Cerebellar Gray Matter Volume Research Articles

Morphometric evaluation of cerebellar structures in late monocular blindness.

Only a few studies have investigated structural and functional changes in monocular blind individuals. Our aim in this study was to segmentally investigate the cerebellar structures of subjects with late-onset monocular blindness (LMB) using a Voxel-based volumetric analysis system. The segmental volumetric values, cortical thickness, gray matter volumes and percentage ratios of the cerebellar lobules of individuals with LMB due to trauma and in healthy individuals with bilateral sight as the control group were calculated at the volBrain CERES 1.0 website ( https://volbrain.upv.es/ ) by using brain 3D fast spoiled gradient recall acquisition in steady-state (3D T1 FSPGR) MRI sequence images in our prospective study. We studied 11 subjects with LMB (8 males/3 females) and 11 healthy control subjects (8 males/3 females). The mean age was 41.45 ± 14.15 and 40 ± 11.11years, respectively (p > 0.05). The mean duration of the LMB status was 20.8 ± 11.2years. Cerebellar lobule crus II volume and cerebellar lobule VIIB/VIIIA volume/percentage were higher in the LMB group, and mean cerebellar cortical thickness, cerebellar lobule VI-cerebellar lobule crus I-II cortical thickness, and cerebellar lobule VI gray matter volume values were lower in the LMB group (p < 0.05). In this study, cerebellar lobule VIIB/VIIIA volume/total percent ratio, cerebellar cortical thickness and cerebellar gray matter volume in the LMB group were found to be different from the control group. To our knowledge, this is the first study to report cerebellar anatomical changes in patients with LMB.

A longitudinal observational population-based study of brain volume associated with changes in sleep timing from middle to late-life.

Sleep behaviors are related to brain structure and function, but the impact of long-term changes in sleep timing on brain health has not been clearly addressed. The purpose of this study was to examine the association of longitudinal changes in sleep timing from middle to late-life with gray matter volume (GMV), an important marker of brain aging. We enrolled 1798 adults (aged 49-82 years, men 54.6%) who underwent magnetic resonance imaging (MRI) between 2011 and 2014. Midsleep time (MST) on free days corrected for sleep debt on workdays was adopted as a marker of sleep timing. Data on MST were available at the time of MRI assessment and at examinations that were given 9 years earlier (2003-2004). Longitudinal changes in MST over the 9-year period were derived and categorized into quartiles. Subjects in quartile 1 were defined as "advancers" (MST advanced ≥ 1 h) while those in quartile 4 were defined as "delayers" (MST delayed ≥ 0.2 h). Quartiles 2-3 defined a reference group (MST change was considered modest). The relationship of GMV with MST changes over 9 years was investigated. Nine-year change in MST were significantly associated with GMV. Compared to the reference group, advancers had smaller GMVs in the frontal and temporal regions. A delay in MST was also associated with smaller cerebellar GMV. In middle-to-late adulthood, the direction of change in MST is associated with GMV. While advancers and delayers in MST tend to present lower GMV, associations appear to differ across brain regions.

Is cardiovascular fitness associated with structural brain integrity in midlife? Evidence from a population-representative birth cohort study.

Improving cardiovascular fitness may buffer against age-related cognitive decline and mitigate dementia risk by staving off brain atrophy. However, it is unclear if such effects reflect factors operating in childhood (neuroselection) or adulthood (neuroprotection). Using data from 807 members of the Dunedin Study, a population-representative birth cohort, we investigated associations between cardiovascular fitness and structural brain integrity at age 45, and the extent to which associations reflected possible neuroselection or neuroprotection by controlling for childhood IQ. Higher fitness, as indexed by VO2Max, was not associated with average cortical thickness, total surface area, or subcortical gray matter volume including the hippocampus. However, higher fitness was associated with thicker cortex in prefrontal and temporal regions as well as greater cerebellar gray matter volume. Higher fitness was also associated with decreased hippocampal fissure volume. These associations were unaffected by the inclusion of childhood IQ in analyses. In contrast, a higher rate of decline in cardiovascular fitness from 26 to 45 years was not robustly associated with structural brain integrity. Our findings are consistent with a neuroprotective account of adult cardiovascular fitness but suggest that effects are not uniformly observed across the brain and reflect contemporaneous fitness more so than decline over time.

