Cerebellar Changes Research Articles

Convolutional Neural Network for Fully Automated Cerebellar Volumetry in Children in Comparison to Manual Segmentation and Developmental Trajectory of Cerebellar Volumes

The purpose of this study was to develop a fully automated and reliable volumetry of the cerebellum of children during infancy and childhood using deep learning algorithms in comparison to manual segmentation. In addition, the clinical usefulness of measuring the cerebellar volume is shown. One hundred patients (0 to 16.3 years old) without infratentorial signal abnormalities on conventional MRI were retrospectively selected from our pool of pediatric MRI examinations. Based on a routinely acquired 3D T1-weighted magnetization prepared rapid gradient echo (MPRAGE) sequence, the cerebella were manually segmented using ITK-SNAP. The data set of all 100 cases was divided into four splits (four-fold cross-validation) to train the network (NN) to delineate the boundaries of the cerebellum. First, the accuracy of the newly created neural network was compared with the manual segmentation. Secondly, age-related volume changes were investigated. Our trained NN achieved an excellent Spearman correlation coefficient of 0.99, a Dice Coefficient of 95.0 ± 2.1%, and an intersection over union (IoU) of 90.6 ± 3.8%. Cerebellar volume increased continuously with age, showing an exponentially rapid growth within the first year of life. Using a convolutional neural network, it was possible to achieve reliable, fully automated cerebellar volume measurements in childhood and infancy, even when based on a relatively small cohort. In this preliminary study, age-dependent cerebellar volume changes could be acquired.

Genetic contribution of synapse-associated protein 97 to cerebellar functional connectivity changes in first-episode schizophrenia

Our previous study data suggested that the synapse-associated protein 97 (SAP97) rs3915512 polymorphism is significantly related to clinical performance in schizophrenia. The cerebellum exhibits abundant expression of SAP97, which is involved with negative symptoms, cognition and emotion in schizophrenia. As functional dysconnectivity with the cortical-subcortical-cerebellar circuitry has been widely shown in patients with schizophrenia, cortical-subcortical-cerebellar dysconnectivity can therefore be considered a possible intermediate phenotype that connects risk genes with schizophrenia. In this study, resting-state functional magnetic resonance imaging (fMRI) was applied to evaluate whether the SAP97 rs3915512 polymorphism changes cortical/subcortical-cerebellar resting-state functional connectivity (RSFC) in 104 Han Chinese subjects (52 first-episode schizophrenia (FES) patients and 52 matched healthy controls (HCs)). To examine RSFC between cortical/subcortical regions and the cerebellum, a ROI (region of interest)-wise functional connectivity analysis was conducted. The association between abnormal cortical/subcortical-cerebellar connectivity and clinical manifestation was further assessed in FES patients with different genotypes. The interactive effect of disease and genotype on RSFC was found between the frontal gyrus (rectus) and cerebellum. A positive correlation was suggested between RSFC in the cerebellum and the hostility scores in FES patients with the A allele, and no correlation was found in FES patients with the TT genotype. The current findings identified that SAP97 may be involved in the process of mental symptoms in FES patients via cerebellar connectivity depending on the rs3915512 polymorphism genotype.

Cognitive impairment in essential tremor assessed by the cerebellar cognitive affective syndrome scale.

Essential tremor (ET) is a movement disorder characterized by cerebellar neurodegenerative changes. ET is also associated with non-motor symptoms including cognitive impairment. The neuropsychologic profile of a patient with ET could relate to cerebellar cognitive affective syndrome (CCAS). This study aimed to assess the prevalence of cognitive impairment in patients with ET and identify whether the cognitive impairment in ET corresponds to a CCAS. Cognitive functions were evaluated with the CCAS-Scale (CCAS-S) in 20 patients with ET and 20 controls matched for age, sex, and level of education. The results of the CCAS-S were compared between patients and controls. The underlying determinant of CCAS inpatients with ET was identified through the correlation between the results of the CCAS-S and age at onset of symptoms, disease duration, and the Essential Tremor Rating Assessment Scale (TETRAS). On a group level, ET patients performed significantly worse than matched controls. In total, 13 individuals with ET had a definite CCAS (CCAS-S failed items ≥ 3). ASO and TETRAS scores significantly correlated with CCAS-S performances in ET patients. CCAS is highly prevalent in patients with ET which supports the cerebellar pathophysiology of associated cognitive impairment and supports a more systematic use of the CCAS-S to cognitively assessed patients with ET.

