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Beyond motor deficits, spinocerebellar ataxia (SCA) patients also suffer cognitive decline and show socio-affective difficulties, negatively impacting on their social functioning. The possibility to modulate cerebello-cerebral networks involved in social cognition through cerebellar neurostimulation has opened up potential therapeutic applications for ameliorating social and affective difficulties. The present review offers an overview of the research on cerebellar neurostimulation for the modulation of socio-affective functions in both healthy individuals and different clinical populations, published in the time period 2000-2022. A total of 25 records reporting either transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) studies were found. The investigated clinical populations comprised different pathological conditions, including but not limited to SCA syndromes. The reviewed evidence supports that cerebellar neurostimulation is effective in improving social abilities in healthy individuals and reducing social and affective symptoms in different neurological and psychiatric populations associated with cerebellar damage or with impairments in functions that involve the cerebellum. These findings encourage to further explore the rehabilitative effects of cerebellar neurostimulation on socio-affective deficits experienced by patients with cerebellar abnormalities, as SCA patients. Nevertheless, conclusions remain tentative at this stage due to the heterogeneity characterizing stimulation protocols, study methodologies and patients' samples.
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Cerebelo , Estimulación Transcraneal de Corriente Directa , Estimulación Magnética Transcraneal , Humanos , Estimulación Transcraneal de Corriente Directa/métodos , Estimulación Magnética Transcraneal/métodos , Cerebelo/fisiología , Ataxias Espinocerebelosas/rehabilitación , Ataxias Espinocerebelosas/fisiopatologíaRESUMEN
Given the key roles of the cerebellum in motor, cognitive, and affective operations and given the decline of brain functions with aging, cerebellar circuitry is attracting the attention of the scientific community. The cerebellum plays a key role in timing aspects of both motor and cognitive operations, including for complex tasks such as spatial navigation. Anatomically, the cerebellum is connected with the basal ganglia via disynaptic loops, and it receives inputs from nearly every region in the cerebral cortex. The current leading hypothesis is that the cerebellum builds internal models and facilitates automatic behaviors through multiple interactions with the cerebral cortex, basal ganglia and spinal cord. The cerebellum undergoes structural and functional changes with aging, being involved in mobility frailty and related cognitive impairment as observed in the physio-cognitive decline syndrome (PCDS) affecting older, functionally-preserved adults who show slowness and/or weakness. Reductions in cerebellar volume accompany aging and are at least correlated with cognitive decline. There is a strongly negative correlation between cerebellar volume and age in cross-sectional studies, often mirrored by a reduced performance in motor tasks. Still, predictive motor timing scores remain stable over various age groups despite marked cerebellar atrophy. The cerebello-frontal network could play a significant role in processing speed and impaired cerebellar function due to aging might be compensated by increasing frontal activity to optimize processing speed in the elderly. For cognitive operations, decreased functional connectivity of the default mode network (DMN) is correlated with lower performances. Neuroimaging studies highlight that the cerebellum might be involved in the cognitive decline occurring in Alzheimer's disease (AD), independently of contributions of the cerebral cortex. Grey matter volume loss in AD is distinct from that seen in normal aging, occurring initially in cerebellar posterior lobe regions, and is associated with neuronal, synaptic and beta-amyloid neuropathology. Regarding depression, structural imaging studies have identified a relationship between depressive symptoms and cerebellar gray matter volume. In particular, major depressive disorder (MDD) and higher depressive symptom burden are associated with smaller gray matter volumes in the total cerebellum as well as the posterior cerebellum, vermis, and posterior Crus I. From the genetic/epigenetic standpoint, prominent DNA methylation changes in the cerebellum with aging are both in the form of hypo- and hyper-methylation, and the presumably increased/decreased expression of certain genes might impact on motor coordination. Training influences motor skills and lifelong practice might contribute to structural maintenance of the cerebellum in old age, reducing loss of grey matter volume and therefore contributing to the maintenance of cerebellar reserve. Non-invasive cerebellar stimulation techniques are increasingly being applied to enhance cerebellar functions related to motor, cognitive, and affective operations. They might enhance cerebellar reserve in the elderly. In conclusion, macroscopic and microscopic changes occur in the cerebellum during the lifespan, with changes in structural and functional connectivity with both the cerebral cortex and basal ganglia. With the aging of the population and the impact of aging on quality of life, the panel of experts considers that there is a huge need to clarify how the effects of aging on the cerebellar circuitry modify specific motor, cognitive, and affective operations both in normal subjects and in brain disorders such as AD or MDD, with the goal of preventing symptoms or improving the motor, cognitive, and affective symptoms.