Early pediatric chronic kidney disease is associated with brain volumetric gray matter abnormalities.

Background:The impact of pediatric chronic kidney disease (pCKD) on the brain remains poorly defined. The objective of this study was to compare brain morphometry between children with early stage pCKD and typically developing peers using structural magnetic resonance imaging (MRI).Methods:The sample age range was 6–16 years. A total of 18 children with a diagnosis of pCKD (CKD stages 1–3) due to congenital anomalies of the kidney and urinary tract and 24 typically developing peers were included. Volumetric data from MRI and neurocognitive testing were compared using linear models including pCKD status, age, maternal education level, and socioeconomic status.Results:Cerebellar gray matter volume was significantly smaller in pCKD, t(38)=−2.71, p = 0.01. In contrast, cerebral gray matter volume was increased in pCKD, t(38)=2.08, p = 0.04. Reduced cerebellum gray matter volume was associated with disease severity, operationalized as estimated glomerular filtration rate (eGFR), t(14)=2.21, p = 0.04 and predicted lower verbal fluency scores in the pCKD sample. Enlarged cerebral gray matter in the pCKD sample predicted lower scores on mathematics assessment.Conclusion:This study provides preliminary evidence for a morphometric underpinning to the cognitive deficits observed in pCKD.

49.3 NEUROCOGNITIVE CORRELATES OF CEREBELLAR VOLUMETRIC ALTERATIONS IN YOUTH WITH BIPOLAR DISORDER

The role of the cerebellum in motor control is well-established, and there are reports on its involvement in cognitive and affective processing. However, research on cerebellar gray matter volume (GMV) and behavioral correlates in pediatric bipolar disorder (PBD) is lacking.

The effects of early-treated phenylketonuria on volumetric measures of the cerebellum

Past murine studies of phenylketonuria (PKU) have documented significant effects on cerebellum at both the gross and cellular levels. The profile of neurocognitive and motor difficulties associated with early-treated PKU (ETPKU) is also consistent with potential cerebellar involvement. Previous neuroanatomical studies of cerebellum in patients with PKU, however, have yielded mixed results. The objective of the present study was to further examine potential differences in cerebellar morphometry between individuals with and without ETPKU. To this end, we analyzed high resolution T1-weighted MR images from a sample of 20 individuals with ETPKU and an age-matched comparison group of 20 healthy individuals without PKU. Measurements of whole brain volume, whole cerebellum volume, cerebellar gray matter volume, and cerebellar white matter volume were collected by means of semiautomatic volumetric analysis. Data analysis revealed no significant group differences in whole brain volume, whole cerebellar volume, or cerebellar white matter volume. A significant reduction in cerebellar gray matter volume, however, was observed for the ETPKU group compared to the non-PKU comparison group. These findings expand on previous animal work suggesting that cerebellar gray matter is impacted by PKU. It is also consistent with the hypothesis that the cognitive difficulties experienced by individuals with ETPKU may be related to disruptions in gray matter. Additional studies are needed to fully elucidate the timing and extent of the impact of ETPKU on cerebellum and the associated neurocognitive consequences.

Cerebellar Grey Matter Volume in Older Persons Is Associated with Worse Cognitive Functioning.

The cerebellum is increasingly recognised for its role in modulation of cognition, behaviour, and affect. The present study examined the relation between structural cerebellar damage (grey matter volume (GMV), white matter hyperintensities (WMHs), lacunar infarcts (LIs) and microbleeds (MBs)) and measures of cognitive, psychological (i.e. symptoms of depression and apathy) and general daily functioning in a population of community-dwelling older persons with mild cognitive deficits, but without dementia. In 194 participants of the Discontinuation of Antihypertensive Treatment in Elderly People (DANTE) Study Leiden, the association between cerebellar GMV, WMHs, LIs and MBs and measures of cognitive, psychological and general daily functioning was analysed with linear regression analysis, adjusted for age, sex, education and cerebral volume. Cerebellar GMV was associated with the overall cognition score (standardised beta 0.20 [95% CI, 0.06-0.33]). Specifically, posterior cerebellar GMV was associated with executive function (standardised beta 0.18 [95% CI, 0.03-0.16]). No relation was found between vascular pathology and cognition. Also, no consistent associations were found on the cerebellar GMV and vascular pathology measures and psychological and general daily functioning. In this population of community-dwelling elderly, less posterior cerebellar GMV but not vascular pathology was associated with worse cognitive function, specifically with poorer executive function. No relation was found between cerebellar pathology and psychological and general daily functioning.

