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Bipolar disorder (BD) is a major mental illness characterized by periods of (hypo) mania and depression with inter-episode remission periods. Functional studies in BD have consistently implicated a set of linked cortical and subcortical limbic regions in the pathophysiology of the disorder, also including the cerebellum. However, the cerebellar role in the neurobiology of BD still needs to be clarified. Seventeen euthymic patients with BD type1 (BD1) (mean age/SD, 38.64/13.48; M/F, 9/8) and 13 euthymic patients with BD type 2 (BD2) (mean age/SD, 41.42/14.38; M/F, 6/7) were compared with 37 sex- and age-matched healthy subjects (HS) (mean age/SD, 45.65/14.15; M/F, 15/22). T1 weighted and resting-state functional connectivity (FC) scans were acquired. The left and right dentate nucleus were used as seed regions for the seed based analysis. FC between each seed and the rest of the brain was compared between patients and HS. Correlations between altered cerebello-cerebral connectivity and clinical scores were then investigated. Different patterns of altered dentate-cerebral connectivity were found in BD1 and BD2. Overall, impaired dentate-cerebral connectivity involved regions of the anterior limbic network specifically related to the (hypo)manic states of BD. Cerebello-cerebral connectivity is altered in BD1 and BD2. Interestingly, the fact that these altered FC patterns persist during euthymia, supports the hypothesis that cerebello-cerebral FC changes reflect the neural correlate of subthreshold symptoms, as trait-based pathophysiology and/or compensatory mechanism to maintain a state of euthymia.

Increasing evidence from neuroimaging and clinical studies demonstrated cerebellar involvement in social cognition components, including the mentalizing process. The aim of this study was to apply transcranial direct current stimulation (tDCS) to modulate cerebellar excitability to investigate the role the cerebellum plays in mental state recognition. Forty-eight healthy subjects were randomly assigned to different groups in which anodal, cathodal, or sham tDCS (2 mA for 20 min) was delivered centring the electrode on the vermis to stimulate the posterior portion of the cerebellum. The ability to attribute mental states to others was tested before and after tDCS using a digital version of the 'Reading the Mind in the Eyes test', which includes visual perceptive and motor stimuli as control conditions. Correct response and reaction times (RT) were recorded. Results revealed a significant reduction in RTs between the baseline and post-stimulation sessions after the cerebellar anodal tDCS only for mental state stimuli, whereas no significant effect was found in the cathodal or sham conditions or for visual perceptive and motor stimuli. Overall, our study suggests that cerebellar anodal tDCS might selectively improve mental state recognition and constitute an effective strategy to positively modulate the mentalizing process.

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.

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.

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.

Several studies have demonstrated that the processing of visuospatial memory for locations in reaching space and in navigational space is supported by independent systems, and that the coding of visuospatial information depends on the modality of the presentation (i.e., sequential or simultaneous). However, these lines of evidence and the most common neuropsychological tests used by clinicians to investigate visuospatial memory have several limitations (e.g., they are unable to analyze all the subcomponents of this function and are not directly comparable). Therefore, we developed a new battery of tests that is able to investigate these subcomponents. We recruited 71 healthy subjects who underwent sequential and simultaneous navigational tests by using an innovative sensorized platform, as well as comparable paper tests to evaluate the same components in reaching space (Exp. 1). Consistent with the literature, the principal-component method of analysis used in this study demonstrated the presence of distinct memory for sequences in different portions of space, but no distinction was found for simultaneous presentation, suggesting that different modalities of eye gaze exploration are used when subjects have to perform different types of tasks. For this purpose, an infrared Tobii Eye-Tracking X50 system was used in both spatial conditions (Exp. 2), showing that a clear effect of the presentation modality was due to the specific strategy used by subjects to explore the stimuli in space. Given these findings, the neuropsychological battery established in the present study allows us to show basic differences in the normal coding of stimuli, which can explain the specific visuospatial deficits found in various neurological conditions.

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.

