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Cerebellum (London, England) Apr 2024Given the key roles of the cerebellum in motor, cognitive, and affective operations and given the decline of brain functions with aging, cerebellar circuitry is... (Review)
Review
Given the key roles of the cerebellum in motor, cognitive, and affective operations and given the decline of brain functions with aging, cerebellar circuitry is attracting the attention of the scientific community. The cerebellum plays a key role in timing aspects of both motor and cognitive operations, including for complex tasks such as spatial navigation. Anatomically, the cerebellum is connected with the basal ganglia via disynaptic loops, and it receives inputs from nearly every region in the cerebral cortex. The current leading hypothesis is that the cerebellum builds internal models and facilitates automatic behaviors through multiple interactions with the cerebral cortex, basal ganglia and spinal cord. The cerebellum undergoes structural and functional changes with aging, being involved in mobility frailty and related cognitive impairment as observed in the physio-cognitive decline syndrome (PCDS) affecting older, functionally-preserved adults who show slowness and/or weakness. Reductions in cerebellar volume accompany aging and are at least correlated with cognitive decline. There is a strongly negative correlation between cerebellar volume and age in cross-sectional studies, often mirrored by a reduced performance in motor tasks. Still, predictive motor timing scores remain stable over various age groups despite marked cerebellar atrophy. The cerebello-frontal network could play a significant role in processing speed and impaired cerebellar function due to aging might be compensated by increasing frontal activity to optimize processing speed in the elderly. For cognitive operations, decreased functional connectivity of the default mode network (DMN) is correlated with lower performances. Neuroimaging studies highlight that the cerebellum might be involved in the cognitive decline occurring in Alzheimer's disease (AD), independently of contributions of the cerebral cortex. Grey matter volume loss in AD is distinct from that seen in normal aging, occurring initially in cerebellar posterior lobe regions, and is associated with neuronal, synaptic and beta-amyloid neuropathology. Regarding depression, structural imaging studies have identified a relationship between depressive symptoms and cerebellar gray matter volume. In particular, major depressive disorder (MDD) and higher depressive symptom burden are associated with smaller gray matter volumes in the total cerebellum as well as the posterior cerebellum, vermis, and posterior Crus I. From the genetic/epigenetic standpoint, prominent DNA methylation changes in the cerebellum with aging are both in the form of hypo- and hyper-methylation, and the presumably increased/decreased expression of certain genes might impact on motor coordination. Training influences motor skills and lifelong practice might contribute to structural maintenance of the cerebellum in old age, reducing loss of grey matter volume and therefore contributing to the maintenance of cerebellar reserve. Non-invasive cerebellar stimulation techniques are increasingly being applied to enhance cerebellar functions related to motor, cognitive, and affective operations. They might enhance cerebellar reserve in the elderly. In conclusion, macroscopic and microscopic changes occur in the cerebellum during the lifespan, with changes in structural and functional connectivity with both the cerebral cortex and basal ganglia. With the aging of the population and the impact of aging on quality of life, the panel of experts considers that there is a huge need to clarify how the effects of aging on the cerebellar circuitry modify specific motor, cognitive, and affective operations both in normal subjects and in brain disorders such as AD or MDD, with the goal of preventing symptoms or improving the motor, cognitive, and affective symptoms.
Topics: Adult; Humans; Aged; Depressive Disorder, Major; Cross-Sectional Studies; Consensus; Quality of Life; Cerebellum; Aging; Magnetic Resonance Imaging
PubMed: 37428408
DOI: 10.1007/s12311-023-01577-7 -
NeuroImage May 2022Background Neural connectome theory has been widely used in system neuroscience, and prompted our comprehension for the topological organizations of human cerebral...
