Cerebro-cerebellar Loops Research Articles

Subject-specific features of excitation/inhibition profiles in neurodegenerative diseases.

Brain pathologies are characterized by microscopic changes in neurons and synapses that reverberate into large scale networks altering brain dynamics and functional states. An important yet unresolved issue concerns the impact of patients’ excitation/inhibition profiles on neurodegenerative diseases including Alzheimer’s Disease, Frontotemporal Dementia, and Amyotrophic Lateral Sclerosis. In this work, we used The Virtual Brain (TVB) simulation platform to simulate brain dynamics in healthy and neurodegenerative conditions and to extract information about the excitatory/inhibitory balance in single subjects. The brain structural and functional connectomes were extracted from 3T-MRI (Magnetic Resonance Imaging) scans and TVB nodes were represented by a Wong-Wang neural mass model endowing an explicit representation of the excitatory/inhibitory balance. Simulations were performed including both cerebral and cerebellar nodes and their structural connections to explore cerebellar impact on brain dynamics generation. The potential for clinical translation of TVB derived biophysical parameters was assessed by exploring their association with patients’ cognitive performance and testing their discriminative power between clinical conditions. Our results showed that TVB biophysical parameters differed between clinical phenotypes, predicting higher global coupling and inhibition in Alzheimer’s Disease and stronger N-methyl-D-aspartate (NMDA) receptor-dependent excitation in Amyotrophic Lateral Sclerosis. These physio-pathological parameters allowed us to perform an advanced analysis of patients’ conditions. In backward regressions, TVB-derived parameters significantly contributed to explain the variation of neuropsychological scores and, in discriminant analysis, the combination of TVB parameters and neuropsychological scores significantly improved the discriminative power between clinical conditions. Moreover, cluster analysis provided a unique description of the excitatory/inhibitory balance in individual patients. Importantly, the integration of cerebro-cerebellar loops in simulations improved TVB predictive power, i.e., the correlation between experimental and simulated functional connectivity in all pathological conditions supporting the cerebellar role in brain function disrupted by neurodegeneration. Overall, TVB simulations reveal differences in the excitatory/inhibitory balance of individual patients that, combined with cognitive assessment, can promote the personalized diagnosis and therapy of neurodegenerative diseases.

Cerebellar Transcranial Magnetic Stimulation (TMS) Impairs Visual Working Memory.

An increasing body of evidence points to the involvement of the cerebellum in cognition. Specifically, previous studies have shown that the superior and inferior portions of the cerebellum are involved in different verbal working memory (WM) mechanisms as part of two separate cerebro-cerebellar loops for articulatory rehearsal and phonological storage mechanisms. In comparison, our understanding of the involvement of the cerebellum in visual WM remains limited. We have previously shown that performance in verbal WM is disrupted by single-pulse transcranial magnetic stimulation (TMS) of the right superior cerebellum. The present study aimed to expand on this notion by exploring whether the inferior cerebellum is similarly involved in visual WM. Here, we used fMRI-guided, double-pulse TMS to probe the necessity of left superior and left inferior cerebellum in visual WM. We first conducted an fMRI localizer using the Sternberg visual WM task, which yielded targets in left superior and inferior cerebellum. Subsequently, TMS stimulation of these regions at the end of the encoding phase resulted in decreased accuracy in the visual WM task. Differences in the visual WM deficits caused by stimulation of superior and inferior left cerebellum raise the possibility that these regions are involved in different stages of visual WM.

