Cerebellar Functional Connectivity Research Articles

Activation and functional connectivity of cerebellum during reading and during arithmetic in children with combined reading and math disabilities.

Reading and math constitute important academic skills, and as such, reading disability (RD or developmental dyslexia) and math disability (MD or developmental dyscalculia) can have negative consequences for children's educational progress. Although RD and MD are different learning disabilities, they frequently co-occur. Separate theories have implicated the cerebellum and its cortical connections in RD and in MD, suggesting that children with combined reading and math disability (RD + MD) may have altered cerebellar function and disrupted functional connectivity between the cerebellum and cortex during reading and during arithmetic processing. Here we compared Control and RD + MD groups during a reading task as well as during an arithmetic task on (i) activation of the cerebellum, (ii) background functional connectivity, and (iii) task-dependent functional connectivity between the cerebellum and the cortex. The two groups (Control, RD + MD) did not differ for either task (reading, arithmetic) on any of the three measures (activation, background functional connectivity, task-dependent functional connectivity). These results do not support theories that children's deficits in reading and math originate in the cerebellum.

Supra- and infra-tentorial degeneration patterns in primary lateral sclerosis: a multimodal longitudinal neuroradiology study

BackgroundPrimary lateral sclerosis (PLS) is traditionally solely associated with progressive upper motor neuron dysfunction manifesting in limb spasticity, gait impairment, bulbar symptoms and pseudobulbar affect. Recent studies have described frontotemporal dysfunction in some patients resulting in cognitive manifestations. Cerebellar pathology is much less well characterised despite sporadic reports of cerebellar disease.MethodsA multi-timepoint, longitudinal neuroimaging study was conducted to characterise the evolution of both intra-cerebellar disease burden and cerebro-cerebellar connectivity. The volumes of deep cerebellar nuclei, cerebellar cortical volumes, cerebro-cerebellar structural and functional connectivity were assessed longitudinally in a cohort of 43 individuals with PLS.ResultsCerebello-frontal, -temporal, -parietal, -occipital and cerebello-thalamic structural disconnection was detected at baseline based on radial diffusivity (RD) and cerebello-frontal decoupling was also evident based on fractional anisotropy (FA) alterations. Functional connectivity changes were also detected in cerebello-frontal, parietal and occipital projections. Volume reductions were identified in the vermis, anterior lobe, posterior lobe, and crura. Among the deep cerebellar nuclei, the dorsal dentate was atrophic. Longitudinal follow-up did not capture statistically significant progressive changes. Significant primary motor cortex atrophy and inter-hemispheric transcallosal degeneration were also captured.ConclusionsPLS is not only associated with upper motor neuron dysfunction, but cerebellar cortical volume loss and deep cerebellar nuclear atrophy can also be readily detected. In addition to intra-cerebellar disease burden, cerebro-cerebellar connectivity alterations also take place. Our data add to the evolving evidence of widespread neurodegeneration in PLS beyond the primary motor regions. Cerebellar dysfunction in PLS is likely to exacerbate bulbar, gait and dexterity impairment and contribute to pseudobulbar affect.

Association of abnormal explicit sense of agency with cerebellar impairment in myoclonus-dystonia.

Non-motor aspects in dystonia are now well recognized. The sense of agency, which refers to the experience of controlling one's own actions, has been scarcely studied in dystonia, even though its disturbances can contribute to movement disorders. Among various brain structures, the cerebral cortex, the cerebellum, and the basal ganglia are involved in shaping the sense of agency. In myoclonus dystonia, resulting from a dysfunction of the motor network, an altered sense of agency may contribute to the clinical phenotype of the condition. In this study, we compared the explicit and implicit sense of agency in patients with myoclonus dystonia caused by a pathogenic variant of SGCE (DYT-SGCE) and control participants. We utilized behavioural tasks to assess the sense of agency and performed neuroimaging analyses, including structural, resting-state functional connectivity, and dynamic causal modelling, to explore the relevant brain regions involved in the sense of agency. Additionally, we examined the relationship between behavioural performance, symptom severity, and neuroimaging findings. We compared 19 patients with DYT-SGCE and 24 healthy volunteers. Our findings revealed that patients with myoclonus-dystonia exhibited a specific impairment in explicit sense of agency, particularly when implicit motor learning was involved. However, their implicit sense of agency remained intact. These patients also displayed grey-matter abnormalities in the motor cerebellum, as well as increased functional connectivity between the cerebellum and pre-supplementary motor area. Dynamic causal modelling analysis further identified reduced inhibitory effects of the cerebellum on the pre-supplementary motor area, decreased excitatory effects of the pre-supplementary motor area on the cerebellum, and increased self-inhibition within the pre-supplementary motor area. Importantly, both cerebellar grey-matter alterations and functional connectivity abnormalities between the cerebellum and pre-supplementary motor area were found to correlate with explicit sense of agency impairment. Increased self-inhibition within the pre-supplementary motor area was associated with less severe myoclonus symptoms. These findings highlight the disruption of higher-level cognitive processes in patients with myoclonus-dystonia, further expanding the spectrum of neurological and psychiatric dysfunction already identified in this disorder.

