Cerebellar Contribution Research Articles

Cerebellar contribution to auditory feedback control of speech production: Evidence from patients with spinocerebellar ataxia.

The cerebellum has been implicated in the feedforward control of speech production. However, the role of the cerebellum in the feedback control of speech production remains unclear. To address this question, the present event-related potential study examined the behavioral and neural correlates of auditory feedback control of vocal production in patients with spinocerebellar ataxia (SCA) and healthy controls. All participants were instructed to produce sustained vowels while hearing their voice unexpectedly pitch-shifted -200 or -500 cents. The behavioral results revealed significantly larger vocal compensations for pitch perturbations in patients with SCA relative to healthy controls. At the cortical level, patients with SCA exhibited significantly smaller cortical P2 responses that were source localized in the right superior temporal gyrus, primary auditory cortex, and supramarginal gyrus than healthy controls. These findings indicate that reduced brain activity in the right temporal and parietal regions are significant neural contributors to abnormal auditory-motor processing of vocal pitch regulation as a consequence of cerebellar degeneration, which may be related to disrupted reciprocal interactions between the cerebellum and cortical regions that support the top-down modulation of auditory-vocal integration. These differences in behavior and cortical activity between healthy controls and patients with SCA demonstrate that the cerebellum is not only essential for feedforward control but also plays a crucial role in the feedback-based control of speech production.

Cerebellar contribution to vocal emotion decoding: Insights from stroke and neuroimaging

While the role of the cerebellum in emotion recognition has been explored with facial expressions, its involvement in the auditory modality (i.e., emotional prosody) remains to be demonstrated. The present study investigated the recognition of emotional prosody in 15 patients with chronic cerebellar ischaemic stroke and 15 matched healthy controls, using a validated task, as well as clinical, motor, neuropsychological, and psychiatric assessments. We explored the cerebellar lesion-behaviour relationship using voxel-based lesion-symptom mapping. Results showed a significant difference between the stroke and healthy control groups, with patients giving erroneous ratings on the Surprise scale when they listened to fearful stimuli. Moreover, voxel-based lesion-symptom mapping revealed that these emotional misattributions correlated with lesions in right Lobules VIIb, VIIIa,b and IX. Interestingly, the posterior cerebellum has previously been found to be involved in affective processing, and Lobule VIIb in rhythm discrimination. These results point to the cerebellum’s functional involvement in vocal emotion decoding.

Cerebellar Contribution to Preparatory Activity in Motor Neocortex

SummaryIn motor neocortex, preparatory activity predictive of specific movements is maintained by a positive feedback loop with the thalamus. Motor thalamus receives excitatory input from the cerebellum, which learns to generate predictive signals for motor control. The contribution of this pathway to neocortical preparatory signals remains poorly understood. Here, we show that, in a virtual reality conditioning task, cerebellar output neurons in the dentate nucleus exhibit preparatory activity similar to that in anterolateral motor cortex prior to reward acquisition. Silencing activity in dentate nucleus by photoactivating inhibitory Purkinje cells in the cerebellar cortex caused robust, short-latency suppression of preparatory activity in anterolateral motor cortex. Our results suggest that preparatory activity is controlled by a learned decrease of Purkinje cell firing in advance of reward under supervision of climbing fiber inputs signaling reward delivery. Thus, cerebellar computations exert a powerful influence on preparatory activity in motor neocortex.

Effects of cerebellar transcranial direct current stimulation on the cognitive stage of sequence learning.

Though the cerebellum has been previously implicated in explicit sequence learning, the exact role of this structure in the acquisition of motor skills is not completely clear. The cerebellum contributes to both motor and nonmotor behavior. Thus, this structure not only may contribute to the motoric aspects of sequence learning but may also play a role in the cognitive components of these learning paradigms. Therefore, we investigated the consequence of both disrupting and facilitating cerebellar function using high-definition transcranial direct current stimulation (tDCS) before the completion of an explicit motor sequence learning paradigm. Using a mixed within- and between-subjects design, we employed cathodal (n = 21) and anodal (n = 23) tDCS (relative to sham), targeting the lateral posterior cerebellum, to temporarily modulate function and investigate the resulting effects on the acquisition of a sequential pattern of finger movements. Results indicate that cathodal stimulation has a positive influence on learning while anodal stimulation has the opposite effect, relative to sham. Though the cerebellum is presumed to be primarily involved in motor function and movement coordination, our results support a cognitive contribution that may come into play during the initial stages of learning. Using tDCS targeting the right posterior cerebellum, which communicates with the prefrontal cortex via closed-loop circuits, we found polarity-specific effects of cathodal and anodal stimulation on sequence learning. Thus, our results substantiate the role of the cerebellum in the cognitive aspect of motor learning and provide important new insights into the polarity-specific effects of tDCS in this area.NEW & NOTEWORTHY The cerebellum contributes to motor and cognitive processes. Investigating the cognitive contributions of the cerebellum in explicit sequence learning stands to provide new insights into this learning domain, and cerebellar function more generally. Using high-definition transcranial direct current stimulation, we demonstrated polarity-specific effects of stimulation on explicit sequence learning. We speculate that this is due to facilitation of working memory processes. This provides new evidence supporting a role for the cerebellum in the cognitive aspects of sequence learning.

