The Cerebellum and Cognitive Function: Anatomical Evidence from a Transdiagnostic Sample.

Multiple lines of evidence across human functional, lesion, and animal data point to a cerebellar role, in particular of crus I, crus II, and lobule VIIB, in cognitive function. However, a mapping of distinct facets of cognitive function to cerebellar structure is missing. We analyzed structural neuroimaging data from the Healthy Brain Network (HBN). Cerebellar parcellation was performed with a validated automated segmentation pipeline (CERES) and stringent visual quality check (n = 662 subjects retained from initial n = 1452). Canonical correlation analyses (CCA) examined regional gray matter volumetric (GMV) differences in association to cognitive function (quantified with NIH Toolbox Cognition domain, NIH-TB), accounting for psychopathology severity, age, sex, scan location, and intracranial volume. Multivariate CCA uncovered a significant correlation between two components entailing a latent cognitive canonical (NIH-TB subscales) and a brain canonical variate (cerebellar GMV and intracranial volume, ICV), surviving bootstrapping and permutation procedures. The components correspond to partly shared cerebellar-cognitive function relationship with a first map encompassing cognitive flexibility (r = 0.89), speed of processing (r = 0.65), and working memory (r = 0.52) associated with regional GMV in crus II (r = 0.57) and lobule X (r = 0.59) and a second map including the crus I (r = 0.49) and lobule VI (r = 0.49) associated with working memory (r = 0.51). We show evidence for a structural subspecialization of the cerebellum topography for cognitive function in a transdiagnostic sample.

Understanding the relationship between cerebellar structure and social abilities.

BACKGROUND: The cerebellum contains more than 50% of all neurons in the brain and is involved in a broad range of cognitive functions, including social communication and social cognition. Inconsistent atypicalities in the cerebellum have been reported in individuals with autism compared to controls suggesting the limits of categorical case control comparisons. Alternatively, investigating how clinical dimensions are related to neuroanatomical features, in line with the Research Domain Criteria approach, might be more relevant. We hypothesized that the volume of the "cognitive" lobules of the cerebellum would be associated with social difficulties. METHODS: We analyzed structural MRI data from a large pediatric and transdiagnostic sample (Healthy Brain Network). We performed cerebellar parcellation with a well-validated automated segmentation pipeline (CERES). We studied how social communication abilities-assessed with the social component of the Social Responsiveness Scale (SRS)-were associated with the cerebellar structure, using linear mixed models and canonical correlation analysis. RESULTS: In 850 children and teenagers (mean age 10.8 ± 3 years; range 5-18 years), we found a significant association between the cerebellum, IQ and social communication performance in our canonical correlation model. LIMITATIONS: Cerebellar parcellation relies on anatomical boundaries, which does not overlap with functional anatomy. The SRS was originally designed to identify social impairments associated with autism spectrum disorders. CONCLUSION: Our results unravel a complex relationship between cerebellar structure, social performance and IQ and provide support for the involvement of the cerebellum in social and cognitive processes.

Electroencephalography microstates imbalance across the spectrum of early psychosis, autism, and mood disorders.

BACKGROUND: Electroencephalography (EEG) microstates translate resting-state temporal dynamics of neuronal networks throughout the brain and could constitute possible markers of psychiatric disorders. We tested the hypothesis of an increased imbalance between a predominant self-referential mode (microstate C) and a decreased attentional mode (microstate D) in psychosis, mood, and autism spectrum disorders. METHODS: We retrospectively included 135 subjects from an early psychosis outpatient unit, with available eyes-closed resting-state 19 electrodes EEG. Individual-level then group-level modified K-means clustering in controls provided four microstate maps that were then backfitted to all groups. Differences between microstate parameters (occurrence, coverage, and mean duration) were computed between controls and each group, and between disease groups. RESULTS: Microstate class D parameters were systematically decreased in disease groups compared with controls, with an effect size increasing along the psychosis spectrum, but also in autism. There was no difference in class C. C/D ratios of mean duration were increased only in SCZ compared with controls. CONCLUSIONS: The decrease in microstate class D may be a marker of stage of psychosis, but it is not specific to it and may rather reflect a shared dimension along the schizophrenia-autism spectrum. C/D microstate imbalance may be more specific to schizophrenia.

Cerebellar Atypicalities in Autism?

BACKGROUND: The cerebellum contains more than 50% of the brain's neurons and is involved in social cognition. Cerebellar anatomical atypicalities have repeatedly been reported in individuals with autism. However, studies have yielded inconsistent findings, likely because of a lack of statistical power, and did not capture the clinical and neuroanatomical diversity of autism. Our aim was to better understand cerebellar anatomy and its diversity in autism. METHODS: We studied cerebellar gray matter morphology in 274 individuals with autism and 219 control subjects of a multicenter European cohort, EU-AIMS LEAP (European Autism Interventions-A Multicentre Study for Developing New Medications; Longitudinal European Autism Project). To ensure the robustness of our results, we conducted lobular parcellation of the cerebellum with 2 different pipelines in addition to voxel-based morphometry. We performed statistical analyses with linear, multivariate (including normative modeling), and meta-analytic approaches to capture the diversity of cerebellar anatomy in individuals with autism and control subjects. Finally, we performed a dimensional analysis of cerebellar anatomy in an independent cohort of 352 individuals with autism-related symptoms. RESULTS: We did not find any significant difference in the cerebellum when comparing individuals with autism and control subjects using linear models. In addition, there were no significant deviations in our normative models in the cerebellum in individuals with autism. Finally, we found no evidence of cerebellar atypicalities related to age, IQ, sex, or social functioning in individuals with autism. CONCLUSIONS: Despite positive results published in the last decade from relatively small samples, our results suggest that there is no striking difference in cerebellar anatomy of individuals with autism.

Direct medical cost of bipolar disorder: Insights from the FACE-BD longitudinal cohort.

BACKGROUND: Bipolar disorder (BD) is a severe chronic psychiatric disorder affecting 0.5 to 1% of the population worldwide. To date, most studies have estimated the cost of BD via information sourced from insurance claims with limited information on clinical characteristics and course of BD. The aims of this study are (i) to estimate the direct healthcare cost associated with BD and to identify contributing factors and (ii) to study the evolution of cost during a two-year follow-up period. METHOD: We analyzed a sample of 1116 individuals with BD included in the Advanced Centers of Expertise in Bipolar Disorder cohort. We estimated the direct healthcare cost per year and per patient, and we identified the clinical features of patients with BD associated with higher direct healthcare costs. In a subsample of patients followed up for two years centers of expertise for BD, we studied the evolution of direct healthcare cost. RESULTS: The average cost of bipolar disorder was € 6910 per year and per patient. Clinical features of BD, sociodemographic characteristics, and associated addiction were associated with higher direct healthcare costs. In the subsample of patients followed-up for two years, direct healthcare cost dropped by more than 50%, strongly suggesting the beneficial effect of specialized care organization. LIMITATION: We did not estimate indirect healthcare and intangible costs. CONCLUSION: Our study investigates the cost of BD and its evolution in a deeply phenotyped longitudinal sample. Cost-utility and cost-effectiveness analyses are required to inform resource allocation decisions and to promote innovative healthcare organizations.