Mapping of long-term cognitive and motor deficits in pediatric cerebellar brain tumor survivors into a cerebellar white matter atlas

PurposeDiaschisis of cerebrocerebellar loops contributes to cognitive and motor deficits in pediatric cerebellar brain tumor survivors. We used a cerebellar white matter atlas and hypothesized that lesion symptom mapping may reveal the critical lesions of cerebellar tracts.MethodsWe examined 31 long-term survivors of pediatric posterior fossa tumors (13 pilocytic astrocytoma, 18 medulloblastoma). Patients underwent neuronal imaging, examination for ataxia, fine motor and cognitive function, planning abilities, and executive function. Individual consolidated cerebellar lesions were drawn manually onto patients’ individual MRI and normalized into Montreal Neurologic Institute (MNI) space for further analysis with voxel-based lesion symptom mapping.ResultsLesion symptom mapping linked deficits of motor function to the superior cerebellar peduncle (SCP), deep cerebellar nuclei (interposed nucleus (IN), fastigial nucleus (FN), ventromedial dentate nucleus (DN)), and inferior vermis (VIIIa, VIIIb, IX, X). Statistical maps of deficits of intelligence and executive function mapped with minor variations to the same cerebellar structures.ConclusionWe identified lesions to the SCP next to deep cerebellar nuclei as critical for limiting both motor and cognitive function in pediatric cerebellar tumor survivors. Future strategies safeguarding motor and cognitive function will have to identify patients preoperatively at risk for damage to these critical structures and adapt multimodal therapeutic options accordingly.

The Importance of Cerebellar Connectivity on Simulated Brain Dynamics.

The brain shows a complex multiscale organization that prevents a direct understanding of how structure, function and dynamics are correlated. To date, advances in neural modeling offer a unique opportunity for simulating global brain dynamics by embedding empirical data on different scales in a mathematical framework. The Virtual Brain (TVB) is an advanced data-driven model allowing to simulate brain dynamics starting from individual subjects’ structural and functional connectivity obtained, for example, from magnetic resonance imaging (MRI). The use of TVB has been limited so far to cerebral connectivity but here, for the first time, we have introduced cerebellar nodes and interconnecting tracts to demonstrate the impact of cerebro-cerebellar loops on brain dynamics. Indeed, the matching between the empirical and simulated functional connectome was significantly improved when including the cerebro-cerebellar loops. This positive result should be considered as a first step, since issues remain open about the best strategy to reconstruct effective structural connectivity and the nature of the neural mass or mean-field models generating local activity in the nodes. For example, signal processing is known to differ remarkably between cortical and cerebellar microcircuits. Tackling these challenges is expected to further improve the predictive power of functional brain activity simulations, using TVB or other similar tools, in explaining not just global brain dynamics but also the role of cerebellum in determining brain states in physiological conditions and in the numerous pathologies affecting the cerebro-cerebellar loops.

Topological Disruption of Structural Brain Networks in Patients With Cognitive Impairment Following Cerebellar Infarction.

Cerebellar lesions can lead to a series of cognitive and emotional disorders by influencing cerebral activity via cerebro-cerebellar loops. To explore changes in cognitive function and structural brain networks in patients with posterior cerebellar infarction, we conducted the current study using diffusion-weighted MRI (32 cerebellar infarction patients, 29 controls). Moreover, a series of neuropsychological tests were used to assess the subject's cognitive performance. We found cognitive impairment following cerebellar infarction involving multiple cognitive domains, including memory, executive functions, visuospatial abilities, processing speed and language functions, and brain topological abnormalities, including changes in clustering coefficients, shortest path lengths, global efficiency, local efficiencies, betweenness centrality and nodal efficiencies. Our results indicated that measures of local efficiency, mainly in the precuneus, cingulate gyrus and frontal-temporal cortex, were significantly reduced with posterior cerebellar infarction. At the same time, The correlation analysis suggested thatthe abnormal alterations in the right PCG, bilateral DCG, right PCUN may play a core role in the cognitive impairment following cerebellar infarctions. The differences in topological features of the structural brain networks within the cerebro-cerebellar circuits may provide a new approach to explore the pathophysiological mechanisms of cognitive impairment following cerebellar infarction.

Prominent Changes in Cerebro-Cerebellar Functional Connectivity During Continuous Cognitive Processing.