Background Neural connectome theory has been widely used in system neuroscience, and prompted our comprehension for the topological organizations of human cerebral cortex. However, how functional connectome is organized topologically in cerebellums remains unclear. Method Resting-state functional connectivity (rs-fcMRI) data were acquired from 1416 healthy adults in two independent samples. In Sample 1 (n = 976), both voxel-wise and node-wise topological properties for functional cerebellar connectome were estimated. Moreover, the network-based topological properties of cerebellum and cerebro-cerebellar topological mapping were investigated, respectively. Given the temporal natures in the neural population, a hidden Markov model (HMM) was further capitalized to uncover the dynamic pattern of cerebellar functional connectome. In order to test the robustness of our findings, we ran all of the analyses in an independent dataset (Sample 2; n = 440). Results We found that Crus I and II exhibited prominently high degree centrality (DC) for cerebellar functional connectome. Further, the cerebellar functional connectome and even the nested network-wise cerebellar connectome was found to be organized by small-world, modular and hierarchical manners significantly. Also, three intrinsic modules were found in cerebellar functional connectome, including attention/executive network, default mode network and task-positive network. In addition, the significant cerebro-cerebellar correlations for small-world organization and hierarchical architecture were found as well. By building cerebro-cerebellar topological mapping, both frontoparietal and subcortical networks were found to be overrepresented into cerebellums than cerebral cortex (3-fold). As for temporal natures, cerebellar functional connectome was observed to be highly flexible and modular, but showed high individual-specific variances in temporal dynamic pattern. Conclusion This study identified the topological architectures and temporal hierarchy of functional cerebellar connectome, and further demonstrated prominent functional cerebro-cerebellar couplings of small-world organization and hierarchical architectures.
Topics: Adult; Attention; Cerebellum; Cerebral Cortex; Connectome; Humans; Magnetic Resonance Imaging
PubMed: 35189360
DOI: 10.1016/j.neuroimage.2022.119015 -
Scientific Reports Oct 2020Recent research has shown that the cerebellum is involved not only in motor control but also in higher-level activities, which are closely related to creativity. This...
Recent research has shown that the cerebellum is involved not only in motor control but also in higher-level activities, which are closely related to creativity. This study aimed to explore the role of the cerebellum in visual divergent thinking based on its intrinsic activity. To this end, we selected the resting-state fMRI data of high- (n = 22) and low-level creativity groups (n = 22), and adopted the voxel-wise, seed-wise, and dynamic functional connectivity to identify the differences between the two groups. Furthermore, the topological properties of the cerebello-cerebral network and their relations with visual divergent thinking were calculated. The voxel-wise functional connectivity results indicated group differences across the cerebellar (e.g. lobules VI, VIIb, Crus I, and Crus II) and cerebral regions (e.g. superior frontal cortex, middle frontal cortex, and inferior parietal gyrus), as well as the cerebellar lobules (e.g. lobules VIIIa, IX, and X) and the cerebral brain regions (the cuneus and precentral gyrus). We found a significant correlation between visual divergent thinking and activities of the left lobules VI, VIIb, Crus I, and Crus II, which are associated with executive functions. Our overall results provide novel insight into the important role of the cerebellum in visual divergent thinking.
Topics: Adolescent; Adult; Cerebellum; Cerebral Cortex; Creativity; Executive Function; Female; Humans; Magnetic Resonance Imaging; Male; Neural Pathways; Photic Stimulation; Thinking; Visual Perception; Young Adult
PubMed: 33024190
DOI: 10.1038/s41598-020-73679-9 -
Frontiers in Neurology 2023This study aimed to comprehensively explore the cerebellar structural and functional changes in temporal lobe epilepsy (TLE) and its association with clinical...
