Cerebellar Volume Research Articles

Quantification of Intracranial Structures Volume in Fetuses Using 3-D Volumetric MRI: Normal Values at 19 to 37 Weeks' Gestation.

ObjectiveThe purpose of this study is to establish a reference of intracranial structure volumes in normal fetuses ranging from 19 to 37 weeks' gestation (mean 27 weeks).Materials and MethodsA retrospective analysis of 188 MRI examinations (1.5 T) of fetuses with a normal brain appearance (19–37 gestational weeks) from January 2018 to December 2021 was included in this study. Three dimensional (3-D) volumetric parameters from slice-to-volume reconstructed (SVR) images, such as total brain volume (TBV), cortical gray matter volume (GMV), subcortical brain tissue volume (SBV), intracranial cavity volume (ICV), lateral ventricles volume (VV), cerebellum volume (CBV), brainstem volume (BM), and extra-cerebrospinal fluid volume (e-CSFV), were quantified by manual segmentation from two experts. The mean, SD, minimum, maximum, median, and 25th and 75th quartiles for intracranial structures volume were calculated per gestational week. A linear regression analysis was used to determine the gestational weekly age-related change adjusted for sex. A t-test was used to compare the mean TBV and ICV values to previously reported values at each gestational week. The formulas to calculate intracranial structures volume derived from our data were created using a regression model. In addition, we compared the predicted mean TBV values derived by our formula with the expected mean TBV predicted by the previously reported Jarvis' formula at each time point. For intracranial volumes, the intraclass correlation coefficient (ICC) was calculated to convey association within and between observers.ResultsThe intracranial volume data are shown in graphs and tabular summaries. The male fetuses had significantly larger VV compared with female fetuses (p = 0.01). Measured mean ICV values at 19 weeks are significantly different from those published in the literature (p < 0.05). Means were compared with the expected TBV generated by the previously reported formula, showing statistically differences at 22, 26, 29, and 30 weeks' gestational age (GA) (all p < 0.05). A comparison between our data-derived formula and the previously reported formula for TBV showed very similar values at every GA. The predicted TBV means derived from the previously reported formula were all within the 95% confidence interval (CI) of the predicted means of this study. Intra- and inter-observer agreement was high, with an intraclass correlation coefficient larger than 0.98.ConclusionWe have shown that the intracranial structural volume of the fetal brain can be reliably quantified using 3-D volumetric MRI with a high degree of reproducibility and reinforces the existing data with more robust data in the earlier second and third stages of pregnancy.

Cerebellar atrophy and its implications on gait in cerebral amyloid angiopathy

ObjectiveRecent data suggest that cerebral amyloid angiopathy (CAA) causes haemorrhagic lesions in cerebellar cortex as well as subcortical cerebral atrophy. However, the potential effect of CAA on cerebellar tissue loss...

Cerebellar Volumes and Sensorimotor Behavior in Autism Spectrum Disorder.

BackgroundSensorimotor issues are common in autism spectrum disorder (ASD), though their neural bases are not well understood. The cerebellum is vital to sensorimotor control and reduced cerebellar volumes in ASD have been documented. Our study examined the extent to which cerebellar volumes are associated with multiple sensorimotor behaviors in ASD.Materials and MethodsFifty-eight participants with ASD and 34 typically developing (TD) controls (8–30 years) completed a structural MRI scan and precision grip testing, oculomotor testing, or both. Force variability during precision gripping as well as absolute error and trial-to-trial error variability of visually guided saccades were examined. Volumes of cerebellar lobules, vermis, and white matter were quantified. The relationships between each cerebellar region of interest (ROI) and force variability, saccade error, and saccade error variability were examined.ResultsRelative to TD controls, individuals with ASD showed increased force variability. Individuals with ASD showed a reduced volume of cerebellar vermis VI-VII relative to TD controls. Relative to TD females, females with ASD showed a reduced volume of bilateral cerebellar Crus II/lobule VIIB. Increased volume of Crus I was associated with increased force variability. Increased volume of vermal lobules VI-VII was associated with reduced saccade error for TD controls but not individuals with ASD. Increased right lobule VIII and cerebellar white matter volumes as well as reduced right lobule VI and right lobule X volumes were associated with greater ASD symptom severity. Reduced volumes of right Crus II/lobule VIIB were associated with greater ASD symptom severity in only males, while reduced volumes of right Crus I were associated with more severe restricted and repetitive behaviors only in females.ConclusionOur finding that increased force variability in ASD is associated with greater cerebellar Crus I volumes indicates that disruption of sensory feedback processing supported by Crus I may contribute to skeletomotor differences in ASD. Results showing that volumes of vermal lobules VI-VII are associated with saccade precision in TD but not ASD implicates atypical organization of the brain systems supporting oculomotor control in ASD. Associations between volumes of cerebellar subregions and ASD symptom severity suggest cerebellar pathological processes may contribute to multiple developmental challenges in ASD.