While task-dependent responses of specific brain areas during cognitive tasks are well established, much less is known about the changes occurring in resting state networks (RSNs) in relation to continuous cognitive processing. In particular, the functional involvement of cerebro-cerebellar loops connecting the posterior cerebellum to associative cortices, remains unclear. In this study, 22 healthy volunteers underwent a multi-session functional magnetic resonance imaging (fMRI) protocol composed of four consecutive 8-min resting state fMRI (rs-fMRI) scans. After a first control scan, participants listened to a narrated story for the entire duration of the second rs-fMRI scan; two further rs-fMRI scans followed the end of story listening. The story plot was purposely designed to stimulate specific cognitive processes that are known to involve the cerebro-cerebellar loops. Almost all of the identified 15 RSNs showed changes in functional connectivity (FC) during and for several minutes after the story. The FC changes mainly occurred in the frontal and prefrontal cortices and in the posterior cerebellum, especially in Crus I-II and lobule VI. The FC changes occurred in cerebellar clusters belonging to different RSNs, including the cerebellar network (CBLN), sensory networks (lateral visual network, LVN; medial visual network, MVN) and cognitive networks (default mode network, DMN; executive control network, ECN; right and left ventral attention networks, RVAN and LVAN; salience network, SN; language network, LN; and working memory network, WMN). Interestingly, a k-means analysis of FC changes revealed clustering of FCN, ECN, and WMN, which are all involved in working memory functions, CBLN, DMN, and SN, which play a key-role in attention switching, and RSNs involved in visual imagery. These results show that the cerebellum is deeply entrained in well-structured network clusters, which reflect multiple aspects of cognitive processing, during and beyond the conclusion of auditory stimulation.

Tremor syndromes: A review.

Among the involuntary movement disorders, tremor is a common phenomenology seen in clinical practice. The important factors that need to be determined while assessing a patient with tremor include the phenomenology of tremor, presence or absence of other neurologic signs, and the effect of medications or alcohol. Tremor can broadly be classified based on the circumstances under which it occurs, i.e., rest or action. The basal ganglia-cerebello-thalamic and dentate-olivary circuits are involved in the generation of tremor. Experimental data have suggested the olivocerebellar system as the site of the central oscillator in essential tremor. Generation of tremor in Parkinson's disease results from loss of dopaminergic neurons of the retrorubral area causing dysfunction of the globus pallidus, which finally leads to abnormal firing pattern of the ventrolateral posterior neurons of the thalamus. Involvement of the cerebello-thalamic pathways leads to orthostatic tremor. Palatal tremor is thought to be generated by the cells of the inferior olive. Holmes tremor usually results from the disruption of the dentate-rubro-thalamic circuit and also the nigro-striatal circuit. Multiple drugs can cause tremors. Demyelinating neuropathies are associated with tremors. Involvement of the deep cerebellar nuclei, cerebellar outflow tracts and the cerebrocerebellar loops has been postulated in the cerebellar tremor production. Electrophysiological methods are valuable in characterizing tremors. In addition to the pharmacological therapy including botulinum toxin therapy, surgical therapies in form of DBS or lesional surgeries are beneficial in reducing the symptoms.

Contralateral cortico-ponto-cerebellar pathways reconstruction in humans in vivo: implications for reciprocal cerebro-cerebellar structural connectivity in motor and non-motor areas

Cerebellar involvement in cognition, as well as in sensorimotor control, is increasingly recognized and is thought to depend on connections with the cerebral cortex. Anatomical investigations in animals and post-mortem humans have established that cerebro-cerebellar connections are contralateral to each other and include the cerebello-thalamo-cortical (CTC) and cortico-ponto-cerebellar (CPC) pathways. CTC and CPC characterization in humans in vivo is still challenging. Here advanced tractography was combined with quantitative indices to compare CPC to CTC pathways in healthy subjects. Differently to previous studies, our findings reveal that cerebellar cognitive areas are reached by the largest proportion of the reconstructed CPC, supporting the hypothesis that a CTC-CPC loop provides a substrate for cerebro-cerebellar communication during cognitive processing. Amongst the cerebral areas identified using in vivo tractography, in addition to the cerebral motor cortex, major portions of CPC streamlines leave the prefrontal and temporal cortices. These findings are useful since provide MRI-based indications of possible subtending connectivity and, if confirmed, they are going to be a milestone for instructing computational models of brain function. These results, together with further multi-modal investigations, are warranted to provide important cues on how the cerebro-cerebellar loops operate and on how pathologies involving cerebro-cerebellar connectivity are generated.

