Cerebellar-cerebral Functional Connectivity Research Articles

Limited cerebellar gradient extension in temporal lobe epilepsy with dystonic posturing.

Dystonic posturing (DP) is a common semiology in temporal lobe epilepsy (TLE). We aimed to explore cerebellar gradient alterations in functional connectivity in TLE patients with and without DP. Resting-state functional MRI data were obtained in 60 TLE patients and 32 matched healthy controls. Patients were further divided into two groups: TLE with DP (TLE + DP, 31 patients) and TLE without DP (TLP-DP, 29 patients). We explored functional gradient alterations in the cerebellum based on cerebellar-cerebral functional connectivity and combined with independent component analysis to evaluate cerebellar-cerebral functional integration and reveal the contribution of the motor components to the gradient. There were no obvious differences in clinical features and postoperative seizure outcomes between TLE + DP and TLE-DP patients. Patients and controls all showed a clear unimodal-to-transmodal gradient transition in the cerebellum, while TLE patients demonstrated an extended principal gradient in functional connectivity compared to healthy controls, which was more limited in TLE + DP patients. Gradient alterations were more widespread in TLE-DP patients, involving bilateral cerebellum, while gradient alterations in TLE + DP patients were limited in the cerebellum ipsilateral to the seizure focus. In addition, more cerebellar motor components contributed to the gradient alterations in TLE + DP patients, mainly in ipsilateral cerebellum. Extended cerebellar principal gradients in functional connectivity revealed excessive functional segregation between unimodal and transmodal systems in TLE. The functional connectivity gradients were more limited in TLE + DP patients. Functional connectivity in TLE patients with dystonic posturing involved more contribution of cerebellar motor function to ipsilateral cerebellar gradient. Dystonic posturing contralateral to epileptic focus is a common symptom in temporal lobe epilepsy, and the cerebellum may be involved in its generation. In this study, we found cerebellar gradients alterations in functional connectivity in temporal lobe epilepsy patients with and without contralateral dystonic posturing. In particular, we found that TLE patients with dystonic posturing may have more limited cerebellar gradient in functional connectivity, involving more contribution of cerebellar motor function to ipsilateral cerebellar gradient. Our study suggests a close relationship between ipsilateral cerebellum and contralateral dystonic posturing.

Cerebellar functional connectivity and its associated genes: A longitudinal study in drug-naive patients with obsessive-compulsive disorder

The role of cerebellar-cerebral functional connectivity (CC-FC) in obsessive-compulsive disorder (OCD), its trajectory post-pharmacotherapy, and its potential as a prognostic biomarker and genetic mechanism remain uncertain. To address these gaps, this study included 37 drug-naive OCD patients and 37 healthy controls (HCs). Participants underwent baseline functional magnetic resonance imaging (fMRI), followed by four weeks of paroxetine treatment for patients with OCD, and another fMRI scan post-treatment. We examined seed-based CC-FC differences between the patients and HCs, and pre- and post-treatment patients. Support vector regression (SVR) based on CC-FC was performed to predict treatment response. Correlation analysis explored associations between CC-FC and clinical features, as well as gene profiles. Compared to HCs, drug-naive OCD patients exhibited reduced CC-FC in executive, affective-limbic, and sensorimotor networks, with specific genetic profiles associated with altered CC-FC. Gene enrichment analyses highlighted the involvement of these genes in various biological processes, molecular functions, and pathways. Post-treatment, the patients showed partial clinical improvement and partial restoration of the previously decreased CC-FC. Abnormal CC-FC at baseline correlated negatively with compulsions severity and social functional impairment, while changes in CC-FC correlated with cognitive function changes post-treatment. CC-FC emerged as a potential predictor of symptom severity in patients following paroxetine treatment. This longitudinal resting-state fMRI study underscores the crucial role of CC-FC in the neuropsychological mechanisms of OCD and its pharmacological treatment. Transcriptome-neuroimaging spatial correlation analyses provide insight into the neurobiological mechanisms underlying OCD pathology. Furthermore, SVR analyses hold promise for advancing precision medicine approaches in treating patients with OCD.

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.