Cerebellar volume and functional connectivity in neonates predicts social and emotional development in toddlers.

Over the past decade, a growing body of research in adults has emphasized the role of the cerebellum in social and emotional cognition. This has been further supported by findings of delayed social and emotional development in toddlers with cerebellar injury during the fetal and newborn periods. However, the contributions of the cerebellum to social-emotional development in typically developing newborns are unclear. To bridge this gap in knowledge, we used multimodal MRI to investigate associations between cerebellar structure and function in 88 healthy neonates (mean ± sd of postmenstrual age, = 42.00 ± 1.91 weeks) and social-emotional development at 18-months assessed using the Infant-Toddler Social-Emotional Assessment (ITSEA) (mean age on ITSEA: 18.32 ± 1.19 months old). We found that cerebellar volume was not associated with ITSEA domain scores at 18 months. We further demonstrated cerebellar functional gradient (FGR) defined using principal component analysis (PCA) was associated with Externalizing domain (linear regression model, false-discovery-rate-adjusted p = 0.013). This cluster (FGR7) included the left dentate, right VI, left Vermis VIIIb, and right V lobules. Finally, we demonstrated that either structural or functional features of the cerebellum reliably predicted scores on the Externalizing and Internalizing domains (correlation between actual and predicted scores: for structural, Fisher's z = 0.48 ± 0.01 for Internalizing, p = 0.01; for functional, Fisher's z = 0.45 ± 0.01 for Externalizing, p = 0.02; with permutation test). Collectively, our findings suggest that the cerebellum plays an important role in social-emotional development during the critical early stages of life.

Cerebellar‐cortical functional connectivity is associated with Alzheimer’s disease pathology and cerebellar atrophy

AbstractBackgroundBrain atrophy has been associated with Alzheimer’s disease (AD) pathology. Previous research also suggests that functional connectivity (FC) among distributed neural networks is disrupted in preclinical AD. The cerebellum has been thought to play a crucial role in motor control, yet recent evidence points to its additional role in non‐motor domains as well as cognitive decline in AD. Cerebellar volume has been shown to decline along the course of AD progression. Moreover, neuroimaging studies have delineated intrinsic cerebellar‐cortical functional networks that presumably support cognitive functions. Despite the accumulating findings on neurodegeneration or FC, how cerebellar FC and atrophy relate to AD pathology in the early stage has not been extensively investigated.MethodData from 83 cognitively normal older adults (mean 71.0 yrs, 66% females) in the Alzheimer’s Disease Neuroimaging Initiative were analyzed. Volumetric data were obtained from FreeSurfer 6.0 segmentation. Resting state fMRI scans were preprocessed using the CONN Toolbox. Aß and tau standardized uptake value ratio (SUVR) data were obtained from [18F]‐Florbetapir or [18F]‐Florbetaben (Aß) and [18F]‐Flortaucipir (tau) PET scans. For Aß, SUVR values were transformed to the Centiloid scale, and a global summary measure was used. For tau, SUVR values in the temporal meta regions of interest were used. Seed‐based functional connectivity metrics were computed using the 7 cerebellar parcellations (Buckner et al., 2011) that are functionally coupled to different cortical networks (Yeo et al., 2011).ResultCerebellar volume showed no significant relationship with amyloid or tau SUVR. By contrast, hippocampal atrophy was positively associated with amyloid or tau SUVR and showed trending significance (ps < 0.1). Increased Aß burden was associated with increased cerebellar‐cortical FC in the attention, frontoparietal, and default mode networks. Increased tau load was associated with increased cerebellar‐cortical FC in the visual, somatomotor, and attention networks. Cerebellar volume was associated with cerebellar‐cortical FC in the visual, somatomotor, attention networks, but not with the limbic, frontoparietal, or default mode networks.ConclusionOur findings suggest that functional cerebellar‐cortical connectivity varies with amyloid and tau pathology in different networks, and such functional changes may precede cerebellar atrophy in preclinical AD.