Abnormal Cerebellar Volume in Patients with Remitted Major Depression with Persistent Cognitive Deficits

Cerebellar involvement in major depressive disorder (MDD) has been demonstrated by a growing number of studies, but it is unknown whether cognitive functioning in depressed individuals is related to cerebellar gray matter volume (GMV) abnormalities. Impaired attention and executive dysfunction are characteristic cognitive deficits in MDD, and critically, they often persist despite remission of mood symptoms. In this study, we investigated cerebellar GMV in patients with remitted MDD (rMDD) that showed persistent cognitive impairment. We applied cerebellum-optimized voxel-based morphometry in 37 patients with rMDD and with cognitive deficits, in 12 patients with rMDD and without cognitive deficits, and in 36 healthy controls (HC). Compared with HC, rMDD patients with cognitive deficits had lower GMV in left area VIIA, crus II, and in vermal area VIIB. In patients with rMDD, regression analyses demonstrated significant associations between GMV reductions in both regions and impaired attention and executive dysfunction. Compared with HC, patients without cognitive deficits showed increased GMV in bilateral area VIIIB. This study supports cerebellar contributions to the cognitive dimension of MDD. The data also point towards cerebellar area VII as a potential target for non-invasive brain stimulation to treat cognitive deficits related to MDD.

Morphometrical study of the cat cerebellum using unbiased design-based stereology.

The objective of the present study was to investigate the morphometrical features of the cat cerebellum using design-based stereology. Cerebellar hemispheres from four male cats were examined. Isotropic, uniform random sections were obtained and processed for light microscopy. Cerebellar total volume (V), white (WM) and grey matter (GM) volume fractions, and the volumes of the molecular and granular layers were measured using the Cavalieri's estimator and the point counting system. Cerebellar surface area was estimated using test lines, and Purkinje cellular and nuclear volumes were analysed using the nucleator technique. The volume of the cat cerebellar hemispheres was 2.06±0.29cm3 . The relative volume fractions of the GM and WM were 70.6±2.6% and 29.3±2.6%, respectively. The surface area of the cerebellar hemisphere was 68.2±17.8cm2 . The volumes of the molecular and granular layers were estimated at 0.89±0.16cm3 and 0.56±0.1cm3 , respectively. The Purkinje cell volumes were found to be ranging from 1,717 to 28,489µm3 , of which cells with a perikaryon volume of 6,994µm3 had a higher incidence. The Purkinje nuclear volume was estimated at 440-3,561µm3 , and nuclei with a volume of 1,252µm3 were the most frequently occurring ones. Our data might contribute to the veterinary comparative neuroanatomy knowledge, help develop experimental studies in this field, and possibly lead to advancement in the diagnosis and treatment of nervous diseases in the cat.

M165. CEREBELLAR VOLUMES REDUCED IN PATIENTS WITH SCHIZOPHRENIA BASED ON ANATOMICAL, TASK-FREE AND TASK-BASED FUNCTIONAL PARCELLATIONS

