The cerebellum and cognitive function: anatomical evidence from a transdiagnostic sample

Abstract

Introduction: The cerebellum, most known for its role in motor control, exerts a key role in cognition. Multiple lines of evidence across human functional, lesion and animal data point to a role of the cerebellum, in particular of Crus I, Crus II and Lobule VIIB, in cognitive function. However, whether cerebellar substrates pertaining to distinct facets of cognitive function exist is not known. Methods: We analyzed structural neuroimaging data from the Healthy Brain Network (HBN). Cerebellar parcellation was performed via a standard validated automated segmentation pipeline (CERES) with stringent visual quality check (n = 662 subjects retained from initial n = 1452). We used data-driven canonical correlation analyses (CCA) to examine regional gray matter volumetric (GMV) differences in association to cognitive function assessed with the NIH Toolbox Cognition Domain (NIH-TB). Our multivariate analyses accounted for psychopathology severity, age, sex, scan location and intracranial volume. Results: Multivariate CCA uncovered a significant correlation between two components entailing a latent cognitive canonical variate composed of NIH-TB subscales and the brain canonical variate (cerebellar regions GMV and intracranial volume, ICV). A bootstrapping and a permutation procedure ensured the results are statistically significant and the CCA model, stable. The identified components correspond to only partly shared cerebellar - cognitive function relationship with a first map encompassing cognitive flexibility (r=0.89) and speed of processing (r=0.65) associated with regional gray matter volume 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 cognitive control (r=-0.51). Working memory associations were similarly present in both these maps (Crus II, Lobule X, Crus I and Lobule VI) for the first (r=0.52) and second (r=0.51) component. Discussion: Our results show evidence in favor of structural sub-specialization in the cerebellum, independently of psychopathology contributions to cognitive function and brain structure. Overall, these findings highlight a prominent role for the human cerebellum in cognitive function for flexible and stable adaptive behavior.

Cognitive Impairment Is Part of the Phenotype of Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome (CANVAS)

“…Speed of processing was negatively correlated to cerebellar manifestations' severity, which is consistent with the role of the cerebellum in this ability. 13 Approximately one third of the patients exhibited episodic memory deficits, mainly resulting from impaired executive control of memory, which is consistent with the initial description of the CCAS 11 and usually observed in frontostriatal dysfunction. 14 However, three patients exhibited a different pattern with significant storage deficits, suggesting damage or dysfunction of the hippocampus or temporal cortex.…”

“…Results from the comprehensive neuropsychological test battery confirm that attention/working memory and executive function were the most affected domains. Speed of processing was negatively correlated to cerebellar manifestations' severity, which is consistent with the role of the cerebellum in this ability 13 . Approximately one third of the patients exhibited episodic memory deficits, mainly resulting from impaired executive control of memory, which is consistent with the initial description of the CCAS 11 and usually observed in frontostriatal dysfunction 14 .…”

New clues for the role of cerebellum in schizophrenia and the associated cognitive impairment

“…Bègue and co-workers used canonical correlation analyses to link cerebellar grey matter volume to cognitive functioning. They proposed two maps: one associated with cognitive flexibility, processing speed and working memory (Crus II and Lobule X) and the other with working memory (Crus I and Lobule VI), both linked also to working memory (Bègue et al, 2023). While cerebellar volume reduction is the 10.3389/fncel.…”

Cerebellum in Alzheimer's disease and other neurodegenerative diseases: an emerging research frontier

“…of studies have demonstrated that nearly the entire cerebellum is involved in cognitive function (Figure 1). [26][27][28][29][30][31][32] Cerebellar activation is associated with various tasks, including those related to working memory, learning, attention, and executive control. 9,33 In particular, Crus I and Crus II contribute to parallel cortico-cerebellar circuits that regulate executive control, salience detection, and scene memory/self-reflection.…”