Altered static and dynamic cerebellar-cerebral functional connectivity in acute pontine infarction.

This study investigates abnormalities in cerebellar-cerebral static and dynamic functional connectivity among patients with acute pontine infarction, examining the relationship between these connectivity changes and behavioral dysfunction. Resting-state functional magnetic resonance imaging was utilized to collect data from 45 patients within seven days post-pontine infarction and 34 normal controls. Seed-based static and dynamic functional connectivity analyses identified divergences in cerebellar-cerebral connectivity features between pontine infarction patients and normal controls. Correlations between abnormal functional connectivity features and behavioral scores were explored. Compared to normal controls, left pontine infarction patients exhibited significantly increased static functional connectivity within the executive, affective-limbic, and motor networks. Conversely, right pontine infarction patients demonstrated decreased static functional connectivity in the executive, affective-limbic, and default mode networks, alongside an increase in the executive and motor networks. Decreased temporal variability of dynamic functional connectivity was observed in the executive and default mode networks among left pontine infarction patients. Furthermore, abnormalities in static and dynamic functional connectivity within the executive network correlated with motor and working memory performance in patients. These findings suggest that alterations in cerebellar-cerebral static and dynamic functional connectivity could underpin the behavioral dysfunctions observed in acute pontine infarction patients.

Dynamic changes in somatosensory and cerebellar activity mediate temporal recalibration of self-touch.

An organism's ability to accurately anticipate the sensations caused by its own actions is crucial for a wide range of behavioral, perceptual, and cognitive functions. Notably, the sensorimotor expectations produced when touching one's own body attenuate such sensations, making them feel weaker and less ticklish and rendering them easily distinguishable from potentially harmful touches of external origin. How the brain learns and keeps these action-related sensory expectations updated is unclear. Here we employ psychophysics and functional magnetic resonance imaging to pinpoint the behavioral and neural substrates of dynamic recalibration of expected temporal delays in self-touch. Our psychophysical results reveal that self-touches are less attenuated after systematic exposure to delayed self-generated touches, while responses in the contralateral somatosensory cortex that normally distinguish between delayed and nondelayed self-generated touches become indistinguishable. During the exposure, the ipsilateral anterior cerebellum shows increased activity, supporting its proposed role in recalibrating sensorimotor predictions. Moreover, responses in the cingulate areas gradually increase, suggesting that as delay adaptation progresses, the nondelayed self-touches trigger activity related to cognitive conflict. Together, our results show that sensorimotor predictions in the simplest act of touching one's own body are upheld by a sophisticated and flexible neural mechanism that maintains them accurate in time.

Cortical-cerebellar circuits changes in preschool ASD children by multimodal MRI.

OBJECTIVE: To investigate the alterations in cortical-cerebellar circuits and assess their diagnostic potential in preschool children with autism spectrum disorder using multimodal magnetic resonance imaging. METHODS: We utilized diffusion basis spectrum imaging approaches, namely DBSI_20 and DBSI_combine, alongside 3D structural imaging to examine 31 autism spectrum disorder diagnosed patients and 30 healthy controls. The participants' brains were segmented into 120 anatomical regions for this analysis, and a multimodal strategy was adopted to assess the brain networks using a multi-kernel support vector machine for classification. RESULTS: The results revealed consensus connections in the cortical-cerebellar and subcortical-cerebellar circuits, notably in the thalamus and basal ganglia. These connections were predominantly positive in the frontoparietal and subcortical pathways, whereas negative consensus connections were mainly observed in frontotemporal and subcortical pathways. Among the models tested, DBSI_20 showed the highest accuracy rate of 86.88%. In addition, further analysis indicated that combining the 3 models resulted in the most effective performance. CONCLUSION: The connectivity network analysis of the multimodal brain data identified significant abnormalities in the cortical-cerebellar circuits in autism spectrum disorder patients. The DBSI_20 model not only provided the highest accuracy but also demonstrated efficiency, suggesting its potential for clinical application in autism spectrum disorder diagnosis.

Ruptured aneurysm in collateral arteries with blood-flow impairment of posterior inferior cerebellar artery: a report of three cases.