Behaviour-correlated profiles of cerebellar-cerebral functional connectivity observed in independent neurodevelopmental disorder cohorts

The cerebellum, through its connectivity with the cerebral cortex, plays an integral role in regulating cognitive and affective processes, and its dysregulation can result in neurodevelopmental disorder (NDD)-related behavioural deficits. Identifying cerebellar-cerebral functional connectivity (FC) profiles in children with NDDs can provide insight into common connectivity profiles and their correlation to NDD-related behaviours. 479 participants from the Province of Ontario Neurodevelopmental Disorders (POND) network (typically developing = 93, Autism Spectrum Disorder = 172, Attention Deficit/Hyperactivity Disorder = 161, Obsessive-Compulsive Disorder = 53, mean age = 12.2) underwent resting-state functional magnetic resonance imaging and behaviour testing (Social Communication Questionnaire, Toronto Obsessive-Compulsive Scale, and Child Behaviour Checklist – Attentional Problems Subscale). FC components maximally correlated to behaviour were identified using canonical correlation analysis. Results were then validated by repeating the investigation in 556 participants from an independent NDD cohort provided from a separate consortium (Healthy Brain Network (HBN)). Replication of canonical components was quantified by correlating the feature vectors between the two cohorts. The two cerebellar-cerebral FC components that replicated to the greatest extent were correlated to, respectively, obsessive-compulsive behaviour (behaviour feature vectors, rPOND-HBN = −0.97; FC feature vectors, rPOND-HBN = −0.68) and social communication deficit contrasted against attention deficit behaviour (behaviour feature vectors, rPOND-HBN = −0.99; FC feature vectors, rPOND-HBN = −0.78). The statistically stable (|z| > 1.96) features of the FC feature vectors, measured via bootstrap re-sampling, predominantly comprised of correlations between cerebellar attentional and control network regions and cerebral attentional, default mode, and control network regions. In both cohorts, spectral clustering on FC loading values resulted in subject clusters mixed across diagnostic categories, but no cluster was significantly enriched for any given diagnosis as measured via chi-squared test (p > 0.05). Overall, two behaviour-correlated components of cerebellar-cerebral functional connectivity were observed in two independent cohorts. This suggests the existence of generalizable cerebellar network differences that span across NDD diagnostic boundaries.

Altered resting-state cerebellar-cerebral functional connectivity in patients with panic disorder before and after treatment

The study aimed to investigate the functional connectivity (FC) between the cerebellum and intrinsic cerebral networks in patients with panic disorder (PD), and to observe changes in the cerebellar-cerebral FC following pharmacotherapy. Fifty-four patients with PD and 54 healthy controls (HCs) underwent clinical assessments and functional magnetic resonance imaging scans before and after a 5-week paroxetine treatment. Seed-based cerebellar-cerebral FC was compared between the PD and HC groups, as well as between patients with PD before and after treatment. Additionally, the correlations between FC and clinical features of PD were analyzed. Compared to HCs, patients with PD had altered cerebellar-cerebral FC in the default mode, affective-limbic, and sensorimotor networks. Moreover, a negative correlation between cerebellar-insula disconnection and the severity of depressive symptoms in patients with PD (Pearson correlation, r = −0.424, p = 0.001, Bonferroni corrected) was found. After treatment, most of the enhanced FCs observed in patients with PD at baseline returned to levels similar to those observed in HCs. However, the reduced FC at baseline did not significantly change after treatment. The findings suggest that patients with PD have specific deficits in resting-state cerebellar-cerebral FC and that paroxetine may improve PD by restoring the balance of cerebellar-cerebral FC. These findings emphasize the crucial involvement of cerebellar-cerebral FC in the neuropsychological mechanisms underlying PD and in the potential pharmacological mechanisms of paroxetine for treating 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.

Altered resting-state cerebellar-cerebral functional connectivity in patients with end-stage renal disease

