Publications by authors named "Giusy Olivito"

21 Publications

  • Page 1 of 1

Comparison of Cerebellar Grey Matter Alterations in Bipolar and Cerebellar Patients: Evidence from Voxel-Based Analysis.

Int J Mol Sci 2021 Mar 29;22(7). Epub 2021 Mar 29.

Ataxia Laboratory, Fondazione Santa Lucia IRCCS, 00179 Rome, Italy.

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 ( = 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.
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http://dx.doi.org/10.3390/ijms22073511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036397PMC
March 2021

The neurobiological underpinning of the social cognition impairments in patients with spinocerebellar ataxia type 2.

Cortex 2021 Feb 13;138:101-112. Epub 2021 Feb 13.

Department of Psychology, Sapienza University, Rome, Italy; Ataxia Laboratory, Fondazione Santa Lucia IRCCS, Rome, Italy.

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.
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http://dx.doi.org/10.1016/j.cortex.2020.12.027DOI Listing
February 2021

Consensus Paper: Cerebellum and Social Cognition.

Cerebellum 2020 Dec;19(6):833-868

Ataxia Laboratory, IRCCS Fondazione Santa Lucia, 00179, Rome, Italy.

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.
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http://dx.doi.org/10.1007/s12311-020-01155-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588399PMC
December 2020

Cerebello-Cortical Alterations Linked to Cognitive and Social Problems in Patients With Spastic Paraplegia Type 7: A Preliminary Study.

Front Neurol 2020 25;11:82. Epub 2020 Feb 25.

Ataxia Laboratory, IRCCS Fondazione Santa Lucia, Rome, Italy.

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. Therefore, we decided to assess whether any particular MRI pattern might be specifically associated with SPG7 mutations and possibly correlated with patients' cognitive profiles. For this purpose, we evaluated six SPG7 patients, studying the cerebello-cortical network by MRI voxel-based morphometry and functional connectivity techniques, compared to 30 healthy control subjects. In parallel, we investigated the cognitive and social functioning of the SPG7 patients. Our results document specific cognitive alterations in language, verbal memory, and executive function in addition to an impairment of social task and emotional functions. The MRI scans showed a diffuse symmetric reduction in the cerebellar gray matter of the right lobule V, right Crus I, and bilateral lobule VI, together with a cerebral gray matter reduction in the lingual gyrus, precuneus, thalamus, and superior frontal gyrus. The evidence of an over-connectivity pattern between both the right and left cerebellar dentate nuclei and specific cerebral regions (the lateral occipital cortex, precuneus, left supramarginal gyrus, and left superior parietal lobule) confirms the presence of cerebello-cortical dysregulation in different networks involved in cognition and social functioning in SPG7 patients.
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http://dx.doi.org/10.3389/fneur.2020.00082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053515PMC
February 2020

Cerebellar dentate nucleus functional connectivity with cerebral cortex in Alzheimer's disease and memory: a seed-based approach.

Neurobiol Aging 2020 05 15;89:32-40. Epub 2020 Jan 15.

Neuroimaging Laboratory, Fondazione Santa Lucia-IRCCS, Rome, Italy; Clinical Imaging Sciences Center, Brighton and Sussex Medical School, Brighton, UK.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by specific patterns of gray and white matter damage and cognitive/behavioral manifestations. The cerebellum has also been implicated in the pathophysiology of AD. Because 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 AD. In the present study, the cerebellar dentate nucleus, the largest cerebellar nucleus and the major output channel to the cerebral cortex, was chosen as the region of interest to test potential cerebellocerebral FC alterations and correlations with patients' memory impairment in a group of patients with AD. Compared to controls, patients with AD showed an increase in FC between the dentate nucleus and regions of the lateral temporal lobe. This study demonstrates that lower memory performances in AD may be related to altered FC within specific cerebellocortical functional modules, thus suggesting the cerebellar contribution to AD pathophysiology and typical memory dysfunctions.
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http://dx.doi.org/10.1016/j.neurobiolaging.2019.10.026DOI Listing
May 2020

Cerebellar White Matter Disruption in Alzheimer's Disease Patients: A Diffusion Tensor Imaging Study.

J Alzheimers Dis 2020 ;74(2):615-624

Neuroimaging Laboratory, Fondazione Santa Lucia, IRCCS, Rome, Italy.