Cerebro-cerebellar circuits in autism spectrum disorder.

The cerebellum is one of the most consistent sites of abnormality in autism spectrum disorder (ASD) and cerebellar damage is associated with an increased risk of ASD symptoms, suggesting that cerebellar dysfunction may play a crucial role in the etiology of ASD. The cerebellum forms multiple closed-loop circuits with cerebral cortical regions that underpin movement, language, and social processing. Through these circuits, cerebellar dysfunction could impact the core ASD symptoms of social and communication deficits and repetitive and stereotyped behaviors. The emerging topography of sensorimotor, cognitive, and affective subregions in the cerebellum provides a new framework for interpreting the significance of regional cerebellar findings in ASD and their relationship to broader cerebro-cerebellar circuits. Further, recent research supports the idea that the integrity of cerebro-cerebellar loops might be important for early cortical development; disruptions in specific cerebro-cerebellar loops in ASD might impede the specialization of cortical regions involved in motor control, language, and social interaction, leading to impairments in these domains. Consistent with this concept, structural, and functional differences in sensorimotor regions of the cerebellum and sensorimotor cerebro-cerebellar circuits are associated with deficits in motor control and increased repetitive and stereotyped behaviors in ASD. Further, communication and social impairments are associated with atypical activation and structure in cerebro-cerebellar loops underpinning language and social cognition. Finally, there is converging evidence from structural, functional, and connectivity neuroimaging studies that cerebellar right Crus I/II abnormalities are related to more severe ASD impairments in all domains. We propose that cerebellar abnormalities may disrupt optimization of both structure and function in specific cerebro-cerebellar circuits in ASD.

The Cerebellum and Premenstrual Dysphoric Disorder.

The cerebellum constitutes ten percent of brain volume and contains the majority of brain neurons. Although it was historically viewed primarily as processing motoric computations, current evidence supports a more comprehensive role, where cerebro-cerebellar feedback loops also modulate various forms of cognitive and affective processing. Here we present evidence for a role of the cerebellum in premenstrual dysphoric disorder (PMDD), which is characterized by severe negative mood symptoms during the luteal phase of the menstrual cycle. Although a link between menstruation and cyclical dysphoria has long been recognized, neuroscientific investigations of this common disorder have only recently been explored. This article reviews functional and structural brain imaging studies of PMDD and the similar but less well defined condition of premenstrual syndrome (PMS). The most consistent findings are that women with premenstrual dysphoria exhibit greater relative activity than other women in the dorsolateral prefrontal cortex and posterior lobules VI and VII of the neocerebellum. Since both brain areas have been implicated in emotional processing and mood disorders, working memory and executive functions, this greater activity probably represents coactivation within a cerebro-cerebellar feedback loop regulating emotional and cognitive processing. Some of the evidence suggests that increased activity within this circuit may preserve cerebellar structure during aging, and possible mechanisms and implications of this finding are discussed.

Disrupted connectivity of motor loops in Parkinson's disease during self-initiated but not externally-triggered movements

Parkinson's disease (PD) reportedly includes altered connectivity of neural loops involving the basal ganglia and cerebellum, although little is known regarding any changes in the connectivity of motor loops. The goal of this study was to further understand the connectivity within the basal ganglia–thalamo-motor (BGTM) and cerebro-cerebellar (CC) loops in PD. Twelve PD patients and 12 age-matched control subjects performed a protocol involving self-initiated (SI) and externally-triggered (ET) finger movements, while being scanned with functional magnetic resonance imaging. Compared with the control subjects, the PD subjects showed hypo-activation in the bilateral putamen, right supplementary motor area and hyper-activation in the right premotor cortex. In the sensorimotor cortex and cerebellar hemisphere, PD subjects tended to show hyper-activation in a main effects analysis, but hypo-activation in a linear effects analysis. Analysis using structural equation modeling (SEM) revealed significant positive interactions within the right BGTM loop during the SI task and within the right (right cerebral hemisphere–left cerebellum) CC loop during the ET task. SEM also revealed task-related quantitative changes between the thalamus and the motor cortices in the control subjects. We found that the PD patients showed reduced connectivity in the right BGTM loop and inter-hemispheric connections in SEM, which is the first demonstration of this phenomenon. Interestingly, PD patients exhibited preserved connectivity within the right CC loop during the ET task. These results suggest disruption of cortico-striatal processing and preservation of relatively intact neural circuits that do not involve the basal ganglia in PD.