Background End-stage renal disease (ESRD) patients have functional and structural brain abnormalities. The cerebellum also showed varying degrees of damage. However, no studies on cerebellar-cerebral functional connectivity (FC) have been conducted in ESRD patients. This study aimed to investigate the changes in cerebellar-cerebral FC in ESRD patients and its relationship with neuropsychological and clinical indexes. Methods Resting-state functional magnetic resonance imaging and neuropsychological assessment were performed on 37 ESRD patients and 35 control subjects. Seed-based FC analysis was performed to investigate inter-group differences in cerebellar-cerebral FC. In addition, the relations of altered FC with the neuropsychological function and clinical indicators were analyzed in ERSD patients. Results ESRD patients exhibited alterations in cerebellar-cerebral FC involving the executive control network, default mode network, and affective-limbic network compared to control subjects (False discovery rate-corrected, p < 0.05). The altered cerebellar-cerebral FC was associated with the Montreal Cognitive Assessment Scale score (p < 0.05), and correlated with serum creatinine and uric acid levels within the ESRD group (p < 0.05). Conclusions The study indicates that cerebellar-cerebral FC is involved in the neural substrates of cognitive impairment in ESRD patients. The findings may provide clinically relevant new neuroimaging biomarkers for the neuropathological mechanisms underlying cognitive impairment of ESRD.

Altered intrinsic cerebellar-cerebral functional connectivity is related to negative symptoms in patients with first-episode psychosis

BackgroundNegative symptoms in schizophrenia include cognitive and affective dysfunction, such as diminished expression and amotivation. Although the cerebellar posterior hemisphere and vermis are involved in cognitive and affective functioning, previous studies on the neural mechanism of negative symptoms have mostly been confined to the cerebral cortex. This study aimed to investigate whether resting-state cerebellar-cerebral functional connectivity (FC) is altered in first-episode psychosis (FEP) patients and whether this connectivity is related to negative symptoms. MethodsResting-state functional magnetic resonance images were obtained from 38 FEP patients and 100 healthy controls (HCs). Using the posterior hemisphere and vermis of the cerebellum as seeds, whole-brain FC was compared between FEP patients and HCs. As cerebellar-parietal cortex connectivity is associated with negative symptoms and sociocognitive dysfunctions in schizophrenia patients, its correlation with negative symptoms was explored in FEP patients. ResultsFEP patients showed hyperconnectivity between the cerebellum and bilateral frontal pole (FP), occipital pole, fusiform gyrus, right lingual gyrus, central opercular cortex, anterior middle temporal gyrus, precuneus, and subcallosal cortex. Hypoconnectivity was found between the cerebellum and left FP, right anterior supramarginal gyrus (aSMG), and cerebellum crus I. FC between the left crus II and right aSMG was negatively correlated with the severity of negative symptoms and diminished expression. ConclusionsAltered FC between the cerebellum and cerebral regions related to cognitive, affective, and sensory processing was found in FEP patients and was connected to negative symptoms. These results suggest that the cerebellum plays a role in the pathophysiology of negative symptoms in schizophrenia.

Cerebellum regulating cerebral functional cortex through multiple pathways in complete thoracolumbar spinal cord injury.

The previous studies have found significant brain structural and functional changes in cerebral regions after spinal cord injury (SCI), but few studies have explored the cerebellar–cerebral circuit changes in SCI. This study aims to study the brain structural changes of cerebellar subregions and its functional connectivity (FC) changes with cerebrum in complete thoracolumbar SCI (CTSCI), and screen out the regions that play relatively important roles in affecting sensorimotor function. Eighteen CTSCI patients and 18 age- and gender-matched healthy controls (HCs) were recruited. Voxel-based morphometry (VBM) was used to characterize the brain structural changes of cerebellar subregions [from the Anatomical Automatic Labeling (AAL116)], seed-based FC was used to evaluate the cerebellar–cerebral FC changes and support vector machine (SVM) analysis was used to search for sensitive imaging indicators. CTSCI patients showed slightly structural atrophy in vermis_3 (p = 0.046) and significantly decreased FC between cerebellum and cerebral sensorimotor-, visual-, cognitive-, and auditory-related regions (cluster-level FWE correction with p < 0.05). Additionally, SVM weight analysis showed that FC values between vermis_10 and right fusiform gyrus had the greatest weight in functional changes of CTSCI. In conclusion, different degrees of structural and functional changes occurred in each subregion of cerebellum following CTSCI, and FC change between vermis_10 and right fusiform gyrus plays the most important role in dysfunction and may become an important neural network index of rehabilitation therapy.

Disruption of Cerebellar-Cerebral Functional Connectivity in Temporal Lobe Epilepsy and the Connection to Language and Cognitive Functions.