Predictive and reactive reward signals conveyed by climbing fiber inputs to cerebellar Purkinje cells.

There is increasing evidence for a cerebellar contribution to cognitive processing, but the specific input pathways conveying this information remain unclear. We probed the role of climbing fiber inputs to Purkinje cells in generating and evaluating predictions about associations between motor actions, sensory stimuli and reward. We trained mice to perform a visuomotor integration task to receive a reward and interleaved cued and random rewards between task trials. Using two-photon calcium imaging and Neuropixels probe recordings of Purkinje cell activity, we show that climbing fibers signal reward expectation, delivery and omission. These signals map onto cerebellar microzones, with reward delivery activating some microzones and suppressing others, and with reward omission activating both reward-activated and reward-suppressed microzones. Moreover, responses to predictable rewards are progressively suppressed during learning. Our findings elucidate a specific input pathway for cerebellar contributions to reward signaling and provide a mechanistic link between cerebellar activity and the creation and evaluation of predictions.

Functional and Structural Connectivity of the Cerebellar Nuclei With the Striatum and Cerebral Cortex in First-Episode Psychosis.

Evidence suggests that the cortico-striatal-thalamo-cortical circuitry plays an important role in schizophrenia pathophysiology. Cerebellar contribution from deep cerebellar nuclei to the circuitry has not yet been examined. The authors investigated resting-state functional connectivity (RSFC) of cerebellar output nuclei with striatal-thalamic-cortical regions in relation to white-matter integrity and regional gray-matter volumes in first-episode psychosis (FEP). Methods: Forty FEP patients and 40 age- and gender-matched healthy control subjects (HCs) participated. RSFC between cerebellar nuclei and striatal-thalamic-cortical regions was examined. Diffusion tensor imaging and volumetric scans were examined for possible structural constraints on RSFC. The authors also examined relationships between neuroimaging variables and cognitive and clinical measures. Results: FEP patients, compared with HCs, exhibited decreased RSFC between the left fastigial nucleus and right putamen, which was associated with poor letter fluency performance and lower global assessment of functioning scores. By contrast, patients showed widespread increased accumbens network connectivity in the left nucleus. The authors further observed both hypo- and hyper-RSFC between the cerebellar nuclei and fronto-parietal areas in patients, independent of striatal activity. Finally, the authors found impaired integrity of the left superior cerebellar peduncle and decreased bilateral putamen volume in patients, whereas structural-functional relationships found in HCs were absent in patients. Conclusions: This study provides evidence of disordered RSFC of cerebellar output nuclei to the striatum and neocortex at the early stage of schizophrenia. Furthermore, dysfunctional cerebellar influences on fronto-parietal areas that are independent of striatal dysfunction in patients with FEP were observed. The results suggest that cortico-striatal abnormalities in patients with FEP are produced by abnormal cerebellar influences.

Cerebellar Contributions to Major Depression.

Extending beyond the motor domain, the cerebellum is involved in various aspects of cognition and affect. Multidisciplinary evidence has demonstrated topographic organization of higher-order cognitive functions within the cerebellum. We here review recent neuroimaging research that indicates cerebellar contributions to major depressive disorder (MDD). At the structural level, increased volume of lobule IX has been demonstrated in MDD patients, independent of acute or remitted disease state. Successful treatment with electroconvulsive therapy has been associated with increased lobule VIIA volume in depressed patients. At the functional level, connectivity analyses have shown reduced cerebro-cerebellar coupling of lobules VI and VIIA/B with prefrontal, posterior parietal, and limbic regions in patients with MDD. As a limitation, most of this evidence is based on smaller patient samples with incomplete phenotypic and neuropsychological characterization and with heterogenous medication. Some studies did not apply cerebellum-optimized data analysis protocols. Taken together, MDD pathophysiology affects distinct subregions of the cerebellum that communicate with cortical networks subserving cognitive and self-referential processing. This mini-review synthesizes research evidence from cerebellar structural and functional neuroimaging in depression, and provides future perspectives for neuroimaging of cerebellar contributions to MDD.