Herein, we report three cases of cerebellar hemorrhage due to a ruptured small aneurysm located on a collateral artery compensating for one or more stenotic or occluded major cerebellar arteries. In each case, endovascular distant parent artery occlusion of both the collateral artery and aneurysm was performed to prevent rebleeding. A ruptured small aneurysm in a collateral artery may be observed in patients with hemorrhage in an atypical cerebellar region, especially in cases of stenosis or occlusion of the vertebral artery or posterior inferior cerebellar artery. Thus, cerebral angiography is recommended to rule out collateral artery aneurysm.

Atypical procedural learning in children with developmental coordination disorder: A combined behavioral and neuroimaging study.

While procedural learning (PL) has been implicated in delayed motor skill observed in developmental coordination disorder (DCD), few studies have considered the impact of co-occurring attentional problems. Furthermore, the neurostructural basis of PL in children remains unclear. We investigated PL in children with DCD while controlling for inattention symptoms, and examined the role of fronto-basal ganglia-cerebellar morphology in PL. Fifty-nine children (6-14 years; nDCD = 19, ncontrol = 40) completed the serial reaction time (SRT) task to measure PL. The Attention-Deficit Hyperactivity Disorder Rating Scale-IV was administered to measure inattention symptoms. Structural T1 images were acquired for a subset of participants (nDCD = 10, ncontrol = 28), and processed using FreeSurfer. Volume was extracted for the cerebellum, basal ganglia, and frontal regions. After controlling for inattention symptoms, the reaction time profile of controls was consistent with learning on the SRT task. This was not the case for those with DCD. SRT task performance was positively correlated with cerebellar cortical volume, and children with DCD trended towards lower cerebellar volume compared to controls. Children with DCD may not engage in PL during the SRT task in the same manner as controls, with this differential performance being associated with atypical cerebellar morphology.

Protocol for combined N-of-1 trials to assess cerebellar neurostimulation for movement disorders in children and young adults with dyskinetic cerebral palsy.

BACKGROUND: Movement and tone disorders in children and young adults with cerebral palsy are a great source of disability. Deep brain stimulation (DBS) of basal ganglia targets has a major role in the treatment of isolated dystonias, but its efficacy in dyskinetic cerebral palsy (DCP) is lower, due to structural basal ganglia and thalamic damage and lack of improvement of comorbid choreoathetosis and spasticity. The cerebellum is an attractive target for DBS in DCP since it is frequently spared from hypoxic ischemic damage, it has a significant role in dystonia network models, and small studies have shown promise of dentate stimulation in improving CP-related movement and tone disorders. METHODS: Ten children and young adults with DCP and disabling movement disorders with or without spasticity will undergo bilateral DBS in the dorsal dentate nucleus, with the most distal contact ending in the superior cerebellar peduncle. We will implant Medtronic Percept, a bidirectional neurostimulator that can sense and store brain activity and deliver DBS therapy. The efficacy of cerebellar DBS in improving quality of life and motor outcomes will be tested by a series of N-of-1 clinical trials. Each N-of-1 trial will consist of three blocks, each consisting of one month of effective stimulation and one month of sham stimulation in a random order with weekly motor and quality of life scales as primary and secondary outcomes. In addition, we will characterize abnormal patterns of cerebellar oscillatory activity measured by local field potentials from the intracranial electrodes related to clinical assessments and wearable monitors. Pre- and 12-month postoperative volumetric structural and functional MRI and diffusion tensor imaging will be used to identify candidate imaging markers of baseline disease severity and response to DBS. DISCUSSION: Our goal is to test a cerebellar neuromodulation therapy that produces meaningful changes in function and well-being for people with CP, obtain a mechanistic understanding of the underlying brain network disorder, and identify physiological and imaging-based predictors of outcomes useful in planning further studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT06122675, first registered November 7, 2023.

Experience of multi-disciplinary treatment of multiple cerebellar diffuse large B-cell lymphoma: A case report.