Cerebellar and cerebral white matter changes in Parkinson's disease with resting tremor.

Cerebellum modulates the amplitude of resting tremor in Parkinson's disease (PD) via cerebello-thalamo-cortical (CTC) circuit. Tremor-related white matter alterations have been identified in PD patients by pathological studies, but in vivo evidence is limited; the influence of such cerebellar white matter alterations on tremor-related brain network, including CTC circuit, is also unclear. In this study, we investigated the cerebral and cerebellar white matter alterations in PD patients with resting tremor using diffusion tensor imaging (DTI). In this study, 30 PD patients with resting tremor (PDWR), 26 PD patients without resting tremor (PDNR), and 30 healthy controls (HCs) from the Parkinson's Progression Markers Initiative (PPMI) cohort were included. Tract-based spatial statistics (TBSS) and region of interest-based analyses were conducted to determine white matter difference. Correlation analysis between DTI measures and clinical characteristics was also performed. In the whole brain, TBSS and region of interest-based analyses identified higher fractional anisotropy (FA) value, lower mean diffusivity (MD) value, and lower radial diffusivity (RD) in multiple fibers. In the cerebellum, TBSS analysis revealed significantly higher FA value, decreased RD value as well as MD value in multiple cerebellar tracts including the inferior cerebellar peduncle (ICP) and middle cerebellar peduncle (MCP) when comparing the PDWR with HC, and higher FA value in the MCP when compared with PDNR. We identified better white matter integrity in the cerebrum and cerebellum in PDWR indicating a potential association between the cerebral and cerebellar white matter and resting tremor in PD.

Structural and functional changes of the cerebellum in temporal lobe epilepsy.

This study aimed to comprehensively explore the cerebellar structural and functional changes in temporal lobe epilepsy (TLE) and its association with clinical information. The SUIT toolbox was utilized to perform cerebellar volume and diffusion analysis. In addition, we extracted the average diffusion values of cerebellar peduncle tracts to investigate microstructure alterations. Seed-based whole-brain analysis was used to investigate cerebellar-cerebral functional connectivity (FC). Subgroup analyses were performed to identify the cerebellar participation in TLE with/without hippocampal sclerosis (HS)/focal-to-bilateral tonic-clonic seizure (FBTCS) and TLE with different lateralization. TLE showed widespread gray matter atrophy in bilateral crusII, VIIb, VIIIb, left crusI, and left VIIIa. Both voxel and tract analysis observed diffusion abnormalities in cerebellar afferent peduncles. Reduced FC between the right crus II and the left parahippocampal cortex was found in TLE. Additionally, TLE showed increased FCs between left lobules VI-VIII and cortical nodes of the dorsal attention and visual networks. Across all patients, decreased FC was associated with poorer cognitive function, while increased FCs appeared to reflect compensatory effects. The cerebellar structural changes were mainly observed in HS and FBTCS subgroups and were regardless of seizure lateralization, while cerebellar-cerebral FC alterations were similar in all subgroups. TLE exhibited microstructural changes in the cerebellum, mainly related to HS and FBTCS. In addition, altered cerebellar-cerebral functional connectivity is associated with common cognitive alterations in TLE.

