Re-examining the Mysterious Role of the Cerebellum in Pain.

Pain is considered a multidimensional experience that embodies not merely sensation, but also emotion and perception. As is appropriate for this complexity, pain is represented and processed by an extensive matrix of cortical and subcortical structures. Of these structures, the cerebellum is gaining increasing attention. Although association between the cerebellum and both acute and chronic pain have been extensively detailed in electrophysiological and neuroimaging studies, a deep understanding of what functions are mediated by these associations is lacking. Nevertheless, the available evidence implies that lobules IV-VI and Crus I are especially pertinent to pain processing, and anatomical studies reveal that these regions connect with higher-order structures of sensorimotor, emotional, and cognitive function. Therefore, we speculate that the cerebellum exerts a modulatory role in pain via its communication with sites of sensorimotor, executive, reward, and limbic function. On this basis, in this review, we propose numerous ways in which the cerebellum might contribute to both acute and chronic pain, drawing particular attention to emotional and cognitive elements of pain. In addition, we emphasise the importance of advancing our knowledge about the relationship between the cerebellum and pain by discussing novel therapeutic opportunities that capitalize on this association.

Cerebello-thalamofrontal dysconnectivity in paroxysmal kinesigenic dyskinesia: A resting-state fMRI study.

INTRODUCTION: The pathophysiology of paroxysmal kinesigenic dyskinesia (PKD) remains elusive to date; however, several lines of evidence from neuroimaging studies suggest involvement of the basal ganglia-thalamocortical network in PKD. We combined fractional amplitude of low-frequency fluctuation (fALFF) and seed-based functional connectivity (FC) analyses in order to comprehensively investigate intrinsic brain activity alterations and their relationships with disease severity in patients with idiopathic PKD. METHODS: Resting-state functional MRI data were obtained and processed in 34 PKD patients and 34 matched controls. fALFF and seed-based FC maps were computed and compared between patients and controls. Linear regression analysis was further performed between regional fALFF values or FC strengths and clinical parameters in patients. RESULTS: PKD patients had a significant increase in fALFF in bilateral thalamus and cerebellum compared with controls. FC analysis seeding at the thalamic clusters revealed significant FC increases in motor cortex and supplementary motor area in PKD patients relative to controls. Longer disease duration was associated with increasing FC strength between the thalamus and motor cortex. CONCLUSION: We have provided evidence for abnormal intrinsic activity in the cerebello-thalamic circuit and increased thalamofrontal FC in PKD patients, implicating interictal cerebello-thalamofrontal dysconnectivity in the pathophysiology of PKD. Given the increasing FC strength in proportion to disease duration, the thalamofrontal hyperconnectivity might reflect either a consequence of recurrent dyskinesias on the brain or an innate pathology causing dyskinesias in PKD.

Immune dysfunction in the cerebellum of mice lacking the autism candidate gene Engrailed 2.

Immune system dysfunction has been described in autism spectrum disorder. Here we tested the hypothesis that cerebellar defects are accompanied by immune dysfunction in adult mice lacking the autism-candidate gene Engrailed 2 (En2). Gene ontology analyses revealed that biological processes related to immune function were over-represented in the cerebellar transcriptome of En2-/- mice. Pro-inflammatory molecules and chemokines were reduced in the En2-/- cerebellum compared to controls. Conversely, pro-inflammatory molecules were increased in the peripheral blood of mutant mice. Our results suggest a link between immune dysfunction and cerebellar defects detected in En2-/- mice.

Programmed cell death in cerebellar Purkinje neurons.

Apoptosis, autophagy and necrosis are the three main types of programmed cell death. One or more of these types of programmed cell death may take place in neurons leading to their death in various neurodegenerative disorders in humans. Purkinje neurons (PNs) are among the most highly vulnerable population of neurons to cell death in response to intrinsic hereditary diseases or extrinsic toxic, hypoxic, ischemic, and traumatic injury. In this review, we will describe the three main types of programmed cell death, including the molecular mechanisms and the sequence of events in each of them, and thus illustrating the intracellular proteins that mediate and regulate each of these types. Then, we will discuss the role of Ca2+ in PN function and increased vulnerability to cell death. Additionally, PN death will be described in animal models, namely lurcher mutant mouse and shaker mutant rat, in order to illustrate the potential therapeutic implications of programmed cell death in PNs by reviewing the previous studies that were carried out to interfere with the programmed cell death in an attempt to rescue PNs from death.

Scn1a gene reactivation after symptom onset rescues pathological phenotypes in a mouse model of Dravet syndrome.

