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International audience; During the past decades, converging evidence from clinical, neuroimaging and neuroanatomical studies has demonstrated the key role of the cerebellum in the processing of non-motor aspects of language. Although more is known about the way in which the cerebellum participates in the mechanisms involved in written language, there is ambiguous information on its role in other aspects of language, such as in non-motor aspects of spoken language. Thus, to contribute additional insight into this important issue, in the present work, we review several original scientific papers focusing on the most frequent non-motor spoken language impairments evidenced in patients affected by cerebellar pathology, namely, verbal working memory, grammar processing and verbal fluency impairments. Starting from the collected data, we provide a common interpretation of the spoken language disorders in cerebellar patients, suggesting that sequential processing could be the main mechanism by which the cerebellum participates in these abilities. Indeed, according to the cerebellar sequential theory, spoken language impairments could be due to altered cerebellar function to supervise, synchronize and coordinate the activity of different functional modules, affecting the correct optimization of linguistic processing.

Background Several studies have shown cerebellar abnormalities during depressive and manic states, although the specific cerebellar role in mood fluctuations remains poorly defined. Therefore, the study of pathologies characterized by frequent mood swings, such as bipolar disorder, is of great interest to investigate the relationship between the cerebellum and mood alterations. Methods A systematic literature search on the occurrence of mood disorders in patients with cerebellar pathologies (1st research strategy) and on the presence of cerebellar alterations in mood disorders (2nd research strategy) was conducted using the PubMed electronic Internet database. For this systematic review all information was written based on the PRISMA-P statement. Results The results of the 1st research strategy generated 9 articles, and in one of these, a direct correlation between cerebellar damage and the onset of mood disorder was reported. The 2nd research strategy generated 14 articles that were grouped according to the patient’s mood phase (manic or depressive) or diagnosis (bipolar I or bipolar II). Conclusions The present review suggests that the cerebellum should be considered a key structure involved in the regulation of mood.

The aim of this study was to compare the patterns of cerebellar alterations associated with bipolar disease with those induced by the presence of cerebellar neurodegenerative pathologies to clarify the potential cerebellar contribution to bipolar affective disturbance. Twenty-nine patients affected by bipolar disorder, 32 subjects affected by cerebellar neurodegenerative pathologies, and 37 age-matched healthy subjects underwent a 3T MRI protocol. A voxel-based morphometry analysis was used to show similarities and differences in cerebellar grey matter (GM) loss between the groups. We found a pattern of GM cerebellar alterations in both bipolar and cerebellar groups that involved the anterior and posterior cerebellar regions (p = 0.05). The direct comparison between bipolar and cerebellar patients demonstrated a significant difference in GM loss in cerebellar neurodegenerative patients in the bilateral anterior and posterior motor cerebellar regions, such as lobules I−IV, V, VI, VIIIa, VIIIb, IX, VIIb and vermis VI, while a pattern of overlapping GM loss was evident in right lobule V, right crus I and bilateral crus II. Our findings showed, for the first time, common and different alteration patterns of specific cerebellar lobules in bipolar and neurodegenerative cerebellar patients, which allowed us to hypothesize a cerebellar role in the cognitive and mood dysregulation symptoms that characterize bipolar disorder.

Clinical studies described emotional and social behaviour alterations in patients with cerebellar diseases, proposing a role of specific cerebello-cerebral circuits in social cognition. However, for a long time these difficulties were underestimated, and no studies have addressed the correlation between social cognition deficits and topography of the cerebellar damage. The present study aims to investigate the social cognition impairment and the neuroanatomical alterations in patients with spinocerebellar ataxia type 2 (SCA2) and to analyze their relationship. To this purpose a social cognition battery composed by three tests, and a MRI protocol were administered to 13 SCA2 patients and 26 healthy subjects. The pattern of gray matter (GM) atrophy was analyzed by voxel-based morphometry, and the GM volumes of each altered area were correlated with the behavioral scores to investigate anatomo-functional relationships. In addition, we investigated the relationship between social deficits and damage to the cerebellar peduncles using DTI diffusivity indices. Our patients showed impairment of the immediate perceptual component of the mental state recognition (i.e., to recognize feelings and thoughts from the eyes expression), and difficulties in anger attribution, and in the understanding of false or mistaken beliefs. They showed a pattern of GM reduction in cerebellar regions, including lobules IX and VIIIb and Crus II, all of which are involved in specific components of the mentalizing process. Interestingly, the behavioral performance, in which SCA2 patients showed impairments compared to controls, correlated with the degree of cerebellar GM reduction and with the presence of microstructural abnormalities in the cerebellar peduncles. The present study provides the first characterization of the social cognition deficits in a homogenous cohort SCA2 patients and demonstrates that alterations in specific cerebellar regions should represent the neurobiological underpinning of their social behavior difficulties. Our results offer a new point of view in considering these aspects in the clinical practice.