Cerebellar‐cortical functional connectivity is associated with Alzheimer’s disease pathology and cerebellar atrophy

AbstractBackgroundBrain atrophy has been associated with Alzheimer’s disease (AD) pathology. Previous research also suggests that functional connectivity (FC) among distributed neural networks is disrupted in preclinical AD. The cerebellum has been thought to play a crucial role in motor control, yet recent evidence points to its additional role in non‐motor domains as well as cognitive decline in AD. Cerebellar volume has been shown to decline along the course of AD progression. Moreover, neuroimaging studies have delineated intrinsic cerebellar‐cortical functional networks that presumably support cognitive functions. Despite the accumulating findings on neurodegeneration or FC, how cerebellar FC and atrophy relate to AD pathology in the early stage has not been extensively investigated.MethodData from 83 cognitively normal older adults (mean 71.0 yrs, 66% females) in the Alzheimer’s Disease Neuroimaging Initiative were analyzed. Volumetric data were obtained from FreeSurfer 6.0 segmentation. Resting state fMRI scans were preprocessed using the CONN Toolbox. Aβ and tau standardized uptake value ratio (SUVR) data were obtained from [18F]‐Florbetapir or [18F]‐Florbetaben (Aβ) and [18F]‐Flortaucipir (tau) PET scans. For Aβ, SUVR values were transformed to the Centiloid scale, and a global summary measure was used. For tau, SUVR values in the temporal meta regions of interest were used. Seed‐based functional connectivity metrics were computed using the 7 cerebellar parcellations (Buckner et al., 2011) that are functionally coupled to different cortical networks (Yeo et al., 2011).ResultCerebellar volume showed no significant relationship with amyloid or tau SUVR. By contrast, hippocampal atrophy was positively associated with amyloid or tau SUVR and showed trending significance (ps < 0.1). Increased Aβ burden was associated with increased cerebellar‐cortical FC in the attention, frontoparietal, and default mode networks. Increased tau load was associated with increased cerebellar‐cortical FC in the visual, somatomotor, and attention networks. Cerebellar volume was associated with cerebellar‐cortical FC in the visual, somatomotor, attention networks, but not with the limbic, frontoparietal, or default mode networks.ConclusionOur findings suggest that functional cerebellar‐cortical connectivity varies with amyloid and tau pathology in different networks, and such functional changes may precede cerebellar atrophy in preclinical AD.

Differences and Changes in Cerebellar Functional Connectivity of Parkinson's Patients with Visual Hallucinations.

Recent studies have discovered that functional connections are impaired in patients with Parkinson's disease (PD) accompanied by hallucinations (PD-H), even at the preclinical stage. The cerebellum has been implicated in playing a role in cognitive processes. However, the functional connectivity (FC) between the cognitive sub-regions of the cerebellum in PD patients with hallucinations needs further clarification. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from three groups (17 PD-H patients, 13 patients with Parkinson's disease not accompanied by hallucinations (PD-NH), and 26 healthy controls (HC)). The data were collected in this study to investigate the impact of cerebellar FC changes on cognitive performance. Additionally, we define cerebellar FC as a training feature for classifying all subjects using Support Vector Machines (SVMs). We found that in the PD-H patients, there was an increase in FC within the left side of the precuneus (PCUN) compared to the HC. Additionally, there was an increase in FC within the bilateral opercular part of the inferior frontal gyrus (IFGoprec) and triangular part of the inferior frontal gyrus (IFCtriang), as well as the left side of the postcentral gyrus (PoCG), inferior parietal lobe (IPL), and PCUN compared to the PD-NH patients. In the machine learning training results, cerebellar FC has also been proven to be an effective biomarker feature, achieving a recognition rate of over 90% for PD-H. These findings indicate that the cortico-cerebellar FC in PD-H and PD-NH patients was significantly disrupted, with different patterns of distribution. The proposed pipeline offers a promising, low-cost alternative for diagnosing preclinical PD-H and may also be beneficial for other degenerative brain disorders.