The traditional view on the cerebellum is that it controls motor behavior. Although recent work has revealed that the cerebellum supports also nonmotor functions such as cognition and affect, only during the last 5 years it has become evident that the cerebellum also plays an important social role. This role is evident in social cognition based on interpreting goal-directed actions through the movements of individuals (social "mirroring") which is very close to its original role in motor learning, as well as in social understanding of other individuals' mental state, such as their intentions, beliefs, past behaviors, future aspirations, and personality traits (social "mentalizing"). Most of this mentalizing role is supported by the posterior cerebellum (e.g., Crus I and II). The most dominant hypothesis is that the cerebellum assists in learning and understanding social action sequences, and so facilitates social cognition by supporting optimal predictions about imminent or future social interaction and cooperation. This consensus paper brings together experts from different fields to discuss recent efforts in understanding the role of the cerebellum in social cognition, and the understanding of social behaviors and mental states by others, its effect on clinical impairments such as cerebellar ataxia and autism spectrum disorder, and how the cerebellum can become a potential target for noninvasive brain stimulation as a therapeutic intervention. We report on the most recent empirical findings and techniques for understanding and manipulating cerebellar circuits in humans. Cerebellar circuitry appears now as a key structure to elucidate social interactions. Frank Van Overwalle, Elien Heleven, Qianying Ma, and Min Pu were supported by an SRP57 grant from the Vrije Universiteit Brussel, and Elien Heleven was additionally supported by an FWO G002319N/AL907 grant from the Flemish government. Zaira Cattaneo was supported by a Bando Ricerca Finalizzata (GR2016-02363640) by the Italian Ministry of Health. Marco Michelutti and Arseny A. Sokolov were supported by aMille E Una Lode fellowship from the University of Padua to MM, and fellowships from the Leenaards Foundation and the Swiss National Science Foundation, and a grant from the Helmut Horten Foundation to AAS. Catherine Stoodley and Laura C. Rice were supported by an NIH R15MH106957 grant. Van Overwalle, F (corresponding author), Vrije Univ Brussel, Dept Psychol, Pl Laan 2, B-1050 Brussels, Belgium; Vrije Univ Brussel, Ctr Neurosci, Pl Laan 2, B-1050 Brussels, Belgium. Frank.VanOverwalle@vub.ac.be; mmanto@ulb.ac.be; zaira.cattaneo@unimib.it; silvia.clausi@uniroma1.it; chiara.ferrari@unipv.it; gabrieli@mit.edu; xguellparadis@mgh.harvard.edu; Elien.Heleven@vub.be; m.lupo@hsantalucia.it; Qianying.Ma@vub.be; michelutti.marco.m@gmail.com; g.olivito@hsantalucia.it; Min.Pu@vub.be; laura.blevins@student.american.edu; jschmahmann@mgh.harvard.edu; libera.siciliano@uniroma1.it; Arseny.Sokolov@chuv.ch; stoodley@american.edu; kim.vandun@uhasselt.be; LVandervert@aol.com; maria.leggio@uniroma1.it

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.

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”.

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease involving the cerebellum and characterized by a typical motor syndrome. In addition, the presence of cognitive impairment is now widely acknowledged as a feature of SCA2. Given the extensive connections between the cerebellum and associative cerebral areas, it is reasonable to hypothesize that cerebellar neurodegeneration associated with SCA2 may impact on the cerebellar modulation of the cerebral cortex, thus resulting in functional impairment. The aim of the present study was to investigate and quantitatively map the pattern of cerebellar gray matter (GM) atrophy due to SCA2 neurodegeneration and to correlate that with patients' cognitive performances. Cerebellar GM maps were extracted and compared between SCA2 patients (n = 9) and controls (n = 33) by using voxel-based morphometry. Furthermore, the relationship between cerebellar GM atrophy and neuropsychological scores of the patients was assessed. Specific cerebellar GM regions were found to be affected in patients. Additionally, GM loss in cognitive posterior lobules (VI, Crus I, Crus II, VIIB, IX) correlated with visuospatial, verbal memory and executive tasks, while additional correlations with motor anterior (V) and posterior (VIIIA, VIIIB) lobules were found for the tasks engaging motor and planning components. Our results provide evidence that the SCA2 neurodegenerative process affects the cerebellar cortex and that MRI indices of atrophy in different cerebellar subregions may account for the specificity of cognitive symptomatology observed in patients, as result of a cerebello-cerebral dysregulation.