RATIONALE: Primary central nervous system lymphoma (PCNSL) is a rare, highly malignant form of non-Hodgkin lymphoma categorized under the diffuse large B-cell type. It accounts for merely 1% of all non-Hodgkin lymphoma cases and comprises approximately 3% of all brain tumors. The involvement of the cerebellum is observed in only 9% of these cases. Recently, we came across an unusual instance: a young man presenting with multiple lesions located specifically within the cerebellum. PATIENT CONCERNS: A 26-year-old male was admitted to the hospital due to severe headaches. He has a medical history of sporadic headaches, accompanied by dizziness, nausea, and vomiting persisting for a month. Over the last 10 days, his headaches have intensified, coupled with decreased vision and protrusion of the eyeballs. Magnetic resonance imaging (MRI) revealed abnormal signals in both cerebellar hemispheres. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: Diagnostic procedures included cerebellar biopsy, posterior fossa decompression, and lateral ventricle drainage. Histopathological examination identified diffuse large B-cell lymphoma (DLBCL) with high proliferative activity. To minimize neurotoxicity, chemotherapy involved intrathecal methotrexate (MTX) injections combined with the CHOP program. The patient has shown good tolerance to the treatment so far. LESSONS: While the definitive optimal treatment approach remains elusive, current chemotherapy centered on high-dose MTX stands as the standard induction therapy. Integrating surgery with radiotherapy and chemotherapy significantly extends patient survival.

Joubert syndrome presenting bilateral peroneal neuropathies: A case report.

RATIONALE: Joubert syndrome (JS) is a rare genetic disorder that presents with various neurological symptoms, primarily involving central nervous system dysfunction. Considering the etiology of JS, peripheral nervous system abnormalities cannot be excluded; however, cases of JS accompanied by peripheral nervous system abnormalities have not yet been reported. Distinct radiological findings on brain magnetic resonance imaging were considered essential for the diagnosis of JS. However, recently, cases of JS with normal or nearly normal brain morphology have been reported. To date, there is no consensus on the most appropriate diagnostic method for JS when imaging-based diagnostic approach is challenging. This report describes the case of an adult patient who exhibited bilateral peroneal neuropathies and was finally diagnosed with JS through genetic testing. PATIENT CONCERNS AND DIAGNOSIS: A 27-year-old man visited our outpatient clinic due to a gait disturbance that started at a very young age. The patient exhibited difficulty maintaining balance, especially when walking slowly. Oculomotor apraxia was observed on ophthalmic evaluation. During diagnostic workups, including brain imaging and direct DNA sequencing, no conclusive findings were detected. Only nerve conduction studies revealed profound bilateral peroneal neuropathies. We performed whole genome sequencing to obtain a proper diagnosis and identify the gene mutation responsible for JS. LESSONS: This case represents the first instance of peripheral nerve dysfunction in JS. Further research is needed to explore the association between JS and peripheral nervous system abnormalities. Detailed genetic testing may serve as a valuable tool for diagnosing JS when no prominent abnormalities are detected in brain imaging studies.

Cerebellar dysconnectivity in schizophrenia and bipolar disorder is associated with cognitive and clinical variables.

BACKGROUND: Abnormal cerebellar functional connectivity (FC) has been implicated in the pathophysiology of schizophrenia (SCZ) and bipolar disorder (BD). However, the patterns of cerebellar dysconnectivity in these two disorders and their association with cognitive functioning and clinical symptoms have not been fully clarified. In this study, we examined cerebellar FC alterations in SCZ and BD-I and their association with cognition and psychotic symptoms. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data of 39 SCZ, 43 BD-I, and 61 healthy controls from the Consortium for Neuropsychiatric Phenomics dataset were examined. The cerebellum was parcellated into ten functional networks, and seed-based FC was calculated for each cerebellar system. Principal component analyses were used to reduce the dimensionality of the diagnosis-related FC and cognitive variables. Multiple regression analyses were used to assess the relationship between FC and cognitive and clinical data. RESULTS: We observed decreased cerebellar FC with the frontal, temporal, occipital, and thalamic areas in individuals with SCZ, and a more widespread decrease in cerebellar FC in individuals with BD-I, involving the frontal, cingulate, parietal, temporal, occipital, and thalamic regions. SCZ had increased within-cerebellum and cerebellar frontal FC compared to BD-I. In BD-I, memory and verbal learning performances, which were higher compared to SCZ, showed a greater interaction with cerebellar FC patterns. Additionally, patterns of increased cortico-cerebellar FC were marginally associated with positive symptoms in patients. CONCLUSIONS: Our findings suggest that shared and distinct patterns of cortico-cerebellar dysconnectivity in SCZ and BD-I could underlie cognitive impairments and psychotic symptoms in these disorders.