BackgroundCerebellum is not only responsible for motor functions but is also involving in cognitive and emotional processes (Strick et al. 2009). Recent advances in imaging technologies allow us to examine the cerebellum in a much more systematic way including functional parcellations of cerebellum (e.g. 7-Network parcellation based on the resting state functional connectivity, Buckner et al., 2011; and task-based functional parcellation, King et al., 2019). These functional parcellations further uncover the important roles of cerebellum in non-motor functions.In the past two decades, altered cerebellar structure and function have been observed in schizophrenia patients, with the anterior (lobules III-V) and the posterior cerebellum (lobules VI, VIIa, Crus I, and Crus II, VIII) as regions commonly reported (Bernard & Mittal 2015). Using the 7-Network task-free parcellation, a recent multisite mega-analysis reported that patients with schizophrenia exhibited robust grey matter reduction in cerebellum (Moberget et al., 2018).The present study aimed to examine the cerebellar grey matter volumes in schizophrenia patients using anatomical, task-free connectivity-based and task-based functional parcellations. We also explored how the cerebellar volumes changes along with age in schizophrenia patients and healthy controls.MethodsTwenty-nine patients with schizophrenia (SCZ, mean age = 22.0±2.5 years) and 55 healthy controls (HC, mean age = 23.5±3.6 years) were recruited to undertake structural magnetic resonance imaging (MRI) brain scan on a GE 750 scanner. Cerebellar volumes were measured by a high-resolution Spatially Unbiased Infratentorial (SUIT) toolbox (Diedrichsen, 2006). Regional cerebellar grey matter volumes were calculated for each participant based on anatomical (SUIT atlas) and functional atlases (7 regions of task-free parcellation; 10 regions of task-based parcellation) of the cerebellum. The group comparisons on regional cerebellar volumes were conducted in SPSS v19.0, taking total ICV as a covariate. The correlations between age and cerebellar volumes of those regions showing significant group differences were conducted. The significance threshold was set at p < 0.05.ResultsRegarding the anatomical atlas, SCZ patients exhibited reduced grey matter volumes of the superior posterior cerebellum, mainly in lobules Crus II, VIIb and VIIIa. Regarding the task-free parcellation, SCZ patients exhibited smaller volumes in cerebellar regions showing functional connectivity with frontoparietal network and default mode network. Regarding the task-based parcellation, smaller volumes of cerebellar regions that activated during verbal fluency task (ROI9) was observed in SCZ patients.Correlation analyses between age and cerebellar volumes of those regions with significant group differences further reported negative correlations between age and lobule Crus II in both SCZ patients and HC (SCZ: r = -0.44, p < 0.05; HC: r = -0.43, p = 0.001). Moreover, negative correlations between age and cerebellar regions showing functional connectivity with frontoparietal network was observed in HC only (r = -0.30, p < 0.05), whereas negative correlations between age and lobules VIIb (r = -0.48, p < 0.01), VIIIa (r = -0.39, p < 0.05) and ROI9 of task-based atlas (r = -0.43, p < 0.05) were observed in SCZ patients.DiscussionOur findings showed reduced cerebellar grey matter volumes and the abnormal age-related changes of cerebellum in SCZ patients, especially in the regions related to frontoparietal network and cognitive function. These findings may highlight an important role of cerebellum underlying the mechanisms of cognitive dysfunction in mental disorders.

Maternal cerebellar gray matter volume is associated with daughters' psychotic experience.

A substantial portion of children and adolescents show subthreshold psychotic symptoms called psychotic experience (PE). Because PE shares its biological and environmental risk factors with psychotic spectrum disorders, parental neuroanatomical variation could reflect a heritable biological underpinning of PE that may predict an offspring's PE. A total of 94 participants from 35 families without a diagnosis of major neuropsychiatric disorders were examined, including 14 mother-daughter, 17 mother-son, 12 father-daughter, and 16 father-son dyads. An offspring's PE was assessed with the Atypicality subscale of the Behavior Assessment System for Children - 2nd Edition, Self-Report of Personality form (BASCaty). We examined correlations between voxel-by-voxel parental gray matter volume and their offspring's BASCaty score. Maternal cerebellar gray matter volume using voxel-based morphometry was positively correlated with their daughters' BASCaty scores. The findings were significant in a more robust approach using cerebellum-specific normalization known. We did not find significant correlation between paternal gray matter volume and BASCaty scores or between offspring gray matter volumes and their BASCaty scores. Expanding upon parent-of-origin effects in psychosis, maternal neuroanatomical variation was associated with daughters' PE. The nature of this sex-specific intergenerational effect is unknown, but maternally transmitted genes may relate cerebellum development to PE pathogenesis.