ObjectiveTo investigate the changes in the cerebellar-cerebral language network in temporal lobe epilepsy (TLE) patients from the cerebellar perspective, the research analyzes the changes of language and cognitive network in terms of functional connectivity (FC), as well as their efficiency of the reorganization were evaluated basing on relationship between the network metrics and neuropsychological scale scores.Methods30 TLE patients and 30 healthy controls were recruited. Brain activity was evaluated by voxel-mirrored homotopic connectivity analysis (VMHC). Two groups were analyzed and compared in terms of language FC using the following methods: Seed-to-Voxel analysis, pairwise correlations [region of interest(ROI)-to-ROI] and graph theory. Correlation analysis was performed between network properties and neuropsychological score.ResultsCompared with healthy participants, VMHC values in the Cerebellum Anterior Lobe, Frontal Lobe, Frontal_Sup_R/L, Cingulum_Ant_R/L, and Cingulum_Mid_R/L were decreased in TLE patients. Decreased FC was observed from the Cerebelum_10_R to the left inferior frontal gyrus, from the Cerebelum_6_R to the left Lingual Gyrus, from the Cerebelum_4_5_R to left Lingual Gyrus, left Cuneal Cortex and Precuneous Cortex, from the Cerebelum_3_R to Brain-Stem, and from the Cerebelum_Crus1_L to Cerebelum_6_R in TLE patients. The FC was enhanced between bilateral Cingulum_Mid and angular gyrus and frontoparietal insular cranium, between Frontal_Sup_Med L and left/right superior temporal gyrus (pSTG l/r), while it was decreased between left middle temporal gyrus and pSTG l/r. Compared with controls, the Betweenness Centrality (BC) of the right superior marginal gyrus (SMG), Temporal_Pole_Mid_R and Temporal_Mid_L as well as the Degree Centrality (DC) and Nodal Efficiency (NE) of the right SMG were lower in TLE patients. Further analysis showed that decreased VMHC in bilateral Cerebellum Anterior Lobe was positively correlated with the Boston Naming Test score in TLE patients, but it was negatively correlated with the Verbal Fluency Test score. The NE and DC of SMG_R were both negatively correlated with visual perception score in Montreal Cognitive Assessment.ConclusionOur results suggest that presence of abnormalities in the static functional connectivity and the language and cognitive network of TLE patients. Cerebellum potentially represents an intervention target for delaying or improving language and cognitive deficits in patients with TLE.

A Prospective Evaluation of Infant Cerebellar-Cerebral Functional Connectivity in Relation to Behavioral Development in Autism Spectrum Disorder

BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disorder diagnosed based on social impairment, restricted interests, and repetitive behaviors. Contemporary theories posit that cerebellar pathology contributes causally to ASD by disrupting error-based learning (EBL) during infancy. The present study represents the first test of this theory in a prospective infant sample, with potential implications for ASD detection. MethodsData from the Infant Brain Imaging Study (n= 94, 68 male) were used to examine 6-month cerebellar functional connectivity magnetic resonance imaging in relation to later (12/24-month) ASD-associated behaviors and outcomes. Hypothesis-driven univariate analyses and machine learning–based predictive tests examined cerebellar–frontoparietal network (FPN; subserves error signaling in support of EBL) and cerebellar–default mode network (DMN; broadly implicated in ASD) connections. Cerebellar-FPN functional connectivity was used as a proxy for EBL, and cerebellar-DMN functional connectivity provided a comparative foil. Data-driven functional connectivity magnetic resonance imaging enrichment examined brain-wide behavioral associations, with post hoc tests of cerebellar connections. ResultsCerebellar-FPN and cerebellar-DMN connections did not demonstrate associations with ASD. Functional connectivity magnetic resonance imaging enrichment identified 6-month correlates of later ASD-associated behaviors in networks of a priori interest (FPN, DMN), as well as in cingulo-opercular (also implicated in error signaling) and medial visual networks. Post hoc tests did not suggest a role for cerebellar connections. ConclusionsWe failed to identify cerebellar functional connectivity–based contributions to ASD. However, we observed prospective correlates of ASD-associated behaviors in networks that support EBL. Future studies may replicate and extend network-level positive results, and tests of the cerebellum may investigate brain-behavior associations at different developmental stages and/or using different neuroimaging modalities.

Aberrant Resting-State Cerebellar-Cerebral Functional Connectivity in Unmedicated Patients With Obsessive-Compulsive Disorder.