Gray matter volume alteration is associated with insistence on sameness and cognitive flexibility in autistic youth.

Restricted and repetitive behaviors (RRBs) are hallmark characteristics of autism spectrum disorder (ASD). Previous studies suggest that insistence on sameness (IS) characterized as higher-order RRBs may be a promising subgrouping variable for ASD. Cognitive inflexibility may underpin IS behaviors. However, the neuroanatomical correlates of IS and associated cognitive functions remain unclear. We analyzed data from 140 autistic youth and 124 typically developing (TD) youth (mean age=15.8 years). Autistic youth were stratified by median-split based on three current IS items in the autism diagnostic interview-revised into two groups (high, HIS, n=70, and low, LIS, n=70). Differences in cognitive flexibility were assessed by the Cambridge neuropsychological test automated battery (CANTAB). T1-weighted brain structural images were analyzed using voxel-based morphometry (VBM) to identify differences in gray matter (GM) volume among the three groups. GM volume of regions showing group differences was then correlated with cognitive flexibility. The HIS group showed decreased GM volumes in the left supramarginal gyrus compared to the LIS group and increased GM volumes in the vermis VIII and left cerebellar lobule VIII compared to TD individuals. We did not find significant correlations between regional GM volumes and extra-dimensional shift errors. IS may be a unique RRB component and a potentially valuable stratifier of ASD. However, the neurocognitive underpinnings require further clarification. LAY SUMMARY: The present study found parietal, temporal and cerebellar gray matter volume alterations in autistic youth with greater insistence on sameness. The findings suggest that insistence on sameness may be a useful feature to parse the heterogeneity of the autism spectrum yet further research investigating the underlying neurocognitive mechanism is warranted.

Diagnostic Accuracy of Magnetic Resonance Imaging Measures of Brain Atrophy Across the Spectrum of Progressive Supranuclear Palsy and Corticobasal Degeneration

The accurate diagnosis of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) is hampered by imperfect clinical-pathological correlations. To assess and compare the diagnostic value of the magnetic resonance parkinsonism index (MRPI) and other magnetic resonance imaging-based measures of cerebral atrophy to differentiate between PSP, CBD, and other neurodegenerative diseases. This prospective diagnostic study included participants with 4-repeat tauopathies (4RT), PSP, CBD, other neurodegenerative diseases and available MRI who appeared in the University of California, San Francisco, Memory and Aging Center database. Data were collected from October 27, 1994, to September 29, 2019. Data were analyzed from March 1 to September 14, 2021. The main outcome of this study was the neuropathological diagnosis of PSP or CBD. The clinical diagnosis at the time of the MRI acquisition was noted. The imaging measures included the MRPI, cortical thickness, subcortical volumes, including the midbrain, pons, and superior cerebellar peduncle volumes. Multinomial logistic regression models (MLRM) combining different cortical and subcortical regions were defined to discriminate between PSP, CBD, and other pathologies. The areas under the receiver operating characteristic curves (AUROC) and cutoffs were calculated to differentiate between PSP, CBD, and other diseases. Of the 326 included participants, 176 (54%) were male, and the mean (SD) age at MRI was 64.1 (8.0) years. The MRPI showed good diagnostic accuracy for the differentiation between PSP and all other pathologies (accuracy, 87%; AUROC, 0.90; 95% CI, 0.86-0.95) and between 4RT and other pathologies (accuracy, 80%; AUROC, 0.82; 95% CI, 0.76-0.87), but did not allow the discrimination of participants with CBD. Its diagnostic accuracy was lower in the subgroup of patients without the canonical PSP-Richardson syndrome (PSP-RS) or probable corticobasal syndrome (CBS) at MRI. MLRM combining cortical and subcortical measurements showed the highest accuracy for the differentiation between PSP and other pathologies (accuracy, 95%; AUROC, 0.98; 95% CI, 0.97-0.99), CBD and other pathologies (accuracy, 83%; AUROC, 0.86; 95% CI, 0.81-0.91), 4RT and other pathologies (accuracy, 89%; AUROC, 0.94; 95% CI, 0.92-0.97), and PSP and CBD (accuracy, 91%; AUROC, 0.95; 95% CI, 0.91-0.99), even in participants without PSP-RS or CBS at MRI. In this study, the combination of widely available cortical and subcortical measures of atrophy on MRI discriminated between PSP, CBD, and other pathologies and could be used to support the diagnosis of 4RT in clinical practice.