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 aetiology of autism spectrum disorder has been acknowledged. Neuroimaging studies have provided a strong support to this view, showing both structural and functional connectivity alterations to affect the cerebellum in autism spectrum disorder. According to the underconnectivity theory, disrupted connectivity within cerebello-cerebral networks has been specifically implicated in the aetiology of autism spectrum disorder. However, inconsistent results have been generated across studies. In this study, an integrated approach has been used in a selected population of adults with autism spectrum disorder to analyse both cerebellar morphometry and functional connectivity. In individuals with autism spectrum disorder, a decreased cerebellar grey matter volume affected the right Crus II, a region showing extensive connections with cerebral areas related to social functions. This grey matter reduction correlates with the degree of autistic traits as measured by autism-spectrum quotient. Interestingly, altered functional connectivity was found between the reduced cerebellar Crus II and contralateral cerebral regions, such as frontal and temporal areas. Overall, the present data suggest that adults with autism spectrum disorder present with specific cerebellar structural alterations that may affect functional connectivity within cerebello-cerebral modules relevant to social processing and account for core autistics traits.

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.\ud To this purpose, 11 SCA2 patients underwent an exhaustive attention battery that evaluated several attention sub-components. The SCA2 group performed below the normal range in tasks assessing selective attention, divided attention, and sustained attention, obtaining negative Z-scores. These results were confirmed by non-parametric Mann-Whitney U tests that showed significant differences between SCA2 and control subjects in the same sub-components of the attention battery, allowing us to speculate on cerebellar involvement when a high cognitive demand is required (i.e., multisensory integration, sequencing, prediction of events, and inhibition of inappropriate response behaviours).\ud The voxel-based morphometry analysis showed a pattern of significantly reduced grey matter volume in specific cerebellar lobules. In particular, the SCA2 patients showed significant grey matter loss in bilateral regions of the anterior cerebellar hemisphere (I-V) and in the posterior lobe (VI-IX) and posterior vermis (VI-IX). \ud Statistical analysis found significant correlations between grey matter reductions in the VIIb/VIIIa cerebellar lobules and impairments in Sustained and Divided Attention tasks and between grey matter reduction in the vermal VI lobule and impairment in the Go/NoGo task. \ud For the first time, the study demonstrated the involvement of specific cerebellar lobules in different sub-components of the attention domain, giving further support to the inclusion of the cerebellum within the attention network.

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.

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease involving the cerebellum. The particular atrophy pattern results in some typical clinical features mainly including motor deficits. In addition, the presence of cognitive impairments, involving language, visuospatial and executive functions, has been also shown in SCA2 patients and it is now widely accepted as a feature of the disease. The aim of the study is to investigate the microstructural patterns and the anatomo-functional substrate that could account for the cognitive symptomatology observed in SCA2 patients. In the present study, diffusion tensor imaging (DTI) based-tractography was performed to map the main cerebellar white matter (WM) bundles, such as Middle and Superior Cerebellar Peduncles, connecting cerebellum with higher order cerebral regions. Damage-related diffusivity measures were used to determine the pattern of pathological changes of cerebellar WM microstructure in patients affected by SCA2 and correlated with the patients' cognitive scores. Our results provide the first evidence that WM diffusivity is altered in the presence of the cerebellar cortical degeneration associated with SCA2 thus resulting in a cerebello-cerebral dysregulation that may account for the specificity of cognitive symptomatology observed in patients.

