The cerebellum is linked to theory of mind alterations in autism. A direct clinical and MRI comparison between individuals with autism and cerebellar neurodegenerative pathologies

Abstract

In recent years, structural and functional alterations in the cerebellum have been reported in autism spectrum disorder (ASD). Intriguingly, recent studies demonstrated that the social behavioral profile of individuals with cerebellar pathologies is characterized by a theory of mind (ToM) impairment, one of the main behavioral hallmarks of ASD. The aim of the present study was to compare ToM abilities and underlying cerebello-cortical structural patterns between ASD individuals and individuals with cerebellar atrophy to further specify the cerebellar role in mentalizing alterations in ASD. Twenty-one adults with ASD without language and intellectual impairments (based on DSM-5), 36 individuals affected by degenerative cerebellar damage (CB), and 67 healthy participants were enrolled in the study. ToM abilities were assessed using the reading the mind in the eyes test and the faux pas test. One-way ANCOVA was conducted to compare the performances between the two cohorts. Three-dimensional T1-weighted magnetic resonance scans were collected, and a voxel-based morphometry analysis was performed to characterize the brain structural alterations in the two cohorts. ASD and CB participants had comparable ToM performance with similar difficulties in both the tests. CB and ASD participants showed an overlapping pattern of gray matter (GM) reduction in a specific cerebellar portion (Crus-II). Our study provides the first direct comparison of ToM abilities between ASD and CB individuals, boosting the idea that specific cerebellar structural alterations impact the mentalizing process. The present findings open a new perspective for considering the cerebellum as a potential target for treatment implementation. The present work will critically advance current knowledge about the cerebellar role in ToM alterations of ASD, in particular, elucidating the presence of common cerebellar structural abnormalities in ASD and cerebellar individuals that may underlie specific mentalizing alterations. These findings may pave the way for alternative therapeutic indications, such as cerebellar neuromodulation, with a strong clinical impact. LAY SUMMARY: The present work will critically advance current knowledge about the cerebellar role in theory of mind alterations of autism spectrum disorder (ASD), in particular, elucidating the presence of common cerebellar structural abnormalities in ASD and cerebellar individuals that may underlie specific mentalizing alterations. These findings may pave the way for alternative therapeutic indications, such as cerebellar neuromodulation, with a strong clinical impact.

Keywords: cerebellar degenerative disease; cerebellar structural changes; mentalizing; neurodevelopmental disorder; voxel-based morphometry.

FIGURE 1

Theory of mind assessment in individuals with degenerative cerebellar damage and individuals with autism Spectrum disorders. (a) RME test. Data are presented as the percentage of the total number of correct responses (max = 36). (b) Faux pas test. Data are presented as the percentage of the total number of correct responses for the faux‐pas stories (max = 60) and no‐faux pas stories (max = 20), for the affective component (max = 10) and the cognitive component (max = 50). Mean and SD of the accuracy percentage, where 0% is totally wrong and 100% is totally correct, are reported for each group; *p < 0.05. RME, Reading the Mind in the Eyes test

FIGURE 2

Between‐group voxel‐based comparison of cerebellar GM volumes. Cerebellar regions showing patterns of significantly reduced GM in individuals with degenerative cerebellar damage (a) and individuals with autism Spectrum disorders (b) compared to healthy participants are reported and superimposed on the spatially unbiased infratentorial template (SUIT) (Diedrichsen et al., 2009) in coronal (y), axial (z), and sagittal (x) slices. The results are significant at p‐values <0.05 after FWE cluster‐level correction. Regions of overlapping cerebellar GM loss (c) between individuals with degenerative cerebellar damage (in blue) and individuals with autism spectrum disorders (in red) are reported in violet. Right = right and left = left. GM, gray matter

FIGURE 3

Between‐group voxel‐based comparison of cerebral GM volumes. Cerebral regions showing significantly reduced GM in individuals with degenerative cerebellar damage compared to healthy participants are reported in coronal (y = 83), sagittal (x = 42), and axial (z = 26) slices in Montreal neurological institute space. The results are significant at p‐values <0.05 after FWE cluster‐level correction. Right = right and left = left. GM, gray matter