Cerebellar Subregions Research Articles

Gray matter volume differences based on sex in first-episode drug-naive patients with major depressive disorder and its molecular analysis.

This study analyzed whether gray matter volume (GMV) differences exist between the sexes in patients with major depressive disorder (MDD) and explored the relationships between these differences and neurotransmitter systems. This study enrolled 190 first-episode drug-naive patients with MDD and 293 healthy controls. All participants underwent T1-weighted high-resolution MRI. The interaction between the diagnosis (healthy controls vs. MDD) and sex (male vs. female) regarding GMV alterations was analyzed. The JuSpace toolbox, which covers a wide range of neurotransmitter systems, was used to identify the relationship between MDD-induced and sex-induced GMV alterations and specific receptor/transporter proteins in the brain. Sex-specific GMV differences were observed in the healthy controls but not in MDD patients. Male healthy controls had a larger GMV in the bilateral parahippocampal, lingual, inferior occipital, fusiform, cerebellar subregions, and left inferior temporal than female healthy controls, but several subregions of the thalamus had a larger GMV in female healthy controls than in male healthy controls. Sex-induced GMV alterations were associated with 5-hydroxytryptamine receptor subtype 1a, cannabinoid receptor, and dopamine receptor (P < 0.01, false discovery rate corrected). GMV differences were not detected in the main effect of diagnosis and the interaction of diagnosis and sex. Sex-specific GMV differences are associated with the spatial distribution of serotonin, dopamine, and cannabinoid neurotransmitter receptor systems. Sex-based physiological differences in the GMV may account for male and female susceptibility to and differences in the clinical symptoms of MDD.

Altered cerebellar-cerebral dynamic functional connectivity in patients with pontine stroke: a resting-state fMRI study.

Potential changes in patterns of dynamic functional network connections at the cerebellar-cerebral level in pontine infarction (PI) patients remain unclear. The study aimed to investigate the abnormal patterns of dynamic functional connectivity (dFC) between the cerebellar subregions within networks and regions of the cerebral cortex in patients with PI. Forty-six chronic left pontine infarction (LPI), 32 chronic right pontine infarction (RPI), and 50 healthy controls (HCs) were recruited to undergo resting-state fMRI scans. Cerebellar-cerebral dFC was characterized using the sliding window method and seed-based connectivity analyses. Correlations between altered dFC values and clinical variables (The Rey Auditory Verbal Learning Test and Flanker task) in PI patients and healthy controls were investigated. Compared with HCs, the PI groups showed significantly aberrant cerebellar-cerebral dFC between cerebellar subregions within networks and supratentorial cerebral cortex, including executive, default-mode, and motor networks. Furthermore, Correlation analysis showed a decoupling between abnormal dFC and cognitive functions in PI patients. These findings indicate that PI patients are accompanied by damage to cerebellar subregions within networks and cerebellar-cerebral pathways, which may provide a potential target for treatment or an indication of therapeutic efficacy.

Identification of schizophrenia by applying interpretable radiomics modeling with structural magnetic resonance imaging of the cerebellum.

The cerebellum is involved in higher-order mental processing as well as sensorimotor functions. Although structural abnormalities in the cerebellum have been demonstrated in schizophrenia, neuroimaging techniques are not yet applicable to identify them given the lack of biomarkers. We aimed to develop a robust diagnostic model for schizophrenia using radiomic features from T1-weighted magnetic resonance imaging (T1-MRI) of the cerebellum. A total of 336 participants (174 schizophrenia; 162 healthy controls [HCs]) were allocated to training (122 schizophrenia; 115 HCs) and test (52 schizophrenia; 47 HCs) cohorts. We obtained 2568 radiomic features from T1-MRI of the cerebellar subregions. After feature selection, a light gradient boosting machine classifier was trained. The discrimination and calibration of the model were evaluated. SHapley Additive exPlanations (SHAP) was applied to determine model interpretability. We identified 17 radiomic features to differentiate participants with schizophrenia from HCs. In the test cohort, the radiomics model had an area under the curve, accuracy, sensitivity, and specificity of 0.89 (95% confidence interval: 0.82-0.95), 78.8%, 88.5%, and 75.4%, respectively. The model explanation by SHAP suggested that the second-order size zone non-uniformity feature from the right lobule IX and first-order energy feature from the right lobules V and VI were highly associated with the risk of schizophrenia. The radiomics model focused on the cerebellum demonstrates robustness in diagnosing schizophrenia. Our results suggest that microcircuit disruption in the posterior cerebellum is a disease-defining feature of schizophrenia, and radiomics modeling has potential for supporting biomarker-based decision-making in clinical practice.