The role of cerebellum in learned vocal communication in adult songbirds.

Injury, tumors, ischemia, and lesions in the cerebellum show the involvement of this region in human speech. The association of the cerebellum with learned birdsong has only been identified recently. Cerebellar dysfunction in young songbirds causes learning disabilities, but its role in adult songbirds has not been established. The aim of this study was to investigate the role of the deep cerebellar nuclei (DCN) in adult birdsong. We created bilateral excitotoxic lesions in the DCN of adult male zebra finches (Taeniopygia guttata) and recorded their songs for up to 4 months. Using magnetic resonance imaging (MRI) and immunohistochemistry, we validated the lesion efficacy. We found that the song duration significantly increased from 14 weeks post-op; the increase in duration was caused by a greater number of introductory notes as well as a greater number of syllables sung after the introductory notes. On the other hand, the motif duration decreased from 8 weeks after DCN lesions were induced, which was due to faster singing of syllables, not changes in inter-syllable interval length. DCN lesions also caused a decrease in the fundamental frequency of syllables. In summary, we showed that DCN lesions influence the temporal and acoustic features of birdsong. These results suggest that the cerebellum influences singing in adult songbirds.

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.

Cognitive Impairment Is Part of the Phenotype of Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome (CANVAS).

BACKGROUND: Little is known about the impact of the cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) on cognition. OBJECTIVE: Our objective was to determine the frequency and severity of cognitive impairment in RFC1-positive patients and describe the pattern of deficits. METHODS: Participants underwent a comprehensive neuropsychological assessment. Volume of the cerebellum and its lobules was measured in those who underwent a 3 Tesla-magnetic resonance scan. RESULTS: Twenty-one patients underwent a complete assessment, including 71% scoring lower than the cutoff at the Montreal Cognitive assessment and 71% having a definite cerebellar cognitive affective/Schmahmann syndrome. Three patients had dementia and seven met the criteria of mild cognitive impairment. Severity of cognitive impairment did not correlate with severity of clinical manifestations. Performance at memory and visuospatial functions tests negatively correlated with the severity of cerebellar manifestations. CONCLUSION: Cognitive manifestations are frequent in RFC1-related disorders. They should be included in the phenotype and screened systematically. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

One step too far: social cerebellum in norm-violating navigation.

Social norms are pivotal in guiding social interactions. The current study investigated the potential contribution of the posterior cerebellum, a critical region involved in perceiving and comprehending the sequential dynamics of social actions, in detecting actions that either conform to or deviate from social norms. Participants engaged in a goal-directed task in which they observed others navigating towards a goal. The trajectories demonstrated either norm-violating (trespassing forbidden zones) or norm-following behaviors (avoiding forbidden zones). Results revealed that observing social norm-violating behaviors engaged the bilateral posterior cerebellar Crus 2 and the right temporoparietal junction (TPJ) from the mentalizing network, and the parahippocampal gyrus (PHG) to a greater extent than observing norm-following behaviors. These mentalizing regions were also activated when comparing social sequences against non-social and non-sequential control conditions. Reproducing norm-violating social trajectories observed earlier, activated the left cerebellar Crus 2 and the right PHG compared to reproducing norm-following trajectories. These findings illuminate the neural mechanisms in the cerebellum associated with detecting norm transgressions during social navigation, emphasizing the role of the posterior cerebellum in detecting and signaling deviations from anticipated sequences.

The Morphology of Brain Neurons: The Box-Counting Method in the Quantitative Analysis of 2D Images.

This chapter begins by showing the difference between fractal geometry and fractal analysis. The text shows the difference between mathematical and natural fractals and how they are best defined by explaining the concept of fractal analysis. Furthermore, the text presents the most famous technique of fractal analysis: the box-counting method. Defining this method and showing the methodology that leads to the precise value of the fractal (i.e., the box) dimension is done by demonstrating the images of human dentate neurons. A more detailed explanation of the methodology was presented in the previous version of this chapter.This version promotes the notion of monofractal analysis and shows how three types of the same neuronal images can quantify four image properties. The results showed that monofractal parameters successfully quantified four image properties in three nuclei of the cerebellum. Finally, the author discusses the results of this chapter and previously published conclusions. The results show how the monofractal parameters discriminate images of neurons from the three nuclei of the human cerebrum. These outcomes are discussed along with the results of previous studies.