Background: Although abnormality of cerebellar-cerebral functional connectivity at rest in obsessive-compulsive disorder (OCD) has been hypothesized, only a few studies have investigated the neural mechanism. To verify the findings of previous studies, a large sample of patients with OCD was studied because OCD shows possible heterogeneity.Methods: Forty-seven medication-free patients with OCD and 62 healthy controls (HCs) underwent resting-state functional magnetic imaging scans. Seed-based connectivity was examined to investigate differences in cerebellar-cerebral functional connectivity in OCD patients compared with HCs. Correlations between functional connectivity and the severity of obsessive-compulsive symptoms were analyzed.Results: In OCD, we found significantly increased functional connectivity between the right lobule VI and the left precuneus, which is a component of the default mode network (DMN), compared to HCs. However, there was no correlation between the connectivity of the right lobule VI-left precuneus and obsessive-compulsive severity.Conclusions: These findings suggest that altered functional connectivity between the cerebellum and DMN might cause changes in intrinsic large-scale brain networks related to the traits of OCD.

Neurological Soft Signs Are Associated With Altered Cerebellar-Cerebral Functional Connectivity in Schizophrenia.

Cerebellar dysfunction is associated with neurological soft signs (NSS), which is a promising endophenotype for schizophrenia spectrum disorders. However, the relationship between cerebellar-cerebral resting-state functional connectivity (rsFC) and NSS is largely unexplored. Moreover, both NSS and cerebellar-cerebral rsFC have been found to be correlated with negative symptoms of schizophrenia. Here, we investigated the correlations between NSS and cerebellar-cerebral rsFC, explored their relationship with negative symptoms in a main dataset, and validated the significant findings in a replication dataset. Both datasets comprised schizophrenia patients and healthy controls. In schizophrenia patients, we found positive correlations between NSS and rsFC of the cerebellum with the inferior frontal gyrus and the precuneus, and negative correlations between NSS and rsFC of the cerebellum with the inferior temporal gyrus. In healthy controls, NSS scores were positively correlated with rsFC of the cerebellum with the superior frontal gyrus and negatively correlated with rsFC between the cerebellum and the middle occipital gyrus. Cerebellar-prefrontal rsFC was also positively correlated with negative symptoms in schizophrenia patients. These findings were validated in the replication dataset. Our results suggest that the uncoupling of rsFC between the cerebellum and the cerebral cortex may underlie the expression of NSS in schizophrenia. NSS-related cerebellar-prefrontal rsFC may be a potential neural pathway for possible neural modulation to alleviate negative symptoms.

Altered Cerebellar-Cerebral Circuits in Patients With Type 2 Diabetes Mellitus.

The role of the cerebellum in type 2 diabetes mellitus (T2DM) has been receiving increased attention. However, the functional connectivity (FC) between the cerebellar subregions and the cerebral cortex has not been investigated in T2DM. Therefore, the purpose of this study was to investigate cerebellar-cerebral FC and the relationship between FC and clinical/cognitive variables in patients with T2DM. A total of 34 patients with T2DM and 30 healthy controls were recruited for this study to receive a neuropsychological assessment and undergo resting-state FC. We selected four subregions of the cerebellum (bilateral lobules IX, right and left Crus I/II, and left lobule VI) as regions of interest (ROIs) to examine the differences in cerebellar-cerebral circuits in patients with T2DM compared to healthy controls. Correlation analysis was performed to examine the relationship between FC and clinical/cognitive variables in the patients. Compared to healthy controls, patients with T2DM showed significantly decreased cerebellar-cerebral FC in the default-mode network (DMN), executive control network (ECN), and visuospatial network (VSN). In the T2DM group, the FC between the left cerebellar lobule VI and the right precuneus was negatively correlated with the Trail Making Test A (TMT-A) score (r = −0.430, P = 0.013), after a Bonferroni correction. In conclusion, patients with T2DM have altered FC between the cerebellar subregions and the cerebral networks involved in cognitive and emotional processing. This suggests that a range of cerebellar-cerebral circuits may be involved in the neuropathology of T2DM cognitive dysfunction.

Aberrant Resting-State Cerebellar-Cerebral Functional Connectivity in Methamphetamine-Dependent Individuals After Six Months Abstinence.