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Trastorno Depresivo Mayor , Adulto , Humanos , Anciano , Estudios Transversales , Consenso , Calidad de Vida , Cerebelo/patología , Envejecimiento , Imagen por Resonancia Magnética/métodosRESUMEN
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.
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Trastorno Bipolar , Manía , Trastorno Bipolar/diagnóstico por imagen , Cerebelo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Vías Nerviosas/diagnóstico por imagenRESUMEN
Accumulating evidence suggests that the cerebellum plays a crucial role not only in the motor and cognitive domains but also in emotions and social behavior. In the present chapter, after a general introduction on the significance of the emotional components of social behavior, we describe recent efforts to understand the contributions of the cerebellum in social cognition focusing on the emotional and affective aspects. Specifically, starting from the description of the cerebello-cortical networks subtending the social-affective domains, we illustrate the most recent findings on the social cerebellum and the possible functional mechanisms by which the cerebellum modulate social-affective behavior. Finally, we discuss the possible consequences of cerebellar dysfunction in the social-affective domain, focusing on those neurological and psychopathological conditions in which emotional and social behavior difficulties have been described as being associated with cerebellar structural or functional alterations.
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Cerebelo , Emociones , Cerebelo/patología , Cognición , Conducta SocialRESUMEN
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.
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Trastorno Bipolar/patología , Enfermedades Cerebelosas/patología , Cerebelo/patología , Sustancia Gris/patología , Adulto , Atrofia/diagnóstico por imagen , Atrofia/patología , Trastorno Bipolar/diagnóstico por imagen , Enfermedades Cerebelosas/diagnóstico por imagen , Cerebelo/diagnóstico por imagen , Femenino , Sustancia Gris/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedades Neurodegenerativas/diagnóstico por imagen , Enfermedades Neurodegenerativas/patologíaRESUMEN
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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Cerebelo/fisiopatología , Mentalización/fisiología , Red Nerviosa/fisiología , Vías Nerviosas/fisiopatología , Ataxias Espinocerebelosas/fisiopatología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
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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Cerebelo/diagnóstico por imagen , Cerebelo/fisiología , Consenso , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiología , Cognición Social , Mapeo Encefálico/métodos , Humanos , Mentalización/fisiología , Desempeño Psicomotor/fisiología , Conducta SocialRESUMEN
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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Trastorno del Espectro Autista , Corteza Cerebelosa , Corteza Cerebral , Conectoma , Adolescente , Adulto , Trastorno del Espectro Autista/diagnóstico por imagen , Trastorno del Espectro Autista/patología , Trastorno del Espectro Autista/fisiopatología , Corteza Cerebelosa/diagnóstico por imagen , Corteza Cerebelosa/patología , Corteza Cerebelosa/fisiopatología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Corteza Cerebral/fisiopatología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
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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Trastorno de Personalidad Limítrofe/etiología , Enfermedades Cerebelosas/complicaciones , Enfermedades Cerebelosas/psicología , Malformaciones Arteriovenosas Intracraneales/complicaciones , Malformaciones Arteriovenosas Intracraneales/psicología , Adulto , Trastorno de Personalidad Limítrofe/diagnóstico por imagen , Trastorno de Personalidad Limítrofe/fisiopatología , Enfermedades Cerebelosas/diagnóstico por imagen , Enfermedades Cerebelosas/fisiopatología , Diagnóstico Diferencial , Progresión de la Enfermedad , Femenino , Humanos , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Malformaciones Arteriovenosas Intracraneales/fisiopatología , Hemorragias Intracraneales/complicaciones , Hemorragias Intracraneales/diagnóstico por imagen , Hemorragias Intracraneales/fisiopatología , Hemorragias Intracraneales/psicología , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/fisiopatología , Accidente Cerebrovascular/psicologíaRESUMEN