Distributed cerebellar plasticity implements adaptable gain control in a manipulation task: a closed-loop robotic simulation

Adaptable gain regulation is at the core of the forward controller operation performed by the cerebro-cerebellar loops and it allows the intensity of motor acts to be finely tuned in a predictive manner. In order to learn and store information about body-object dynamics and to generate an internal model of movement, the cerebellum is thought to employ long-term synaptic plasticity. LTD at the PF-PC synapse has classically been assumed to subserve this function (Marr, 1969). However, this plasticity alone cannot account for the broad dynamic ranges and time scales of cerebellar adaptation. We therefore tested the role of plasticity distributed over multiple synaptic sites (Hansel et al., 2001; Gao et al., 2012) by generating an analog cerebellar model embedded into a control loop connected to a robotic simulator. The robot used a three-joint arm and performed repetitive fast manipulations with different masses along an 8-shape trajectory. In accordance with biological evidence, the cerebellum model was endowed with both LTD and LTP at the PF-PC, MF-DCN and PC-DCN synapses. This resulted in a network scheme whose effectiveness was extended considerably compared to one including just PF-PC synaptic plasticity. Indeed, the system including distributed plasticity reliably self-adapted to manipulate different masses and to learn the arm-object dynamics over a time course that included fast learning and consolidation, along the lines of what has been observed in behavioral tests. In particular, PF-PC plasticity operated as a time correlator between the actual input state and the system error, while MF-DCN and PC-DCN plasticity played a key role in generating the gain controller. This model suggests that distributed synaptic plasticity allows generation of the complex learning properties of the cerebellum. The incorporation of further plasticity mechanisms and of spiking signal processing will allow this concept to be extended in a more realistic computational scenario.

Seeking a unified framework for cerebellar function and dysfunction: from circuit operations to cognition

Following the fundamental recognition of its involvement in sensory-motor coordination and learning, the cerebellum is now also believed to take part in the processing of cognition and emotion. This hypothesis is recurrent in numerous papers reporting anatomical and functional observations, and it requires an explanation. We argue that a similar circuit structure in all cerebellar areas may carry out various operations using a common computational scheme. On the basis of a broad review of anatomical data, it is conceivable that the different roles of the cerebellum lie in the specific connectivity of the cerebellar modules, with motor, cognitive, and emotional functions (at least partially) segregated into different cerebro-cerebellar loops. We here develop a conceptual and operational framework based on multiple interconnected levels (a meta-levels hypothesis): from cellular/molecular to network mechanisms leading to generation of computational primitives, thence to high-level cognitive/emotional processing, and finally to the sphere of mental function and dysfunction. The main concept explored is that of intimate interplay between timing and learning (reminiscent of the “timing and learning machine” capabilities long attributed to the cerebellum), which reverberates from cellular to circuit mechanisms. Subsequently, integration within large-scale brain loops could generate the disparate cognitive/emotional and mental functions in which the cerebellum has been implicated. We propose, therefore, that the cerebellum operates as a general-purpose co-processor, whose effects depend on the specific brain centers to which individual modules are connected. Abnormal functioning in these loops could eventually contribute to the pathogenesis of major brain pathologies including not just ataxia but also dyslexia, autism, schizophrenia, and depression.