BackgroundStructural and functional alterations in the cerebellum have been consistently reported in addiction literatures. However, evidence implicating the resting-state cerebellar-cerebral functional connectivity in methamphetamine (MA) use disorder still remains limited.MethodsResting-state functional magnetic resonance imaging (fMRI) scans were obtained from 34 MA dependent individuals with about six months abstinence and 31 healthy controls (well matched for age, gender and education) in this study. Seed-based functional connectivity analysis was employed to investigate the differences in cerebellar-cerebral functional connectivity between two groups. The correlations between significant functional connectivity and each clinical characteristic were also explored.ResultsCompared to healthy controls, MA dependent individuals showed disrupted functional connectivity between the cerebellum and several cerebral functional networks, including the default-mode, affective-limbic, and sensorimotor networks. Within the MA group, functional connectivity of the right cerebellar lobule VI-precuneus coupling was negatively correlated with addiction severity.ConclusionThe present study suggests that cerebellar dysfunction, in particular aberrant cerebellar-cerebral functional connectivity, might involve in neurobiological mechanism of MA dependence, which supply a potential target for therapeutic interventions in the future.

Hormone levels are related to functional compensation in prolactinomas: A resting-state fMRI study

Prolactinomas are tumors of the pituitary gland, which overproduces prolactin leading to dramatic fluctuations of endogenous hormone levels throughout the body. While it is not fully understood how endogenous hormone disorders affect a patient's brain, it is well known that fluctuating hormone levels can have negative neuropsychological effects. Using resting-state functional magnetic resonance imaging (rs-fMRI), we investigated whole-brain functional connectivity (FC) and its relationship with hormone levels in prolactinomas. By performing seed-based FC analyses, we compared FC metrics between 33 prolactinoma patients and 31 healthy controls matched for age, sex, and hand dominance. We then carried out a partial correlation analysis to examine the relationship between FC metrics and hormone levels. Compared to healthy controls, prolactinoma patients showed significantly increased thalamocortical and cerebellar-cerebral FC. Endogenous hormone levels were also positively correlated with increased FC metrics, and these hormone-FC relationships exhibited sex differences in prolactinoma patients. Our study is the first to reveal altered FC patterns in prolactinomas and to quantify the hormone-FC relationships. These results indicate the importance of endogenous hormones on functional compensation of the brain in patients with prolactinomas.

Altered Functional Connectivity Between the Cerebellum and the Cortico-Striato-Thalamo-Cortical Circuit in Obsessive-Compulsive Disorder.

Background: Altered resting-state functional connectivity of the cerebellum in obsessive-compulsive disorder (OCD) has been previously reported. However, the previous study investigating cerebellar–cerebral functional connectivity relied on a priori–defined seeds from specific networks. In this study, we aimed to explore the connectivity alterations of the cerebellum in OCD under resting-state conditions with a hypothesis-free approach. Methods: Thirty patients with OCD and 26 healthy controls (HCs) underwent functional magnetic resonance imaging (fMRI) scanning at resting state. Regional cerebral function was evaluated by measuring the fraction of amplitude of low-frequency fluctuation (fALFF). Regions with mean fALFF (mfALFF) alterations were used as seeds in seed correlation analysis (SCA). An independent samples t test was used to compare the differences in mfALFF and functional connection (FC) between the two groups. Pearson correlation analysis was performed to identify the association between functional neural correlates and OCD symptom severity evaluated using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Results: Compared with the HC group, the OCD group showed significantly increased mfALFF values in bilateral cerebellar. The results of FC analysis showed weakened connectivity among the left Crus II, lobule VIII, and right striatum and between the right lobule VIII and the right striatum, and cingulate in the OCD group compared with the HC group. Some of the abovementioned results were associated with symptom severity. Conclusions: OCD patients showed abnormal spontaneous cerebellar activity and weakened functional connectivity between the cerebellum and the cortico-striato-thalamo-cortical (CSTC) circuit (striatum and cingulate), suggesting that the cerebellum may play an essential role in the pathophysiology of OCD.

Disrupted Cerebellar Connectivity With the Central Executive Network and the Default-Mode Network in Unmedicated Bipolar II Disorder.