Cerebellar contributions to tactile perception in people with varying sensorimotor experiences: Examining the sensory acquisition hypothesis

The sensory acquisition hypothesis states that the sensory demand of a task is the most crucial factor in determining the level of cerebellar activity. The present study was conducted to examine whether the prediction of sensory demand holds when participants have different sensorimotor training experiences. Archery athletes and non-athletic control participants were asked to perform tactile discrimination tasks during fMRI scanning. In archery athletes, a pattern of reduced cerebellar activation accompanying higher sensory cortical activity was observed, whereas in non-athletic control participants the visual network was found to be in concert with extensive cerebellar activation. These findings are in accordance with the prediction that the cerebellum plays a supportive role for the cerebral cortex in sensory data acquisition.

Cerebellar contributions to sequence prediction in verbal working memory

Verbal working memory is one of the most studied non-motor functions with robust cerebellar involvement. While the superior cerebellum (lobule VI) has been associated with articulatory control, the inferior cerebellum (lobule VIIIa) has been linked to phonological storage. The present study was aimed to elucidate the differential roles of these regions by investigating whether the cerebellum might contribute to verbal working memory via predictions based on sequence learning/detection. 19 healthy adult subjects completed an fMRI-based Sternberg task which included repeating and novel letter sequences that were phonologically similar or dissimilar. It was hypothesized that learning a repeating sequence of study letters would reduce phonological storage demand and associated right inferior cerebellar activations and that this effect would be modulated by phonological similarity of the study letters. Specifically, while increased phonological storage demand due to high phonological similarity was expected to be reflected in increased right inferior cerebellar activations for similar relative to dissimilar study letters, the reduction in activation for repeating relative to novel sequences was expected to be more profound for phonologically similar than for dissimilar study letters, especially at higher memory load. Results confirmed the typical effects of cognitive load (5 vs. 2 study letters) and phonological similarity in several cerebellar and neocortical brain regions as well as in behavioral data (accuracy and response time). Importantly, activations in superior and inferior cerebellar regions were differentially modulated as a function of similarity and sequence novelty, indicating that particularly lobule VIIIa may contribute to verbal working memory by generating predictions of letter sequences that reduce the likelihood of phonological loop failure before stored items need to be retrieved. The present study is consistent with other investigations that support prediction, which can be based on sequence learning or detection, as an overarching cerebellar function.

Evidence for Brainstem Contributions to Autism Spectrum Disorders.

Autism spectrum disorder (ASD) is a neurodevelopmental condition that affects one in 59 children in the United States. Although there is a mounting body of knowledge of cortical and cerebellar contributions to ASD, our knowledge about the early developing brainstem in ASD is only beginning to accumulate. Understanding how brainstem neurotransmission is implicated in ASD is important because many of this condition’s sensory and motor symptoms are consistent with brainstem pathology. Therefore, the purpose of this review was to integrate epidemiological, behavioral, histological, neuroimaging, and animal evidence of brainstem contributions to ASD. Because ASD is a neurodevelopmental condition, we examined the available data through a lens of hierarchical brain development. The review of the literature suggests that developmental alterations of the brainstem could have potential cascading effects on cortical and cerebellar formation, ultimately leading to ASD symptoms. This view is supported by human epidemiology findings and data from animal models of ASD, showing that perturbed development of the brainstem substructures, particularly during the peak formation of the brainstem’s monoaminergic centers, may relate to ASD or ASD-like behaviors. Furthermore, we review evidence from human histology, psychophysiology, and neuroimaging suggesting that brainstem development and maturation may be atypical in ASD and may be related to key ASD symptoms, such as atypical sensorimotor features and social responsiveness. From this review there emerges the need of future research to validate early detection of the brainstem-based somatosensory and psychophysiological behaviors that emerge in infancy, and to examine the brainstem across the life span, while accounting for age. In all, there is preliminary evidence for brainstem involvement in ASD, but a better understanding of the brainstem’s role would likely pave the way for earlier diagnosis and treatment of ASD.

Extinction and Renewal of Conditioned Eyeblink Responses in Focal Cerebellar Disease.