Sex-steroid hormones relate to cerebellar structure and functional connectivity across adulthood.

Aging involves complex biological changes that affect disease susceptibility and aging trajectories. Although females typically live longer than males, they have a higher susceptibility to diseases like Alzheimer's, speculated to be influenced by menopause, and reduced ovarian hormone production. Understanding sex-specific differences is crucial for personalized medical interventions and gender equality in health. Our study aims to elucidate sex differences in regional cerebellar structure and connectivity during normal aging by investigating both structural and functional connectivity variations, with a focus on investigating these differences in the context of sex-steroid hormones. The study included 138 participants (mean age = 57(13.3) years, age range = 35-86 years, 54% women). The cohort was divided into three groups: 38 early middle-aged individuals (EMA) (mean age = 41(4.7) years), 48 late middle-aged individuals (LMA) (mean age = 58(4) years), and 42 older adults (OA) (mean age = 72(6.3) years). All participants underwent MRI scans, and saliva samples were collected for sex-steroid hormone quantification (17β-estradiol (E), progesterone (P), and testosterone (T)). We found less connectivity in females between Lobule I-IV and the cuneus, and greater connectivity in females between Crus I, Crus II, and the precuneus with increased age. Higher 17β-estradiol levels were linked to greater connectivity in Crus I and Crus II cerebellar subregions. Analyzing all participants together, testosterone was associated with both higher and lower connectivity in Lobule I-IV and Crus I, respectively, while higher progesterone levels were linked to lower connectivity in females. Structural differences were observed, with EMA males having larger volumes compared to LMA and OA groups, particularly in the right I-IV, right Crus I, right V, and right VI. EMA females showed higher volumes in the right lobules V and VI. These results highlight the significant role of sex hormones in modulating cerebellar connectivity and structure across adulthood, emphasizing the need to consider sex and hormonal status in neuroimaging studies to better understand age-related cognitive decline and neurological disorders.

QOL-16. IMPACT OF LESION LOCATION ON MOTOR AND COGNITIVE OUTCOMES IN PEDIATRIC CEREBELLAR TUMORS

Abstract BACKGROUND Children with cerebellar damage are at increased risk for various adverse outcomes, including higher rates of autism and long term neurocognitive challenges. Traditionally considered a motor structure, extensive evidence links the cerebellum to a range of behaviors and atypical cerebellar structure and function have been reported in multiple neurodevelopmental and psychiatric conditions. A key feature of cerebellar neuroanatomy are the functional subregions that support sensorimotor and non-motor functions, leading to the hypothesis that motor, cognitive and behavioral outcomes should be predicted by the cerebellar lesion location.We aimed to determine how lesion location relates to outcomes in pediatric cerebellar patients. We predicted that lesions of the anterior lobe would disrupt motor performance, posterolateral lesions would impact cognitive functions, and behavioral dysregulation would be associated with posterior midline damage. METHODS We conducted lesion-symptom mapping in 30 children with a history of cerebellar tumor resection (sex: 19 male, 11 female; age at diagnosis, mean 6.8 years [SD 4.2]). Clinical MRI scans and neuropsychological data were used to evaluate the impact of lesion location on motor (pegboard), cognitive (verbal comprehension, verbal fluency, working memory, processing speed) and behavioral control measures (BRIEF). We mapped individual lesions using T1-weighted MRIs and normalized the lesion maps into standard template space for group analyses. RESULTS Behavioral scores ranged from impaired to above average. Lesion overlap maps were used to assess the lesion patterns associated with performance. As predicted, anterior and medial lesions disrupted motor performance and processing speed; posterolateral lesions were associated with impaired cognitive scores. CONCLUSIONS These preliminary analyses indicate that long-term outcomes are associated with disruption of specific cerebellar subregions. This could aid in prognosis and management of pediatric cerebellar tumor patients. Future work will address age of surgery, longitudinal changes in performance, and the developmental impact of early cerebellar disruption on supratentorial structures.