Objective: Bipolar disorder (BD) is a common psychiatric disease. Although structural and functional abnormalities of the cerebellum in BD patients have been reported by recent neuroimaging studies, the cerebellar-cerebral functional connectivity (FC) has not yet been examined. The present study aims to investigate the FC between the cerebellum and cerebrum, particularly the central executive network (CEN) and the default-mode network (DMN) in bipolar II disorder (BD II).Methods: Ninety-four patients with unmedicated BD II depression and 100 healthy controls (HCs) underwent the resting-state functional magnetic resonance imaging. Seed-based connectivity analyses were performed using cerebellar seeds previously identified as being involved in the CEN (bilateral Crus Ia) and DMN (bilateral Crus Ib).Results: Compared with HCs, BD II depression patients appeared decreased FC in the right Crus Ia-left dorsal lateral prefrontal cortex (dlPFC) and -left anterior cingulate cortex (ACC), the right Crus Ib-left medial prefrontal cortex (mPFC), -left middle temporal gyrus (MTG), and -left inferior temporal gyrus (ITG). No altered FC between the left Crus Ia or Crus Ib and the cerebral regions was found.Conclusions: Patients with BD II depression showed disrupted FC between the cerebellum and the CEN (mainly in the left dlPFC and ACC) and DMN (mainly in the left mPFC and temporal lobe), suggesting the significant role of the cerebellum-CEN and -DMN connectivity in the pathogenesis of BD.

Aberrant Cerebellar-Cerebral Functional Connectivity in Children and Adolescents With Autism Spectrum Disorder.

The cerebellum, which forms widespread functional networks with many areas in the cerebral cortices and subcortical structures, is one of the brain regions most consistently reported to exhibit neuropathological features in patients with autism spectrum disorder (ASD). However, cerebellar functional connectivity (FC) studies in patients with ASD have been very sparse. Using resting state functional connectivity (rsFC) analysis, we investigated the FC of the hemispheric/vermal subregions and the dentate nucleus of the cerebellum with the cerebral regions in 36 children and adolescents [16 participants with ASD, 20 typically developing (TD) participants, age: 6–15 years]. Furthermore, an independent larger sample population (42 participants with ASD, 88 TD participants, age: 6–15 years), extracted from the Autism Brain Imaging Data Exchange (ABIDE) II, was included for replication. The ASD group showed significantly increased or decreased FC between “hubs” in the cerebellum and cerebral cortices, when compared with the TD group. Findings of aberrant FCs converged on the posterior hemisphere, right dentate nucleus, and posterior inferior vermis of the cerebellum. Furthermore, these aberrant FCs were found to be related to motor, executive, and socio-communicative functions in children and adolescents with ASD when we examined correlations between FC and behavioral measurements. Results from the original dataset were partially replicated in the independent larger sample population. Our findings suggest that aberrant cerebellar–cerebral FC is associated with motor, socio-communicative, and executive functions in children and adolescents with ASD. These observations improve the current knowledge regarding the neural substrates that underlie the symptoms of ASD.

Altered resting-state cerebellar-cerebral functional connectivity in obsessive-compulsive disorder.

The role of the cerebellum in obsessive-compulsive disorder (OCD) has drawn increasing attention. However, the functional connectivity between the cerebellum and the cerebral cortex has not been investigated in OCD, nor has the relationship between such functional connectivity and clinical symptoms. A total of 27 patients with OCD and 21 healthy controls (HCs) matched on age, sex and education underwent magnetic resonance imaging (MRI). Seed-based connectivity analyses were performed to examine differences in cerebellar-cerebral connectivity in patients with OCD compared with HCs. Associations between functional connectivity and clinical features in OCD were analyzed. Compared with HCs, OCD patients showed significantly decreased cerebellar-cerebral functional connectivity in executive control and emotion processing networks. Within the OCD group, decreased functional connectivity in an executive network spanning the right cerebellar Crus I and the inferior parietal lobule was positively correlated with symptom severity, and decreased connectivity in an emotion processing network spanning the left cerebellar lobule VI and the lingual gyrus was negatively correlated with illness duration. Altered functional connectivity between the cerebellum and cerebral networks involved in cognitive-affective processing in patients with OCD provides further evidence for the involvement of the cerebellum in the pathophysiology of OCD, and is consistent with impairment in executive control and emotion regulation in this condition.