Extinction of conditioned aversive responses (CR) has been shown to be context-dependent. The hippocampus and prefrontal cortex are of particular importance. The cerebellum may contribute to context-related processes because of its known connections with the hippocampus and prefrontal cortex. Context dependency of extinction can be demonstrated by the renewal effect. When CR acquisition takes place in context A and is extinguished in context B, renewal refers to the recovery of the CR in context A (A-B-A paradigm). In the present study acquisition, extinction and renewal of classically conditioned eyeblink responses were tested in 18 patients with subacute focal cerebellar lesions and 18 age- and sex-matched healthy controls. Standard delay eyeblink conditioning was performed using an A-B-A paradigm. All cerebellar patients underwent a high-resolution T1-weighted brain MRI scan to perform lesion-symptom mapping. CR acquisition was not significantly different between cerebellar and control participants allowing to draw conclusions on extinction. CR extinction was significantly less in cerebellar patients. Reduction of CR extinction tended to be more likely in patients with lesions in the lateral parts of lobule VI and Crus I. A significant renewal effect was present in controls only. The present data provide further evidence that the cerebellum contributes to extinction of conditioned eyeblink responses. Because acquisition was preserved and extinction took place in another context than acquisition, more lateral parts of the cerebellar hemisphere may contribute to context-related processes. Furthermore, lack of renewal in cerebellar patients suggest a contribution of the cerebellum to context-related processes.

Distinct cerebellar contributions to FTD subtypes.

Distinct cerebellar contributions to FTD subtypes.

A subcortical circuit linking the cerebellum to the basal ganglia engaged in vocal learning.

Speech is a complex sensorimotor skill, and vocal learning involves both the basal ganglia and the cerebellum. These subcortical structures interact indirectly through their respective loops with thalamo-cortical and brainstem networks, and directly via subcortical pathways, but the role of their interaction during sensorimotor learning remains undetermined. While songbirds and their song-dedicated basal ganglia-thalamo-cortical circuitry offer a unique opportunity to study subcortical circuits involved in vocal learning, the cerebellar contribution to avian song learning remains unknown. We demonstrate that the cerebellum provides a strong input to the song-related basal ganglia nucleus in zebra finches. Cerebellar signals are transmitted to the basal ganglia via a disynaptic connection through the thalamus and then conveyed to their cortical target and to the premotor nucleus controlling song production. Finally, cerebellar lesions impair juvenile song learning, opening new opportunities to investigate how subcortical interactions between the cerebellum and basal ganglia contribute to sensorimotor learning.

Participation of the caudal cerebellar lobule IX to the dorsal attentional network

BackgroundWe seeked for specific cerebellar contribution within the dorsal attentional network (DAN), using Independent Component Analysis (ICA).MethodsICA-based analysis was performed on brain resting-state functional images of 19 volunteers.ResultsWe confirmed that DAN includes bilaterally: lobules VI-VII (crus I) and VIIB-VIIIA, as previously reported by Region-Of-Interest (ROI)-based functional connectivity studies. We also found that lobule IX (tonsillae), and as well as the superior and, likely, inferior colliculi. Also belong to DAN. The part of lobule IX in relation to DAN is located more caudally and laterally, and less extensive than the more rostral part of this lobule belonging to the default-mode network (DMN).ConclusionRostral and caudal tonsillae partake in the DMN and DAN, respectively. The latter could subserve either eye movement control in relation to the oculomotor parieto-frontal network, partially congruent with the DAN, or more cognitive functions due to functional reallocation within the DAN.

Cerebellar α6 -subunit-containing GABAA receptors: a novel therapeutic target for disrupted prepulse inhibition in neuropsychiatric disorders.

