Cerebellar Volume Research Articles

Neurodevelopmental trajectories of cerebellar grey matter associated with verbal abilities in males with autism spectrum disorder

Autism spectrum disorder (ASD) is a neurodevelopmental condition frequently associated with structural cerebellar abnormalities. Whether cerebellar grey matter volumes (GMV) are linked to verbal impairments remains controversial. Here, the association between cerebellar GMV and verbal abilities in ASD was examined across the lifespan. Lobular segmentation of the cerebellum was performed on structural MRI scans from the ABIDE I dataset in male individuals with ASD (N=144, age: 8.5–64.0 years) and neurotypical controls (N=188; age: 8.0–56.2 years). Stepwise linear mixed effects modeling including group (ASD vs. neurotypical controls), lobule-wise GMV, and age was performed to identify cerebellar lobules which best predicted verbal abilities as measured by verbal IQ (VIQ). An age-specific association between VIQ and GMV of bilateral Crus II was found in ASD relative to neurotypical controls. In children with ASD, higher VIQ was associated with larger GMV of left Crus II but smaller GMV of right Crus II. By contrast, in adults with ASD, higher VIQ was associated with smaller GMV of left Crus II and larger GMV of right Crus II. These findings indicate that relative to the contralateral hemisphere, an initial reliance on the language-nonspecific left cerebellar hemisphere is offset by more typical right-lateralization in adulthood.

Altered cerebellar volumes and intrinsic cerebellar networks in patients with transient global amnesia.

This study aimed to investigate the differences in cerebellar volumes and intrinsic cerebellar networks between patients with transient global amnesia (TGA) and healthy controls. We retrospectively enrolled patients with TGA and age- and sex-matched healthy controls. We used three-dimensional T1-weighted imaging at the time of TGA diagnosis to obtain cerebellar volumes, and the intrinsic cerebellar network was calculated by applying graph theory based on cerebellar volumes. The nodes were defined as individual cerebellar volumes, and edges as partial correlations, controlling for the effects of age and sex. The cerebellar volumes and intrinsic cerebellar networks were compared between the two groups. We enrolled 44 patients with TGA and 47 healthy controls. The volume of the left cerebellar white matter in patients with TGA was significantly lower than that in healthy controls (1.0328 vs. 1.0753%, p = 0.0094). In addition, there were significant differences in intrinsic cerebellar networks between the two groups. The small-worldness index in patients with TGA was higher than that in the healthy controls (0.951 vs. 0.880, p = 0.038). In the correlation analysis, the volumes of the right cerebellar cortex and lobules VIIIB were significantly correlated with age in patients with TGA (r = -0.323, p = 0.033; r = -0.313, p = 0.038, respectively). Patients with TGA exhibit alterations in cerebellar volumes and intrinsic cerebellar networks compared with healthy controls. These findings may contribute to a better understanding of the pathophysiology of the TGA.

Associations between cerebellar development and autistic traits during adolescence: a population-based cohort study

IntroductionBrain maturation is associated with adolescent socio-cognitive development. The lateral posterior region of the cerebellum plays a critical role in higher cognitive processes, and deviations of this region are associated with autism-related behaviors. Hence, it is plausible that developmental changes in this region of the cerebellum during adolescence are different along a variation in autistic traits. Additionally, its difference may be moderated by parental age at birth and weight growth during infancy, which have effects on brain development.ObjectivesThe aim of this study was two folds: (1) to test whether cerebellar development during adolescence is different along a variation in autistic traits (2) to test whether parental age at birth and weight growth during infancy moderate the results of (1).MethodsLongitudinal study was conducted over a 6-year period with 256, 230 and 187 participants ranging from 10.5 to 17.6 years, observing adolescent development respectively at 2-year time periods. We undertook a detailed investigation into differences in the lateral posterior region of the cerebellum volume. The 50-item Autism-Spectrum Quotient (AQ) was rated by primary parents. Weight growth and parental age were evaluated using maternal and child health handbook records. A multiple regression analysis was performed to examine whether AQ subscales, sex, and their interactions affected cerebellar development. Moderation analysis assessed whether parental age and weight growth moderated associations between cerebellar development and autistic traits. All participants provided written informed consent, and the study was approved by the Ethics Committee (No.10069).ResultsInteractions between sex and attention switching and sex and attention to detail were significantly associated with cerebellar development in the bilateral gray matter (GM) and white matter (WM) of Crus I and Crus II (Fig1, 2). Simple slope analyses showed that the slopes of cerebellar development were significant for girls (pFDR < 0.001). Although no significant interaction was found between them, the main effect of attention to detail was significantly associated with cerebellar development in WM of VIIB (pFDR = 0.006). Further, moderation analysis found that the association between the cerebellar development and autistic traits were significantly moderated by maternal age; the magnitude of its effect was significant for high maternal age in boys (pFDR = 0.036, Fig3). Paternal age, early (0-9 months) and late weight growth (4-18 months) also moderated associations between them, however, no significance remained after FDR controlling.Image:Image 2:Image 3:ConclusionsThere are significant associations between cerebellar development during adolescence and autistic traits, and its pattern of association can be moderated by parental ages at birth and weight growth during infancy in a cerebellar region- and sex-specific manner.Disclosure of InterestNone Declared