Resting-state functional connectivity of the cerebellum-cerebrum in older women with depressive symptoms

BackgroundAlthough there has been much neurobiological research on major depressive disorder, research on the neurological function of depressive symptoms (DS) or subclinical depression is still scarce, especially in older women with DS.ObjectivesResting-state functional magnetic resonance imaging (rs-fMRI) was used to compare functional connectivity (FC) between the cerebellum and cerebral in older women with DS and normal controls (NC), to explore unique changes in cerebellar FC in older women with DS.MethodsIn all, 16 older women with DS and 17 NC were recruited. All subjects completed rs-fMRI. The 26 sub-regions of the cerebellum divided by the AAL3 map were used as regions of interest (ROI) to analyze the difference in FC strength of cerebellar seeds from other cerebral regions between the two groups. Finally, partial correlation analysis between abnormal FC strength and Geriatric Depression Scale (GDS) score and Reminiscence Functions Scale (RFS) score in the DS group.ResultsCompared with NC group, the DS group showed significantly reduced FC between Crus I, II and the left frontoparietal region, and reduced FC between Crus I and the left temporal gyrus. Reduced FC between right insula (INS), right rolandic operculum (ROL), right precentral gyrus (PreCG) and the Lobule IX, X. Moreover, the negative FC between Crus I, II, Lobule IX and visual regions was reduced in the DS group. The DS group correlation analysis showed a positive correlation between the left Crus I and the right cuneus (CUN) FC and GDS. In addition, the abnormal FC strength correlated with the scores in different dimensions of the RFS, such as the negative FC between the Crus I and the left middle temporal gyrus (MTG) was positively associated with intimacy maintenance, and so on.ConclusionOlder women with DS have anomalous FC between the cerebellum and several regions of the cerebrum, which may be related to the neuropathophysiological mechanism of DS in the DS group.

Machine Learning of Functional Connectivity to Biotype Alcohol and Nicotine Use Disorders

BackgroundMagnetic resonance imaging provides noninvasive tools to investigate alcohol use disorder (AUD) and nicotine use disorder (NUD) and neural phenotypes for genetic studies. A data-driven transdiagnostic approach could provide a new perspective on the neurobiology of AUD and NUD. MethodsUsing samples of individuals with AUD (n = 140), individuals with NUD (n = 249), and healthy control participants (n = 461) from the UK Biobank, we integrated clinical, neuroimaging, and genetic markers to identify biotypes of AUD and NUD. We partitioned participants with AUD and NUD based on resting-state functional connectivity (FC) features associated with clinical metrics. A multitask artificial neural network was trained to evaluate the cluster-defined biotypes and jointly infer AUD and NUD diagnoses. ResultsThree biotypes—primary NUD, mixed NUD/AUD with depression and anxiety, and mixed AUD/NUD—were identified. Multitask classifiers incorporating biotype knowledge achieved higher area under the curve (AUD: 0.76, NUD: 0.74) than single-task classifiers without biotype differentiation (AUD: 0.61, NUD: 0.64). Cerebellar FC features were important in distinguishing the 3 biotypes. The biotype of mixed NUD/AUD with depression and anxiety demonstrated the largest number of FC features (n = 5), all related to the visual cortex, that significantly differed from healthy control participants and were validated in a replication sample (p < .05). A polymorphism in TNRC6A was associated with the mixed AUD/NUD biotype in both the discovery (p = 7.3 × 10−5) and replication (p = 4.2 × 10−2) sets. ConclusionsBiotyping and multitask learning using FC features can characterize the clinical and genetic profiles of AUD and NUD and help identify cerebellar and visual circuit markers to differentiate the AUD/NUD group from the healthy control group. These markers support a new growing body of literature.

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.

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.

Familial Adult Myoclonus Epilepsy: A Non-Coding Repeat Expansion Disorder of Cerebellar-Thalamic-Cortical Loop.