Gene expression changes in the cerebellum are associated with persistent post-injury pain in adolescent rats exposed to early life stress

Chronic pain develops following injury in approximately 20% of adolescents, at twice the rate in females than males. Adverse childhood experiences also increase the risk for poor health outcomes, such as chronic pain. Emerging literature suggests the cerebellum to be involved in pain processing, however detailed explorations into how the cerebellum contributes to pain are lacking. Therefore, this study aimed to characterise chronic pain outcomes and cerebellar gene expression changes following early life stress and injury in both sexes. The adverse childhood experience of neglect was modelled using a maternal separation (MS) paradigm, which was combined with a subsequent injury (mild traumatic brain injury (mTBI) or plantar incision surgery) in adolescent male and female Sprague-Dawley rats. We measured behavioural nociceptive sensitivity, systemic modulators of pain such as calcitonin gene-related protein (CGRP) and Substance P, as well as gene expression of IL1β, GFAP, GR, MR, GABRA1, CNR1, MAOA, and DAT1 in the cerebellum to examine associations between pain and neuroinflammation, the stress response, inhibitory neurotransmission, and monoaminergic function. We found increases in mechanical nociceptive sensitivity following plantar incision surgery. Sex differences were observed in anxiety-like behaviour and neuroinflammation, whereas systemic pain modulators showed cumulative effects with the addition of stressors. Most interestingly however, the increases in nociceptive sensitivity were associated with the suppressed expression of cerebellar genes that regulate stress, inhibition, cannabinoid function, and dopaminergic function, alongside sex-dependent distinctions for genes involved in inflammation and injury. This study highlights a novel link between nociception and molecular function in the cerebellum. Further investigation into how the cerebellum contributes to pain in males and females will facilitate novel therapeutic insights and opportunities.

Neuroprotective effect of quercetin nanoparticles: A possible prophylactic effect in cerebellar neurodegenerative disorders

Memory deficit, anxiety, coordination deficit and depression are common neurological disorders attributed to aluminum (Al) buildup in the nervous system. Quercetin nanoparticles (QNPs) are a newly developed effective neuroprotectant. We aimed to investigate the potential protective and therapeutic effects of QNPs in Al induced toxicity in rat cerebellum. A rat model of Al-induced cerebellar damage was created by AlCl3 (100 mg/kg) administration orally for 42 days. QNPs (30 mg/kg) was administered for 42-days as a prophylactic (along with AlCl3 administration) or therapeutic for 42-days (following AlCl3 induced cerebellar damage). Cerebellar tissues were assessed for structural and molecular changes. The results showed that Al induced profound cerebellar structural and molecular changes, including neuronal damage, astrogliosis and tyrosine hydroxylase downregulation. Prophylactic QNPs significantly reduced Al induced cerebellar neuronal degeneration. QNPs is a promising neuroprotectant that can be used in elderly and vulnerable subjects to protect against neurological deterioration. It could be a promising new line for therapeutic intervention in neurodegenerative diseases.

Cerebellar functional connectivity change is associated with motor and neuropsychological function in early stage drug-naïve patients with Parkinson's disease.

Parkinson's Disease (PD) is a progressive neurodegenerative disorder affecting both motor and cognitive function. Previous neuroimaging studies have reported altered functional connectivity (FC) in distributed functional networks. However, most neuroimaging studies focused on patients at an advanced stage and with antiparkinsonian medication. This study aims to conduct a cross-sectional study on cerebellar FC changes in early-stage drug-naïve PD patients and its association with motor and cognitive function. Twenty-nine early-stage drug-naïve PD patients and 20 healthy controls (HCs) with resting-state fMRI data and motor UPDRS and neuropsychological cognitive data were extracted from the Parkinson's Progression Markers Initiative (PPMI) archives. We used seed-based resting-state fMRI (rs-fMRI) FC analysis and the cerebellar seeds were defined based on the hierarchical parcellation of the cerebellum (AAL atlas) and its topological function mapping (motor cerebellum and non-motor cerebellum). The early stage drug-naïve PD patients had significant differences in cerebellar FC when compared with HCs. Our findings include: (1) Increased intra-cerebellar FC within motor cerebellum, (2) increase motor cerebellar FC in inferior temporal gyrus and lateral occipital gyrus within ventral visual pathway and decreased motor-cerebellar FC in cuneus and dorsal posterior precuneus within dorsal visual pathway, (3) increased non-motor cerebellar FC in attention, language, and visual cortical networks, (4) increased vermal FC in somatomotor cortical network, and (5) decreased non-motor and vermal FC within brainstem, thalamus and hippocampus. Enhanced FC within motor cerebellum is positively associated with the MDS-UPDRS motor score and enhanced non-motor FC and vermal FC is negatively associated with cognitive function test scores of SDM and SFT. These findings provide support for the involvement of cerebellum at an early stage and prior to clinical presentation of non-motor features of the disease in PD patients.