Age-related reductions in whole brain mass and telencephalon volume in very old white Carneau pigeons (Columba livia)

While studies have identified age-related cognitive impairment in pigeons (Columba livia), no study has detected the brain atrophy which typically accompanies cognitive impairment in older mammals. Instead, Coppola and Bingman (Aging is associated with larger brain mass and volume in homing pigeons (Columba livia), Neurosci. Letters 698 (2019) 39–43) reported increased whole brain mass and telencephalon volume in older, compared to younger, homing pigeons. One reason for this unexpected finding might be that the older pigeons studied were not old enough to display age-related brain atrophy. Therefore, the current study repeated Coppola and Bingman, but with a sample of older white Carneau pigeons that were on average 5.34 years older. Brains from young and old homing pigeons were weighed and orthogonal measurements of the telencephalon, cerebellum, and optic tectum were obtained. Despite having a heavier body mass than younger pigeons, older pigeons had a significant reduction in whole brain mass and telencephalon volume, but not cerebellum or optic tectum volume. This study is therefore the first to find that pigeons experience age-related brain atrophy.

Psychosis spectrum symptoms among individuals with schizophrenia-associated copy number variants and evidence of cerebellar correlates of symptom severity

The 3q29 deletion (3q29Del) is a copy number variant (CNV) with one of the highest effect sizes for psychosis-risk (>40-fold). Systematic research offers avenues for elucidating mechanism; however, compared to CNVs like 22q11.2Del, 3q29Del remains understudied. Emerging findings indicate that posterior fossa abnormalities are common among carriers, but their clinical relevance is unclear. We report the first in-depth evaluation of psychotic symptoms in participants with 3q29Del (N=23), using the Structured Interview for Psychosis-Risk Syndromes, and compare this profile to 22q11.2Del (N=31) and healthy controls (N=279). We also explore correlations between psychotic symptoms and posterior fossa abnormalities. Cumulatively, 48% of the 3q29Del sample exhibited a psychotic disorder or attenuated positive symptoms, with a subset meeting criteria for clinical high-risk. 3q29Del had more severe ratings than controls on all domains and only exhibited less severe ratings than 22q11.2Del in negative symptoms; ratings demonstrated select sex differences but no domain-wise correlations with IQ. An inverse relationship was identified between positive symptoms and cerebellar cortex volume in 3q29Del, documenting the first clinically-relevant neuroanatomical connection in this syndrome. Our findings characterize the profile of psychotic symptoms in the largest 3q29Del sample reported to date, contrast with another high-impact CNV, and highlight cerebellar involvement in psychosis-risk.

Role of the Cerebellum in Bipolar Disorder: A Systematic Literature Review.

