Neurocognitive disorders in the elderly: altered functional resting-state hyperconnectivities in postoperative delirium patients

Postoperative delirium (POD) represents a confusional state during days/weeks after surgery and is particularly frequent in elderly patients. Hardly any fMRI studies were conducted to understand the underlying pathophysiology of POD patients. This prospective observational cohort study aims to examine changes of specific resting-state functional connectivity networks across different time points (pre- and 3-5 months postoperatively) in delirious patients compared to no-POD patients. Two-hundred eighty-three elderly surgical patients underwent preoperative resting-state fMRI (46 POD). One-hundred seventy-eight patients completed postoperative scans (19 POD). For functional connectivity analyses, three functional connectivity networks with seeds located in the orbitofrontal cortex (OFC), nucleus accumbens (NAcc), and hippocampus were investigated. The relationship of POD and connectivity changes between both time points (course connectivity) were examined (ANOVA). Preoperatively, delirious patients displayed hyperconnectivities across the examined functional connectivity networks. In POD patients, connectivities within NAcc and OFC networks demonstrated a decrease in course connectivity [max. F = 9.03, p = 0.003; F = 4.47, p = 0.036, resp.]. The preoperative hyperconnectivity in the three networks in the patients at risk for developing POD could possibly indicate existing compensation mechanisms for subtle brain dysfunction. The observed pathophysiology of network function in POD patients at least partially involves dopaminergic pathways

Adolescent to young adult longitudinal development of subcortical volumes in two European sites with four waves

Adolescent subcortical structural brain development might underlie psychopathological symptoms, which often emerge in adolescence. At the same time, sex differences exist in psychopathology, which might be mirrored in underlying sex differences in structural development. However, previous studies showed inconsistencies in subcortical trajectories and potential sex differences. Therefore, we aimed to investigate the subcortical structural trajectories and their sex differences across adolescence using for the first time a single cohort design, the same quality control procedure, software, and a general additive mixed modeling approach. We investigated two large European sites from ages 14 to 24 with 503 participants and 1408 total scans from France and Germany as part of the IMAGEN project including four waves of data acquisition. We found significantly larger volumes in males versus females in both sites and across all seven subcortical regions. Sex differences in age-related trajectories were observed across all regions in both sites. Our findings provide further evidence of sex differences in longitudinal adolescent brain development of subcortical regions and thus might eventually support the relationship of underlying brain development and different adolescent psychopathology in boys and girls.</p

Machine learning models for diagnosis and risk prediction in eating disorders, depression, and alcohol use disorder

This study uses machine learning models to uncover diagnostic and risk prediction markers for eating disorders (EDs), major depressive disorder (MDD), and alcohol use disorder (AUD). Utilizing case-control samples (ages 18-25 years) and a longitudinal population-based sample (n=1,851), the models, incorporating diverse data domains, achieved high accuracy in classifying EDs, MDD, and AUD from healthy controls. The area under the receiver operating characteristic curves (AUC-ROC [95% CI]) reached 0.92 [0.86-0.97] for AN and 0.91 [0.85-0.96] for BN, without relying on body mass index as a predictor. The classification accuracies for MDD (0.91 [0.88-0.94]) and AUD (0.80 [0.74-0.85]) were also high. Each data domain emerged as accurate classifiers individually, with personality distinguishing AN, BN, and their controls with AUC-ROCs ranging from 0.77 to 0.89. The models demonstrated high transdiagnostic potential, as those trained for EDs were also accurate in classifying AUD and MDD from healthy controls, and vice versa (AUC-ROCs, 0.75-0.93). Shared predictors, such as neuroticism, hopelessness, and symptoms of attention-deficit/hyperactivity disorder, were identified as reliable classifiers. For risk prediction in the longitudinal population sample, the models exhibited moderate performance (AUC-ROCs, 0.64-0.71), highlighting the potential of combining multi-domain data for precise diagnostic and risk prediction applications in psychiatry.</p

16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy

Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65 046 European population controls (5/393 cases versus 32/65 046 controls; Fisher's exact test P = 2.83 × 10−6, odds ratio = 26.2, 95% confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 × 10−4). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical R

Psychotic Like Experiences in Healthy Adolescents are Underpinned by Lower Fronto-Temporal Cortical Gyrification: a Study from the IMAGEN Consortium