Familial adult myoclonus Epilepsy (FAME) is a non-coding repeat expansion disorder that has been reported under different acronyms and initially linked to four main loci: FAME1 (8q23.3-q24.1), FAME 2 (2p11.1-q12.1), FAME3 (5p15.31-p15.1), and FAME4 (3q26.32-3q28). To date, it is known that the genetic mechanism underlying FAME consists of the expansion of similar non-coding pentanucleotide repeats, TTTCA and TTTTA, in different genes. FAME is characterized by cortical tremor and myoclonus usually manifesting within the second decade of life, and infrequent seizures by the third or fourth decade. Cortical tremor is the core feature of FAME and is considered part of a spectrum of cortical myoclonus. Neurophysiological investigations as jerk-locked back averaging (JLBA) and corticomuscular coherence analysis, giant somatosensory evoked potentials (SEPs), and the presence of long-latency reflex I (or C reflex) at rest support cortical tremor as the result of the sensorimotor cortex hyperexcitability. Furthermore, the application of transcranial magnetic stimulation (TMS) protocols in FAME patients has recently shown that inhibitory circuits are also altered within the primary somatosensory cortex and the concomitant involvement of subcortical networks. Moreover, neuroimaging studies and postmortem autoptic studies indicate cerebellar alterations and abnormal functional connectivity between the cerebellum and cerebrum in FAME. Accordingly, the pathophysiological mechanism underlying FAME has been hypothesized to reside in decreased sensorimotor cortical inhibition through dysfunction of the cerebellar-thalamic-cortical loop, secondary to primary cerebellar pathology. In this context, the non-coding pentameric expansions have been proposed to cause cerebellar damage through an RNA-mediated toxicity mechanism. The elucidation of the underlying pathological mechanisms of FAME paves the way to novel therapeutic possibilities, such as RNA-targeting treatments, possibly applicable to other neurodegenerative non-coding disorders.

374. Altered Cerebellar Ventral Tegmental Area Functional Connectivity With Decreased Social Motivation in Schizophrenia Using Resting State Bold Signal Variability - Preliminary Results

374. Altered Cerebellar Ventral Tegmental Area Functional Connectivity With Decreased Social Motivation in Schizophrenia Using Resting State Bold Signal Variability - Preliminary Results

Functional hyperconnectivity between corticocerebellar networks and altered decision making in young adult cannabis users: Evidence from 7T and multivariate pattern analysis

Decision-making (DM) impairments are important predictors of cannabis initiation and continued use. In cannabis users, how decision-making abnormalities related to structural and functional connectivity in the brain are not fully understood. We employed a three-method multimodal image analysis and multivariate pattern analysis (MVPA) on high dimensional 7 tesla MRI images examining functional connectivity, white matter microstructure and gray matter volume in a group of cannabis users and non-users. Neuroimaging and cognitive analyses were performed on 92 CU and 92 age- matched NU from a total of 187 7T scans. CU were selected on the basis of their scores on the Semi-Structured Assessment for the Genetics of Alcoholism. The groups were first compared on a decision-making test and then on ICA based functional connectivity between corticocerebellar networks. An MVPA was done as a confirmatory analysis. The anatomy of these networks was then assessed using Diffusion Tensor imaging (DTI) and cortical volume analyses. Cannabis Users had significantly higher scores on the Iowa Gambling task (IGT) [Gambling task Percentage larger] and significantly lower scores on the [Gambling task reward Percentage smaller]. Left accumbens (L NAc) volume was significantly larger in cannabis users. DTI analysis between the groups yielded no significant (FWE corrected) differences. Resting state FC analysis of the left Cerebellum region 9 showed enhanced functional connectivity with the right nucleus accumbens and left pallidum and left putamen in CU. In addition, posterior cerebellum showed enhanced functional connectivity (FWE corrected) with 2 nodes of the DMN and left and right paracingulate (sub genual ACC) and the sub callosal cortex in CU. IGT percentage larger scores correlated with posterior cerebellar functional connectivity in non-user women. A multivariate pattern analysis confirmed this cerebellar hyperconnectivity in both groups. Our results demonstrate for the first time that deficits in DM observed in cannabis users are mirrored in hyper connectivity in corticocerebellar networks. Cortical volumes of some of the nodes of these networks showed increases in users. However, the underlying white matter was largely intact in CU. The observed DM deficits and hyper connectivity in resting networks may contribute to difficulties in quitting and/or facilitating relapse.