The aim of this systematic literature review was to investigate the role of the cerebellum in the affective symptoms observed in patients with bipolar disorder. The present systematic literature review included clinical studies conducted from 2013-2023 among adult populations with bipolar I and II disorders, along with their specifiers. With regard to cerebellar pathology, it was found that those with bipolar disorder performed worse than their healthy counterparts in their ability to comprehend the mental states of others and in identifying negative mental states. Additionally, individuals with bipolar disorder had reduced gray matter loss in regions such as lobules I-IX, crus I, and crus II, different functional activation patterns of the thalamus, striatum, and hippocampus on functional magnetic resonance imaging (fMRI), and increased cortical thickness. Cerebro-cerebellar functional connectivities were altered in patients with bipolar disorder. The effects of lamotrigine and lithium on cerebellar volume and abnormalities are also discussed in this paper. The present systematic literature review illustrates the emerging involvement of the cerebellum in bipolar disorder and its affective symptoms and paves the way for future research and a better understanding of bipolar disorder.

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.

Quantification of Solid Embryonic Cerebellar Graft Volume in a Degenerative Ataxia Model.

Substitution of lost neurons by neurotransplantation would be a possible management of advanced degenerative cerebellar ataxias in which insufficient cerebellar reserve remains. In this study, we examined the volume and structure of solid embryonic cerebellar grafts in adult Lurcher mice, a model of olivocerebellar degeneration, and their healthy littermates. Grafts taken from enhanced green fluorescent protein (EGFP)-positive embryos were injected into the cerebellum of host mice. Two or six months later, the brains were examined histologically. The grafts were identified according to the EGFP fluorescence in frozen sections and their volumes were estimated using the Cavalieri principle. For gross histological evaluation, graft-containing slices were processed using Nissl and hematoxylin-eosin staining. Adjustment of the volume estimation approach suggested that it is reasonable to use all sections without sampling, but that calculation of values for up to 20% of lost section using linear interpolation does not constitute substantial error. Mean graft volume was smaller in Lurchers than in healthy mice when examined 6months after the transplantation. We observed almost no signs of graft destruction. In some cases, compact grafts disorganized the structure of the host's cerebellar cortex. In Lurchers, the grafts had a limited contact with the host's cerebellum. Also, graft size was of greater variability in Lurchers than in healthy mice. The results are in compliance with our previous findings that Lurcher phenotype-associated factors have a negative effect on graft development. These factors can hypothetically include cerebellar morphology, local tissue milieu, or systemic factors such as immune system abnormalities.

Placental Pathology Contributes to Impaired Volumetric Brain Development in Neonates With Congenital Heart Disease.

Neonates with congenital heart disease are at risk for impaired brain development in utero, predisposing children to postnatal brain injury and adverse long-term neurodevelopmental outcomes. Given the vital role of the placenta in fetal growth, we assessed the incidence of placental pathology in fetal congenital heart disease and explored its association with total and regional brain volumes, gyrification, and brain injury after birth. Placentas from 96 term singleton pregnancies with severe fetal congenital heart disease were prospectively analyzed for macroscopic and microscopic pathology. We applied a placental pathology severity score to relate placental abnormalities to neurological outcome. Postnatal, presurgical magnetic resonance imaging was used to analyze brain volumes, gyrification, and brain injuries. Placental analyses revealed the following abnormalities: maternal vascular malperfusion lesions in 46%, nucleated red blood cells in 37%, chronic inflammatory lesions in 35%, delayed maturation in 30%, and placental weight below the 10th percentile in 28%. Severity of placental pathology was negatively correlated with cortical gray matter, deep gray matter, brainstem, cerebellar, and total brain volumes (r=-0.25 to -0.31, all P<0.05). When correcting for postmenstrual age at magnetic resonance imaging in linear regression, this association remained significant for cortical gray matter, cerebellar, and total brain volume (adjusted R2=0.25-0.47, all P<0.05). Placental pathology occurs frequently in neonates with severe congenital heart disease and may contribute to impaired brain development, indicated by the association between placental pathology severity and reductions in postnatal cortical, cerebellar, and total brain volumes.

A One-Stone-Two-Birds Strategy of Targeting Microbubbles with "Dual" Anti-Inflammatory and Blood-Brain Barrier "Switch" Function for Ischemic Stroke Treatment.