Dravet syndrome is a severe epileptic encephalopathy caused primarily by haploinsufficiency of the SCN1A gene. Repetitive seizures can lead to endurable and untreatable neurological deficits. Whether this severe pathology is reversible after symptom onset remains unknown. To address this question, we generated a Scn1a conditional knock-in mouse model (Scn1a Stop/+) in which Scn1a expression can be re-activated on-demand during the mouse lifetime. Scn1a gene disruption leads to the development of seizures, often associated with sudden unexpected death in epilepsy (SUDEP) and behavioral alterations including hyperactivity, social interaction deficits and cognitive impairment starting from the second/third week of age. However, we showed that Scn1a gene re-activation when symptoms were already manifested (P30) led to a complete rescue of both spontaneous and thermic inducible seizures, marked amelioration of behavioral abnormalities and normalization of hippocampal fast-spiking interneuron firing. We also identified dramatic gene expression alterations, including those associated with astrogliosis in Dravet syndrome mice, that, accordingly, were rescued by Scn1a gene expression normalization at P30. Interestingly, regaining of Nav1.1 physiological level rescued seizures also in adult Dravet syndrome mice (P90) after months of repetitive attacks. Overall, these findings represent a solid proof-of-concept highlighting that disease phenotype reversibility can be achieved when Scn1a gene activity is efficiently reconstituted in brain cells.

2 Years into the Pandemic: What Did We Learn About the COVID-19 and Cerebellum?

Highly contagious pandemic due to novel coronavirus SARS-CoV-2, COVID-19 has significantly affected humankind. At the onset of the pandemic, it was believed that it primarily affects the respiratory and hematological system, and has minimal influence on the human brain, even less so on the cerebellum. It was thought that the effects of a pandemic on cerebellar disorders would be the same as it would affect any other chronic neurological disease. It turned out that our understanding of the effects of COVID-19 on the cerebellar system was premature. Over the last 2 years, we appreciated many diverse and direct effects of COVID-19 on cerebellar function. SARS-CoV-2 affects the cerebellum via direct viral invasion, but even more so through its effects on immune, hematological, and metabolic pathways. Increasing evidence suggested the indirect effects of COVID-19 on preexisting chronic cerebellar disease due to lack of in-person care and social isolation. This editorial concisely summarizes critical literature on COVID-19 and the cerebellum published over the last 2 years.

The neurotoxic effect of lactational PFOS exposure on cerebellar functional development in male mice.

Recent studies showed a possible association between perfluorooctane sulfonate (PFOS) and developmental disabilities. We previously found the specific effects of PFOS exposure on learning and memory, however, its effect on the other developmental disabilities such as motor and social deficits remains unclear. We examined the effect of early lactational PFOS exposure on motor coordination, social activity, and anxiety in male mice. We orally administered a PFOS solution to dams from postnatal day 1-14. At 10 weeks old, we conducted a behavior test battery to evaluate motor performance, social activity, and anxiety, followed by electrophysiology and Western blot analysis. PFOS-exposed mice displayed impaired motor coordination. Whole-cell patch-clamp recordings from Purkinje cells revealed that the short-term and long-term plasticity at parallel fiber-Purkinje cell synapses are affected by PFOS exposure. Western blot analysis indicated that PFOS exposure increased syntaxin binding protein 1 (Munc18-1) and glutamate metabotropic receptor 1 (mGluR1) protein levels, which may be associated with the change in neurotransmitter release from parallel fibers and the level of long-term depression, respectively. The present study demonstrates that lactational PFOS exposure may have disrupted the pre- and postsynaptic plasticity at parallel fiber-Purkinje cell synapses, causing profound, long-lasting abnormal effects on the cerebellar function.

tDCS modulates effective connectivity during motor command following; a potential therapeutic target for disorders of consciousness.