The pathophysiological role of α6 -subunit-containing GABAA receptors, which are mainly expressed in cerebellar granule cells, remains unclear. Recently, we demonstrated that hispidulin, a flavonoid isolated from a local herb that remitted a patient's intractable motor tics, attenuated methamphetamine-induced hyperlocomotion in mice as a positive allosteric modulator (PAM) of cerebellar α6 GABAA receptors. Here, using hispidulin and a selective α6 GABAA receptor PAM, the pyrazoloquinolinone Compound 6, we revealed an unprecedented role of cerebellar α6 GABAA receptors in disrupted prepulse inhibition of the startle response (PPI), which reflects sensorimotor gating deficits manifested in several neuropsychiatric disorders. PPI disruptions were induced by methamphetamine and NMDA receptor antagonists in mice. Effects of the tested compounds were measured in Xenopus oocytes expressing recombinant α6 β3 γ2S GABAA receptors. Hispidulin given i.p. or by bilateral intracerebellar (i.cb.) injection rescued PPI disruptions induced by methamphetamine, ketamine, MK-801 and phencyclidine. Intracerebellar effects of hispidulin were mimicked by Ro15-4513 and loreclezole (two α6 GABAA receptor PAMs), but not by diazepam (an α6 GABAA receptor-inactive benzodiazepine) and were antagonized by furosemide (i.cb.), an α6 GABAA receptor antagonist. Importantly, Compound 6 (i.p.) also rescued methamphetamine-induced PPI disruption, an effect prevented by furosemide (i.cb.). Both hispidulin and Compound 6 potentiated α6 β3 γ2S GABAA receptor-mediated GABA currents. Positive allosteric modulation of cerebellar α6 GABAA receptors rescued disrupted PPI by attenuating granule cell activity. α6 GABAA receptor-selective PAMs are potential medicines for treating sensorimotor gating deficits in neuropsychiatric disorders. A mechanistic hypothesis is based on evidence for cerebellar contributions to cognitive functioning including sensorimotor gating.

F194. Cerebellar contributions to somatosensory induced neuroplasticity

Monitoring, processing and integration of sensory inputs by the cerebellar circuitry is important for learning and adaptation in order to anticipate sensory events. The aim of this transcranial magnetic stimulation (TMS) study is to investigate the cerebellar involvement in the formation of cortical plasticity in response of vibrotactile hand stimulation. Such somatosensory-induced plasticity within the sensorimotor area was demonstrated in our previous studies. However, the afferent signals to the sensorimotor area are gated by extrinsic vertical pathways such as the cerebello-thalamo-cortical pathway, which raise the assumption of possible influence from subcortical relays along this neuronal route. Examining this hypothesis is of potential importance for patients with cerebellar lesions. The activation of the cerebello-thalamo-cortical networks in response to vibrotactile hand stimulation was assessed using TMS and twin coil for conditioning stimulation of the ipsilateral cerebellum and test stimulation of the contralateral motor cortex. Motor evoked potentials (MEP) were recorded from the right first dorsal interosseus muscle. The cerebellocortical inhibition (CBI) was tested before and after hand stimulation at 25 Hz for 20 min (HANDSTIM) versus SHAM in 14 healthy subjects in within subject design. Additionally vibration threshold (using a bone conduction probe of a clinical audiometer) and motor performance (Pegboard test) were evaluated. Following HANDSTIM the normalized MEP amplitude was increased which shows reduced effect of CBI. The vibration threshold was decreased for 30 min while the Pegboard test motor performance remained unchanged. No effects were found in response to SHAM stimulation. The reduction of CBI in response to hand vibrotactile stimulation confirms the cerebellar involvement in mediating the sensory information to the cortex and will be compared in a follow-up study to patients with an infarct on the territory of the posterior inferior cerebellar artery. These patients often show sensorimotor/learning deficits, whereby the processes staying behind these effects are still not clarified.

Cerebellar contribution to locomotor behavior: A neurodevelopmental perspective.

The developmental trajectory of the formation of cerebellar circuitry has significant implications for locomotor plasticity and adaptive learning at later stages. While there is a wealth of knowledge on the development of locomotor behavior in human infants, children, and adolescents, pre-clinical animal models have fallen behind on the study of the emergence of behavioral motifs in locomotor function across postnatal development. Since cerebellar development is protracted, it is subject to higher risk of genetic or environmental disruption, potentially leading to abnormal behavioral development. This highlights the need for more sophisticated and specific functional analyses of adaptive cerebellar behavior within the context of whole-body locomotion across the entire span of postnatal development. Here we review evidence on cerebellar contribution to adaptive locomotor behavior, highlighting methodologies employed to quantify and categorize behavior at different developmental stages, with the ultimate goal of following the course of early behavioral alterations in neurodevelopmental disorders. Since experimental paradigms used to study cerebellar behavior are lacking in both specificity and applicability to locomotor contexts, we highlight the use of the Erasmus Ladder - an advanced, computerized, fully automated system to quantify adaptive cerebellar learning in conjunction with locomotor function. Finally, we emphasize the need to develop objective, quantitative, behavioral tasks which can track changes in developmental trajectories rather than endpoint measurement at the adult stage of behavior.

Purkinje Cell Signaling Deficits in Animal Models of Ataxia.