Inflammation is considered to be the main target of the development of new stroke therapies. There are three key issues in the treatment of stroke inflammation: the first one is how to overcome the blood-brain barrier (BBB) to achieve drug delivery, the second one is how to select drugs to treat stroke inflammation, and the third one is how to achieve targeted drug delivery. In this study, we constructed hydrocortisone-phosphatidylserine microbubbles and combined them with ultrasound (US)-targeted microbubble destruction technology to successfully open the BBB to achieve targeted drug delivery. Phosphatidylserine on the microbubbles was used for its "eat me" effect to increase the targeting of the microvesicles. In addition, we found that hydrocortisone can accelerate the closure of the BBB, achieving efficient drug delivery while reducing the entry of peripheral toxins into the brain. In the treatment of stroke inflammation, it was found that hydrocortisone itself has anti-inflammatory effects and can also change the polarization of microglia from the harmful pro-inflammatory M1 phenotype to the beneficial anti-inflammatory M2 phenotype, thus achieving dual anti-inflammatory effects and enhancing the anti-inflammatory effects in ischemic areas after stroke, well reducing the cerebellar infarction volume by inhibiting the inflammatory response after cerebral ischemia. A confocal microendoscope was used to directly observe the polarization of microglial cells in living animal models for dynamic microscopic visualization detection showing the advantage of being closer to clinical work. Taken together, this study constructed a multifunctional targeted US contrast agent with the function of "one-stone-two-birds", which can not only "on-off" the BBB but also have "two" anti-inflammatory functions, providing a new strategy of integrated anti-inflammatory targeted delivery and imaging monitoring for ischemic stroke treatment.

Patterns of subregional cerebellar atrophy across epilepsy syndromes: An ENIGMA-Epilepsy study.

The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current corticocentric models of this disease. We quantified cross-sectional regional cerebellar lobule volumes using structural magnetic resonance imaging in 1602 adults with epilepsy and 1022 healthy controls across 22 sites from the global ENIGMA-Epilepsy working group. A state-of-the-art deep learning-based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in (1) all epilepsies, (2) temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), (3) nonlesional temporal lobe epilepsy, (4) genetic generalized epilepsy, and (5) extratemporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness. Across all epilepsies, reduced total cerebellar volume was observed (d = .42). Maximum volume loss was observed in the corpus medullare (dmax = .49) and posterior lobe gray matter regions, including bilateral lobules VIIB (dmax = .47), crus I/II (dmax = .39), VIIIA (dmax = .45), and VIIIB (dmax = .40). Earlier age at seizure onset ( = .05) and longer epilepsy duration ( = .06) correlated with reduced volume in these regions. Findings were most pronounced in TLE-HS and ETLE, with distinct neuroanatomical profiles observed in the posterior lobe. Phenytoin treatment was associated with reduced posterior lobe volume. Cerebellum volume correlated with cerebral cortical thinning more strongly in the epilepsy cohort than in controls. We provide robust evidence of deep cerebellar and posterior lobe subregional gray matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in nonmotor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellar subregional damage into neurobiological models of epilepsy.

Measurement of synaptic density in Down syndrome using PET imaging: a pilot study

Down syndrome (DS) is the most prevalent genetic cause of intellectual disability, resulting from trisomy 21. Recently, positron emission tomography (PET) imaging has been used to image synapses in vivo. The motivation for this pilot study was to investigate whether synaptic density in low functioning adults with DS can be evaluated using the PET radiotracer [11C]UCB-J. Data were acquired from low functioning adults with DS (n = 4) and older neurotypical (NT) adults (n = 37). Motion during the scans required the use of a 10-minute acquisition window for the calculation of synaptic density using SUVR50–60,CS which was determined to be a suitable approximation for specific binding in this analysis using dynamic data from the NT group. Of the regions analyzed a large effect was observed when comparing DS and NT hippocampus and cerebral cortex synaptic density as well as hippocampus and cerebellum volumes. In this pilot study, PET imaging of [11C]UCB-J was successfully completed and synaptic density measured in low functioning DS adults. This work provides the basis for studies where synaptic density may be compared between larger groups of NT adults and adults with DS who have varying degrees of baseline cognitive status.