Transcranial direct current stimulation (tDCS) is attracting increasing interest as a potential therapeutic route for unresponsive patients with prolonged disorders of consciousness (PDOC). However, research to date has had mixed results. Here, we propose a new direction by directly addressing the mechanisms underlying lack of responsiveness in PDOC, and using these to define our targets and the success of our intervention in the healthy brain first. We report 2 experiments that assess whether tDCS to the primary motor cortex (M1-tDCS; Experiment 1) and the cerebellum (cb-tDCS; Experiment 2) administered at rest modulate thalamo-cortical coupling in a subsequent command following task typically used to clinically assess awareness. Both experiments use sham- and polarity-controlled, randomised, double-blind, crossover designs. In Experiment 1, 22 participants received anodal, cathodal, and sham M1-tDCS sessions while in the MRI scanner. A further 22 participants received the same protocol with cb-tDCS in Experiment 2. We used Dynamic Causal Modelling of fMRI to characterise the effects of tDCS on brain activity and dynamics during simple thumb movements in response to command. We found that M1-tDCS increased thalamic excitation and that Cathodal cb-tDCS increased excitatory coupling from thalamus to M1. All these changes were polarity specific. Combined, our experiments demonstrate that tDCS can successfully modulate long range thalamo-cortical dynamics during command following via targeting of cortical regions. This suggests that M1- and cb-tDCS may allow PDOC patients to overcome the motor deficits at the root of their reduced responsiveness, improving their rehabilitation options and quality of life as a result.

Compound heterozygous ADAMTS9 variants in Joubert syndrome-related disorders without renal manifestation.

BACKGROUND: Ciliopathies are the outcomes of defects of primary cilia structures and functions which cause multisystemic developmental disorders, such as polycystic kidney disease, nephronophthisis, retinitis pigmentosa, Joubert syndrome (JS), and JS-related disorders (JSRD) with additional organ involvement including oral-facial-digital syndrome and so on. They often share common and unexpected phenotypic features. CASE PRESENTATION: We report a 4-year-old-boy case with compound heterozygous variants of ADAMTS9. Unlike the cases with ADAMTS9 variants in the previous report, which identified that homozygous variants of ADAMTS9 were responsible for nephronophthisis-related ciliopathies in two cases, the current case did not have nephronophthisis nor renal dysfunction, and his clinical features, such as oculomotor apraxia, hypotonia, developmental delay, bifid tongue, and mild hypoplasia of cerebellar vermis indicated JSRD. CONCLUSIONS: The case suggested a possible association between the clinical presentation of JSRD and ADAMTS9-related disease, and it shows a wide spectrum of ADAMTS9 phenotype.

Cerebellar malfunction and postoperative sleep disturbances after general anesthesia: a narrative review.

The cerebellum is widely regarded as a brain region involved in motor processing, non-motor processing, and even sleep-wake cycles. Cerebellar dysfunction may cause changes in the sleep-wake cycle, leading to sleep disturbances. At present, there is limited research on its effect on postoperative sleep after general anesthesia, despite the suspicion of its implication in postoperative sleep disturbances. With this review, we aim to provide a clear and comprehensive review of the cerebellar activity during the normal sleep-wake cycle, the correlation between cerebellar dysfunction and postoperative sleep disturbances, and the effects of general anesthesia on cerebellar dysfunction. Future large-scale multicenter trials are needed to objectively support the present results, identify the initial cerebellar dysfunction to prevent postoperative sleep disturbances, and develop new therapeutic measures targeting sleep disturbances with possible far-reaching implications for neurodegenerative diseases in general.

Striatal networks for tinnitus treatment targeting.

Neuromodulation treatment effect size for bothersome tinnitus may be larger and more predictable by adopting a target selection approach guided by personalized striatal networks or functional connectivity maps. Several corticostriatal mechanisms are likely to play a role in tinnitus, including the dorsal/ventral striatum and the putamen. We examined whether significant tinnitus treatment response by deep brain stimulation (DBS) of the caudate nucleus may be related to striatal network increased functional connectivity with tinnitus networks that involve the auditory cortex or ventral cerebellum. The first study was a cross-sectional 2-by-2 factorial design (tinnitus, no tinnitus; hearing loss, normal hearing, n = 68) to define cohort level abnormal functional connectivity maps using high-field 7.0 T resting-state fMRI. The second study was a pilot case-control series (n = 2) to examine whether tinnitus modulation response to caudate tail subdivision stimulation would be contingent on individual level striatal connectivity map relationships with tinnitus networks. Resting-state fMRI identified five caudate subdivisions with abnormal cohort level functional connectivity maps. Of those, two connectivity maps exhibited increased connectivity with tinnitus networks-dorsal caudate head with Heschl's gyrus and caudate tail with the ventral cerebellum. DBS of the caudate tail in the case-series responder resulted in dramatic reductions in tinnitus severity and loudness, in contrast to the nonresponder who showed no tinnitus modulation. The individual level connectivity map of the responder was in alignment with the cohort expectation connectivity map, where the caudate tail exhibited increased connectivity with tinnitus networks, whereas the nonresponder individual level connectivity map did not.