Heritability of cerebellar subregion volumes in adolescent and young adult twins.

Twin studies have found gross cerebellar volume to be highly heritable. However, whether fine-grained regional volumes within the cerebellum are similarly heritable is still being determined. Anatomical MRI scans from two independent datasets (QTIM: Queensland Twin IMaging, N = 798, mean age 22.1 years; QTAB: Queensland Twin Adolescent Brain, N = 396, mean age 11.3 years) were combined with an optimised and automated cerebellum parcellation algorithm to segment and measure 28 cerebellar regions. We show that the heritability of regional volumetric measures varies widely across the cerebellum ( 47%-91%). Additionally, the good to excellent test-retest reliability for a subsample of QTIM participants suggests that non-genetic variance in cerebellar volumes is due primarily to unique environmental influences rather than measurement error. We also show a consistent pattern of strong associations between the volumes of homologous left and right hemisphere regions. Associations were predominantly driven by genetic effects shared between lobules, with only sparse contributions from environmental effects. These findings are consistent with similar studies of the cerebrum and provide a first approximation of the upper bound of heritability detectable by genome-wide association studies.

Altered functional connectivity of cerebellar subregions in male patients with obstructive sleep apnea: A resting-state fMRI study.

Previous studies have demonstrated impaired cerebellar function in patients with obstructive sleep apnea (OSA), which is associated with impaired cognition. However, the effects of OSA on resting-state functional connectivity (FC) in the cerebellum has not been determined. The purpose of this study was to investigate resting-state FC of the cerebellar subregions and its relevance to clinical symptoms in patients with OSA. Sixty-eight patients with OSA and seventy-two healthy controls (HCs) were included in the study. Eight subregions of the cerebellum were selected as regions of interest, and the FC values were calculated for each subregion with other voxels. A correlation analysis was performed to examine the relationship between clinical and cognitive data. Patients with OSA showed higher FC in specific regions, including the right lobule VI with the right posterior middle temporal gyrus and right angular gyrus, the right Crus I with the bilateral precuneus/left superior parietal lobule, and the right Crus II with the precuneus/right posterior cingulate cortex. Furthermore, the oxygen depletion index was negatively correlated with aberrant FC between the right Crus II and the bilateral precuneus / right posterior cingulate cortex in OSA patients (p = 0.004). The cerebellum is functionally lateralized and closely linked to the posterior default mode network. Higher FC is related to cognition, emotion, language, and sleep in OSA. Abnormal FC may offer new neuroimaging evidence and insights for a deeper comprehension of OSA-related alterations.

The Role of the Human Cerebellum for Learning from and Processing of External Feedback in Non-Motor Learning: A Systematic Review