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. In the present study, the network-based statistics approach was used to assess functional connectivity (FC) differences within this mentalizing cerebello-cerebral network associated with a specific cerebellar damage. To this aim, patients affected by spinocerebellar ataxia type 2 (SCA2), a neurodegenerative disease specifically affecting regions of the cerebellar cortex, and age-matched healthy subjects have been enrolled. The dmPFC, left and right TPJ, the precuneus, and the cerebellar Crus II were used as regions of interest to construct the mentalizing network to be analyzed and evaluate pairwise functional relations between them. When compared with controls, SCA2 patients showed altered internodal connectivity between dmPFC, left (L-) and right (R-) TPJ, and right posterior cerebellar Crus II.The present results indicate that FC changes affect a function-specific mentalizing network in patients affected by cerebellar damage. In particular, they allow to better clarify functional alteration mechanisms driven by the cerebellar damage associated with SCA2 suggesting that selective cortico-cerebellar functional disconnections may underlie patients' social impairment in domain-specific complex and abstract forms of social functioning.

Human beings are continuously exposed to external and internal emotional stimuli which are processed to create adaptive social relations. Based on the nature of emotional phenomena and on the effort required for their elaboration, emotional processing could be viewed along a continuum, ranging from an implicit/unconscious level to an explicit/conscious level (Lane, 2000). The implicit processing of emotions is meant to be an automatic, procedural, and non-conceptual process that does not require conscious access to be executed. Instead, explicit processing requires declarative evaluation and involves higher cognitive resources to define conscious emotional states (Damasio, 1994; Lane, 2000). Within the extended neural network involved in the emotional field, the implicit processing of emotions has been linked to the amygdala and the anterior cingulated cortex (Critchley et al., 2005; Webb et al., 2010), while the temporoparietal junction and the medial prefrontal cortex have been reported to be mainly involved when the conscious attribution of emotions and intentions is required (Saxe and Kanwisher, 2003; Saxe and Powell, 2006). However, the neural networks underpinning these processes are still far from being well-defined (Schaller and Rauh, 2017). Over the years, many scientific studies have recognized the cerebellum as being part of these brain networks (Stoodley and Schmahmann, 2010; Baumann and Mattingley, 2012; Leggio and Olivito, 2018; Clausi et al., 2019a; Van Overwalle et al., 2019a) and have evidenced its role in affective and emotional functioning (Adamaszek et al., 2015; Clausi et al., 2015, 2019b; Lupo et al., 2015, 2018). Accordingly, functional and anatomical connections have been found between the cerebellum and the cortical and subcortical structures involved in both implicit and explicit emotional processing (Critchley et al., 2000; Singer et al., 2004; Schutter et al., 2009; Stoodley and Schmahmann, 2010; Schraa-Tam et al., 2012). The contribution of the cerebellum to implicit and explicit mechanisms underlying emotion processing has been recently acknowledged (Clausi et al., 2017). Indeed, the cerebellum is involved in implicit aspects such as the modulation of autonomic reactions, the automatic component of emotional learning associated, e.g., with fear conditioning (Critchley et al., 2000; Sacchetti et al., 2005; Timmann et al., 2010), and in the implicit processing of emotional facial expression (Schutter et al., 2009; Clausi et al., 2017). The cerebellar vermis might play a role in this stage of emotion elaboration through its connections with the brainstem (catecholamine neurons), the hypothalamus (Snider and Maiti, 1976), and the limbic areas, such as the amygdala and hippocampus (Sacchetti et al., 2005). Instead, regarding the explicit aspects, the cerebellum is involved in the self-perception of negative emotions and in the integration of internal state information with external environmental stimuli to consciously and adaptively elaborate emotions (Timmann et al., 2010; Clausi et al., 2017, 2019a). The posterior portions of the cerebellum might contribute to these aspects by means of their connections with cortical areas involved in more complex features of emotional evaluation (i.e., the medial prefrontal cortex and temporoparietal junction) (Rudebeck et al., 2008; Buckner et al., 2011). Evidence about the “emotional cerebellum” has also been conveyed by clinical studies. Indeed, a pattern of emotional and affective disorders has been found in patients with cerebellar damage as part of the well-known cerebellar cognitive affective syndrome (Schmahmann and Sherman, 1998; Tavano et al., 2007). Intriguingly, converging clinical and neuroimaging evidence points to a cerebellar involvement in the emotional disturbances and social cognition impairments described in people with autism spectrum disorders (ASD) (Fatemi et al., 2012; D'Mello and Stoodley, 2015). ASD are clinically complex and heterogeneous neurodevelopmental conditions characterized by core impairments in social interaction, repetitive behaviors, and restricted