Fetal Cerebellar Area: Ultrasound Reference Ranges at 13-39 Weeks of Gestation.

The present study aims to provide prenatal 2-dimensional ultrasonographic (2D-US) nomograms of the normal cerebellar area. This is a prospective cross-sectional analysis of 252 normal singleton pregnancies, ranging from 13 to 39 weeks of gestation. The operator performed measurements of the fetal cerebellar area in the transverse plane using 2D-US. The relationship between cerebellar area and gestational age (GA) was determined through regression equations. A significant, strong positive correlation was investigated between the cerebellar area with GA (r-value = 0.89), and a positive correlation indicates that with increasing GA, the cerebellar area increased in all the participants of the study. Several 2D-US nomograms of the normal cerebellar area were provided, and an increase of 0.4% in the cerebellar area each week of GA was reported. We presented information on the typical dimensions of the fetal cerebellar area throughout gestation. In future studies, it could be evaluated how the cerebellar area changes with cerebellar abnormalities. It should be established if calculating the cerebellar area in addition to the routine transverse cerebellar diameter may help in discriminating posterior fossa anomalies or even help to identify anomalies that would otherwise remain undetected.

Cerebellar Structural Abnormality in Autism Spectrum Disorder: A Magnetic Resonance Imaging Study.

This study uses structural magnetic resonance imaging to explore changes in the cerebellar lobules in patients with autism spectrum disorder (ASD) and further analyze the correlation between cerebellar structural changes and clinical symptoms of ASD. A total of 75 patients with ASD and 97 typically developing (TD) subjects from Autism Brain Imaging Data Exchange dataset were recruited. We adopted an advanced automatic cerebellar lobule segmentation technique called CEREbellum Segmentation to segment each cerebellar hemisphere into 12 lobules. Normalized cortical thickness of each lobule was recorded, and group differences in the cortical measures were evaluated. Correlation analysis was also performed between the normalized cortical thickness and the score of Autism Diagnostic Interview-Revised. Results from analysis of variance showed that the normalized cortical thickness of the ASD group differed significantly from that of the TD group; specifically, the ASD group had lower normalized cortical thickness than the TD group. Post-hoc analysis revealed that the differences were more predominant in the left lobule VI, left lobule Crus I and left lobule X, and in the right lobule VI and right lobule Crus I. Lowered normalized cortical thickness in the left lobule Crus I in the ASD patients correlated positively with the abnormality of development evident at or before 36 months subscore. These results suggest abnormal development of cerebellar lobule structures in ASD patients, and such abnormality might significantly influence the pathogenesis of ASD. These findings provide new insights into the neural mechanisms of ASD, which may be clinically relevant to ASD diagnosis.