This review aimed to systematically identify and comprehensively review the role of the cerebellum in performance monitoring, focusing on learning from and on processing of external feedback in non-motor learning. While 1078 articles were screened for eligibility, ultimately 36 studies were included in which external feedback was delivered in cognitive tasks and which referenced the cerebellum. These included studies in patient populations with cerebellar damage and studies in healthy subjects applying neuroimaging. Learning performance in patients with different cerebellar diseases was heterogeneous, with only about half of all patients showing alterations. One patient study using EEG demonstrated that damage to the cerebellum was associated with altered neural processing of external feedback. Studies assessing brain activity with task-based fMRI or PET and one resting-state functional imaging study that investigated connectivity changes following feedback-based learning in healthy participants revealed involvement particularly of lateral and posterior cerebellar regions in processing of and learning from external feedback. Cerebellar involvement was found at different stages, e.g., during feedback anticipation and following the onset of the feedback stimuli, substantiating the cerebellum’s relevance for different aspects of performance monitoring such as feedback prediction. Future research will need to further elucidate precisely how, where, and when the cerebellum modulates the prediction and processing of external feedback information, which cerebellar subregions are particularly relevant, and to what extent cerebellar diseases alter these processes.

The Cerebellum Is Sensitive to the Lexical Properties of Words During Spoken Language Comprehension.

Over the past few decades, research into the function of the cerebellum has expanded far beyond the motor domain. A growing number of studies are probing the role of specific cerebellar subregions, such as Crus I and Crus II, in higher-order cognitive functions including receptive language processing. In the current fMRI study, we show evidence for the cerebellum's sensitivity to variation in two well-studied psycholinguistic properties of words-lexical frequency and phonological neighborhood density-during passive, continuous listening of a podcast. To determine whether, and how, activity in the cerebellum correlates with these lexical properties, we modeled each word separately using an amplitude-modulated regressor, time-locked to the onset of each word. At the group level, significant effects of both lexical properties landed in expected cerebellar subregions: Crus I and Crus II. The BOLD signal correlated with variation in each lexical property, consistent with both language-specific and domain-general mechanisms. Activation patterns at the individual level also showed that effects of phonological neighborhood and lexical frequency landed in Crus I and Crus II as the most probable sites, though there was activation seen in other lobules (especially for frequency). Although the exact cerebellar mechanisms used during speech and language processing are not yet evident, these findings highlight the cerebellum's role in word-level processing during continuous listening.

The Reduced Gray Matter Volume and Functional Connectivity of the Cerebellum in Type 2 Diabetes Mellitus with High Insulin Resistance

Introduction: Insulin resistance is widely thought to be a critical feature in type 2 diabetes mellitus (T2DM), and there is significant evidence indicating a higher abundance of insulin receptors in the human cerebellum than cerebrum. However, the specific structural or functional changes in the cerebellum related to T2DM remain unclear, and the association between cerebellar alterations, insulin resistance, cognition, and emotion is yet to be determined. Methods: We investigated neuropsychological performance, and structural and functional changes in specific cerebellar subregions in 43 T2DM patients with high insulin resistance (T2DM-highIR), 72 T2DM patients with low insulin resistance (T2DM-lowIR), and 50 controls. Furthermore, the correlation and stepwise multiple linear regression analysis were performed. Results: Compared to the controls, T2DM exhibited lower cognitive scores and higher depressive/anxious scores. Furthermore, T2DM-highIR patients showed reduced gray matter volume (GMV) in the right cerebellar lobules VIIb, Crus I/II, and T2DM showed reduced GMV in left lobules I–IV compared to controls. Additionally, functional connectivity decrease was observed between the right lobules I–V and orbital part of the superior frontal gyrus in T2DM-highIR compared to both T2DM-lowIR and controls. Notably, there were negative correlations between the GMV of the lobules VIIb, Crus I/II, and updated homeostatic model assessment of insulin resistance, and positive correlation with executive/visuospatial performance in T2DM patients. Conclusions: These results suggest that the cerebellar lobules VIIb, Crus I/II, represent vulnerable brain regions in the context of insulin resistance. Overall, this study offers new insights into the neuropathophysiological mechanisms of brain impairment in patients with T2DM.

