Ricerc@Sapienza

Autism Spectrum disorder is a neurodevelopmental disorder characterized by core deficits in social functioning. Core autistics traits refer to poor social and imagination skills, poor attention-switching/strong focus of attention, exceptional attention to detail, as expressed by the Autism-Spectrum Quotient. Over the years, the importance of the cerebellum in the etiology of Autism Spectrum Disorder has been acknowledged.

We described the cerebello-cerebral functional connectivity in a subject who developed a manic state after a cerebellar lesion. Whole brain investigation, performed by means of an advanced MRI examination, evidenced an isolated lesion involving the left lobules VI, VIIa (crus I), and IX and the posterior area of the vermis. The cerebello-cerebral functional connectivity analysis detected a pattern of altered connectivity in specific areas of the prefrontal-striatal-thalamic circuits that are typically altered in bipolar subjects during the manic state.

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease characterized by a progressive cerebellar syndrome and multiple-domain cognitive impairments. The cerebellum is known to contribute to distinct functional networks related to higher-level functions. The aims of the present study were to investigate the different sub-components of attention and to analyse possible correlations between attention deficits and specific cerebellar regions in SCA2 patients.

In the last few decades, there have been an increasing number of studies focusing on better characterizing the cerebellar functions beyond motor control, including emotional and social domains. Anatomical and functional evidence strongly contributes to delineating the cerebellar functional subdivisions and their integration with cerebral functional networks strictly related to emotional regulation and social functioning, thus suggesting a model of cerebellar organization that resembles that of the cerebral cortex.

Objectives Cerebellar dysfunction plays a critical role in neurodevelopmental disorders with long-term behavior and neuropsychiatric symptoms. Case A 43-year-old woman with a cerebellum arteriovenous malformation and history of behavioral dysregulation since childhood is described. After the ruptured of the cerebellar malformation in adulthood, her behavior morphed into specific psychiatric symptoms and cognitive deficits occurred. Results The neuropsychological assessment evidenced impaired performances in attention, visuospatial, memory, and language domains.

The most common deficits in processing written language result from damage to the graphemic buffer system and refer to semantic and lexical problems or difficulties in phoneme-grapheme conversion. However, a writing disorder that has not yet been studied in depth is the non-linear spelling phenomenon. Indeed, although some cases have been described, no report has exhaustively explained the cognitive mechanism and the anatomical substrates underlying this process.

Recent studies have focused on the role of the cerebellum in the social domain, including in Theory of Mind (ToM). ToM, or the "mentalizing" process, is the ability to attribute mental states, such as emotion, intentions and beliefs, to others to explain and predict their behavior. It is a fundamental aspect of social cognition and crucial for social interactions, together with more automatic mechanisms, such as emotion contagion. Social cognition requires complex interactions between limbic, associative areas and subcortical structures, including the cerebellum.

Spastic paraplegia type 7 (SPG7), which represents one of the most common forms of autosomal recessive spastic paraplegia (MIM#607259), often manifests with a complicated phenotype, characterized by progressive spastic ataxia with evidence of cerebellar atrophy on brain MRI. Recent studies have documented the presence of peculiar dentate nucleus hyperintensities on T2-weighted images and frontal executive dysfunction in neuropsychological tests in SPG7 patients.

Alzheimer Disease (AD) is a chronic neurodegenerative disorder characterized by specific patterns of grey and white matter damage and cognitive/behavioral manifestations. The cerebellum has also been implicated in the pathophysiology of AD. Since the cerebellum is known to have strong functional connectivity (FC) with associative cerebral cortex regions, it is possible to hypothesize that it is incorporated into intrinsic FC networks relevant to cognitive manifestation of Alzheimer disease.

In recent years, increasing evidence of the cerebellar role in social cognition has emerged. The cerebellum has been shown to modulate cortical activity of social brain regions serving as a regulator of function-specific mentalizing and mirroring processes. In particular, a mentalizing area in the posterior cerebellum, specifically Crus II, is preferentially recruited for more complex and abstract forms of social processing, together with mentalizing cerebral areas including the dorsal medial prefrontal cortex (dmPFC), the temporo-parietal junction (TPJ), and the precuneus.