P584. Low Premorbid Cognitive Function in Psychosis is Associated With Smaller Cognitive and Motor Cerebellar Regions

Prominent neural models hypothesize that the cerebellum contributes to psychosis pathophysiology and may be developmental in nature. Studies find smaller cerebellar grey matter volume, with recent region-specific studies noting robust effects in posterior (‘cognitive’-related) lobules in schizophrenia. Whether these deficits are associated with clinical phenotypes, including cognitive impairment, remains unclear.

P657. Cerebellum Structural Covariance Networks in PTSD and Depression

The cerebellum has an important role in sensorimotor function, cognition, and emotion. Neuroimaging studies have reported altered cerebellum activation, functional connectivity, and volume in posttraumatic stress disorder and depression. The aim of the study was to identify the structural covariance networks of the cerebellum in PTSD and depression using neuroimaging meta-analysis.

Dynamic Effects of Immersive Bilingualism on Cortical and Subcortical Grey Matter Volumes.

Bilingualism has been shown to induce neuroplasticity in the brain, but conflicting evidence regarding its specific effects in grey matter continues to emerge, probably due to methodological differences between studies, as well as approaches that may miss the variability and dynamicity of bilingual experience. In our study, we devised a continuous score of bilingual experiences and we investigated their non-linear effects on regional GM volume in a sample of young healthy participants from an immersive and naturalistic bilingual environment. We focused our analyses on cortical and subcortical regions that had been previously proposed as part of the bilingual speech pipeline and language control network. Our results showed a non-linear relationship between bilingualism score and grey matter volume of the inferior frontal gyrus. We also found linear increases in volumes of putamen and cerebellum as a function of bilingualism score. These results go in line with predictions for immersive and naturalistic bilingual environments with increased intensity and diversity of language use and provide further evidence supporting the dynamicity of bilingualism’s effects on brain structure.

Increased Cerebellar Gray Matter Volume in Athletes: A Voxel-Wise Coordinate-Based Meta-Analysis

ABSTRACT Purpose: The purpose of this systematic review and meta-analysis study was to investigate distinct brain structural characteristics in athletes as compared with those in non-athletes by quantifying regional gray matter (GM) volume changes using voxel-based morphometry analysis based on a whole-brain approach.Methods: The systematic literature search was conducted from November 1, 2020 to October 18, 2021 via the two search engines including the PubMed and Web of Science. We included 13 studies that reported GM volume data in 229 athletes as compared 219 non-athletes based on the whole-brain analysis with specific three-dimensional coordinates in a standard stereotactic space. Thus, we performed a coordinate-based meta-analysis using the seed-based d mapping via permutation of subject images methods.Result: The coordinate-based meta-analysis reported that the athletes significantly reveal greater regional GM volume across right cerebellar lobules IV–V and Brodmann area 37 regions than those in the non-athletes with minimal levels of heterogeneity and publication bias between the included studies. The subgroup analyses show that greater GM volume for athletes in closed-skill sports appeared across the right cerebellar hemispheric lobules VIII and the right cingulum than those for non-athletes.Conclusion: These cumulative findings from multiple brain imaging studies suggest potential brain plasticity evidence in the athletes who experienced extensive motor training.