The role of the cerebellum in fluid intelligence: An fMRI study

Traditionally, neuroimaging studies of fluid intelligence have focused on brain activation in frontal-parietal regions. In the past decade there has been accumulating evidence regarding the involvement of the cerebellum in higher cognitive function. In the current study we aimed to further investigate the role of the cerebellum in processing of fluid intelligence. We therefore scanned thirty-nine healthy participants (13 females and 26 males), recruited from the general population. Participant performed a novel abstract reasoning functional Magnetic Resonance Imaging task, modeled after stimuli from the advanced Raven's Progressive Matrices test. Analyses of both brain function and network architecture focusing on hubness were performed. We demonstrate activation in frontal and parietal well-known regions, together with an extensive activation in several cerebellar sub-regions. Moreover, four cerebellar regions served as crucial hub regions. Therefore, we provide evidence of the role of the cerebellum in fluid intelligence both by means of task brain activation and graph theory topology. Future studies should further assess in-depth the cerebellar contribution to cognitive processing in different brain disorders involving neural network alterations, allowing a better understanding of cognitive deficits.

Volumetric Differences in Cerebellum and Brainstem in Patients with Migraine: A UK Biobank Study.

Background: The cerebellum and the brainstem are two brain structures involved in pain processing and modulation that have also been associated with migraine pathophysiology. The aim of this study was to investigate possible associations between the morphology of the cerebellum and brainstem and migraine, focusing on gray matter differences in these brain areas. Methods: The analyses were based on data from 712 individuals with migraine and 45,681 healthy controls from the UK Biobank study. Generalized linear models were used to estimate the mean gray matter volumetric differences in the brainstem and the cerebellum. The models were adjusted for important biological covariates such as BMI, age, sex, total brain volume, diastolic blood pressure, alcohol intake frequency, current tobacco smoking, assessment center, material deprivation, ethnic background, and a wide variety of health conditions. Secondary analyses investigated volumetric correlation between cerebellar sub-regions. Results: We found larger gray matter volumes in the cerebellar sub-regions V (mean difference: 72 mm3, 95% CI [13, 132]), crus I (mean difference: 259 mm3, 95% CI [9, 510]), VIIIa (mean difference: 120 mm3, 95% CI [0.9, 238]), and X (mean difference: 14 mm3, 95% CI [1, 27]). Conclusions: Individuals with migraine show larger gray matter volumes in several cerebellar sub-regions than controls. These findings support the hypothesis that the cerebellum plays a role in the pathophysiology of migraine.

Neurocognitive and cerebellar function in ADHD, autism and spinocerebellar ataxia.

The cerebellum plays a major role in balance, motor control and sensorimotor integration, but also in cognition, language, and emotional regulation. Several neuropsychiatric disorders such as attention deficit-hyperactivity disorder (ADHD), autism spectrum disorder (ASD), as well as neurological diseases such as spinocerebellar ataxia type 3 (SCA3) are associated with differences in cerebellar function. Morphological abnormalities in different cerebellar subregions produce distinct behavioral symptoms related to the functional disruption of specific cerebro-cerebellar circuits. The specific contribution of the cerebellum to typical development may therefore involve the optimization of the structure and function of cerebro-cerebellar circuits underlying skill acquisition in multiple domains. Here, we review cerebellar structural and functional differences between healthy and patients with ADHD, ASD, and SCA3, and explore how disruption of cerebellar networks affects the neurocognitive functions in these conditions. We discuss how cerebellar computations contribute to performance on cognitive and motor tasks and how cerebellar signals are interfaced with signals from other brain regions during normal and dysfunctional behavior. We conclude that the cerebellum plays a role in many cognitive functions. Still, more clinical studies with the support of neuroimaging are needed to clarify the cerebellum's role in normal and dysfunctional behavior and cognitive functioning.

Emotional and behavioral problems change the development of cerebellar gray matter volume, thickness, and surface area from childhood to adolescence: A longitudinal cohort study.