Automatic segmentation of the cerebellum using volBrain software in normal paediatric population

Morphological differences that can lead to cerebellar volume changes are associated with the pathogenesis of paediatric diseases. The aim of this study was to examine cerebellum volume in a healthy paediatric population. To provide MRI-based volumetric measurements of the cerebellum, images from the years 2019 to 2021 were scanned retrospectively. A total of 100 images, including the paediatric population aged 0-15 years, were imported into the volBrain software. Volumetric segmentations were obtained automatically, and each lobular cerebellar volume was obtained. The samples were divided into groups of 0-2years (n = 18), 3-5years (n = 24), 6-11 years (n = 34) and 12-15 years (n = 24). Obtained cerebellar volumes, age groups, gender and bilateral side comparisons were made. In the comparative analyses performed for the total cerebellum and each of the 12 lobular segments, statistically significant differences were found between the age groups in all measurements except Crus II, lobules VIIB, VIIIA and VIIIB (p < 0.05). In multiple comparison tests, statistically significant differences were found between defined age groups, especially infants and toddlers and early adolescence groups (p < 0.05). There was a significant positive correlation between the ages of the subjects and their cerebellum volumes (p < 0.05). Statistically significant differences were found in lobules I-II, VI, VIIIB, IX and X in right and left side volumes (p < 0.05). There is a tendency to increase in cerebellar volume during the transition from childhood to adolescence. The cerebellum has volumetric differences in the first years of life and during adolescence. When the development of a healthy cerebellum is analysed based on volumetric segmentation, differences are observed. The findings of this study may be useful in confirming various theories attributed to the cerebellum in the clinic.

Ethanol-induced cerebellar transcriptomic changes in a postnatal model of fetal alcohol spectrum disorders: Focus on disease onset.

Fetal alcohol spectrum disorders (FASD) are a group of neurodevelopmental disorders caused by ethanol exposure in utero, which can result in neurocognitive and behavioral impairments, growth defects, and craniofacial anomalies. FASD affects up to 1-5% of school-aged children in the United States, and there is currently no cure. The underlying mechanisms involved in ethanol teratogenesis remain elusive and need greater understanding to develop and implement effective therapies. Using a third trimester human equivalent postnatal mouse model of FASD, we evaluate the transcriptomic changes induced by ethanol exposure in the cerebellum on P5 and P6, after only 1 or 2 days of ethanol exposure, with the goal of shedding light on the transcriptomic changes induced early during the onset and development of FASD. We have highlighted key pathways and cellular functions altered by ethanol exposure, which include pathways related to immune function and cytokine signaling as well as the cell cycle. Additionally, we found that ethanol exposure resulted in an increase in transcripts associated with a neurodegenerative microglia phenotype, and acute- and pan-injury reactive astrocyte phenotypes. Mixed effects on oligodendrocyte lineage cell associated transcripts and cell cycle associated transcripts were observed. These studies help to elucidate the underlying mechanisms that may be involved with the onset of FASD and provide further insights that may aid in identifying novel targets for interventions and therapeutics.

Cerebellar Plasticity Changes in an Experimental Model of Autism Induced by Maternal Separation

Autism is a neurodevelopmental disorder with a complex pathophysiology that affects different areas of the brain. Evidence over the past decade indicated a role for the cerebellum in social skills in connection with neuropathological changes. In this study, we examined cerebellar plasticity in rats that exhibited autistic-like behaviors after maternal separation (MS). We showed that autistic-like behaviors were associated with changes in cerebellar volume size. We for the first time showed the decreased volume of the cerebellum in the maternal separation animal model of autism, supporting the involvement of the cerebellum in the pathophysiology of autism.

The Effect of Ketamine Anesthesia on Balance Behavior and Histopathological Changes of the Cerebellum in Rat Neonates