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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Trastorno del Espectro Autista/fisiopatología , Núcleos Cerebelosos/fisiopatología , Corteza Cerebral/fisiopatología , Adolescente , Adulto , Trastorno del Espectro Autista/diagnóstico por imagen , Mapeo Encefálico , Núcleos Cerebelosos/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Descanso , Conducta Social , Teoría de la Mente , Adulto JovenRESUMEN
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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Función Ejecutiva/fisiología , Ataxia de Friedreich/patología , Ataxia de Friedreich/fisiopatología , Inhibición Psicológica , Actividad Motora/fisiología , Desempeño Psicomotor/fisiología , Ataxias Espinocerebelosas/patología , Ataxias Espinocerebelosas/fisiopatología , Adulto , Atrofia/patología , Corteza Cerebelosa/patología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Neuroimaging studies on healthy subjects described the causal effective connectivity of cerebellar-cerebral social mentalizing networks, revealing the presence of closed-loops. These studies estimated effective connectivity by applying Dynamic Causal Modeling on task-related fMRI data of healthy subjects performing mentalizing tasks. Thus far, few studies have applied Dynamic Causal Modeling to resting-state fMRI (rsfMRI) data to test the effective connectivity within the cerebellar-cerebral mentalizing network in the absence of experimental manipulations, and no study applied Dynamic Causal Modeling on fMRI data of patients with cerebellar disorders typically showing social cognition deficits. Thus, in this research we applied spectral Dynamic Causal Modeling, to rsfMRI data of 13 patients affected by spinocerebellar ataxia type 2 (SCA2) and of 23 matched healthy subjects. Specifically, effective connectivity was tested between acknowledged mentalizing regions of interest: bilateral cerebellar Crus II, dorsal and ventral medial prefrontal cortex, bilateral temporo-parietal junctions and precuneus. SCA2 and healthy subjects shared some similarities in cerebellar-cerebral mentalizing effective connectivity at rest, confirming the presence of closed-loops between cerebellar and cerebral mentalizing regions in both groups. However, relative to healthy subjects, SCA2 patients showed effective connectivity variations mostly in cerebellar-cerebral closed loops, namely weakened inhibitory connectivity from the cerebellum to the cerebral cortex, but stronger inhibitory connectivity from the cerebral cortex to the cerebellum. The present study demonstrated that effective connectivity changes affect a function-specific mentalizing network in SCA2 patients, allowing to deepen the direction and strength of the causal effective connectivity mechanisms driven by the cerebellar damage associated with SCA2.
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Objective: To identify the cortical and subcortical distribution of atrophy and the disorganization of white matter bundles underlying the apraxic disorders in a patient with corticobasal degeneration (CBD). Method: Patient underwent appropriate neuropsychological tasks aimed at identifying the nature of the apraxic disorder and morphometric structural MRI with whole-brain voxel-wise analysis. Results: Progressive limbkinetic apraxia (LKA) with onset in the right upper limb with subsequent extension to the limbs, trunk, orofacial district, and eye movements was documented, associated with element of ideomotor apraxia (IMA). The MRI study showed grey matter atrophy extending to much of the frontal cortex bilaterally, including the precentral cortex, and into the inferior parietal regions. Caudate and putamen were involved on the left. Significant clusters of white matter atrophy were found in the bilateral superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF) and corpus callosum (CC). Sensory evoked potentials (SEPs) and motor evoked potentials (MEPs) were normal. Conclusion: Previous observations in CBD indicate lack of inhibitory control from the sensory to the primary motor cortex with dysfunctional frontoparietal and cortico-motoneuron projections. Our neuroimaging data are partially consistent with these observations suggesting that the apraxic disorder in our patient might be produced by the disconnection of the primary motor cortex from the parietal areas that prevents selection and control of muscle movements, in the presence of preserved cortico-motoneuron as demonstrated by normal PEM. Apraxic disorders in CBD are high-level deficits of movement control that spare the motoneuron.
