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.

Irritability Is Associated With Decreased Cortical Surface Area and Anxiety With Decreased Gyrification During Brain Development.

Background: Brain development is of utmost importance for the emergence of psychiatric disorders, as the most severe of them arise before 25 years old. However, little is known regarding how early transdiagnostic symptoms, in a dimensional framework, are associated with cortical development. Anxiety and irritability are central vulnerability traits for subsequent mood and anxiety disorders. In this study, we investigate how these dimensions are related to structural changes in the brain to understand how they may increase the transition risk to full-blown disorders. Methods: We used the opportunity of an open access developmental cohort, the Healthy Brain Network, to investigate associations between cortical surface markers and irritability and anxiety scores as measured by parents and self-reports. Results: We found that in 658 young people (with a mean age of 11.6) the parental report of irritability is associated with decreased surface area in the bilateral rostral prefrontal cortex and the precuneus. Furthermore, parental reports of anxiety were associated with decreased local gyrification index in the anterior cingulate cortex and dorsomedial prefrontal cortex. Conclusions: These results are consistent with current models of emotion regulation network maturation, showing decreased surface area or gyrification index in regions associated with impaired affective control in mood and anxiety disorders. Our results highlight how dimensional traits may increase vulnerability for these disorders.

Cortical signatures in behaviorally clustered autistic traits subgroups: a population-based study.

Extensive heterogeneity in autism spectrum disorder (ASD) has hindered the characterization of consistent biomarkers, which has led to widespread negative results. Isolating homogenized subtypes could provide insight into underlying biological mechanisms and an overall better understanding of ASD. A total of 1093 participants from the population-based "Healthy Brain Network" cohort (Child Mind Institute in the New York City area, USA) were selected based on score availability in behaviors relevant to ASD, aged 6-18 and IQ >= 70. All participants underwent an unsupervised clustering analysis on behavioral dimensions to reveal subgroups with ASD traits, identified by the presence of social deficits. Analysis revealed three socially impaired ASD traits subgroups: (1) high in emotionally dysfunctional traits, (2) high in ADHD-like traits, and (3) high in anxiety and depressive symptoms. 527 subjects had good quality structural MRI T1 data. Site effects on cortical features were adjusted using the ComBat method. Neuroimaging analyses compared cortical thickness, gyrification, and surface area, and were controlled for age, gender, and IQ, and corrected for multiple comparisons. Structural neuroimaging analyses contrasting one combined heterogeneous ASD traits group against controls did not yield any significant differences. Unique cortical signatures, however, were observed within each of the three individual ASD traits subgroups versus controls. These observations provide evidence of ASD traits subtypes, and confirm the necessity of applying dimensional approaches to extract meaningful differences, thus reducing heterogeneity and paving the way to better understanding ASD traits.

Morphological brain changes associated with negative symptoms in patients with 22q11.2 Deletion Syndrome.

Approximately 30% of individuals with 22q11.2 Deletion Syndrome (22q11DS) develop schizophrenia during adolescence/early adulthood, making this syndrome a model for the disorder. Furthermore, negative symptoms exist in up to 80% of patients diagnosed with 22q11DS. The present study aims to uncover morphological brain alterations associated with negative symptoms in a cohort of patients with 22q11DS who are at-risk for developing schizophrenia. A total of 71 patients with 22q11DS aged 12 to 35 (54% females) with no past or present diagnosis of a schizophrenia were included in the study. Psychotic symptom scores were used to divide patients into subgroups by means of a cluster analysis. Three major subgroups were evident: patients with low negative and positive symptoms; patients with high negative symptoms and low positive symptoms; and patients with high negative and positive symptoms. Cortical volume, thickness and gyrification were compared between subgroups using FreeSurfer software. Results showed that patients with high negative symptoms, compared to those with low negative symptoms, have decreased gyrification in the medial occipito-temporal (MOT) and lateral temporo-parietal (LTP) cortices of the left hemisphere, and in the medial temporal (MT)/posterior cingulate (PCC) cortices of the right hemisphere. These findings suggest that high negative symptoms are associated with gyrification reductions predominantly in medial occipital and temporal regions, which are areas implicated in social cognition and early visual processing. Furthermore, as cortical folding develops in utero and during the first years of life, reduced gyrification may represent an early biomarker predicting the development of negative symptoms.