Cerebello-Thalamo-Cortical Hyperconnectivity Classifies Patients and Predicts Long-Term Treatment Outcome in First-Episode Schizophrenia.

It has previously been shown that cerebello-thalamo-cortical (CTC) hyperconnectivity is likely a state-independent neural signature for psychosis. However, the potential clinical utility of this change has not yet been evaluated. Here, using fMRI and clinical data acquired from 214 untreated first-episode patients with schizophrenia (62 of whom were clinically followed-up at least once at the 12th and 24th months after treatment initiation) and 179 healthy controls, we investigated whether CTC hyperconnectivity would serve as an individualized biomarker for diagnostic classification and prediction of long-term treatment outcome. Cross-validated LASSO regression was conducted to estimate the accuracy of baseline CTC connectivity for patient-control classification, with the generalizability of classification performance tested in an independent sample including 42 untreated first-episode patients and 65 controls. Associations between baseline CTC connectivity and clinical outcomes were evaluated using linear mixed model and leave-one-out cross validation. We found significantly increased baseline CTC connectivity in patients (P = .01), which remained stable after treatment. Measures of CTC connectivity discriminated patients from controls with moderate classification accuracy (AUC = 0.68, P < .001), and the classification model had good generalizability in the independent sample (AUC = 0.70, P < .001). Higher CTC connectivity at baseline significantly predicted poorer long-term symptom reduction in negative symptoms (R = 0.31, P = .01) but not positive or general symptoms. These findings provide initial evidence for the putative "CTC hyperconnectivity" anomaly as an individualized diagnostic and prognostic biomarker for schizophrenia, and highlight the potential of this measure in precision psychiatry.

Electrode montage-dependent intracranial variability in electric fields induced by cerebellar transcranial direct current stimulation.

Transcranial direct current stimulation (tDCS) is an increasingly popular tool to investigate the involvement of the cerebellum in a variety of brain functions and pathologies. However, heterogeneity and small effect sizes remain a common issue. One potential cause may be interindividual variability of the electric fields induced by tDCS. Here, we compared electric field distributions and directions between two conventionally used electrode montages (i.e., one placing the return electrode over the ipsilateral buccinator muscle and one placing the return electrode [25 and 35 cm2 surface area, respectively] over the contralateral supraorbital area; Experiment 1) and six alternative montages (electrode size: 9 cm2; Experiment 2) targeting the right posterior cerebellar hemisphere at 2 mA. Interindividual and montage differences in the achieved maximum field strength, focality, and direction of current flow were evaluated in 20 head models and the effects of individual differences in scalp-cortex distance were examined. Results showed that while maximum field strength was comparable for all montages, focality was substantially improved for the alternative montages over inferior occipital positions. Our findings suggest that compared to several conventional montages extracerebellar electric fields are significantly reduced by placing smaller electrodes in closer vicinity of the targeted area.

Increased neural motor activation and functional reorganization in patients with idiopathic rapid eye movement sleep behavior disorder.

INTRODUCTION: Altered brain activity and functional reorganization patterns during self-initiated movements have been reported in early pre-motor and motor stages of Parkinson's disease. The aim of this study was to investigate whether similar alterations can be observed in patients with idiopathic REM-sleep behavior disorder (RBD). METHODS: 13 polysomnography-confirmed male and right-handed RBD patients and 13 healthy controls underwent a bilateral hand-movement fMRI task including internally selected (INT) and externally-guided (EXT) movement conditions for each hand. We examined functional activity and connectivity differences between groups and task-conditions, structural differences using voxel-based morphometry, as well as associations between functional activity and clinical variables. RESULTS: No group differences were observed in fMRI-task performance or in voxel-based morphometry. Both groups showed faster reaction times and exhibited greater neural activation when movements were internally selected compared to externally-guided tasks. Compared to controls, RBD patients displayed stronger activation in the dorsolateral prefrontal cortex and primary somatosensory cortex during INT-tasks, and in the right fronto-insular cortex during EXT-tasks performed with the non-dominant hand. Stronger activation in RBD patients was associated with cognitive and olfactory impairment. Connectivity analysis demonstrated overall less interregional coupling in patients compared to controls. In particular, patients showed reduced temporo-cerebellar, occipito-cerebellar and intra-cerebellar connectivity, but stronger connectivity in fronto-cerebellar and fronto-occipital pathways. CONCLUSION: The observed stronger activation during hand-movement tasks and connectivity changes in RBD may reflect early compensatory and reorganization patterns in order to preserve motor functioning. Our findings may contribute to a better understanding and prognosis of prodromal stages of α-synucleinopathies.