Association of Prenatal Exposure to Early-Life Adversity With Neonatal Brain Volumes at Birth

Exposure to early-life adversity alters the structural development of key brain regions underlying neurodevelopmental impairments. The association between prenatal exposure to adversity and brain structure at birth remains poorly understood. To examine whether prenatal exposure to maternal social disadvantage and psychosocial stress is associated with neonatal global and regional brain volumes and cortical folding. This prospective, longitudinal cohort study included 399 mother-infant dyads of sociodemographically diverse mothers recruited in the first or early second trimester of pregnancy and their infants, who underwent brain magnetic resonance imaging in the first weeks of life. Mothers were recruited from local obstetric clinics in St Louis, Missouri from September 1, 2017, to February 28, 2020. Maternal social disadvantage and psychosocial stress in pregnancy. Confirmatory factor analyses were used to create latent constructs of maternal social disadvantage (income-to-needs ratio, Area Deprivation Index, Healthy Eating Index, educational level, and insurance status) and psychosocial stress (Perceived Stress Scale, Edinburgh Postnatal Depression Scale, Everyday Discrimination Scale, and Stress and Adversity Inventory). Neonatal cortical and subcortical gray matter, white matter, cerebellum, hippocampus, and amygdala volumes were generated using semiautomated, age-specific, segmentation pipelines. A total of 280 mothers (mean [SD] age, 29.1 [5.3] years; 170 [60.7%] Black or African American, 100 [35.7%] White, and 10 [3.6%] other race or ethnicity) and their healthy, term-born infants (149 [53.2%] male; mean [SD] infant gestational age, 38.6 [1.0] weeks) were included in the analysis. After covariate adjustment and multiple comparisons correction, greater social disadvantage was associated with reduced cortical gray matter (unstandardized β = -2.0; 95% CI, -3.5 to -0.5; P = .01), subcortical gray matter (unstandardized β = -0.4; 95% CI, -0.7 to -0.2; P = .003), and white matter (unstandardized β = -5.5; 95% CI, -7.8 to -3.3; P < .001) volumes and cortical folding (unstandardized β = -0.03; 95% CI, -0.04 to -0.01; P < .001). Psychosocial stress showed no association with brain metrics. Although social disadvantage accounted for an additional 2.3% of the variance of the left hippocampus (unstandardized β = -0.03; 95% CI, -0.05 to -0.01), 2.3% of the right hippocampus (unstandardized β = -0.03; 95% CI, -0.05 to -0.01), 3.1% of the left amygdala (unstandardized β = -0.02; 95% CI, -0.03 to -0.01), and 2.9% of the right amygdala (unstandardized β = -0.02; 95% CI, -0.03 to -0.01), no regional effects were found after accounting for total brain volume. In this baseline assessment of an ongoing cohort study, prenatal social disadvantage was associated with global reductions in brain volumes and cortical folding at birth. No regional specificity for the hippocampus or amygdala was detected. Results highlight that associations between poverty and brain development begin in utero and are evident early in life. These findings emphasize that preventive interventions that support fetal brain development should address parental socioeconomic hardships.

A gain-of-function mutation in the acid-sensing ion channel 2a induces marked cerebellar maldevelopment in rats