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Apraxias , Degeneración Corticobasal , Humanos , Pruebas Neuropsicológicas , Imagen por Resonancia Magnética , Atrofia/complicacionesRESUMEN
BACKGROUND: Autonomic dysfunctions are prevalent in several cerebellar disorders, but they have not been systematically investigated in spinocerebellar ataxias (SCAs). Studies investigating autonomic deficits in SCAs are fragmented, with each one focusing on different autonomic dysfunctions and different SCA subtypes. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we conducted a systematic review of the literature to assess the presence of autonomic dysfunctions in various SCAs. PubMed served as the primary database, and the Rayyan web application was employed for study screening. RESULTS: We identified 46 articles investigating at least one autonomic function in patients with SCA. The results were analyzed and categorized based on the genetic subtype of SCA, thereby characterizing the specific autonomic deficits associated with each subtype. CONCLUSION: This review confirms the presence of autonomic dysfunctions in various genetic subtypes of SCA, underscoring the cerebellum's role in the autonomic nervous system (ANS). It also emphasizes the importance of investigating these functions in clinical practice.
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Disautonomías Primarias , Ataxias Espinocerebelosas , Humanos , Ataxias Espinocerebelosas/genética , Cerebelo , Sistema Nervioso AutónomoRESUMEN
Pre-existing or enhanced cognitive abilities influence symptom onset and severity in neurodegenerative diseases, which improve an individual's ability to deal with neurodegeneration. This process is named cognitive reserve (CR), and it has acquired high visibility in the field of neurodegeneration. However, the investigation of CR has been neglected in the context of cerebellar neurodegenerative disorders. The present study assessed CR and its impact on cognitive abilities in spinocerebellar ataxia type 2 (SCA2), which is a rare cerebellar neurodegenerative disease. We investigated the existence of CR networks in terms of compensatory mechanisms and neural reserve driven by increased cerebello-cerebral functional connectivity. The CR of 12 SCA2 patients was assessed using the Cognitive Reserve Index Questionnaire (CRIq), which was developed for appraising life-span CR. Patients underwent several neuropsychological tests to evaluate cognitive functioning and a functional MRI examination. Network based statistics analysis was used to assess functional brain networks. The results revealed significant correlations of CRIq measures with cognitive domains and patterns of increased connectivity in specific cerebellar and cerebral regions, which likely indicated CR networks. This study showed that CR may influence disease-related cognitive deficits, and it was related to the effective use of specific cerebello-cerebral networks that reflect a CR biomarker.
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Reserva Cognitiva , Ataxias Espinocerebelosas , Humanos , Ataxias Espinocerebelosas/complicaciones , Ataxias Espinocerebelosas/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Cerebelo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Pruebas NeuropsicológicasRESUMEN
Introduction: Advances in the operational mode of the cerebellum indicate a role in sequencing and predicting non-social and social events, crucial for individuals to optimize high-order functions, such as Theory of Mind (ToM). ToM deficits have been described in patients with remitted bipolar disorders (BD). The literature on BD patients' pathophysiology reports cerebellar alterations; however, sequential abilities have never been investigated and no study has previously focused on prediction abilities, which are needed to properly interpret events and to adapt to changes. Methods: To address this gap, we compared the performance of BD patients in the euthymic phase with healthy controls using two tests that require predictive processing: a ToM test that require implicit sequential processing and a test that explicitly assesses sequential abilities in non-ToM functions. Additionally, patterns of cerebellar gray matter (GM) alterations were compared between BD patients and controls using voxel-based morphometry. Results: Impaired ToM and sequential skills were detected in BD patients, specifically when tasks required a greater predictive load. Behavioral performances might be consistent with patterns of GM reduction in cerebellar lobules Crus I-II, which are involved in advanced human functions. Discussion: These results highlight the importance of deepening the cerebellar role in sequential and prediction abilities in patients with BD.
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Social prediction is a key feature of social cognition (SC), a function in which the modulating role of the cerebellum is recognized. Accordingly, cerebellar alterations are reported in cerebellar pathologies, neurodevelopmental disorders, and psychiatric conditions that show SC deficits. Nevertheless, to date, no study has directly compared populations representative of these three conditions with respect to SC and cerebellar alterations. Therefore, the present exploratory study aimed to compare the SC profiles of individuals with cerebellar neurodegenerative disorders (CB), autism (ASD), bipolar disorder type 2 (BD2), or healthy subjects (HS) using a battery of social tests requiring different degrees of prediction processing. The patterns of cerebellar gray matter (GM) alterations were compared among the groups using voxel-based morphometry. Compared to HS, the clinical groups showed common SC deficits in tasks involving a moderate to high level of prediction. The behavioral results of the clinical groups are consistent with the presence of overlapping GM reduction in cerebellar right Crus II, an area notably involved in complex social processing and prediction. Although exploratory and preliminary, these results deepen the cerebellar role in social prediction and highlight the transdiagnostic value of the cerebellum in social functioning and prediction in pathologies of different aetiologies, forecasting novel possibilities for shared interventions.