Purkinje cell (PC) dysfunction or degeneration is the most frequent finding in animal models with ataxic symptoms. Mutations affecting intrinsic membrane properties can lead to ataxia by altering the firing rate of PCs or their firing pattern. However, the relationship between specific firing alterations and motor symptoms is not yet clear, and in some cases PC dysfunction precedes the onset of ataxic signs. Moreover, a great variety of ionic and synaptic mechanisms can affect PC signaling, resulting in different features of motor dysfunction. Mutations affecting Na+ channels (NaV1.1, NaV1.6, NaVβ4, Fgf14 or Rer1) reduce the firing rate of PCs, mainly via an impairment of the Na+ resurgent current. Mutations that reduce Kv3 currents limit the firing rate frequency range. Mutations of Kv1 channels act mainly on inhibitory interneurons, generating excessive GABAergic signaling onto PCs, resulting in episodic ataxia. Kv4.3 mutations are responsible for a complex syndrome with several neurologic dysfunctions including ataxia. Mutations of either Cav or BK channels have similar consequences, consisting in a disruption of the firing pattern of PCs, with loss of precision, leading to ataxia. Another category of pathogenic mechanisms of ataxia regards alterations of synaptic signals arriving at the PC. At the parallel fiber (PF)-PC synapse, mutations of glutamate delta-2 (GluD2) or its ligand Crbl1 are responsible for the loss of synaptic contacts, abolishment of long-term depression (LTD) and motor deficits. At the same synapse, a correct function of metabotropic glutamate receptor 1 (mGlu1) receptors is necessary to avoid ataxia. Failure of climbing fiber (CF) maturation and establishment of PC mono-innervation occurs in a great number of mutant mice, including mGlu1 and its transduction pathway, GluD2, semaphorins and their receptors. All these models have in common the alteration of PC output signals, due to a variety of mechanisms affecting incoming synaptic signals or the way they are processed by the repertoire of ionic channels responsible for intrinsic membrane properties. Although the PC is a final common pathway of ataxia, the link between specific firing alterations and neurologic symptoms has not yet been systematically studied and the alterations of the cerebellar contribution to motor signals are still unknown.

Anti-Saccades in Cerebellar Ataxias Reveal a Contribution of the Cerebellum in Executive Functions.

Increasing evidence suggests a cerebellar contribution to modulate cognitive aspects of motor behavior and executive functions. Supporting findings come from studies on patients with neurodegenerative diseases, in which however, given the extent of the disease, the specific role of the cerebellum, could not be clearly isolated. Anti-saccades are considered a sensitive tool to test executive functions. The anti-saccade underlying neural network, consisting of different cortical areas and their downstream connections including the lateral cerebellum, has been largely clarified. To separate the role of the cerebellum with respect to other cortical structures in executive control, we compared the anti-saccade performances in two distinct cohorts of patients with cerebellar disorders (with and without cerebral cortical involvement). Eye movements during the execution of anti-saccades were recorded in 12 patients with spinocerebellar ataxia type 2 (a cortical-subcortical neurodegenerative disease), 10 patients with late onset cerebellar ataxia (an isolated cerebellar atrophy), and 34 matched controls. In the anti-saccade task, besides dynamic changes already demonstrated in the pro-saccades of these patients, we found in both groups of cerebellar patients prolonged latency with larger variability than normal and increased directional error rate. Errors, however, were corrected by cerebellar patients as frequently as normal. No significant differences were found in patients with and without cortical involvement. Our results indicate, in a large cohort of cerebellar patients, that the cerebellum plays a critical role in the regulation of executive motor control not only, as well known, by controlling the end of a movement, but also modulating its initiation and reducing reflexive responses that would perturb voluntary actions.

Cerebellar contribution to spatial realignment: A tDCS study during multiple-step prism adaptation

Several processes are devoted to error reduction in response to a visual displacement, such as the one induced by wedge prisms. Strategic calibration and spatial realignment contribute to the iteratively process that allows a progressive adjustment of motor commands to reduce the magnitude of errors. Isolating the specific contributions to motor behaviour coming from these distinct processes is not possible using traditional single-step Prism Adaptation (PA), where participants are directly exposed to full prismatic shift. Here, we selectively investigated the effect of realignment on motor behaviour by means of a PA paradigm (the multiple-step PA) that allows to elude the development of strategic calibration. We tested for a specific cerebellar contribution to realignment by means of transcranial Direct Current Stimulation (tDCS) in healthy subjects. Confirming and expanding previous imaging and stimulation results, our study causally demonstrates cerebellar involvement in spatial realignment. Additionally, our results point to a possible contribution of the cerebellum in automatic online control. The role of a cortico-cerebellar network accounting for this results and possible clinical applications are proposed and discussed.