Abnormal cerebellum connectivity patterns related to motor subtypes of Parkinson’s disease

Cerebellar dysfunction may substantially contribute to the clinical symptoms of Parkinson’s disease (PD). The role of cerebellar subregions in tremors and gait disturbances in PD remains unknown. To investigate alterations in cerebellar subregion volumes and functional connectivity (FC), as well as FC between the dentate nucleus (DN) and ventral lateral posterior nucleus (VLp) of the thalamus, which are potentially involved in different PD motor subtypes. We conducted morphometric and resting-state functional connectivity analyses in various cerebellar subregions in 22 tremor-dominant (TD)-PD and 35 postural instability gait difficulty dominant (PIGD)-PD patients and 38 sex- and age-matched healthy controls (HCs). The volume and FC alterations in various cerebellar subregions and the neural correlates of these changes with the clinical severity scores were investigated. The PIGD-PD group showed greater FC between the right motor cerebellum (CBMm) and left postcentral gyrus than the HC group, and a higher FC was associated with less severe PIGD symptoms. In contrast, the TD-PD group had decreased FC between the right DN and left VLp compared with the PIGD-PD and HC groups, and lower FC was associated with worse TD symptoms. Furthermore, the PIGD-PD group had higher FC between the left DN and left inferior temporal gyrus than the TD-PD group. Morphometric analysis revealed that the TD-PD group showed a significantly higher volume of left CBMm than the HC group. Our findings point to differential alteration patterns in cerebellar subregions and offer a new perspective on the pathophysiology of motor subtypes of PD.

Cerebellar functional disruption and compensation in mesial temporal lobe epilepsy.

Cerebellar functional alterations are common in patients with mesial temporal lobe epilepsy (MTLE), which contribute to cognitive decline. This study aimed to deepen our knowledge of cerebellar functional alterations in patients with MTLE. In this study, participants were recruited from an ongoing prospective cohort of 13 patients with left TLE (LTLE), 17 patients with right TLE (RTLE), and 30 healthy controls (HCs). Functional magnetic resonance imaging data were collected during a Chinese verbal fluency task. Group independent component (IC) analysis (group ICA) was applied to segment the cerebellum into six functionally separated networks. Functional connectivity was compared among cerebellar networks, cerebellar activation maps, and the centrality parameters of cerebellar regions. For cerebellar functional profiles with significant differences, we calculated their correlation with clinical features and neuropsychological scores. Compared to HCs and patients with LTLE, patients with RTLE had higher cerebellar functional connectivity between the default mode network (DMN) and the oculomotor network and lower cerebellar functional connectivity from the frontoparietal network (FPN) to the dorsal attention network (DAN) (p < 0.05, false discovery rate- (FDR-) corrected). Cerebellar degree centrality (DC) of the right lobule III was significantly higher in patients with LTLE compared to HC and patients with RTLE (p < 0.05, FDR-corrected). Higher cerebellar functional connectivity between the DMN and the oculomotor network, as well as lower cerebellar degree centrality of the right lobule III, was correlated with worse information test performance. Cerebellar functional profiles were altered in MTLE and correlated with long-term memory in patients.

Intrinsic Therapeutic Link between Recuperative Cerebellar Con-Nectivity and Psychiatry Symptom in Schizophrenia Patients with Comorbidity of Metabolic Syndrome.

Components of metabolic syndrome might be predictors of the therapeutic outcome of psychiatric symptom in schizophrenia, whereas clinical results are inconsistent and an intrinsic therapeutic link between weaker psychiatric symptoms and emergent metabolic syndrome remains unclear. This study aims to reveal the relationship and illustrate potential mechanism by exploring the alteration of cerebellar functional connectivity (FC) in schizophrenia patients with comorbidity metabolic syndrome. Thirty-six schizophrenia patients with comorbidity of metabolic syndrome (SCZ-MetS), 45 schizophrenia patients without metabolic syndrome (SCZ-nMetS) and 39 healthy controls (HC) were recruited in this study. We constructed FC map of cerebello-cortical circuit and used moderation effect analysis to reveal complicated relationship among FC, psychiatric symptom and metabolic disturbance. Components of metabolic syndrome were significantly correlated with positive symptom score and negative symptom score. Importantly, the dysconnectivity between cognitive module of cerebellum and left middle frontal gyrus in SCZ-nMetS was recuperative increased in SCZ-MetS, and was significantly correlated with general symptom score. Finally, we observed significant moderation effect of body mass index on this correlation. The present findings further supported the potential relationship between emergence of metabolic syndrome and weaker psychiatric symptom, and provided neuroimaging evidence. The mechanism of intrinsic therapeutic link involved functional change of cerebello-cortical circuit.

Altered cerebellar functional connectivity in chronic subcortical stroke patients.