Specific amino acid substitutions in degenerin mechano-gated channels (DEGs) of C. elegans convert these channels into constitutively active mutants that induce the degeneration of neurons where DEGs are expressed. Acid-sensing ion channel-2a (ASIC2a), a proton-gated cation channel predominantly expressed in central neurons, is a mammalian ortholog of DEGs, and it can remain unclosed to be cytotoxic once the same mutations as the DEG mutants are introduced into its gene. Here we show that heterozygous transgenic (Tg) rats expressing ASIC2a-G430F (ASIC2aG430F), the most active form of the gain-of-function mutants, under the control of the intrinsic ASIC2a promoter exhibited marked cerebellar maldevelopment with mild whole-brain atrophy. The Tg rats were small and developed an early-onset ataxic gait, as evidenced by rotarod and footprint tests. The overall gross-anatomy of the Tg brain was normal just after birth, but a reduction in brain volume, especially cerebellar volume, gradually emerged with age. Histological examination of the adult Tg brain revealed that the cell-densities of cerebellar Purkinje and granule cells were markedly reduced, while the cytoarchitecture of other brain regions was not significantly altered. RT-PCR and immunoblot analyses demonstrated that ASIC2aG430F transcripts and proteins were already present in various regions of the neonatal Tg brain before the deforming cerebellum became apparent. These results suggest that, according to the spatiotemporal pattern of the wild-type (WT) ASIC2a gene expression, the ASIC2aG430F channel induced lethal degeneration in Tg brain neurons expressing both ASIC2aG430F and ASIC2a channels.

Relation of sensorimotor and cognitive cerebellum functional connectivity with brain structural damage in patients with multiple sclerosis and no disability.

Background and purposeTo investigate the relationship between the functional connectivity (FC) of the sensorimotor and cognitive cerebellum and measures of structural damage in patients with multiple sclerosis (MS) and no physical disability.MethodsWe selected 144 relapsing–remitting MS patients with an Expanded Disability Status Scale score of ≤1.5 and 98 healthy controls from the Italian Neuroimaging Network Initiative database. From multimodal 3T magnetic resonance imaging (MRI), including functional MRI at rest, we calculated lesion load, cortical thickness, and white matter, cortical gray matter, and caudate, putamen, thalamic, and cerebellar volumes. Voxel‐wise FC of the sensorimotor and cognitive cerebellum was assessed with seed‐based analysis, and multiple regression analysis was used to evaluate the relationship between FC and structural damage.ResultsWhole brain, white matter, caudate, putamen, and thalamic volumes were reduced in patients compared to controls, whereas cortical gray matter was not significantly different in patients versus controls. Both the sensorimotor and cognitive cerebellum showed a widespread pattern of increased and decreased FC that were negatively associated with structural measures, indicating that the lower the FC, the greater the tissue loss. Lastly, among multiple structural measures, cortical gray matter and white matter volumes were the best predictors of cerebellar FC alterations.ConclusionsIncreased and decreased cerebellar FC with several brain areas coexist in MS patients with no disability. Our data suggest that white matter loss hampers FC, whereas, in the absence of atrophy, cortical volume represents the framework for FC to increase.

Zika virus vertical transmission in interferon receptor1-antagonized Rag1\u2212/\u2212 mice results in postnatal brain abnormalities and clinical disease

The mechanisms by which vertically transmitted Zika virus (ZIKV) causes postnatal brain development abnormalities and congenital disease remain poorly understood. Here, we optimized the established anti-IFNAR1 treated, Rag1−/− (AIR) mouse model of ZIKV infection to examine the consequence of vertical transmission on neonate survival and postnatal brain development. We found that modulating the infectious dose and the frequency of anti-IFNAR1 treatment of pregnant mice (termed AIRlow mice) prolonged neonatal survival allowing for pathogenesis studies of brain tissues at critical postnatal time points. Postnatal AIRlow mice all had chronic ZIKV infection in the brain that was associated with decreased cortical thickness and cerebellar volume, increased gliosis, and higher levels of cell death in many brain areas including cortex, hippocampus and cerebellum when compared to controls. Interestingly, despite active infection and brain abnormalities, the neurodevelopmental program remained active in AIRlow mice as indicated by elevated mRNA expression of critical neurodevelopmental genes in the brain and enlargement of neural-progenitor rich regions of the cerebellum at a developmental time point analogous to birth in humans. Nevertheless, around the developmental time point when the brain is fully populated by neurons, AIRlow mice developed neurologic disease associated with persistent ZIKV infection in the brain, gliosis, and increased cell death. Together, these data show that vertically transmitted ZIKV infection in the brain of postnatal AIRlow mice strongly influences brain development resulting in structural abnormalities and cell death in multiple regions of the brain.