Effective Connectivity of the Human Cerebellum during Visual Attention

Insights from both lesion and neuroimaging studies increasingly substantiate the view that the human cerebellum not only serves motor control but also supports various cognitive processes. Higher cognitive functions like working memory or executive control have been associated with the phylogenetically younger parts of the cerebellum, crus I and crus II. Functional connectivity studies corroborate this notion as activation of the cerebellum correlates with activity in numerous areas of the cerebral cortex. Moreover, these cerebrocerebellar loops were shown to be topographically organized. We used an attention-to-motion paradigm to elaborate on the effective connectivity of cerebellar crus I during visual attention. Psychophysiological interaction analyses demonstrated enhanced connectivity of the cerebellum--during attention--with dorsal visual stream regions including posterior parietal cortex (PPC) and left secondary visual cortex (V5). Dynamic causal modeling revealed a modulation of the connections from V5 to PPC and from crus I to V5 by attention. Remarkably, the influence which V5 exerted on PPC was reduced during attention, resulting in a suppression of the sensitivity of PPC to bottom-up information. Moreover, the sensitivity of V5 populations to inputs from crus I was increased under attention. This might underscore the presumed role of the cerebellum as a state estimator that provides hierarchically lower regions (V5) with top-down predictions, which in turn might be based on endogenous inputs from PPC to the cerebellum. These results are in line with formulations of attention in predictive coding, where attention increases the precision or sensitivity of hierarchically lower neuronal populations that may encode prediction error.

Mechanisms of cerebellar contributions to cognition in humans.

The role of the human cerebellum in cognitive processes is the subject of ongoing debate. On the basis of neuroanatomical findings of closed cerebro-cerebellar loops in monkeys, which originate not only in motor but also in nonmotor regions of the cerebral cortex, this article addresses mechanisms of the involvement of the human cerebellum in two well-studied cognitive domains, executive function, working memory in particular, and associative learning, with special emphasis on the nature of a potential cerebellar contribution to these cognitive processes. The uniform organization of cortico-cerebellar connections suggests parallels in cerebellar information processing in motor- and nonmotor contexts. Taking into account recent models on cerebellar function, it is suggested that the main contribution of the cerebellum to motor as well as to cognitive tasks may be to provide accurate predictions of future sensations, actions, and events. WIREs Cogn Sci 2012, 3:171-184. doi: 10.1002/wcs.1161 For further resources related to this article, please visit the WIREs website.

Cognitive Impairment in ARCA-1, a Newly Discovered Pure Cerebellar Ataxia Syndrome

Cerebellar contribution to non-motor functions has been supported by several animal, human and functional neuroimaging studies. Which cognitive skills and to what extent the cerebrocerebellar loops contribute remain unclear, however. Among other reasons, this may be explained by the fact that authors have studied patients with extracerebellar lesions. The goal of this study was to explore the role of the cerebellum in cognition and affect in patients with autosomal recessive cerebellar ataxia type 1 (ARCA-1), a newly described inherited cerebellar disease characterised by middle-age onset of ataxia as well as pure, severe and diffuse cerebellar atrophy. To this end, the performance of 21 ARCA-1 patients was compared to that of 21 normal controls paired for age and education on a 3-h battery of attention, executive, visuospatial and memory skills. Results indicated similar IQ, naming and declarative memory abilities between groups. ARCA-1 patients showed significant deficits in attention (attention span, speed of information processing, sustained attention), verbal working memory and visuospatial/visuoconstructional skills (3-D drawings, copy of a complex figure). Functional brain imaging in a subset of patients showed diffuse severe cerebellar hypometabolism associated with a small area of right parietal hypometabolism. None of the patients presented a significant affective syndrome. Correlational analyses suggested that cognitive deficits could not be explained by the severity of motor deficits, duration of disease or mood. Altogether, this study confirms that pure cerebellar damage as seen in ARCA-1 is associated with significant cognitive impairments but not with psychiatric comorbidity. These deficits are correlated with an overall moderate impact on patient's autonomy. Our data favour an indirect participation of the dorsolateral prefrontal and posterior parietal cortical areas to the cerebrocerebellar circuit.