Distinct Fastigial Output Channels and Their Impact on Temporal Lobe Seizures.

Despite being canonically considered a motor control structure, the cerebellum is increasingly recognized for important roles in processes beyond this traditional framework, including seizure suppression. Excitatory fastigial neurons project to a large number of downstream targets, and it is unclear whether this broad targeting underlies seizure suppression, or whether a specific output may be sufficient. To address this question, we used the intrahippocampal kainic acid mouse model of temporal lobe epilepsy, male and female animals, and a dual-virus approach to selectively label and manipulate fastigial outputs. We examined fastigial neurons projecting to the superior colliculus, medullary reticular formation, and central lateral nucleus of the thalamus, and found that these comprise largely nonoverlapping populations of neurons that send collaterals to unique sets of additional, somewhat overlapping, thalamic and brainstem regions. We found that neither optogenetic stimulation of superior colliculus nor reticular formation output channels attenuated hippocampal seizures. In contrast, on-demand stimulation of fastigial neurons targeting the central lateral nucleus robustly inhibited seizures. Our results indicate that fastigial control of hippocampal seizures does not require simultaneous modulation of many fastigial output channels. Rather, selective modulation of the fastigial output channel to the central lateral thalamus, specifically, is sufficient for seizure control. More broadly, our data highlight the concept of specific cerebellar output channels, whereby discrete cerebellar nucleus neurons project to specific aggregates of downstream targets, with important consequences for therapeutic interventions.SIGNIFICANCE STATEMENT The cerebellum has an emerging relationship with nonmotor systems and may represent a powerful target for therapeutic intervention in temporal lobe epilepsy. We find, as previously reported, that fastigial neurons project to numerous brain regions via largely segregated output channels, and that projection targets cannot be predicted simply by somatic locations within the nucleus. We further find that on-demand optogenetic excitation of fastigial neurons projecting to the central lateral nucleus of the thalamus-but not fastigial neurons projecting to the reticular formation, superior colliculus, or ventral lateral thalamus-is sufficient to attenuate hippocampal seizures.

Brain Motor Region Diffusion Tensor Imaging in Patients with Catatonic Schizophrenia: A Case-Control Study.

BACKGROUND: Only a small proportion of schizophrenia patients present with catatonic symptoms. Imaging studies suggest that brain motor circuits are involved in the underlying pathology of catatonia. However, data about diffusivity dysregulation of these circuits in catatonic schizophrenia are scarce. OBJECTIVES: To assess the involvement of brain motor circuits in schizophrenia patients with catatonia. METHODS: Diffusion tensor imaging (DTI) was used to measure white matter signals in selected brain regions linked to motor circuits. Relevant DTI data of seven catatonic schizophrenia patients were compared to those of seven non-catatonic schizophrenia patients, matched for sex, age, and education level. RESULTS: Significantly elevated fractional anisotropy values were found in the splenium of the corpus callosum, the right peduncle of the cerebellum, and the right internal capsule of the schizophrenia patients with catatonia compared to those without catatonia. This finding showed altered diffusivity in selected motor-related brain areas. CONCLUSIONS: Catatonic schizophrenia is associated with dysregulation of the connectivity in specific motoric brain regions and corresponding circuits. Future DTI studies are needed to address the neural correlates of motor abnormalities in schizophrenia-related catatonia during the acute and remitted state of the illness to identify the specific pathophysiology of this disorder.

Integrity of the Inferior Cerebellar Peduncle Correlates with Ambulatory Function after Hemorrhagic Stroke.

OBJECTIVES: Cerebro-cerebellar connectivity plays a critical role in motor recovery after stroke; however, the underlying mechanism of walking recovery is unclear. The dorsal spinocerebellar pathway has been suggested as a biomarker of poststroke ambulatory function. We aimed to explore the association between ambulatory function and the dorsal spinocerebellar pathway's integrity after intracerebral hemorrhage (ICH). MATERIALS AND METHODS: Twenty-seven patients with ICH who were admitted for inpatient rehabilitation during the subacute phase of stroke and 27 age-matched healthy controls were included retrospectively. Ambulatory function was assessed using the Berg Balance Scale and Mobility score. We measured the fractional anisotropy (FA) values of the corticospinal tract (CST) and inferior cerebellar peduncle (ICP) as the final route of the dorsal spinocerebellar pathway. The FA laterality indices, representing the degree of degeneration, were calculated. A Spearman correlation analysis and multivariate linear regression models were used to determine the associations between the FA laterality indices and ambulatory function. RESULTS: An FA reduction was found in both the ipsilesional CST and contralesional ICP of the patients. The ICP FA laterality index exhibited a moderate correlation with ambulatory function (Berg Balance Scale, ρBBS=0.589; Mobility score, ρMS=0.619). On dividing the patient group into the moderate (mRS 3, 4) and severe disability (mRS 5) groups, a stronger correlation was found (ρBBS=0.777, ρMS=0.856, moderate disability; ρBBS=0.732, ρMS=0.797, severe disability). The ICP FA laterality index and age were independently associated with the Mobility score (R2=0.525). CONCLUSIONS: ICP degeneration occurs after ICH, and its degree is associated with ambulatory function after ICH.