The long-term impact of elevated C-reactive protein levels during pregnancy on brain morphology in late childhood

ImportanceAnimal studies show that Maternal Immune Activation (MIA) may have detrimental effects on fetal brain development. Clinical studies provide evidence for structural brain abnormalities in human neonates following MIA, but no study has investigated the long-term effects of MIA (as measured with biomarkers) on human brain morphology ten years after the exposure. ObjectiveOur aim was to evaluate the long-term impact of MIA on brain morphology in 10-year-old children, including the possible mediating role of gestational age at birth. DesignWe leveraged data from Generation R, a large-scale prospective pregnancy cohort study. Pregnant women were included between 2002 and 2006, and their children were invited to participate in the MRI study between 2013 and 2015. To be included, mother-child dyads had to have data on maternal C-reactive protein levels during gestation and a good quality MRI-scan of the child’s brain at age 10 years. Of the 3,992 children scanned, a total of 2,053 10-year-old children were included in this study. ExposureMaternal C-reactive protein was measured in the first 18 weeks of gestation. For the analyses we used both a continuous approach as well as a categorical approach based on clinical cut-offs to determine if there was a dose-response relationship. Main outcomes and measuresHigh-resolution MRI brain morphology measures were used as the primary outcome. Gestational age at birth, established using ultrasound, was included as a mediator using a causal mediation analysis. Corrections were made for relevant confounders and multiple comparisons. Biological sex was investigated as moderator. ResultsWe found a direct association between continuous MIA and lower cerebellar volume. In girls, we demonstrated a negative indirect association between continuous MIA and total brain volume, through the mediator gestational age at birth. We observed no associations with categorical MIA after multiple testing correction. Conclusion and relevanceOur results suggest sex-specific long-term effects in brain morphology after MIA. Categorical analyses suggest that this association might be driven by acute infections or other sources of severe inflammation, which is of clinical relevance given that the COVID-19 pandemic is currently affecting millions of pregnant women worldwide.

Cerebellum and nucleus caudatus asymmetry in major depressive disorder

Background/Aim: The relationship between major depressive disorder (MDD) and specific brain regions was investigated using neuroimaging methods. Although the findings show structural hemispheric asymmetry, research has often focused on the specific brain region involved in MDD. This study aimed to investigate asymmetry in the brain regions of MDD patients for the first time with volBrain, which is a fully automated segmentation technique. Methods: Our study was designed as a case-control study. Structural asymmetry was evaluated using the current web-based fully automated segmentation algorithm, volBrain, that analyzes volumetric T1 axial magnetic resonance imaging data. Sixteen cases with MDD and 14 healthy controls were analyzed. For comparison of continuous data between binary groups, an independent T-test was used for data that follow a normal distribution and Mann–Whitney U (MWU) test was used for data that did not follow a normal distribution while categorical data were evaluated using Chi-square test (or Fisher’s exact test when needed). Results: There was no significant difference in terms of gender (χ2 [1, n = 30] = 0.117, P = 0.732), education level (2 [1, n = 30] = 0.002; P = 0.961] and marital status (P = 0.596, Fisher exact chi-square test). However, both groups were found to be similar in terms of age (P = 0.608, MWU test). Right/left nucleus caudatus volume ratios (P = 0.028, MWU test) and right/left cerebellum volume ratios were significantly smaller in the case group (P = 0.006, independent T-test). When the volumes of the right and left parts were compared, only the volume of the right globus pallidus was larger (statistically significant) in the case group (P = 0.008, independent T-test). Conclusion: In line with our hypothesis, our study supports the notion of cortico–striatal–pallidal–thalamic circuit abnormalities in current MDD research and found that some regions in this phase may contain structural asymmetry. In addition, this study contributed to the literature consisting of studies that have examined the relationship between cerebellum and MDD by adding that the cerebellum may show structural asymmetry. The results of our study suggest that research using volBrain may be beneficial to patients with MDD. Current web-based fully automatic segmentation algorithms can restrict both the rater-induced differences in manual segmentation applications and the differences that various segmentation algorithms can create. The challenge of multicenter research can be overcome by using web-based fully automated segmentation volumetry systems and data containing the same standardized magnetic resonance imaging (MRI) acquisition parameters because it is easy for clinicians around the world to access web-based fully automated segmentation volumetry systems. Research on fully automatic segmentation techniques might be the driving force behind fully understanding biological foundations of MDD in the future.