Introduction: Ketamine is a popular drug for use in various populations, including pregnant women. Of note, the high prevalence of ketamine use may cause disorders, especially in the nervous system. This study aimed to investigate the effect of repeated short-term and long-term anesthesia with ketamine on balance behavior and cerebellar tissue changes in neonatal rats. Method: In total, 15 female and 3 male rats were prepared and then randomly divided into 3 groups of 5 including control, long-term, as well as short-term and repeated anesthesia with ketamine. Pregnant female rats in the group of long-term anesthesia with ketamine were anesthetized once a week (at a dose of 75 mg/kg), and those in the groups of short-term and repeated anesthesia with ketamine were anesthetized 3 times a week (at a dose of 25 mg/kg). Ketamine injections were given weekly and regularly until the end of pregnancy. In order to evaluate the balance behavior of rats, a balance behavior test was conducted after lactation of all neonates of different groups. Moreover, tissue sampling was performed at the end of the whole period. Results: Most tissue changes were related to the Purkinje layer in the long-term group. In terms of balance, there were significant differences among different groups in terms of traveling distances and the number of slips. Conclusion: Increasing the dose of ketamine has mild effects on cerebellar tissue alongside significant effects on balance behavior.

Differential Diagnosis of Middle Cerebellar Peduncle Signal Changes on Brain MRI

Differential Diagnosis of Middle Cerebellar Peduncle Signal Changes on Brain MRI

The impact of aging on morphometric changes in the cerebellum: A voxel-based morphometry study.

Aging influences the morphology of the central nervous system. While several previous studies focused on morphometric changes of the supratentorial parts, investigations on age-related cerebellar changes are rare. The literature concerning the morphological changes in the cerebellum is heterogenous depending (i) on the methods used (cerebellar analysis in the context of a whole brain analysis or specific methods for a cerebellar analysis), (ii) the life span that was investigated, and (iii) the analytic approach (i.e., using linear or non-linear methods). We fill this research gap by investigating age-dependent cerebellar changes in the aging process occurring before the age of 70 in healthy participants, using non-linear methods and the spatially unbiased infratentorial template (SUIT) toolbox which is specifically developed to examine the cerebellum. Furthermore, to derive an overview of the possible behavioral correlates, we relate our findings to functional maps of the cerebellum. Twenty-four older participants (mean age 64.42 years, SD ± 4.8) and 25 younger participants (mean age 24.6 years, SD ± 2.14) were scanned using a 3 T-MRI, and the resulting data were processed using a SUIT. Gray matter (GM) volume loss was found in older participants in three clusters in the right cerebellar region, namely crus I/II and lobule VI related to the frontoparietal network, with crus I being functionally related to the default-mode network and lobule VI extending into vermis VIIa related to the ventral-attention-network. Our results underline an age-related decline in GM volume in the right cerebellar regions that are functionally predominantly related to non-motor networks and cognitive tasks regions of the cerebellum before the age of 70.

Cerebellar network changes in depressed patients with and without autism spectrum disorder: A case-control study

Pathophysiological difference of depression in patients with and without autistic spectrum disorder (ASD) has not been investigated previously. Therefore, we sought to determine whether there were differences between non-ASD and ASD groups on resting-state functional magnetic resonance imaging (rs-fMRI) in patients with depression. We performed 3T MRI under resting state in 8 patients with depression and ASD and 12 patients with depression but without ASD. The ASD group showed increased functional connectivity in the cerebellar network of the left posterior inferior temporal gyrus and anterior cerebellar lobes compared to the non-ASD group in an analysis of covariance. Adding antipsychotics, antidepressants, benzodiazepines, nonbenzodiazepines, anxiolytics, hypnotics, or age as covariates showed a similar increase in functional connectivity. Thus, this study found that depressive patients with ASD had increased functional connectivity in the cerebellar network. Our findings suggest that fMRI may be able to evaluate differences in depressed patients with and without ASD.