Fractal Dimension Studies of the Brain Shape in Aging and Neurodegenerative Diseases.

The fractal dimension is a morphometric measure that has been used to investigate the changes of brain shape complexity in aging and neurodegenerative diseases. This chapter reviews fractal dimension studies in aging and neurodegenerative disorders in the literature. Research has shown that the fractal dimension of the left cerebral hemisphere increases until adolescence and then decreases with aging, while the fractal dimension of the right hemisphere continues to increase until adulthood. Studies in neurodegenerative diseases demonstrated a decline in the fractal dimension of the gray matter and white matter in Alzheimer's disease, amyotrophic lateral sclerosis, and spinocerebellar ataxia. In multiple sclerosis, the white matter fractal dimension decreases, but conversely, the fractal dimension of the gray matter increases at specific stages of disease. There is also a decline in the gray matter fractal dimension in frontotemporal dementia and multiple system atrophy of the cerebellar type and in the white matter fractal dimension in epilepsy and stroke. Region-specific changes in fractal dimension have also been found in Huntington's disease and Parkinson's disease. Associations were found between the fractal dimension and clinical scores, showing the potential of the fractal dimension as a marker to monitor brain shape changes in normal or pathological processes and predict cognitive or motor function.

Reduced cerebral blood flow and cognitive dysfunction following isolated cerebellar infarction: two case reports.

Cognitive impairment in focal cerebellar disorders has been widely recognized and is described as cerebellar cognitive affective syndrome (CCAS). However, the relationship between CCAS and crossed cerebello-cerebral diaschisis (CCD) has rarely been discussed. The present report describes the uncommon phenomenon of CCD in two cases with isolated cerebellar infarction, and discuss its contribution to cognitive impairment. Cognitive performance was examined using the CCAS scale and a battery of neuropsychological assessments. Moreover, the relative distribution of cerebral and cerebellar blood flow was measured using three-dimensional arterial spin labeling imaging. Case 1 showed deficits in general cognition and had impaired language, episodic memory, and executive function. Case 2 showed deficits in general cognition at baseline, and cognitive deterioration of visuospatial abilities, language, episodic memory, and executive function was observed at the 3-month follow-up. Both cases met the diagnosis criteria of CCAS. Reduced cerebral blood flow was observed in the cerebral hemisphere contralateral to the cerebellar infarction at baseline in Case 1, and at the 3-month follow-up in Case 2. The present report describes cognitive decline after isolated cerebellar infarction in combination with contralateral cerebral hypoperfusion, as measured using quantitative arterial spin labeling. One possible mechanism involves the functional depression of cerebello-cerebral pathways.

Cerebellar and thalamic connector hubs facilitate the involvement of visual and cognitive networks in essential tremor.

INTRODUCTION: Connector hubs are specialized brain regions that connect multiple brain networks and therefore have the potential to affect the functions of multiple systems. This study aims to examine the involvement of connector hub regions in essential tremor. METHODS: We examined whole-brain functional connectivity alterations across multiple brain networks in 27 patients with essential tremor and 27 age- and sex-matched healthy controls to identify affected hub regions using a network metric called functional connectivity overlap ratio estimated from resting-state functional MRI. We also evaluated the relationships of affected hubs with cognitive and tremor scores in all patients and with motor function improvement scores in 15 patients who underwent postoperative follow-up evaluations after focused ultrasound thalamotomy. RESULTS: We have identified affected connector hubs in the cerebellum and thalamus. Specifically, the dentate nucleus in the cerebellum and the dorsomedial thalamus exhibited more extensive connections with the sensorimotor network in patients. Moreover, the connections of the thalamic pulvinar with the visual network were also significantly widespread in the patient group. The connections of these connector hub regions with cognitive networks were negatively associated (FDR q < 0.05) with cognitive, tremor, and motor function improvement scores. CONCLUSION: In patients with essential tremor, connector hub regions within the cerebellum and thalamus exhibited widespread functional connections with sensorimotor and visual networks, leading to alternative pathways outside the classical tremor axis. Their connections with cognitive networks also affect patients' cognitive function.