interests (American Psychiatric Association, 2013; Goldson, 2016). Emotional processing is a challenge for people with ASD, whose impairments have been reported for both implicit and explicit components (Senju, 2013; Lozier et al., 2014; Kana et al., 2016). Nevertheless, these aspects are often separately investigated, leading to controversial conclusions (Ben-Shalom et al., 2006). Indeed, while most of the literature on people with ASD agrees on the existence of implicit emotional processing impairment, i.e., when the task requires the elaboration of emotional facial expression (Baron-Cohen et al., 1997, 2001), controversial results emerge when the task requires the explicit elaboration of emotions. In the latest case, the heterogeneous nature of the ASD condition and camouflaging phenomena due to learned compensatory strategies might lead to the fallacious assumption that people with high-functioning ASD (hf-ASD) do not show such deficits (Senju, 2012; Schuwerk et al., 2014; Schaller and Rauh, 2017). For example, this could happen in tasks in which context information can help the person explicitly attribute emotions to others (Frith and Frith, 2012; Senju, 2012; Schaller and Rauh, 2017). However, it must be considered that when the amount of context information increases, the environment becomes more confusing, and the compensation ability may no longer guarantee the processing of emotional information (Frith and Frith, 2012). Indeed, when the complexity increases, the person has to integrate emotional processing with mentalizing ability to correctly infer emotional states (Mier et al., 2010). This complex social elaboration is impaired in people with hf-ASD when dynamic video-based stimuli close to everyday life are used or when various aspects of social situations are analyzed (Dziobek et al., 2006; Schaller and Rauh, 2011, 2017). Thus, the heterogeneity of capacities shown in a complex condition such as ASD, together with the variety of tasks used in different studies, may lead to controversial results. The complex behavioral outcome of people with ASD has been linked to the functional alteration of complex neural circuits encompassing several brain areas, such as the parietal, temporal, and frontal regions (Abell et al., 1999; Carper et al., 2002; Hazlett et al., 2006; Minshew and Williams, 2007), as well as subcortical structures (Sparks et al., 2002; Amaral et al., 2008; Cauda et al., 2011). Among these, the cerebellum has been consistently recognized as part of the distributed neural networks affected in people with ASD (Wang et al., 2014; D'Mello and Stoodley, 2015; Olivito et al., 2017; Stoodley et al., 2017). Indeed, evidence of structural and functional alterations in specific cerebellar regions and in cerebello-cortical networks underlying emotional processing has been reported in this population (Courchesne et al., 1988; Khan et al., 2015; Stoodley et al., 2017; Arnold Anteraper et al., 2019). In particular, a decrease in the Purkinje cell number in the cerebellar vermis and a gray matter reduction in the posterior cerebellum have been found in people with ASD (Ritvo et al., 1986; Bauman and Kemper, 2005; Fatemi et al., 2012), together with altered functional connectivity between the posterior cerebellum and the frontal and temporal areas involved in mentalizing abilities (Olivito et al., 2017). In this framework, considering the suggested connections between the cerebellum and the cortical and subcortical structures involved in implicit and explicit emotional processing (Schutter et al., 2009; Stoodley and Schmahmann, 2010; Clausi et al., 2017) and the association between the cerebellum and the social-emotional impairments in ASD (Wang et al., 2014; D'Mello and Stoodley, 2015), in the present opinion, we will provide some novel insights into the possible nature of implicit and explicit emotion processing deficits in ASD related to cerebellar-specific involvement. To this aim, we will take into account the most primitive ability to process facial emotions to analyze the implicit emotional process and the capacity to integrate intricate environmental information with the theory of mind abilities to explicitly infer complex emotional states.

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-graphene 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. In the present study, we analyzed the modality of non-linear writing in a patient affected by a focal cerebellar lesion, who presented with an alteration of the normal trend to write the order of the letters. Based on this evidence, we analyzed the functional connectivity between the cerebellum and the brain network that subtends handwriting and demonstrated how the cerebellar lesion of the patient affected the connections between the cerebellum and cortical areas that support the anatomical system of writing. This is the first report of non-linear spelling in a patient with a lesion outside the fronto-parietal network, specifically with a focal cerebellar lesion. We propose that non-linear writing can be interpreted in view of the role of the cerebellum in timing and sequential processing. Thus, considering the current functional connectivity data, we hypothesize that the cerebellum might be relevant in the mechanism that allows the correct activation timing of letters within a string and placement of the letters in a specific sequential writing order.