Cerebellar gray matter alterations predict deep brain stimulation outcomes in Meige syndrome

BackgroundThe physiopathologic mechanism of Meige syndrome (MS) has not been clarified, and neuroimaging studies centering on cerebellar changes in MS are scarce. Moreover, even though deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been recognized as an effective surgical treatment for MS, there has been no reliable biomarker to predict its efficacy. ObjectiveTo characterize the volumetric alterations of gray matter (GM) in the cerebellum in MS and to identify GM measurements related to a good STN-DBS outcome. MethodsWe used voxel-based morphometry and lobule-based morphometry to compare the regional and lobular GM differences in the cerebellum between 47 MS patients and 52 normal human controls (HCs), as well as between 31 DBS responders and 10 DBS non-responders. Both volumetric analyses were achieved using the Spatially Unbiased Infratentorial Toolbox (SUIT). Further, we performed partial correlation analyses to probe the relationship between the cerebellar GM changes and clinical scores. Finally, we plotted the receiver operating characteristic (ROC) curve to select biomarkers for MS diagnosis and DBS outcomes prediction. ResultsCompared to HCs, MS patients had GM atrophy in lobule Crus I, lobule VI, lobule VIIb, lobule VIIIa, and lobule VIIIb. Compared to DBS responders, DBS non-responders had lower GM volume in the left lobule VIIIb. Moreover, partial correlation analyses revealed a positive relationship between the GM volume of the significant regions/lobules and the symptom improvement rate after DBS surgery. ROC analyses demonstrated that the GM volume of the significant cluster in the left lobule VIIIb could not only distinguish MS patients from HCs but also predict the outcomes of STN-DBS surgery with high accuracy. ConclusionMS patients display bilateral GM shrinkage in the cerebellum relative to HCs. Regional GM volume of the left lobule VIIIb can be a reliable biomarker for MS diagnosis and DBS outcomes prediction.

Aberrant single-subject morphological cerebellar connectome in chronic insomnia

BackgroundTo systematically investigate the topological organisation of morphological networks of the cerebellum using structural MRI and examine their clinical relevance in chronic insomnia (CI). MethodsOne hundred and one patients with CI and 102 healthy controls (HCs) were recruited in this study. Individual morphological networks of the cerebellum were constructed based on regional grey matter volume, and topologically characterised using weighted graph theory-based network approaches. Between-group comparisons were performed using permutation tests, and Spearman’s correlation was used to examine the relationships between topological alterations and clinical variables. ResultsCompared with HCs, patients with CI exhibited a lower normalised clustering coefficient. Locally, CI patients exhibited lower nodal efficiency in the cerebellar lobule VIIb and vermis regions, but higher nodal efficiency in the right cerebellar lobule VIIIa regions. No correlations were observed between network alterations and clinical variables. ConclusionsIndividual morphological network analysis provides a new strategy for investigating cerebellar morphometric changes in CI, and our findings may have important implications in establishing diagnostic and categorical biomarkers.

Sleep deprivation aggravated amyloid β oligomers-induced damage to the cerebellum of rats: Evidence from magnetic resonance imaging

For quite a long time, researches on Alzheimer's disease (AD) primarily focused on the cortex and hippocampus, while the cerebellum has been ignored because of its abnormalities considered to appear in the late stage of AD. In recent years, increasing evidence suggest that the cerebellar pathological changes possibly occur in the preclinical phase of AD, which is also associated with sleep disorder. Sleep disturbance is a high risk factor of AD. However, the changes and roles of cerebellum has rarely been reported under conditions of AD accompanied with sleep disorders. In this study, using an amyloid-β oligomers (AβO)-induced rat model of AD subjected to sleep deprivation, combining with a 7.0 T animals structural magnetic resonance imaging (MRI), we assessed structural changes of cerebellum in MRI. Our results showed that sleep deprivation combined with AβO led to an increased FA value in the anterior lobe of cerebellum, decreased ADC value in the cerebellar lobes and cerebellar nuclei, and increased cerebellum volume. Besides that, sleep deprivation exacerbated the damage of AβO to the cerebellar structural network. This study demonstrated that sleep deprivation could aggravate the damage to cerebellum induced by AβO. The present findings provide supporting evidence for the involvement of cerebellum in the early pathology of AD and sleep loss. Our data would contribute to advancing the understanding of the mysterious role of cerebellum in AD and sleep disorders, as well as would be helpful for developing non-invasive MRI biomarkers for screening early AD patients with self-reported sleep disturbances.