Cerebellar Neurostimulation for Boosting Social and Affective Functions: Implications for the Rehabilitation of Hereditary Ataxia Patients.

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.

Consensus Paper: Cerebellum and Ageing.

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.

The Role of the Posterior Cerebellum in Dysfunctional Social Sequencing.

Recent advances in social neuroscience have highlighted the critical role of the cerebellum in social cognition, and especially the posterior cerebellum. Studies have supported the view that the posterior cerebellum builds internal action models of our social interactions to predict how other people's actions will be executed and what our most likely responses are to these actions. This mechanism allows to better anticipate action sequences during social interactions in an automatic and intuitive way and to fine-tune these anticipations, making it easier to understand other's social behaviors and mental states (e.g., beliefs, intentions, traits). In this paper, we argue that the central role of the posterior cerebellum in identifying and automatizing social action sequencing provides a fruitful starting point for investigating social dysfunctions in a variety of clinical pathologies, such as autism, obsessive-compulsive and bipolar disorder, depression, and addiction. Our key hypothesis is that dysfunctions of the posterior cerebellum lead to under- or overuse of inflexible social routines and lack of plasticity for learning new, more adaptive, social automatisms. We briefly review past research supporting this view and propose a program of research to test our hypothesis. This approach might alleviate a variety of mental problems of individuals who suffer from inflexible automatizations that stand in the way of adjustable and intuitive social behavior, by increasing posterior cerebellar plasticity using noninvasive neurostimulation or neuro-guided training programs.

Aberrant Cerebello-Cerebral Connectivity in Remitted Bipolar Patients 1 and 2: New Insight into Understanding the Cerebellar Role in Mania and Hypomania.

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.

Cerebellum and Emotion in Social Behavior.

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.

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

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.

The Cerebellar Cognitive Affective/Schmahmann Syndrome: a Task Force Paper.

Sporadically advocated over the last two centuries, a cerebellar role in cognition and affect has been rigorously established in the past few decades. In the clinical domain, such progress is epitomized by the "cerebellar cognitive affective syndrome" ("CCAS") or "Schmahmann syndrome." Introduced in the late 1990s, CCAS reflects a constellation of cerebellar-induced sequelae, comprising deficits in executive function, visuospatial cognition, emotion-affect, and language, over and above speech. The CCAS thus offers excellent grounds to investigate the functional topography of the cerebellum, and, ultimately, illustrate the precise mechanisms by which the cerebellum modulates cognition and affect. The primary objective of this task force paper is thus to stimulate further research in this area. After providing an up-to-date overview of the fundamental findings on cerebellar neurocognition, the paper substantiates the concept of CCAS with recent evidence from different scientific angles, promotes awareness of the CCAS as a clinical entity, and examines our current insight into the therapeutic options available. The paper finally identifies topics of divergence and outstanding questions for further research.

Consensus Paper: Cerebellum and Social Cognition.

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.

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

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.

Development of a Psychiatric Disorder Linked to Cerebellar Lesions.

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.

New protocol for dissociating visuospatial working memory ability in reaching space and in navigational space.

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.

Interhemispheric Connectivity Characterizes Cortical Reorganization in Motor-Related Networks After Cerebellar Lesions.

Although cerebellar-cortical interactions have been studied extensively in animal models and humans using modern neuroimaging techniques, the effects of cerebellar stroke and focal lesions on cerebral cortical processing remain unknown. In the present study, we analyzed the large-scale functional connectivity at the cortical level by combining high-density electroencephalography (EEG) and source imaging techniques to evaluate and quantify the compensatory reorganization of brain networks after cerebellar damage. The experimental protocol comprised a repetitive finger extension task by 10 patients with unilateral focal cerebellar lesions and 10 matched healthy controls. A graph theoretical approach was used to investigate the functional reorganization of cortical networks. Our patients, compared with controls, exhibited significant differences at global and local topological level of their brain networks. An abnormal rise in small-world network efficiency was observed in the gamma band (30-40 Hz) during execution of the task, paralleled by increased long-range connectivity between cortical hemispheres. Our findings show that a pervasive reorganization of the brain network is associated with cerebellar focal damage and support the idea that the cerebellum boosts or refines cortical functions. Clinically, these results suggest that cortical changes after cerebellar damage are achieved through an increase in the interactions between remote cortical areas and that rehabilitation should aim to reshape functional activation patterns. Future studies should determine whether these hypotheses are limited to motor tasks or if they also apply to cerebro-cerebellar dysfunction in general.