Increasing evidence indicates that major neurodevelopmental disorders have potential links to abnormal cerebellar development. However, the developmental trajectories of cerebellar subregions from childhood to adolescence are lacking, and it is not clear how emotional and behavioral problems affect them. We aim to map the developmental trajectories of gray matter volume (GMV), cortical thickness (CT), and surface area (SA) in cerebellar subregions from childhood to adolescence and examine how emotional and behavioral problems change the cerebellar development trajectory in a longitudinal cohort study. This population-based longitudinal cohort study used data on a representative sample of 695 children. Emotional and behavioral problems were assessed at baseline and at three annual follow-ups with the Strengths and Difficulties Questionnaire (SDQ). Using an innovative automated image segmentation technique, we quantified the GMV, CT, and SA of the whole cerebellum and 24 subdivisions (lobules I-VI, VIIB, VIIIA&B, and IX-X plus crus I-II) with 1319 MRI scans from a large longitudinal sample of 695 subjects aged 6-15 years and mapped their developmental trajectories. We also examined sex differences and found that boys showed more linear growth, while girls showed more nonlinear growth. Boys and girls showed nonlinear growth in the cerebellar subregions; however, girls reached the peak earlier than boys. Further analysis found that emotional and behavioral problems modulated cerebellar development. Specifically, emotional symptoms impede the expansion of the SA of the cerebellar cortex, and no gender differences; conduct problems lead to inadequate cerebellar GMV development only in girls, but not boys; hyperactivity/inattention delays the development of cerebellar GMV and SA, with left cerebellar GMV, right VIIIA GMV and SA in boys and left V GMV and SA in girls; peer problems disrupt CT growth and SA expansion, resulting in delayed GMV development, with bilateral IV, right X CT in boys and right Crus I GMV, left V SA in girls; and prosocial behavior problems impede the expansion of the SA and lead to excessive CT growth, with bilateral IV, V, right VI CT, left cerebellum SA in boys and right Crus I GMV in girls. This study maps the developmental trajectories of GMV, CT, and SA in cerebellar subregions from childhood to adolescence. In addition, we provide the first evidence for how emotional and behavioral problems affect the dynamic development of GMV, CT, and SA in the cerebellum, which provides an important basis and guidance for the prevention and intervention of cognitive and emotional behavioral problems in the future.

Functional Segregation of the Human Cerebellum in Social Cognitive Tasks Revealed by TMS.

The role of the posterior cerebellum in social cognition is well established; however, it is still unclear whether different cerebellar subregions contribute to different social cognitive processes by exerting specific functions. Here, we employed transcranial magnetic stimulation (TMS) in male and female healthy humans to test the hypothesis of the existence of a medial-to-lateral gradient in the functional organization of the posterior cerebellum, according to which the phylogenetically newer cerebellar hemispheres are involved in tasks requiring higher-level social inferences whereas vermal/medial sectors are involved in basic perceptual emotional mechanisms. We found that interfering via TMS with activity of the medial cerebellum significantly impaired basic emotional recognition/discrimination. In turn, only TMS over the lateral cerebellum affected a task requiring recognizing an emotion considering the social context in which it was experienced. Overall, our data support the existence of a medial-to-lateral gradient in the posterior cerebellum, with medial sectors supporting basic emotion recognition and lateral sectors being recruited when the task taps on higher inferential processing/mentalizing. Interestingly, the contribution of the cerebellum in these different processes seems to be restricted to negative emotional stimuli.SIGNIFICANCE STATEMENT The cerebellum has been recently recognized as a critical component of the social brain, however, the functional topography of this structure in relation to social and emotional processes is still debated. By adopting a causative approach through the use of transcranial magnetic stimulation (TMS), the present study critically insights into the functional organization of the posterior cerebellum by testing the hypothesis of a medial-to-lateral gradient that reflects increasing complexity of social cognitive processes. Our findings demonstrate that lateral and medial cerebellar regions exert partially distinguishable functions in the social cognitive domain, with the medial cerebellum that mainly mediates basic perceptual emotional mechanisms while the lateral cerebellum, although supporting more basic functions, further subserves higher-level social operations.