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease characterized by a progressive cerebellar syndrome, which can be isolated or associated with extracerebellar signs. It has been shown that patients affected by SCA2 present also cognitive impairments and psychiatric symptoms. The cerebellum is known to modulate cortical activity and to contribute to distinct functional networks related to higher-level functions beyond motor control. It is therefore conceivable that one or more networks, rather than isolated regions, may be dysfunctional in cerebellar degenerative diseases and that an abnormal connectivity within specific cerebello-cortical regions might explain the widespread deficits typically observed in patients. In the present study, the network-based statistics (NBS) approach was used to assess differences in functional connectivity between specific cerebellar and cerebral “nodes” in SCA2 patients. Altered inter-nodal connectivity was found between more posterior regions in the cerebellum and regions in the cerebral cortex clearly related to cognition and emotion. Furthermore, more anterior cerebellar lobules showed altered inter-nodal connectivity with motor and somatosensory cerebral regions. The present data suggest that in SCA2 a cerebellar dysfunction affects long-distance cerebral regions and that the clinical symptoms may be specifically related with connectivity changes between motor and non-motor cerebello-cortical nodes., Highlights • A cerebellar dysfunction affects long-distance cerebral regions in SCA2 patients. • Connectivity changes affect sensorimotor and cognitive cerebello-cortical nodes. • Cerebellar symptoms may be related to altered cerebello-cerebral connectivity.

Recent studies have implicated the cerebellum as part of a circuitry that is necessary to modulate higher order and behaviorally relevant information in emotional domains. However, little is known about the relationship between the cerebellum and emotional processing. This study examined cerebellar function specifically in the processing of negative emotions. Transcranial Doppler ultrasonography was performed to detect selective changes in middle cerebral artery flow velocity during emotional stimulation in patients affected by focal or degenerative cerebellar lesions and in matched healthy subjects. Changes in flow velocity during non-emotional (motor and cognitive tasks) and emotional (relaxing and negative stimuli) conditions were recorded. In the present study, we found that during negative emotional task, the hemodynamic pattern of the cerebellar patients was significantly different to that of controls. Indeed, whereas relaxing stimuli did not elicit an increase in mean flow velocity in any group, negative stimuli increased the mean flow velocity in the right compared with left middle cerebral artery only in the control group. The patterns by which mean flow velocity increased during the motor and cognitive tasks were similar within patients and controls. These findings support that the cerebellum is part of a network that gives meaning to external stimuli, and this particular involvement in processing negative emotional stimuli corroborates earlier phylogenetic hypotheses, for which the cerebellum is part of an older circuit in which negative emotions are crucial for survival and prepare the organism for rapid defense.

Studies from the past three decades have demonstrated that there is cerebellar involvement in the emotional domain. Emotional processing in humans requires both unconscious and conscious mechanisms. A significant amount of evidence indicates that the cerebellum is one of the cerebral structures that subserve emotional processing, although conflicting data has been reported on its function in unconscious and conscious mechanisms. This review discusses the available clinical, neuroimaging, and neurophysiological data on this issue. We also propose a model in which the cerebellum acts as a mediator between the internal state and external environment for the unconscious and conscious levels of emotional processing.

The cerebellar role in non-motor functions is supported by the clinical finding that lesions confined to cerebellum produce the cerebellar cognitive affective syndrome. Nevertheless, there is no consensus regarding the overall cerebellar contribution to cognition. Among other reasons, this deficiency might be attributed to the small sample sizes and narrow breadths of existing studies on lesions in cerebellar patients, which have focused primarily on a single cognitive domain. The aim of this study was to examine the expression of cerebellar cognitive affective syndrome with regard to lesion topography in a large group of subjects with cerebellar damage. We retrospectively analysed charts from patients in the Ataxia Lab of Santa Lucia Foundation between 1997 and 2007. Of 223 charts, 156 were included in the study, focusing on the importance of the cerebellum in cognition and the relevance of lesion topography in defining the cognitive domains that have been affected. Vascular topography and the involvement of deep cerebellar nuclei were the chief factors that determined the cognitive profile. Of the various cognitive domains, the ability to sequence was the most adversely affected in nearly all subjects, supporting the hypothesis that sequencing is a basic cerebellar operation.