AIMS
This study aimed to comprehensively explore the cerebellar structural and functional changes in temporal lobe epilepsy (TLE) and its association with clinical information.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
PubMed: 37602268
DOI: 10.3389/fneur.2023.1213224 -
Frontiers in Neuroscience 2015The cerebellum is one of the most consistent sites of abnormality in autism spectrum disorder (ASD) and cerebellar damage is associated with an increased risk of ASD... (Review)
Review
The cerebellum is one of the most consistent sites of abnormality in autism spectrum disorder (ASD) and cerebellar damage is associated with an increased risk of ASD symptoms, suggesting that cerebellar dysfunction may play a crucial role in the etiology of ASD. The cerebellum forms multiple closed-loop circuits with cerebral cortical regions that underpin movement, language, and social processing. Through these circuits, cerebellar dysfunction could impact the core ASD symptoms of social and communication deficits and repetitive and stereotyped behaviors. The emerging topography of sensorimotor, cognitive, and affective subregions in the cerebellum provides a new framework for interpreting the significance of regional cerebellar findings in ASD and their relationship to broader cerebro-cerebellar circuits. Further, recent research supports the idea that the integrity of cerebro-cerebellar loops might be important for early cortical development; disruptions in specific cerebro-cerebellar loops in ASD might impede the specialization of cortical regions involved in motor control, language, and social interaction, leading to impairments in these domains. Consistent with this concept, structural, and functional differences in sensorimotor regions of the cerebellum and sensorimotor cerebro-cerebellar circuits are associated with deficits in motor control and increased repetitive and stereotyped behaviors in ASD. Further, communication and social impairments are associated with atypical activation and structure in cerebro-cerebellar loops underpinning language and social cognition. Finally, there is converging evidence from structural, functional, and connectivity neuroimaging studies that cerebellar right Crus I/II abnormalities are related to more severe ASD impairments in all domains. We propose that cerebellar abnormalities may disrupt optimization of both structure and function in specific cerebro-cerebellar circuits in ASD.
PubMed: 26594140
DOI: 10.3389/fnins.2015.00408 -
Journal of Psychopharmacology (Oxford,... Jul 2021Cannabis use has been associated with abnormalities in cerebellar mediated motor and non-motor (i.e. cognition and personality) phenomena. Since the cerebellum is a...
BACKGROUND
Cannabis use has been associated with abnormalities in cerebellar mediated motor and non-motor (i.e. cognition and personality) phenomena. Since the cerebellum is a region with high cannabinoid type 1 receptor density, these impairments may reflect alterations of signaling between the cerebellum and other brain regions.
AIMS
We hypothesized that cerebellar-cortical resting-state functional connectivity (rsFC) would be altered in cannabis users, relative to their non-using peers. It was also hypothesized that differences in rsFC would be associated with cannabis use features, such as age of initiation and lifetime use.
METHODS
Cerebellar-cortical and subcortical rsFCs were computed between 28 cerebellar lobules, defined by a spatially unbiased atlas template of the cerebellum, and individual voxels in the cerebral regions, in 41 regular cannabis users (20 female) and healthy non-using peers ( = 31; 18 female). We also investigated associations between rsFC and cannabis use features (e.g. lifetime cannabis use and age of initiation).
RESULTS
Cannabis users demonstrated hyperconnectivity between the anterior cerebellar regions (i.e. lobule I-IV) with the posterior cingulate cortex, and hypoconnectivity between the rest of the cerebellum (i.e. Crus I and II, lobule VIIb, VIIIa, VIIIb, IX, and X) and the cortex. No associations were observed between features of cannabis use and rsFC.
CONCLUSIONS
Cannabis use was associated with altered patterns of rsFC from the cerebellum to the cerebral cortex which may have a downstream impact on behavior and cognition.
Topics: Adolescent; Adult; Cerebellum; Cerebral Cortex; Connectome; Female; Humans; Magnetic Resonance Imaging; Male; Marijuana Use; Young Adult
PubMed: 34034553
DOI: 10.1177/02698811211019291 -
Frontiers in Neuroscience 2020The role of the cerebellum in type 2 diabetes mellitus (T2DM) has been receiving increased attention. However, the functional connectivity (FC) between the cerebellar...
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 ( = -0.430, = 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.
PubMed: 33071743
DOI: 10.3389/fnins.2020.571210 -
Frontiers in Neuroscience 2022Subcortical vascular mild cognitive impairment (svMCI) is associated with structural and functional changes in the cerebral cortex affecting major brain networks. While...