Background and HypothesisPsychotic Like Experiences (PLEs) are widely prevalent in children and adolescents and increase the risk of developing psychosis. Cortical gyrification characterizes brain development from in utero till about the first 2 years of life and can be measured in later years as static gyrification changes demonstrating neurodevelopment and dynamic gyrification changes reflecting brain maturation during adolescence. We hypothesized that PLEs would be associated with static cortical gyrification changes reflecting a neurodevelopmental abnormality.Study DesignWe studied 1252 adolescents recruited in the IMAGEN consortium. We used a longitudinal study design, with Magnetic Resonance Imaging measurements at age 14 years and age 19 years; measurement of PLEs using the Community Assessment of Psychic Experiences (CAPE) questionnaire at age 19 years; and clinical diagnoses at age 23 years.Study ResultsOur results show static gyrification changes in adolescents with elevated PLEs on 3 items of the CAPE—voice hearing, unusual experiences of receiving messages, and persecutory ideas—with lower cortical gyrification in fronto-temporal regions in the left hemisphere. This group also demonstrated dynamic gyrification changes with higher cortical gyrification in right parietal cortex in late adolescence; a finding that we replicated in an independent sample of patients with first-episode psychosis. Adolescents with high PLEs were also 5.6 times more likely to transition to psychosis in adulthood by age 23 years.ConclusionsThis is the largest study in adolescents that demonstrates fronto-temporal abnormality of cortical gyrification as a potential biomarker for vulnerability to PLEs and transition to psychosis

The Role of Empathy in Alcohol Use of Bullying Perpetrators and Victims: Lower Personal Empathic Distress Makes Male Perpetrators of Bullying More Vulnerable to Alcohol Use

International audienceBullying often results in negative coping in victims, including an increased consumption of alcohol. Recently, however, an increase in alcohol use has also been reported among perpetrators of bullying. The factors triggering this pattern are still unclear. We investigated the role of empathy in the interaction between bullying and alcohol use in an adolescent sample (IMAGEN) at age 13.97 (±0.53) years (baseline (BL), N = 2165, 50.9% female) and age 16.51 (±0.61) years (follow-up 1 (FU1), N = 1185, 54.9% female). General empathic distress served as a significant moderator of alcohol use in perpetrators (F9, 493 = 17.978, p < 0.01), which was specific for males and FU1. Male perpetrators, who are generally less sensitive to distress, might thus be more vulnerable to alcohol abuse

Hemispheric asymmetry in cortical thinning reflects intrinsic organization of the neurotransmitter systems and homotopic functional connectivity

International audienceHemispheric lateralization and its origins have been of great interest in neuroscience for over a century. The left–right asymmetry in cortical thickness may stem from differential maturation of the cerebral cortex in the two hemispheres. Here, we investigated the spatial pattern of hemispheric differences in cortical thinning during adolescence, and its relationship with the density of neurotransmitter receptors and homotopic functional connectivity. Using longitudinal data from IMAGEN study (N = 532), we found that many cortical regions in the frontal and temporal lobes thinned more in the right hemisphere than in the left. Conversely, several regions in the occipital and parietal lobes thinned less in the right (vs. left) hemisphere. We then revealed that regions thinning more in the right (vs. left) hemispheres had higher density of neurotransmitter receptors and transporters in the right (vs. left) side. Moreover, the hemispheric differences in cortical thinning were predicted by homotopic functional connectivity. Specifically, regions with stronger homotopic functional connectivity showed a more symmetrical rate of cortical thinning between the left and right hemispheres, compared with regions with weaker homotopic functional connectivity. Based on these findings, we suggest that the typical patterns of hemispheric differences in cortical thinning may reflect the intrinsic organization of the neurotransmitter systems and related patterns of homotopic functional connectivity

Characterizing reward system neural trajectories from adolescence to young adulthood.