The cognitive role of the cerebellum has recently gained much attention, and its pivotal role in Alzheimer's disease (AD) has now been widely recognized. Diffusion tensor imaging (DTI) has been used to evaluate the disruption of the microstructural milieu in AD, and though several white matter (WM) tracts such as corpus callosum, inferior and superior longitudinal fasciculus, cingulum, fornix, and uncinate fasciculus have been evaluated in AD, data on cerebellar WM tracts are currently lacking. We performed a tractography-based DTI reconstruction of the middle cerebellar peduncle (MCP), and the left and right superior cerebellar peduncles separately (SCPL and SCPR) and addressed the differences in fractional anisotropy (FA), axial diffusivity (Dax), radial diffusivity (RD), and mean diffusivity (MD) in the three tracts between 50 patients with AD and 25 healthy subjects. We found that AD patients showed a lower FA and a higher RD compared to healthy subjects in MCP, SCPL, and SCPR. Moreover, higher MD was found in SCPR and SCPL and higher Dax in SCPL. This result is important as it challenges the traditional view that WM bundles in the cerebellum are unaffected in AD and might identify new targets for therapeutic interventions.
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http://dx.doi.org/10.3233/JAD-191125DOI Listing
January 2020

Functional Changes of Mentalizing Network in SCA2 Patients: Novel Insights into Understanding the Social Cerebellum.

Cerebellum 2020 Apr;19(2):235-242

Department of Psychology, Sapienza University of Rome, Via De Marsi, 78, 00185, Rome, Italy.

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.
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http://dx.doi.org/10.1007/s12311-019-01081-xDOI Listing
April 2020

Non-linear spelling in writing after a pure cerebellar lesion.

Neuropsychologia 2019 09 11;132:107143. Epub 2019 Jul 11.

Ataxia Laboratory, IRCCS Fondazione Santa Lucia, Rome, Italy; Department of Psychology, Sapienza University of Rome, Rome, Italy.

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.
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http://dx.doi.org/10.1016/j.neuropsychologia.2019.107143DOI Listing
September 2019

The Cerebellar Predictions for Social Interactions: Theory of Mind Abilities in Patients With Degenerative Cerebellar Atrophy.

Front Cell Neurosci 2018 8;12:510. Epub 2019 Jan 8.

Ataxia Laboratory, IRCCS Fondazione Santa Lucia, Rome, Italy.

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 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.
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http://dx.doi.org/10.3389/fncel.2018.00510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332472PMC
January 2019

Patterns of Cerebellar Gray Matter Atrophy Across Alzheimer's Disease Progression.

Front Cell Neurosci 2018 20;12:430. Epub 2018 Nov 20.

Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.

The role of the cerebellum in cognitive function has been broadly investigated in the last decades from an anatomical, clinical, and functional point of view and new evidence points toward a significant contribution of the posterior lobes of the cerebellum in cognition in Alzheimer's disease (AD). In the present work we used SUIT-VBM (spatially unbiased infratentorial template, voxel-based morphometry) to perform an analysis of the pattern of cerebellar gray matter (GM) atrophy in amnestic mild cognitive impairment (a-MCI) and AD dementia patients compared to healthy subjects (HS), in order to follow the changes of non-motor features of cerebellar degeneration throughout disease progression. This template has been validated to guarantee a significant improvement in voxel-to-voxel alignment of the individual fissures and the deep cerebellar nuclei compared to Montreal Neurological Institute (MNI) whole-brain template. Our analysis shows a progression of cerebellar GM volume changes throughout a continuous spectrum from early to late clinical stages of AD. In particular vermis and paravermian areas of the anterior (I-V) and posterior (VI) lobes are involved since the a-MCI stage, with a later involvement of the hemispheric part of the posterior lobes (VI lobule) and Crus I in AD dementia patients only. These findings support the role of the cerebellum in higher-level functions, and whilst confirming previous data on the involvement of Crus I in AD dementia, provide new evidence of an involvement of the vermis in the early stages of the disease.
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http://dx.doi.org/10.3389/fncel.2018.00430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255820PMC
November 2018

Depression disorder in patients with cerebellar damage: Awareness of the mood state.

J Affect Disord 2019 02 6;245:386-393. Epub 2018 Nov 6.

Ataxia Lab, Fondazione Santa Lucia IRCCS, Rome, Italy; Department of Psychology, Sapienza University of Rome, Italy.

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".
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http://dx.doi.org/10.1016/j.jad.2018.11.029DOI Listing
February 2019

Evidence of Cerebellar Involvement in the Onset of a Manic State.

Front Neurol 2018 12;9:774. Epub 2018 Sep 12.

Ataxia Laboratory, IRCCS Fondazione Santa Lucia, Rome, Italy.

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.
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http://dx.doi.org/10.3389/fneur.2018.00774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143664PMC
September 2018

The cerebellar topography of attention sub-components in spinocerebellar ataxia type 2.

Cortex 2018 11 31;108:35-49. Epub 2018 Jul 31.

Ataxia Laboratory, IRCCS Fondazione Santa Lucia, Rome, Italy; Department of Psychology, Sapienza University of Rome, Rome, Italy.