Longitudinal development of the cerebellum in human infants during the first 800 days

Revealing early dynamic development of the normative cerebellar structures contributes to exploring cerebellum-related neurodevelopmental disorders. Here, leveraging infant-tailored cerebellar image processing techniques, we studied the dynamic volumetric developmental trajectories of cerebellum and 27 cerebellar sub-regions and their relationships with behavioral scores based on 511 high-resolution structural MRI scans during the first 800 postnatal days. The ratio of the entire cerebellum to the intracranial volume increases rapidly at first and then peaks at 13months after birth. Both the absolute and relative volumes of most cerebellar sub-structures exhibit rapid increase at first, then the relative volumes decrease slightly after arriving at peaks (except for X lobules). Each lobule depicts larger absolute volume in males than in females. The within-subject variation of the cerebellar volumetric percentile score is generally stable. The volumetric development of several lobules (e.g., V, Crus I, and Crus II) has a significantly positive correlation with fine motor skills during the age range examined.

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 correlates of social dysfunction among individuals at clinical high risk for psychosis.

Social deficits are a significant feature among both individuals with psychosis and those at clinical high-risk (CHR) for developing psychosis. Critically, the psychosis risk syndrome emerges in adolescence and young adulthood, when social skill development is being fine-tuned. Yet, the underlying pathophysiology of social deficits in individuals at CHR for psychosis remains unclear. Literature suggests the cerebellum plays a critical role in social functioning. Cerebellar dysfunction in psychosis and CHR individuals is well-established, yet limited research has examined links between the cerebellum and social functioning deficits in this critical population. In the current study, 68 individuals at CHR for developing psychosis and 66 healthy controls (HCs) completed social processing measures (examining social interaction, social cognition, and global social functioning) and resting-state MRI scans. Seed-to-voxel resting-state connectivity analyses were employed to examine the relationship between social deficits and lobular cerebellar network connectivity. Analyses indicated that within the CHR group, each social domain variable was linked to reduced connectivity between social cerebellar subregions (e.g., Crus II, lobules VIIIa and VIIIb) and cortical regions (e.g., frontal pole and frontal gyrus), but a control cerebellar subregion (e.g., lobule X) and was unrelated to these social variables. These results indicate an association between several cerebellar lobules and specific deficits in social processing. The cerebellum, therefore, may be particularly salient to the social domain and future research is need to examine the role of the cerebellum in psychosis.

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.

Cerebro-cerebellar Dysconnectivity in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder.

Abnormal cerebellar development has been implicated in attention-deficit/hyperactivity disorder (ADHD), although cerebro-cerebellar functional connectivity (FC) has yet to be examined in ADHD. Our objective is to investigate the disturbed cerebro-cerebellar FC in children and adolescents with ADHD. We analyzed a dataset of 106 individuals with ADHD (68 children, 38 adolescents) and 62 healthy comparison individuals (34 children, 28 adolescents) from the publicly available ADHD-200 dataset. We identified 7 cerebellar subregions based on cerebro-cerebellar FC and subsequently obtained the FC maps of cerebro-cerebellar networks. The main effects of ADHD and age and their interaction were examined using 2-way analysis of variance. Compared to comparisons, ADHD showed higher cerebro-cerebellar FC in the superior temporal gyrus within the somatomotor network. Interactions of diagnosis and age were identified in the supplementary motor area and postcentral gyrus within the somatomotor network and middle temporal gyrus within the ventral attention network. Follow-up Pearson correlation analysis revealed decreased cerebro-cerebellar FC in these regions with increasing age in comparisons, whereas the opposite pattern of increased cerebro-cerebellar FC occurred in ADHD. Increased cerebro-cerebellar FC in the superior temporal gyrus within the somatomotor network could underlie impairments in cognitive control and somatic motor function in ADHD. In addition, increasing cerebro-cerebellar FC in older participants with ADHD suggests that enhanced cerebellar involvement may compensate for dysfunctions of the cerebral cortex in ADHD.