Mixed findings exist in studies comparing brain responses to reward in adolescents and adults. Here we examined the trajectories of brain response, functional connectivity and task-modulated network properties during reward processing with a large-sample longitudinal design. Participants from the IMAGEN study performed a Monetary Incentive Delay task during fMRI at timepoint 1 (T1; n = 1304, mean age=14.44 years old) and timepoint 2 (T2; n = 1241, mean age=19.09 years). The Alcohol Use Disorders Identification Test (AUDIT) was administrated at both T1 and T2 to assess a participant's alcohol use during the past year. Voxel-wise linear mixed effect models were used to compare whole brain response as well as functional connectivity of the ventral striatum (VS) during reward anticipation (large reward vs no-reward cue) between T1 and T2. In addition, task-modulated networks were constructed using generalized psychophysiological interaction analysis and summarized with graph theory metrics. To explore alcohol use in relation to development, participants with no/low alcohol use at T1 but increased alcohol use to hazardous use level at T2 (i.e., participants with AUDIT≤2 at T1 and ≥8 at T2) were compared against those with consistently low scores (i.e., participants with AUDIT≤2 at T1 and ≤7 at T2). Across the whole sample, lower brain response during reward anticipation was observed at T2 compared with T1 in bilateral caudate nucleus, VS, thalamus, midbrain, dorsal anterior cingulate as well as left precentral and postcentral gyrus. Conversely, greater response was observed bilaterally in the inferior and middle frontal gyrus and right precentral and postcentral gyrus at T2 (vs. T1). Increased functional connectivity with VS was found in frontal, temporal, parietal and occipital regions at T2. Graph theory metrics of the task-modulated network showed higher inter-regional connectivity and topological efficiency at T2. Interactive effects between time (T1 vs. T2) and alcohol use group (low vs. high) on the functional connectivity were observed between left middle temporal gyrus and right VS and the characteristic shortest path length of the task-modulated networks. Collectively, these results demonstrate the utility of the MID task as a probe of typical brain response and network properties during development and of differences in these features related to adolescent drinking, a reward-related behaviour associated with heightened risk for future negative health outcomes

Structural differences in adolescent brainscan predict alcohol misuse.

Alcohol misuse during adolescence (AAM) has been associated with disruptive development of adolescent brains. In this longitudinal machine learning (ML) study, we could predict AAM significantly from brain structure (T1-weighted imaging and DTI) with accuracies of 73 -78% in the IMAGEN dataset (n∼1182). Our results not only show that structural differences in brain can predict AAM, but also suggests that such differences might precede AAM behavior in the data. We predicted 10 phenotypes of AAM at age 22 using brain MRI features at ages 14, 19, and 22. Binge drinking was found to be the most predictable phenotype. The most informative brain features were located in the ventricular CSF, and in white matter tracts of the corpus callosum, internal capsule, and brain stem. In the cortex, they were spread across the occipital, frontal, and temporal lobes and in the cingulate cortex. We also experimented with four different ML models and several confound control techniques. Support Vector Machine (SVM) with rbf kernel and Gradient Boosting consistently performed better than the linear models, linear SVM and Logistic Regression. Our study also demonstrates how the choice of the predicted phenotype, ML model, and confound correction technique are all crucial decisions in an explorative ML study analyzing psychiatric disorders with small effect sizes such as AAM

The bidirectional effects between cognitive ability and brain morphology:A life course Mendelian randomization analysis

INTRODUCTION: Little is understood about the dynamic interplay between brain morphology and cognitive ability across the life course. Additionally, most existing research has focused on global morphology measures such as estimated total intracranial volume, mean thickness, and total surface area.METHODS: Mendelian randomization was used to estimate the bidirectional effects between cognitive ability, global and regional measures of cortical thickness and surface area, estimated total intracranial volume, total white matter, and the volume of subcortical structures (N=37,864). Analyses were stratified for developmental periods (childhood, early adulthood, mid-to-late adulthood; age range: 8-81 years).RESULTS: The earliest effects were observed in childhood and early adulthood in the frontoparietal lobes. A bidirectional relationship was identified between higher cognitive ability, larger estimated total intracranial volume (childhood, mid-to-late adulthood) and total surface area (all life stages). A thicker posterior cingulate cortex and a larger surface area in the caudal middle frontal cortex and temporal pole were associated with greater cognitive ability. Contrary, a thicker temporal pole was associated with lower cognitive ability.DISCUSSION: Stable effects of cognitive ability on brain morphology across the life course suggests that childhood is potentially an important window for intervention.</p