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

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.

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

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.

Inability to Process Negative Emotions in Cerebellar Damage: a Functional Transcranial Doppler Sonographic Study.

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.

Consensus paper: the role of the cerebellum in perceptual processes.

Various lines of evidence accumulated over the past 30 years indicate that the cerebellum, long recognized as essential for motor control, also has considerable influence on perceptual processes. In this paper, we bring together experts from psychology and neuroscience, with the aim of providing a succinct but comprehensive overview of key findings related to the involvement of the cerebellum in sensory perception. The contributions cover such topics as anatomical and functional connectivity, evolutionary and comparative perspectives, visual and auditory processing, biological motion perception, nociception, self-motion, timing, predictive processing, and perceptual sequencing. While no single explanation has yet emerged concerning the role of the cerebellum in perceptual processes, this consensus paper summarizes the impressive empirical evidence on this problem and highlights diversities as well as commonalities between existing hypotheses. In addition to work with healthy individuals and patients with cerebellar disorders, it is also apparent that several neurological conditions in which perceptual disturbances occur, including autism and schizophrenia, are associated with cerebellar pathology. A better understanding of the involvement of the cerebellum in perceptual processes will thus likely be important for identifying and treating perceptual deficits that may at present go unnoticed and untreated. This paper provides a useful framework for further debate and empirical investigations into the influence of the cerebellum on sensory perception.

Consensus paper: Language and the cerebellum: an ongoing enigma.

In less than three decades, the concept "cerebellar neurocognition" has evolved from a mere afterthought to an entirely new and multifaceted area of neuroscientific research. A close interplay between three main strands of contemporary neuroscience induced a substantial modification of the traditional view of the cerebellum as a mere coordinator of autonomic and somatic motor functions. Indeed, the wealth of current evidence derived from detailed neuroanatomical investigations, functional neuroimaging studies with healthy subjects and patients and in-depth neuropsychological assessment of patients with cerebellar disorders shows that the cerebellum has a cardinal role to play in affective regulation, cognitive processing, and linguistic function. Although considerable progress has been made in models of cerebellar function, controversy remains regarding the exact role of the "linguistic cerebellum" in a broad variety of nonmotor language processes. This consensus paper brings together a range of different viewpoints and opinions regarding the contribution of the cerebellum to language function. Recent developments and insights in the nonmotor modulatory role of the cerebellum in language and some related disorders will be discussed. The role of the cerebellum in speech and language perception, in motor speech planning including apraxia of speech, in verbal working memory, in phonological and semantic verbal fluency, in syntax processing, in the dynamics of language production, in reading and in writing will be addressed. In addition, the functional topography of the linguistic cerebellum and the contribution of the deep nuclei to linguistic function will be briefly discussed. As such, a framework for debate and discussion will be offered in this consensus paper.

Effective connectivity analysis of resting-state mentalizing brain networks in spinocerebellar ataxia type 2: A dynamic causal modeling study.

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.

Clinical and MRI characterization of apraxic syndrome in corticobasal degeneration: A single-case study.

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.

Consensus paper: current views on the role of cerebellar interpositus nucleus in movement control and emotion.

In the present paper, we examine the role of the cerebellar interpositus nucleus (IN) in motor and non-motor domains. Recent findings are considered, and we share the following conclusions: IN as part of the olivo-cortico-nuclear microcircuit is involved in providing powerful timing signals important in coordinating limb movements; IN could participate in the timing and performance of ongoing conditioned responses rather than the generation and/or initiation of such responses; IN is involved in the control of reflexive and voluntary movements in a task- and effector system-dependent fashion, including hand movements and associated upper limb adjustments, for quick effective actions; IN develops internal models for dynamic interactions of the motor system with the external environment for anticipatory control of movement; and IN plays a significant role in the modulation of autonomic and emotional functions.