Modification of effective connectivity of cerebro-cerebellar loop by movement of the opposing limb

Parkinson's disease (PD) reportedly includes altered connectivity of neural loops involving the basal ganglia and cerebellum, although little is known regarding any changes in the connectivity of motor loops. The goal of this study was to further understand the connectivity within the basal ganglia–thalamo-motor (BGTM) and cerebro-cerebellar (CC) loops in PD. Twelve PD patients and 12 age-matched control subjects performed a protocol involving self-initiated (SI) and externally-triggered (ET) finger movements, while being scanned with functional magnetic resonance imaging. Compared with the control subjects, the PD subjects showed hypo-activation in the bilateral putamen, right supplementary motor area and hyper-activation in the right premotor cortex. In the sensorimotor cortex and cerebellar hemisphere, PD subjects tended to show hyper-activation in a main effects analysis, but hypo-activation in a linear effects analysis. Analysis using structural equation modeling (SEM) revealed significant positive interactions within the right BGTM loop during the SI task and within the right (right cerebral hemisphere–left cerebellum) CC loop during the ET task. SEM also revealed task-related quantitative changes between the thalamus and the motor cortices in the control subjects. We found that the PD patients showed reduced connectivity in the right BGTM loop and inter-hemispheric connections in SEM, which is the first demonstration of this phenomenon. Interestingly, PD patients exhibited preserved connectivity within the right CC loop during the ET task. These results suggest disruption of cortico-striatal processing and preservation of relatively intact neural circuits that do not involve the basal ganglia in PD.

Weakened synchronization of internal representations and reality in autism. A role of the cerebellum?

Event Abstract Back to Event Weakened synchronization of internal representations and reality in autism. A role of the cerebellum? Marianna Boso1, 2*, Matteo Rocchetti1, 2, Enzo Emanuele2, Francesca Prestori1, 3, Pierluigi Politi2, Francesco Barale2 and Egidio D‘Angelo1, 4 1 University of Pavia, Department of Physiology, Italy 2 University of Pavia, Department of Applied Health and Behavioral Sciences, Section of Psychiatry, Italy 3 Pavia Unit, CNISM, Italy 4 IRCCS C. Mondino, BCC, Italy Despite its involvement in sensori-motor processing, the cerebellum is strongly implicated in emotion and cognition. In particular, the cerebellum is involved in the analysis of biophysical components and in the synthetization of high-level percepts or concepts. This continuous crosstalk between analysis and synthesis, generating a virtual reality that in real time is confronted with the actual world, assures a tuneful flow of emotional and cognitive motor processes and at the same time minimizes the reactivity time, improving the identification of errors and novelty. Autism, a severe neurodevelopmental disorder affecting interaction and communication, provides a complex case in which not only the analysis of details is dissociated from the whole but also the relationship between internal representations and reality is weakened. Results of this alterations are the impaired social attunements, the insistence in routine and rituals and the intense desire of sameness find in this condition. At an anatomical level, relevant connections have been shown between the cerebellum and prefrontal lobe (PFL), inferior parietal lobe (IPL), left anterior temporal lobe (LATL) and recent data suggests a possible role of the cerebello-cortical loops in determining the autism core features. These suggestions derive from some critical neurophysiological findings of abnormal excitatory/inhibitory balance, which have as anatomical/functional correlates the patterns of local hyperconnectivity associated with weak long-range connectivity largely demonstrated in autism. These alterations could weak the ability of the brain to generate a complex system of rhythms that can entrain the network modules into coherent oscillations. Of note, a similar dysfunction seem to involve necessarily the cerebellum which is considered the time-keeper of the whole brain. The potential involvement of rhythm-entrained systems and cerebro-cerebellar loops opens new perspectives for the investigation of autistic disorders. Besides the studies on animal models, that could help understanding the molecular basis of the disease and its anomalies in short-range connectivity, research on long-range connectivity in humans is required addressing the functional connectivity between PFL, IPL, LATL and cerebellum and including fMRI, TMS and MEG investigations. Keywords: Cerebellum Conference: The Cerebellum: from neurons to higher control and cognition, Pavia, Italy, 8 Jul - 9 Jul, 2010. Presentation Type: Poster Presentation Topic: The Cerebellum: from neurons to higher control and cognition Citation: Boso M, Rocchetti M, Emanuele E, Prestori F, Politi P, Barale F and D‘Angelo E (2010). Weakened synchronization of internal representations and reality in autism. A role of the cerebellum? . Front. Neurosci. Conference Abstract: The Cerebellum: from neurons to higher control and cognition. doi: 10.3389/conf.fnins.2010.83.00001 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 17 Aug 2010; Published Online: 29 Aug 2010. * Correspondence: Dr. Marianna Boso, University of Pavia, Department of Physiology, Pavia, Italy, m_boso@yahoo.it Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Marianna Boso Matteo Rocchetti Enzo Emanuele Francesca Prestori Pierluigi Politi Francesco Barale Egidio D‘Angelo Google Marianna Boso Matteo Rocchetti Enzo Emanuele Francesca Prestori Pierluigi Politi Francesco Barale Egidio D‘Angelo Google Scholar Marianna Boso Matteo Rocchetti Enzo Emanuele Francesca Prestori Pierluigi Politi Francesco Barale Egidio D‘Angelo PubMed Marianna Boso Matteo Rocchetti Enzo Emanuele Francesca Prestori Pierluigi Politi Francesco Barale Egidio D‘Angelo Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. 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Cerebellar contributions to speech production and speech perception: psycholinguistic and neurobiological perspectives