Subcortical vascular mild cognitive impairment (svMCI) is associated with structural and functional changes in the cerebral cortex affecting major brain networks. While recent studies have shown that the intrinsic cerebral connectivity networks can be mapped onto the cerebellum, and the cortex and cerebellum are interconnected the cortico-basal ganglia-cerebellar circuit, structural and functional disruptions in cerebellum in svMCI are rarely studied. In this study, we conducted voxel-based morphometry analysis to investigate gray matter atrophy pattern across cerebellar regions in 40 svMCI patients, and explored alterations in functional connectivity between the basal ganglia and cerebellum. The results showed that the amount of cerebellar atrophy within the default mode, salience, and frontoparietal networks correlated with their counterpart in the cerebral cortex. Moreover, key regions of the cerebellum, including the lobule VI, VIIb, VIII, and Crus I, which are reported to have a role in cognitive function, showed both anatomical atrophy and decreased functional connectivity with the striatum. These atrophy and connectivity patterns in the cerebellum also correlated with memory performances. These findings demonstrate that there are coupled changes in cerebral and cerebellar circuits, reflecting that degeneration patterns in svMCI are not limited to the cerebral cortex but similarly extend to the cerebellum as well, and suggest the cortico-basal ganglia-cerebellar circuit may play an important role in the pathology of svMCI.
PubMed: 36711147
DOI: 10.3389/fnins.2022.1006231 -
BMC Psychiatry Oct 2023Although there has been much neurobiological research on major depressive disorder, research on the neurological function of depressive symptoms (DS) or subclinical...
BACKGROUND
Although 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.
OBJECTIVES
Resting-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.
METHODS
In 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.
RESULTS
Compared 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.
CONCLUSION
Older 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.
Topics: Humans; Female; Aged; Depression; Depressive Disorder, Major; Cerebellum; Temporal Lobe; Parietal Lobe; Magnetic Resonance Imaging
PubMed: 37817133
DOI: 10.1186/s12888-023-05232-7 -
Frontiers in Neuroscience 2022Auditory verbal hallucinations (AVHs) are a major symptom of schizophrenia and are connected with impairments in auditory and speech-related networks. In schizophrenia...
OBJECTIVE
Auditory verbal hallucinations (AVHs) are a major symptom of schizophrenia and are connected with impairments in auditory and speech-related networks. In schizophrenia with AVHs, alterations in resting-state cerebral blood flow (CBF) and functional connectivity have been described. However, the neurovascular coupling alterations specific to first-episode drug-naïve schizophrenia (FES) patients with AVHs remain unknown.
METHODS
Resting-state functional MRI and arterial spin labeling (ASL) was performed on 46 first-episode drug-naïve schizophrenia (FES) patients with AVHs (AVH), 39 FES drug-naïve schizophrenia patients without AVHs (NAVH), and 48 healthy controls (HC). Then we compared the correlation between the CBF and functional connection strength (FCS) of the entire gray matter between the three groups, as well as the CBF/FCS ratio of each voxel. Correlation analyses were performed on significant results between schizophrenia patients and clinical measures scale.
RESULTS
The CBF/FCS ratio was reduced in the cognitive and emotional brain regions in both the AVH and NAVH groups, primarily in the crus I/II, vermis VI/VII, and cerebellum VI. In the AVH group compared with the HC group, the CBF/FCS ratio was higher in auditory perception and language-processing areas, primarily the left superior and middle temporal gyrus (STG/MTG). The CBF/FCS ratio in the left STG and left MTG positively correlates with the score of the Auditory Hallucination Rating Scale in AVH patients.
CONCLUSION
These findings point to the difference in neurovascular coupling failure between AVH and NAVH patients. The dysfunction of the forward model based on the predictive and computing role of the cerebellum may increase the excitability in the auditory cortex, which may help to understand the neuropathological mechanism of AVHs.
PubMed: 35546878
DOI: 10.3389/fnins.2022.821078