Previous studies demonstrated that cerebellar subregions are involved in different functions. Especially the cerebellar anterior lobe (CAL) and cerebellar posterior lobe (CPL) have been postulated to primarily account for sensorimotor and cognitive function, respectively. However, the functional connectivity (FC) alterations of CAL and CPL, and their relationships with behavior performance in chronic stroke participants are unclear so far. The present study collected resting-state fMRI data from thirty-six subcortical chronic stroke participants and thirty-eight well-matched healthy controls (HCs). We performed the FC analysis with bilateral CAL and CPL as seeds for each participant. Then, we detected the FC difference between the two groups by using a two-sample t-test and evaluated the relationship between the FC and scores of motor and cognitive assessments across all post-stroke participants by using partial correlation analysis. The CAL showed increased FCs in the prefrontal cortex, superior/inferior temporal gyrus, and lingual gyrus, while the CPL showed increased FCs in the inferior parietal lobule, precuneus, and cingulum gyrus in the stroke participants compared with HCs. Moreover, the FC alteration in the right CAL and the right CPL were negatively correlated with executive and memory functions across stroke participants, respectively. These findings shed light on the different increased FC alteration patterns of CAL and CPL that help understand the neuro-mechanisms underlying behavior performance in chronic stroke survivors.

Development of Cerebellar Reserve

The cerebellar reserve is defined as the capacity of the cerebellum for compensation and restoration following injury. This unique cerebellar ability is attributed to various forms of synaptic plasticity that incorporate multimodal and redundant cerebellar inputs, two major features of the cerebellar circuitry. It is assumed that the cerebellar reserve is acquired from the age of 12 years after the maturation of both the cerebellar adaptative behaviors and cerebellar functional connectivity. However, acquiring the cerebellar reserve is also affected by two other factors: vulnerability and growth potential in the developing cerebellum. First, cerebellar injury during the critical period of neural circuit formation (especially during fetal and neonatal life and infancy) leads to persistent dysfunction of the cerebellum and its targets, resulting in the limitation of the cerebellar reserve. Secondly, growth potential appears to facilitate cerebellar reserve during the stage when the cerebellar reserve is still immature. Based on these findings, the present mini-review proposes a possible developmental trajectory underlying the acquisition of cerebellar reserve. We highlight the importance of studies dedicated to the understanding of the cerebellar resilience to injuries.

Structural and Functional Characterization of Gray Matter Alterations in Female Patients With Neuropsychiatric Systemic Lupus.

ObjectiveTo investigate morphological and functional alterations within gray matter (GM) in female patients with neuropsychiatric systemic lupus (NPSLE) and to explore their clinical significance.Methods54 female patients with SLE (30 NPSLE and 24 non-NPSLE) and 32 matched healthy controls were recruited. All subjects received a quantitative MRI scan (FLAIR, 3DT1, resting-state functional MRI). GM volume (GMV), fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and degree of centrality (DC) were obtained. Between-group comparison, clinical correlation, and discrimination of NPSLE from non-NPSLE were achieved by voxel-based analysis, cerebellar seed-based functional connectivity analysis, regression analysis, and support vector machine (SVM), respectively.ResultsPatients with NPSLE showed overt subcortical GM atrophy without significantly abnormal brain functions in the same region compared with controls. The dysfunction within the left superior temporal gyri (L-STG) was found precede the GM volumetric loss. The function of the nodes in default mode network (DMN) and salience network (SN) were weakened in NPSLE patients compared to controls. The function of the cerebellar posterior lobes was significantly activated in non-NPSLE patients but attenuated along with GM atrophy and presented higher connectivity with L-STG and DMN in NPSLE patients, while the variation of the functional activities in the sensorimotor network (SMN) was the opposite. These structural and functional alterations were mainly correlated with disease burden and anti-phospholipid antibodies (aPLs) (r ranges from -1.53 to 1.29). The ReHos in the bilateral cerebellar posterior lobes showed high discriminative power in identifying patients with NPSLE with accuracy of 87%.ConclusionPatients with NPSLE exhibit both structural and functional alterations in the GM of the brain, which especially involved the deep GM, the cognitive, and sensorimotor regions, reflecting a reorganization to compensate for the disease damage to the brain which was attenuated along with pathologic burden and cerebral vascular risk factors. The GM within the left temporal lobe may be one of the direct targets of lupus-related inflammatory attack. The function of the cerebellar posterior lobes might play an essential role in compensating for cortical functional disturbances and may contribute to identifying patients with suspected NPSLE in clinical practice.