Functional Outcomes in Conservatively vs Surgically Treated Cerebellar Infarcts

According to the current American Heart Association/American Stroke Association guidelines, decompressive surgery is indicated in patients with cerebellar infarcts that demonstrate severe cerebellar swelling. However, there is no universal definition of swelling and/or infarct volume(s) available to support a decision for surgery. To evaluate functional outcomes in surgically compared with conservatively managed patients with cerebellar infarcts. In this retrospective multicenter cohort study, patients with cerebellar infarcts treated at 5 tertiary referral hospitals or stroke centers within Germany between 2008 and 2021 were included. Data were analyzed from November 2020 to November 2023. Surgical treatment (ie, posterior fossa decompression plus standard of care) vs conservative management (ie, medical standard of care). The primary outcome examined was functional status evaluated by the modified Rankin Scale (mRS) at discharge and 1-year follow-up. Secondary outcomes included the predicted probabilities for favorable outcome (mRS score of 0 to 3) stratified by infarct volumes or Glasgow Coma Scale score at admission and treatment modality. Analyses included propensity score matching, with adjustments for age, sex, Glasgow Coma Scale score at admission, brainstem involvement, and infarct volume. Of 531 included patients with cerebellar infarcts, 301 (57%) were male, and the mean (SD) age was 68 (14.4) years. After propensity score matching, a total of 71 patients received surgical treatment and 71 patients conservative treatment. There was no significant difference in favorable outcomes (ie, mRS score of 0 to 3) at discharge for those treated surgically vs conservatively (47 [66%] vs 45 [65%]; odds ratio, 1.1; 95% CI, 0.5-2.2; P > .99) or at follow-up (35 [73%] vs 33 [61%]; odds ratio, 1.8; 95% CI, 0.7-4.2; P > .99). In patients with cerebellar infarct volumes of 35 mL or greater, surgical treatment was associated with a significant improvement in favorable outcomes at 1-year follow-up (38 [61%] vs 3 [25%]; odds ratio, 4.8; 95% CI, 1.2-19.3; P = .03), while conservative treatment was associated with favorable outcomes at 1-year follow-up in patients with infarct volumes of less than 25 mL (2 [34%] vs 218 [74%]; odds ratio, 0.2; 95% CI, 0-1.0; P = .047). Overall, surgery was not associated with improved outcomes compared with conservative management in patients with cerebellar infarcts. However, when stratifying based on infarct volume, surgical treatment appeared to be beneficial in patients with larger infarct volumes, while conservative management appeared favorable in patients with smaller infarct volumes.

Cerebellar Volumetry in Ataxias: Relation to Ataxia Severity and Duration.

Cerebellar atrophy is the neuropathological hallmark of most ataxias. Hence, quantifying the volume of the cerebellar grey and white matter is of great interest. In this study, we aim to identify volume differences in the cerebellum between spinocerebellar ataxia type 1 (SCA1), SCA3 and SCA6 as well as multiple system atrophy of cerebellar type (MSA-C). Our cross-sectional data set comprised mutation carriers of SCA1 (N=12), SCA3 (N=62), SCA6 (N=14), as well as MSA-C patients (N=16). Cerebellar volumes were obtained from T1-weighted magnetic resonance images. To compare the different atrophy patterns, we performed a z-transformation and plotted the intercept of each patient group's model at the mean of 7 years of ataxia duration as well as at the mean ataxia severity of 14 points in the SARA sum score. In addition, we plotted the extrapolation at ataxia duration of 0 years as well as 0 points in the SARA sum score. Patients with MSA-C demonstrated the most pronounced volume loss, particularly in the cerebellar white matter, at the late time intercept. Patients with SCA6 showed a pronounced volume loss in cerebellar grey matter with increasing ataxia severity compared to all other patient groups. MSA-C, SCA1 and SCA3 showed a prominent atrophy of the cerebellar white matter. Our results (i) confirmed SCA6 being considered as a pure cerebellar grey matter disease, (ii) emphasise the involvement of cerebellar white matter in the neuropathology of SCA1, SCA3 and MSA-C, and (iii) reflect the rapid clinical progression in MSA-C.

Brain function in classic galactosemia, a galactosemia network (GalNet) members review.