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. 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). 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 (IV) and in the posterior lobe (VI-IX) and posterior vermis (VI-IX). 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. 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.
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http://dx.doi.org/10.1016/j.cortex.2018.07.011DOI Listing
November 2018

Topography of the cerebellum in relation to social brain regions and emotions.

Handb Clin Neurol 2018 ;154:71-84

Department of Psychology, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy; Ataxia Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy; Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.

In the last few decades, an increasing number of studies have focused on better characterizing the cerebellar functions beyond motor control, including emotional and social domains. Anatomic 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. Overcoming the traditional segregation of cerebrocerebellar networks in sensorimotor/cognitive functional modules, during emotional/social processes, the cerebellar activity reflects a domain-specific mentalizing functionality that is strongly connected with corresponding mentalizing networks in the cerebrum. Additionally, the cerebrocerebellar organization has been shown to have a specific functional and maturational trajectory that is only in part dependent on a structural maturational process and that is protracted from an early stage of life through adolescence and adulthood, when the mature control networks involve both segregation and integration of the brain regions that comprise them. Altogether, these findings underscore the importance of regional functional differences within the cerebellum in relation to emotional and social processing and raise questions about the clinical implication of cerebellar injury on emotional/social behaviors, both in the developing and the adult brain.
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http://dx.doi.org/10.1016/B978-0-444-63956-1.00005-9DOI Listing
September 2018

Development of a Psychiatric Disorder Linked to Cerebellar Lesions.

Cerebellum 2018 Aug;17(4):438-446

Ataxia Laboratory, IRCCS Fondazione Santa Lucia, 00179, Rome, Italy.

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.
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http://dx.doi.org/10.1007/s12311-018-0926-5DOI Listing
August 2018

Lobular patterns of cerebellar resting-state connectivity in adults with Autism Spectrum Disorder.

Eur J Neurosci 2018 03 14;47(6):729-735. Epub 2017 Nov 14.

Ataxia Laboratory, IRCCS Santa Lucia Foundation, Via Ardeatina 306, 00179, Rome, Italy.

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.
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http://dx.doi.org/10.1111/ejn.13752DOI Listing
March 2018

Atrophic degeneration of cerebellum impairs both the reactive and the proactive control of movement in the stop signal paradigm.

Exp Brain Res 2017 10 17;235(10):2971-2981. Epub 2017 Jul 17.

Department of Physiology and Pharmacology, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy.

The cognitive control of movement suppression, including performance monitoring, is one of the core properties of the executive system. A complex cortical and subcortical network involving cerebral cortex, thalamus, subthalamus, and basal ganglia has been regarded as the neural substrate of inhibition of programmed movements. Using the countermanding task, a suitable tool to explore behavioral components of movement suppression, the contribution of the cerebellum in the proactive control and monitoring of voluntary action has been recently described in patients affected by focal lesions involving in particular the cerebellar dentate nucleus. Here, we evaluated the performance on the countermanding task in a group of patients with cerebellar degeneration, in which the cerebellar cortex was diffusely affected, and showed that they display additionally a longer latency in countermanding engaged movements. Overall, the present data confirm the role of the cerebellum in executive control of action inhibition by extending the contribution to reactive motor suppression.
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http://dx.doi.org/10.1007/s00221-017-5027-zDOI Listing
October 2017

Bilateral effects of unilateral cerebellar lesions as detected by voxel based morphometry and diffusion imaging.

PLoS One 2017 10;12(7):e0180439. Epub 2017 Jul 10.

Neuroimaging Laboratory, Santa Lucia Foundation, Rome, Italy.

Over the last decades, the importance of cerebellar processing for cortical functions has been acknowledged and consensus was reached on the strict functional and structural cortico-cerebellar interrelations. From an anatomical point of view strictly contralateral interconnections link the cerebellum to the cerebral cortex mainly through the middle and superior cerebellar peduncle. Diffusion MRI (dMRI) based tractography has already been applied to address cortico-cerebellar-cortical loops in healthy subjects and to detect diffusivity alteration patterns in patients with neurodegenerative pathologies of the cerebellum. In the present study we used dMRI-based tractography to determine the degree and pattern of pathological changes of cerebellar white matter microstructure in patients with focal cerebellar lesions. Diffusion imaging and high-resolution volumes were obtained in patients with left cerebellar lesions and in normal controls. Middle cerebellar peduncles and superior cerebellar peduncles were reconstructed by multi fiber diffusion tractography. From each tract, measures of microscopic damage were assessed, and despite the presence of unilateral lesions, bilateral diffusivity differences in white matter tracts were found comparing patients with normal controls. Consistently, bilateral alterations were also evidenced in specific brain regions linked to the cerebellum and involved in higher-level functions. This could be in line with the evidence that in the presence of unilateral cerebellar lesions, different cognitive functions can be affected and they are not strictly linked to the side of the cerebellar lesion.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0180439PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503258PMC
September 2017

Resting-State Functional Connectivity Changes Between Dentate Nucleus and Cortical Social Brain Regions in Autism Spectrum Disorders.