The assessment of cognitive functions in patients with isolated cerebellar infarctions: A follow-up study.

The role of the cerebellum on cognitive functions have been well-defined; however, the information related to the progress in time process is limited. In this study, we aimed to evaluate the cognitive function of patients with isolated cerebellar infarction in both the acute stage and the follow-up period. Twenty-three patients with isolated cerebellar infarction and 22 healthy control were examined through an extensive neuropsychological assessment battery. The patients were evaluated in the acute stage and at least six months after the stroke in the follow-up period. There were no significant differences between the patients and the controls regarding age (52.2 ± 7.0 and 54.9 ± 6.6, p = 0.184) and gender (Female/Male: 6/17 and 7/15, p = 0.672). There was no statistically significant difference between patients with right cerebellar infarction and left cerebellar infarction in terms of cognitive functions. Verbal fluency, attention, and verbal and non-verbal episodic memory scores were significantly lower in patient group in the acute stage when compared to the control group. When the follow-up evaluation was compared to acute stage, it was revealed that patients had recovered in all areas; however, less improvement was seen in word reading time. Our results support that lesions of the cerebellum affect cognitive functions in the acute stage. However, the improvement was demonstrated in all cognitive functions in the follow-up period.

Temporo-cerebellar connectivity underlies timing constraints in audition.

The flexible and efficient adaptation to dynamic, rapid changes in the auditory environment likely involves generating and updating of internal models. Such models arguably exploit connections between the neocortex and the cerebellum, supporting proactive adaptation. Here, we tested whether temporo-cerebellar disconnection is associated with the processing of sound at short timescales. First, we identify lesion-specific deficits for the encoding of short timescale spectro-temporal non-speech and speech properties in patients with left posterior temporal cortex stroke. Second, using lesion-guided probabilistic tractography in healthy participants, we revealed bidirectional temporo-cerebellar connectivity with cerebellar dentate nuclei and crura I/II. These findings support the view that the encoding and modeling of rapidly modulated auditory spectro-temporal properties can rely on a temporo-cerebellar interface. We discuss these findings in view of the conjecture that proactive adaptation to a dynamic environment via internal models is a generalizable principle.

Right-hemispheric language reorganization in patients with brain arteriovenous malformations: A functional magnetic resonance imaging study.

Brain arteriovenous malformation (AVM), a presumed congenital lesion, may involve traditional language areas but usually does not lead to language dysfunction unless it ruptures. The objective of this research was to study right-hemispheric language reorganization patterns in patients with brain AVMs using functional magnetic resonance imaging (fMRI). We prospectively enrolled 30 AVM patients with lesions involving language areas and 32 age- and sex-matched healthy controls. Each subject underwent fMRI during three language tasks: visual synonym judgment, oral word reading, and auditory sentence comprehension. The activation differences between the AVM and control groups were investigated by voxelwise analysis. Lateralization indices (LIs) for the frontal lobe, temporal lobe, and cerebellum were compared between the two groups, respectively. Results suggested that the language functions of AVM patients and controls were all normal. Voxelwise analysis showed no significantly different activations between the two groups in visual synonym judgment and oral word reading tasks. In auditory sentence comprehension task, AVM patients had significantly more activations in the right precentral gyrus (BA 6) and right cerebellar lobule VI (AAL 9042). According to the LI results, the frontal lobe in oral word reading task and the temporal lobe in auditory sentence comprehension task were significantly more right-lateralized in the AVM group. These findings suggest that for patients with AVMs involving language cortex, different language reorganization patterns may develop for different language functions. The recruitment of brain areas in the right cerebral and cerebellar hemispheres may play a compensatory role in the reorganized language network of AVM patients.