Association between acute kidney injury and brain injury on term-equivalent age brain magnetic resonance imaging in very preterm infants.

This study aimed to investigate the relationship between acute kidney injury (AKI) in the first 2weeks of life and brain injury on term-equivalent age magnetic resonance imaging in very preterm infants. We included 116 infants with a birth weight of < 1500g who were born at the King Saud Medical City at ≤ 32 gestational weeks. They were admitted to the neonatal intensive care unit and underwent term-equivalent age and pre-discharge brain magnetic resonance imaging. A negative binomial with generalized linear models and a robust variance estimator (Huber-White) was applied for univariate relative risk analysis. The Kidokoro score was then used to determine the effect of AKI on brain morphology and growth at term-equivalent age. Sixty-eight (64.2%) infants had developed an AKI in the first 2weeks of life. AKI was significantly associated with cerebellum signal abnormalities, cerebellar volume reduction, and a high total cerebellum score (P = 0.04, P < 0.001, P < 0.001, respectively). AKI in the first 2weeks of life is associated with brain insult, especially in the cerebellum. More well-designed studies are required to investigate the association and impact of AKI on the central nervous system. A higher resolution version of the Graphical abstract is available as Supplementary information.

Cerebellar Structure and Cognitive Ability in Psychosis

BackgroundDysconnectivity theories, combined with advances in fundamental cognitive neuroscience, have led to increased interest in characterizing cerebellar abnormalities in psychosis. Smaller cerebellar gray matter volume has been found in schizophrenia spectrum disorders. However, the course of these deficits across illness stage, specificity to schizophrenia (vs. psychosis more broadly), and relationship to clinical phenotypes, primarily cognitive impairment, remain unclear. MethodsThe Spatially Unbiased Infratentorial toolbox, a gold standard for analyzing human neuroimaging data of the cerebellum, was used to quantify cerebellar volumes and conduct voxel-based morphometry on structural magnetic resonance images obtained from 574 individuals (249 schizophrenia spectrum, 108 bipolar with psychotic features, 217 nonpsychiatric control). Analyses examining diagnosis (schizophrenia spectrum, bipolar disorder), illness stage (early, chronic), and cognitive effects on cerebellum structure in psychosis were performed. ResultsCerebellar structure in psychosis did not differ significantly from healthy participants, regardless of diagnosis and illness stage (effect size = 0.01–0.14). In contrast, low premorbid cognitive functioning was associated with smaller whole and regional cerebellum volumes, including cognitive (lobules VI and VII, Crus I, frontoparietal and attention networks) and motor (lobules I–IV, V, and X; somatomotor network) regions in psychosis (effect size = 0.36−0.60). These effects were not present in psychosis cohorts with average estimated premorbid cognition. ConclusionsCerebellar structural abnormalities in psychosis are related to lower premorbid cognitive functioning implicating early antecedents, atypical neurodevelopment, or both in cerebellar dysfunction. Future research focused on identifying the impact of early-life risk factors for psychosis on the development of the cerebellum and cognition is warranted.

Hemispheric Cortical, Cerebellar and Caudate Atrophy Associated to Cognitive Impairment in Metropolitan Mexico City Young Adults Exposed to Fine Particulate Matter Air Pollution.