Articulate speech represents a unique trait of our species. Besides other structures, the cerebellum pertains to the brain network engaged in spoken language production. Data from different sources point at a dual role of this organ within the verbal domain: (i) the cerebellum appears to subserve the online sequencing of syllables into fast, smooth and rhythmically organized larger utterances, and (ii) furthermore, the cerebellum seems to participate in the temporal organization of internal speech, that is, a prearticulatory verbal code. Impaired prearticulatory verbal coding mechanisms could explain at least some of the perceptual and cognitive deficits observed in cerebellar disorders. Recent genetic studies indicate that distinct mutations of a specific regulatory gene (FOXP2) promoted the emergence of articulate speech during the course of hominid evolution. Conceivably, structural changes of the expressed FOXP2 protein supported the 'vocal elaboration' of phylogenetically older brain networks engaged in upper limb motor control, such as the cerebro-cerebellar loops.

Cerebellar contributions to cognitive functions: A progress report after two decades of research

Accumulating evidence from both human lesion and functional neuroimaging studies appears to support the hypothesis that the cerebellum contributes to non-motor functions. Along similar lines, cognitive, affective and behavioural changes in psychiatric disorders, such as autism, schizophrenia and dyslexia, have been linked to structural cerebellar abnormalities. The aim of this special issue was to evaluate the current knowledge base after more than 20 years of controversial discussion. The contributions of the special issue cover the most important cognitive domains, i.e., attention, memory and learning, executive control, language and visuospatial function. The available empirical evidence suggests that cognitive changes in patients with cerebellar dysfunction are mild and clearly less severe than the impairments observed after lesions to neocortical areas to which the cerebellum is closely connected via different cerebro-cerebellar loops. Frequently cited early findings, e.g., with respect to a specific cerebellar involvement in attention, have not been replicated or might be confounded by motor or working memory demands of the respective attention task. On the other hand, there is now convincing evidence for a cerebellar involvement in the mediation of a range of cognitive domains, most notably verbal working memory. Verbal working memory problems may partly underlie the compromised performance of cerebellar lesion patients on at least some complex cognitive tasks. Although investigations have moved from anecdotical case reports to hypothesis-driven controlled clinical group studies based on sound methods which are complemented by state-of-the-art functional neuroimaging studies, the empirical evidence available so far does not yet allow a convincing theory of the mechanisms of a cerebellar involvement in cognitive function. Future studies are clearly needed to further elucidate the nature of the processes linked to cerebellar mediation of cognitive processes and their possible link to motor theories of cerebellar function, e.g., its role in prediction and/or timing.