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. It has been hypothesized that the typical cerebellar role in adaptive control and predictive coding could also be extended to social behavior. The present study aimed to investigate the social cognition abilities of patients with degenerative cerebellar atrophy to understand whether the cerebellum acts in specific ToM components playing a role as predictive structure. To this aim, an ad hoc social cognition battery was administered to 27 patients with degenerative cerebellar pathology and 27 healthy controls. In addition, 3D T1-weighted and resting-state fMRI scans were collected to characterize the structural and functional changes in cerebello-cortical loops. The results evidenced that the patients were impaired in lower-level processes of immediate perception as well as in the more complex conceptual level of mentalization. Furthermore, they presented a pattern of GM reduction in cerebellar portions that are involved in the social domain such as crus I-II, lobule IX and lobule VIIIa. These areas showed decreased functional connectivity with projection cerebral areas involved in specific aspects of social cognition. These findings boost the idea that the cerebellar modulatory function on the cortical projection areas subtends the social cognition process at different levels. Particularly, regarding the lower-level processes, the cerebellum may act by implicitly matching the external information (i.e., expression of the eyes) with the respective internal representation to guarantee an immediate judgment about the mental state of others. Otherwise, at a more complex conceptual level, the cerebellum seems to be involved in the construction of internal models of mental processes during social interactions in which the prediction of sequential events plays a role, allowing us to anticipate the other person's behavior.

Background Although depressive symptoms are often reported to be comorbid with degenerative cerebellar diseases, the role of the cerebellum in depressive disorder needs to be elucidated. To address this aim, we investigated self-perception of the negative mood state in patients with cerebellar pathology and depressive symptoms. Methods Thirty-eight patients with cerebellar damage (10 with depressive symptoms – CB-DP and 28 with no depressive symptoms – CB-nDP), 11 subjects with depressive disorders without cerebellar damage (DP) and 29 healthy controls (CTs) were enrolled. A device for self-monitoring of the mood state (MoMo) and validated scales such as the Profile of Mood States questionnaire (POMS), the Self-Report Symptom Inventory-Revised (SCL-90-R) and the Hamilton Depression Rating Scale (HDRS) were used to evaluate depressive symptoms. Results Both CB-DP and DP patients showed higher scores than CTs on the POMS and SCL-90-R for depressive factors and on the HDRS. DP patients showed a lower frequency of ‘good’ mood and a higher frequency of ‘bad’ mood than CTs when using the MoMo device. However, although the two depressed populations showed comparable scores on these validated scales, CB-DP patients showed impaired self-awareness of the mood experience in ‘the here and now’, as evidenced by the absence of significant differences, compared with CTs, in the subjective mood evaluation performed with the MoMo device. Limitations The number of CB patients and inhomogeneity across MRI scans were study limitations. Conclusion Cerebellar dysfunction might slow the data integration necessary for mood state awareness, resulting in difficulty of depressed CB patients in explicitly recognizing their mood “in the here and now”.

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. Specifically, a pattern of hypo-connectivity was found between the cerebellum and cerebral regions known to be implicated in emotion modulation and social interaction. Conversely, a pattern of hyper-connectivity was found between the cerebellum and posterior cerebral cortical regions that are involved in sensorimotor functions. The present study represents the first evidence that dysregulation of cerebral networks consequent to a cerebellar lesion is at the root of bipolar disorder, at least the manic state, and provides a new framework for interpreting cerebellar modulation in the regulation of mood in specific psychiatric conditions.

Cerebellar dysfunction plays a critical role in neurodevelopmental disorders with long-term behavioral and neuropsychiatric symptoms. A 43-year-old woman with a cerebellum arteriovenous malformation and history of behavioral dysregulation since childhood is described. After the rupture of the cerebellar malformation in adulthood, her behavior morphed into specific psychiatric symptoms and cognitive deficits occurred. The neuropsychological assessment evidenced impaired performance in attention, visuospatial, memory, and language domains. Moreover, psychiatric assessment indicated a borderline personality disorder. Brain MRI examination detected macroscopic abnormalities in the cerebellar posterior lobules VI, VIIa (Crus I), and IX, and in the posterior area of the vermis, regions usually involved in cognitive and emotional processing. The described patient suffered from cognitive and behavioral symptoms that are part of the cerebellar cognitive affective syndrome. This case supports the hypothesis of a cerebellar role in personality disorders emphasizing the importance of also examining the cerebellum in the presence of behavioral disturbances in children and adults.