Exposures to fine particulate matter PM2.5 are associated with Alzheimer’s, Parkinson’s (AD, PD) and TDP-43 pathology in young Metropolitan Mexico City (MMC) residents. High-resolution structural T1-weighted brain MRI and/or Montreal Cognitive Assessment (MoCA) data were examined in 302 volunteers age 32.7 ± 6.0 years old. We used multivariate linear regressions to examine cortical surface area and thickness, subcortical and cerebellar volumes and MoCA in ≤30 vs. ≥31 years old. MMC residents were exposed to PM2.5 ~ 30.9 µg/m3. Robust hemispheric differences in frontal and temporal lobes, caudate and cerebellar gray and white matter and strong associations between MoCA total and index scores and caudate bilateral volumes, frontotemporal and cerebellar volumetric changes were documented. MoCA LIS scores are affected early and low pollution controls ≥ 31 years old have higher MoCA vs. MMC counterparts (p ≤ 0.0001). Residency in MMC is associated with cognitive impairment and overlapping targeted patterns of brain atrophy described for AD, PD and Fronto-Temporal Dementia (FTD). MMC children and young adult longitudinal studies are urgently needed to define brain development impact, cognitive impairment and brain atrophy related to air pollution. Identification of early AD, PD and FTD biomarkers and reductions on PM2.5 emissions, including poorly regulated heavy-duty diesel vehicles, should be prioritized to protect 21.8 million highly exposed MMC urbanites.

Comparing brain asymmetries independently of brain size

Studies examining cerebral asymmetries typically divide the l-R Measure (e.g., Left–Right Volume) by the L + R Measure to obtain an Asymmetry Index (AI). However, contrary to widespread belief, such a division fails to render the AI independent from the L + R Measure and/or from total brain size. As a result, variations in brain size may bias correlation estimates with the AI or group differences in AI. We investigated how to analyze brain asymmetries in to distinguish global from regional effects, and report unbiased group differences in cerebral asymmetries in the UK Biobank (N = 40, 028).We used 306 global and regional brain measures provided by the UK Biobank. Global gray and white matter volumes were taken from Freesurfer ASEG, subcortical gray matter volumes from Freesurfer ASEG and subsegmentation, cortical gray matter volumes, mean thicknesses, and surface areas from the Destrieux atlas applied on T1-and T2-weighted images, cerebellar gray matter volumes from FAST FSL, and regional white matter volumes from Freesurfer ASEG.We analyzed the extent to which the L + R Measure, Total Cerebral Measure (TCM, e.g., Total Brain Volume), and l-R TCM predict regional asymmetries. As a case study, we assessed the consequences of omitting each of these predictors on the magnitude and significance of sex differences in asymmetries.We found that the L + R Measure, the TCM, and the l-R TCM predicted the AI of more than 89% of regions and that their relationships were generally linear. Removing any of these predictors changed the significance of sex differences in 33% of regions and the magnitude of sex differences across 13–42% of regions. Although we generally report similar sex and age effects on cerebral asymmetries to those of previous large-scale studies, properly adjusting for regional and global brain size revealed additional sex and age effects on brain asymmetry.

Volume fraction of the cerebellum in Parkinson’s patients

Most investigations on Parkinson’s disease (PD) focus on the basal ganglia and brainstem, whereas the cerebellum has often been overlooked. The cerebellum is critical for motor control and increasing evidence suggests that it may be associated with the pathophysiology of PD. The aim of this study was to describe cerebral and cerebellar volumes in patients with PD and to compare results with healthy subjects. In the present study, 18 patients with PD (8 female, 10 male) and 19 controls (9 females, 10 males) were included. Structural magnetic resonance (MR) imaging was performed in both groups with a 1.5 Tesla scanner. The images were analyzed using ImageJ software. Volumes were estimated via planimetry and threshold stereological methods. The mean total cerebral volumes were 943.19 ± 91.67 cm3 in control group and 909.83 ± 95.88 cm3 in patients. The mean total cerebellar volumes and the volume fractions were found 140.44 ± 21.68 cm3, 14.94 ± 2.17 % in control group and 140.52 ± 15.96 cm3, 15.52 ± 1.73% in patients, respectively. There were no significant differences found in terms of cerebral and cerebellar parameters. Our knowledge about cerebellum and PD interaction remains limited, although, the cerebellum is a potential target for some parkinsonian symptoms. Further investigations are needed to understand the role of cerebellum in PD using newly developing imaging techniques.