Cerebellum 2017 04;16(2):283-292

Ataxia Laboratory, IRCCS Santa Lucia Foundation, Via Ardeatina 306, 00179, Rome, Italy.

Autism spectrum disorders (ASDs) are known to be characterized by restricted and repetitive behaviors and interests and by impairments in social communication and interactions mainly including "theory of mind" (ToM) processes. The cerebellum has emerged as one of the brain regions affected by ASDs. As the cerebellum is known to influence cerebral cortex activity via cerebello-thalamo-cortical (CTC) circuits, it has been proposed that cerebello-cortical "disconnection" could in part underlie autistic symptoms. We used resting-state (RS) functional magnetic resonance imaging (fMRI) to investigate the potential RS connectivity changes between the cerebellar dentate nucleus (DN) and the CTC circuit targets, that may contribute to ASD pathophysiology. When comparing ASD patients to controls, we found decreased connectivity between the left DN and cerebral regions known to be components of the ToM network and the default mode network, implicated in specific aspects of mentalizing, social cognition processing, and higher order emotional processes. Further, a pattern of overconnectivity was also detected between the left DN and the supramodal cerebellar lobules associated with the default mode network. The presented RS-fMRI data provide evidence that functional connectivity (FC) between the dentate nucleus and the cerebral cortex is altered in ASD patients. This suggests that the dysfunction reported within the cerebral cortical network, typically related to social features of ASDs, may be at least partially related to an impaired interaction between cerebellum and key cortical social brain regions.
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http://dx.doi.org/10.1007/s12311-016-0795-8DOI Listing
April 2017

How genetics affects the brain to produce higher-level dysfunctions in myotonic dystrophy type 1.

Funct Neurol 2015 Jan-Mar;30(1):21-31

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder dominated by muscular impairment and brain dysfunctions. Although brain damage has previously been demonstrated in DM1, its associations with the genetics and clinical/neuropsychological features of the disease are controversial. This study assessed the differential role of gray matter (GM) and white matter (WM) damage in determining higher-level dysfunctions in DM1. Ten patients with genetically confirmed DM1 and 16 healthy How genetics affects the brain to produce higher-level dysfunctions in myotonic dystrophy type 1 matched controls entered the study. The patients underwent a neuropsychological assessment and quantification of CTG triplet expansion. All the subjects underwent MR scanning at 3T, with studies including T1-weighted volumes and diffusion-weighted images. Voxel-based morphometry and tractbased spatial statistics were used for unbiased quantification of regional GM atrophy and WM integrity. The DM1 patients showed widespread involvement of both tissues. The extent of the damage correlated with CTG triplet expansion and cognition. This study supports the idea that genetic abnormalities in DM1mainly target the WM, but GM involvement is also crucial in determining the clinical characteristics of DM1.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520669PMC
April 2016

Cerebellar damage impairs executive control and monitoring of movement generation.

PLoS One 2014 17;9(1):e85997. Epub 2014 Jan 17.

Department of Psychology, Sapienza University, Rome, Italy ; Ataxia Research Lab, IRCCS Santa Lucia Foundation, Rome, Italy.

Executive control of motor responses is a psychological construct of the executive system. Several studies have demonstrated the involvement of the cerebral cortex, basal ganglia, and thalamus in the inhibition of actions and monitoring of performance. The involvement of the cerebellum in cognitive function and its functional interaction with basal ganglia have recently been reported. Based on these findings, we examined the hypothesis of cerebellar involvement in executive control by administering a countermanding task in patients with focal cerebellar damage. The countermanding task requires one to make a movement in response to a 'go' signal and to halt it when a 'stop' signal is presented. The duration of the go process (reaction time; RT), the duration of the stop process (stop signal reaction time; SSRT), and their relationship, expressed by a psychometric function, are recorded as measures of executive control. All patients had longer go process duration in general and in particular, as a proactive control, as demonstrated by the increase in RT after erroneously performed stop trials. Further, they were defective in the slope of the psychometric function indicating a difficulty on triggering the stop process, although the SSRT did not differ from controls. Notably, their performance was worse when lesions affected deep cerebellar nuclei. Our results support the hypothesis that the cerebellum regulates the executive control of voluntary actions. We speculate that its activity is attributed to specific cerebellar influence over the cortico-striatal loop.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0085997PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895022PMC
September 2014