSch). METHODS: We investigated cortical surface abnormalities in 137 FEP patients and 240 ChSch subjects compared to 297 Healthy Controls (HC) contributed by five cohorts. Maps showing results of vertexwise between-group comparisons of cortical thickness, area, and gyrification were produced using T1-weighted datasets processed using FreeSurfer 5.3, followed by validated quality control protocols. RESULTS: FEP subjects showed large clusters of increased area and gyrification relative to HC in prefrontal and insuli cortices (Cohen's d: 0.049 to 0.28). These between-group differences occurred partially beyond the effect of sample. ChSch subjects displayed reduced cortical thickness relative to HC in smaller fronto-temporal foci (d: -0.73 to -0.35), but not beyond the effect of sample. Differences between FEP and HC subjects were associated with male gender, younger age, and earlier illness onset, while differences between ChSch and HC were associated with treatment-resistance and first-generation antipsychotic (FGA) intake independently of sample effect. CONCLUSIONS: Separate assessments of FEP and ChSch revealed abnormalities that differed in regional distribution, phenotypes affected and effect size. In FEP, associations of greater cortical area and gyrification abnormalities with earlier age of onset suggest an origin on anomalous neurodevelopment, while thickness reductions in ChSch are at least partially explained by treatment-resistance and FGA intake. Associations of between-group differences with clinical variables retained statistical significance beyond the effect of sample.

Long-term stability of the cortical volumetric profile and the functional human connectome throughout childhood and adolescence.

There is compelling evidence showing that between-subject variability in several functional and structural brain features is sufficient for unique identification in adults. However, individuation of brain functional connectomes depends on the stabilization of neurodevelopmental processes during childhood and adolescence. Here, we aimed to (1) evaluate the intra-subject functional connectome stability over time for the whole brain and for large scale functional networks and (2) determine the long-term identification accuracy or 'fingerprinting' for the cortical volumetric profile and the functional connectome. For these purposes, we analysed a longitudinal cohort of 239 children and adolescents scanned in two sessions with an interval of approximately 3 years (age range 6-15 years at baseline and 9-18 years at follow-up). Corroborating previous results using short between-scan intervals in children and adolescents, we observed a moderate identification accuracy (38%) for the whole functional profile. In contrast, identification accuracy using cortical volumetric profile was 95%. Among the large-scale networks, the default-mode (26.8%), the frontoparietal (23.4%) and the dorsal-attention (27.6%) networks were the most discriminative. Our results provide further evidence for a protracted development of specific individual structural and functional connectivity profiles.

Intra-session test-retest reliability of functional connectivity in infants.

Resting functional MRI studies of the infant brain are increasingly becoming an important tool in developmental neuroscience. Whereas the test-retest reliability of functional connectivity (FC) measures derived from resting fMRI data have been characterized in the adult and child brain, similar assessments have not been conducted in infants. In this study, we examined the intra-session test-retest reliability of FC measures from 119 infant brain MRI scans from four neurodevelopmental studies. We investigated edge-level and subject-level reliability within one MRI session (between and within runs) measured by the Intraclass correlation coefficient (ICC). First, using an atlas-based approach, we examined whole-brain connectivity as well as connectivity within two common resting fMRI networks - the default mode network (DMN) and the sensorimotor network (SMN). Second, we examined the influence of run duration, study site, and scanning manufacturer (e.g., Philips and General Electric) on ICCs. Lastly, we tested spatial similarity using the Jaccard Index from networks derived from independent component analysis (ICA). Consistent with resting fMRI studies from adults, our findings indicated poor edge-level reliability (ICC = 0.14-0.18), but moderate-to-good subject-level intra-session reliability for whole-brain, DMN, and SMN connectivity (ICC = 0.40-0.78). We also found significant effects of run duration, site, and scanning manufacturer on reliability estimates. Some ICA-derived networks showed strong spatial reproducibility (e.g., DMN, SMN, and Visual Network), and were labelled based on their spatial similarity to analogous networks measured in adults. These networks were reproducibly found across different study sites. However, other ICA-networks (e.g. Executive Control Network) did not show strong spatial reproducibility, suggesting that the reliability and/or maturational course of functional connectivity may vary by network. In sum, our findings suggest that developmental scientists may be on safe ground examining the functional organization of some major neural networks (e.g. DMN and SMN), but judicious interpretation of functional connectivity is essential to its ongoing success.