Classic galactosemia (CG, OMIM #230400, ORPHA: 79,239) is a hereditary disorder of galactose metabolism that, despite treatment with galactose restriction, affects brain function in 85% of the patients. Problems with cognitive function, neuropsychological/social emotional difficulties, neurological symptoms, and abnormalities in neuroimaging and electrophysiological assessments are frequently reported in this group of patients, with an enormous individual variability. In this review, we describe the role of impaired galactose metabolism on brain dysfunction based on state of the art knowledge. Several proposed disease mechanisms are discussed, as well as the time of damage and potential treatment options. Furthermore, we combine data from longitudinal, cross-sectional and retrospective studies with the observations of specialist teams treating this disease to depict the brain disease course over time. Based on current data and insights, the majority of patients do not exhibit cognitive decline. A subset of patients, often with early onset cerebral and cerebellar volume loss, can nevertheless experience neurological worsening. While a large number of patients with CG suffer from anxiety and depression, the increased complaints about memory loss, anxiety and depression at an older age are likely multifactorial in origin.

Compressed cerebellar functional connectome hierarchy in spinocerebellar ataxia type 3.

Spinocerebellar ataxia type 3 (SCA3) is an inherited movement disorder characterized by a progressive decline in motor coordination. Despite the extensive functional connectivity (FC) alterations reported in previous SCA3 studies in the cerebellum and cerebellar-cerebral pathways, the influence of these FC disturbances on the hierarchical organization of cerebellar functional regions remains unclear. Here, we compared 35 SCA3 patients with 48 age- and sex-matched healthy controls using a combination of voxel-based morphometry and resting-state functional magnetic resonance imaging to investigate whether cerebellar hierarchical organization is altered in SCA3. Utilizing connectome gradients, we identified the gradient axis of cerebellar hierarchical organization, spanning sensorimotor to transmodal (task-unfocused) regions. Compared to healthy controls, SCA3 patients showed a compressed hierarchical organization in the cerebellum at both voxel-level (p < .05, TFCE corrected) and network-level (p < .05, FDR corrected). This pattern was observed in both intra-cerebellar and cerebellar-cerebral gradients. We observed that decreased intra-cerebellar gradient scores in bilateral Crus I/II both negatively correlated with SARA scores (left/right Crus I/II: r = -.48/-.50, p = .04/.04, FDR corrected), while increased cerebellar-cerebral gradients scores in the vermis showed a positive correlation with disease duration (r = .48, p = .04, FDR corrected). Control analyses of cerebellar gray matter atrophy revealed that gradient alterations were associated with cerebellar volume loss. Further FC analysis showed increased functional connectivity in both unimodal and transmodal areas, potentially supporting the disrupted cerebellar functional hierarchy uncovered by the gradients. Our findings provide novel evidence regarding alterations in the cerebellar functional hierarchy in SCA3.

Maternal usage of varying levels of dietary folate affects the postnatal development of cerebellar folia and cortical layer volumes

ABSTRACT Objective The cerebellum has a long, protracted developmental period; therefore, it is more sensitive to intrauterine and postnatal insults like nutritional deficiencies. Folate is an essential nutrient in fetal and postnatal brain development, and its supplementation during pregnancy is widely recommended. This study aimed to describe the effects of maternal folate intake on postnatal cerebellum development. Methods Twelve adult female Rattus norwegicus (6–8 weeks old) rats were randomly assigned to one of four groups and given one of four premixed diets: a standard diet (2 mg/kg), a folate-deficient (folate 0 mg/kg), folate-supplemented (8 mg/kg), or folate supra-supplemented (40 mg/kg). The rats began consuming their specific diets 14 days before mating and were maintained on them throughout pregnancy and lactation. Five pups from each group were sacrificed, and their brains processed for light microscopic examination on postnatal days 1, 7, 21, and 35. The data gathered included the morphology of the cerebellar folia and an estimate of the volume of the cerebellar cortical layer using the Cavalieri method. Results Folia of the folate-supplemented and supra-supplemented groups were thicker and showed extensive branching with sub-lobule formation. The folate-deficient diet group's folia were smaller, had more inter-folial spaces, or fused. When compared to the folate-deficient group, the volumes of the cerebellum and individual cerebellar cortical layers were significantly larger in the folate-supplemented and supra-supplemented groups (p<0.05). Conclusion Folate supplementation during pregnancy and lactation improves the degree and complexity of the cerebellar folia and the volumes of individual cerebellar cortical layers.