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BACKGROUND: Brain imaging studies on eating disorders (EDs) often reported volumetric and functional changes involving the cerebellum. Nevertheless, few studies performed in-depth examinations and suggested a cerebellar role in the EDs' pathophysiology. METHODS: A systematic literature search on volumetric changes and functional alterations involving the cerebellum in individuals with EDs was conducted using PubMed, PsychInfo and Web of Science. This review was conducted according to the Preferred Reporting Items for Systematic Reviews (PRISMA) statement and Rayyan web application for screening studies. RESULTS: Twenty-four papers reporting cerebellar alterations in individuals with EDs were included in the study: 9 assessing brain volumetric changes, 9 investigating task-based functional brain activation and 6 investigating brain functional connectivity at rest. Most studies focused on anorectic-type EDs (n.22), while fewer involved bulimic-type EDs (n.9) and eating disorders not otherwise specified (n.2), revealing subtypes-specific patterns of altered cerebellar volume and functionality. CONCLUSIONS: This review proposes critical arguments to consider the cerebellum as a key structure in the pathophysiology of EDs that requires further forthcoming exploration.
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Anorexia Nerviosa , Depresores del Apetito , Bulimia Nerviosa , Trastornos de Alimentación y de la Ingestión de Alimentos , Cerebelo/diagnóstico por imagen , HumanosRESUMEN
The ability to resiliently cope with neuropathological lesions is a key scientific concern. Accordingly, this study aims to investigate whether motor reserve (MR), likely to be boosted by exercise engagement in a lifetime, affects motor symptom severity, cognitive functioning, and functional brain networks in spinocerebellar ataxia type 2 (SCA2)-a cerebellar neurodegenerative disease. The MR of 12 SCA2 patients was assessed using the Motor Reserve Index Questionnaire (MRIq), developed ad hoc for estimating lifespan MR. The International Cooperative Ataxia Rating Scale was used to assess clinical motor features, and neuropsychological tests were used to evaluate cognitive functioning. Patients underwent an MRI examination, and network-based statistics (NBS) analysis was carried out to detect patterns of functional connectivity (FC). Significant correlations were found between MRIq measures and the severity of motor symptoms, educational and intellectual levels, executive function, and processing speed. NBS analysis revealed a higher FC within subnetworks consisting of specific cerebellar and cerebral areas. FC patterns were positively correlated with MRIq measures, likely indicating the identification of an MR network. The identified network might reflect a biomarker likely to underlie MR, influenced by education and cognitive functioning, and impacting the severity of motor symptoms.
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The behavioural variant of frontotemporal dementia (bvFTD) is primarily characterized by deficits in social behaviour and theory of mind (ToM). Although a consensus has been reached on the roles of the cerebellum in social cognition and ToM, its specific contribution to social impairments of bvFTD has never been specifically investigated. The aim of this study was to assess cerebellar structural and functional changes in patients with bvFTD and their potential association with ToM deficits of patients. Therefore, 15 patients with bvFTD and 34 healthy subjects underwent an MRI examination. Voxel-based morphometry was used to assess cerebellar (GM) changes, and a seed-based analysis was performed to test cerebello-cerebral functional connectivity (FC). The performance of bvFTD patients in a ToM task was then correlated with FC patterns. Compared to healthy subjects, patients with bvFTD showed significant cerebellar GM loss specifically involving cerebellar Crus I-II. Additionally, FC changes FC were observed between the cerebellum and cerebral regions related to ToM. Interestingly, patterns of changes in cerebello-cerebral FC correlated with altered ToM performances explored using the "Reading the Mind with the Eyes" test (RMET) of patients. The present findings suggest that specific changes in cerebello-cerebral FC may underlie ToM alterations in patients with bvFTD.