Impairments of cerebellar structure and function in a zebrafish KO of neuropsychiatric risk gene znf536

Genetic variants in ZNF536 contribute to the risk for neuropsychiatric disorders such as schizophrenia, autism, and others. The role of this putative transcriptional repressor in brain development and function is, however, largely unknown. We generated znf536 knockout (KO) zebrafish and studied their behavior, brain anatomy, and brain function. Larval KO zebrafish showed a reduced ability to compete for food, resulting in decreased total body length and size. This phenotype can be rescued by segregating the homozygous KO larvae from their wild-type and heterozygous siblings, enabling studies of adult homozygous KO animals. In adult KO zebrafish, we observed significant reductions in anxiety-like behavior and social interaction. These znf536 KO zebrafish have decreased cerebellar volume, corresponding to decreased populations of specific neuronal cells, especially in the valvular cerebelli (Va). Finally, using a Tg[mbp:mgfp] line, we identified a previously undetected myelin structure located bilaterally within the Va, which also displayed a reduction in volume and disorganization in KO zebrafish. These findings indicate an important role for ZNF536 in brain development and implicate the cerebellum in the pathophysiology of neuropsychiatric disorders.

Altered cerebellar and caudate gray-matter volumes and structural covariance networks preceding dual cognitive and mobility impairments in older people.

The neuroanatomical changes driving both cognitive and mobility impairments, an emerging preclinical dementia syndrome, are not fully understood. We examined gray-matter volumes (GMVs) and structural covariance networks (SCNs) abnormalities in community-based older people preceding the conversion to physio-cognitive decline syndrome (PCDS). Voxel-wise brain GMV and established SCNs were compared between PCDS and non-PCDS converters. The study included 343 individuals (60.2±6.9 years, 49.6% men) with intact cognitive and mobility functions. Over an average 5.6-year follow-up, 116 transitioned to PCDS. Identified regions with abnormal GMVs in PCDS converters were over cerebellum and caudate, which served as seeds for SCNs establishment. Significant differences in cerebellum-based (to right frontal pole and left middle frontal gyrus) and caudate-based SCNs (to right caudate putamen, right planum temporale, left precentral gyrus, right postcentral gyrus, and left parietal operculum) between converters and nonconverters were observed. This study reveals early neuroanatomic changes, emphasizing the cerebellum's role, in dual cognitive and mobility impairments. Neuroanatomic precursors of dual cognitive and mobility impairments are identified. Cerebellar GMV reductions and increased right caudate GMV precede the onset of PCDS. Altered cerebellum- and caudate-based SCNs drive PCDS transformation. This research establishes a foundation for understanding PCDS as a specific dementia syndrome.

Faecal Microbiota Transplantation Alleviates Ferroptosis after Ischaemic Stroke

Ischaemic stroke can induce changes in the abundance of gut microbiota constituents, and the outcome of stroke may also be influenced by the gut microbiota. This study aimed to determine whether gut microbiota transplantation could rescue changes in the gut microbiota and reduce ferroptosis after stroke in rats. Male Sprague-Dawley rats (6 weeks of age) were subjected to ischaemic stroke by middle cerebral artery occlusion (MCAO). Fecal samples were collected for 16S ribosomal RNA (rRNA) sequencing to analyze the effects of FMT on the gut microbiota. Neurological deficits were evaluated using the Longa score. triphenyl tetrazolium chloride (TTC) staining was performed in the brain, and kits were used to measure malondialdehyde (MDA), iron, and glutathione (GSH) levels in the ipsilateral brain of rats. Western blotting was used to detect the protein expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and the transferrin receptor 2 (TFR2) in the ipsilateral brain of rats. Stroke induced significant changes in the gut microbiota, and FMT ameliorated these changes. TTC staining results showed that FMT reduced cerebral infarct volume. In addition, FMT diminished MDA and iron levels and elevated GSH levels in the ipsilateral brain. Western blot analysis showed that FMT increased GPX4 and SLC7A11 protein expression and decreased TFR2 protein expression in the ipsilateral brain after stroke. FMT can reverse gut microbiota dysbiosis, reduce cerebellar infarct volume, and decrease ferroptosis after stroke.