The depression GWAS risk allele predicts smaller cerebellar gray matter volume and reduced SIRT1 mRNA expression in Chinese population

Major depressive disorder (MDD) is recognized as a primary cause of disability worldwide, and effective management of this illness has been a great challenge. While genetic component is supposed to play pivotal roles in MDD pathogenesis, the genetic and phenotypic heterogeneity of the illness has hampered the discovery of its genetic determinants. In this study, in an independent Han Chinese sample (1824 MDD cases and 3031 controls), we conducted replication analyses of two genetic loci highlighted in a previous Chinese MDD genome-wide association study (GWAS), and confirmed the significant association of a single nucleotide polymorphism (SNP) rs12415800 near SIRT1. Subsequently, using hypothesis-free whole-brain analysis in two independent Han Chinese imaging samples, we found that individuals carrying the MDD risk allele of rs12415800 exhibited aberrant gray matter volume in the left posterior cerebellar lobe compared with those carrying the non-risk allele. Besides, in independent Han Chinese postmortem brain and peripheral blood samples, the MDD risk allele of rs12415800 predicted lower SIRT1 mRNA levels, which was consistent with the reduced expression of this gene in MDD patients compared with healthy subjects. These results provide further evidence for the involvement of SIRT1 in MDD, and suggest that this gene might participate in the illness via affecting the development of cerebellum, a brain region that is potentially underestimated in previous MDD studies.

Systemic Mitochondrial Oxidative Phosphorylation Protein Levels Correlate with Neuroimaging Measures in Chronically HIV-Infected Individuals.

Few studies have examined systemic mitochondrial function in conjunction with brain imaging in human immunodeficiency virus (HIV) disease. Oxidative phosphorylation enzyme protein levels of peripheral blood mononuclear cells were measured in association with neuroimaging indices in 28 HIV+ individuals. T1-weighted magnetic resonance imaging yielded volumes of seven brain regions of interest; diffusion tensor imaging determined fractional anisotropy (FA) and mean diffusivity (MD) in the corpus callosum (CC). Higher nicotinamide adenine dinucleotide dehydrogenase levels correlated with lower volumes of thalamus (p = .005) and cerebral white matter (p = .049) and, in the CC, with lower FA (p = .011, body; p = .005, genu; p = .009, total CC) and higher MD (p = .023, body; p = .035, genu; p = .019, splenium; p = .014, total CC). Greater cytochrome c oxidase levels correlated with lower thalamic (p = .034) and cerebellar gray matter (p = .021) volumes. The results indicate that systemic mitochondrial cellular bioenergetics are associated with brain health in HIV.

SUITer: An Automated Method for Improving Segmentation of Infratentorial Structures at Ultra-High-Field MRI.

The advent of high and ultra-high-field MRI has significantly improved the investigation of infratentorial structures by providing high-resolution images. However, none of the publicly available methods for cerebellar image analysis has been optimized for high-resolution images yet. We present the implementation of an automated algorithm-SUITer (spatially unbiased infratentorial for enhanced resolution) method for cerebellar lobules parcellation on high-resolution MR images acquired at both 3 and 7T MRI. SUITer was validated on five manually segmented data and compared with SUIT, FreeSurfer, and convolutional neural networks (CNN). SUITer was then applied to 3 and 7T MR images from 10 multiple sclerosis (MS) patients and 10 healthy controls (HCs). The difference in volumes estimation for the cerebellar grey matter (GM), between the manual segmentation (ground truth), SUIT, CNN, and SUITer was reduced when computed by SUITer compared to SUIT (5.56 vs. 29.23 mL) and CNN (5.56 vs. 9.43 mL). FreeSurfer showed low volumes difference (3.56 mL). SUITer segmentations showed a high correlation (R2 = .91) and a high overlap with manual segmentations for cerebellar GM (83.46%). SUITer also showed low volumes difference (7.29 mL), high correlation (R2 = .99), and a high overlap (87.44%) for cerebellar GM segmentations across magnetic fields. SUITer showed similar cerebellar GM volume differences between MS patients and HC at both 3T and 7T (7.69 and 7.76 mL, respectively). SUITer provides accurate segmentations of infratentorial structures across different resolutions and MR fields.

Cerebellar volume loss in radiologically isolated syndrome

Radiologically isolated syndrome (RIS), in which asymptomatic demyelinating-appearing lesions are detected incidentally on MRI, can be a pre-clinical form of multiple sclerosis (MS). In this study, we measured cerebellar volumes on 3D T1-weighted 3T MR images in 21 individuals with RIS and 38 age- and sex-matched healthy controls (HC). Normalized cerebellar white matter volume and the anterior cerebellar gray matter volume were significantly decreased in RIS compared to HC (p = 0.003 and p = 0.005, respectively). Our findings support reports of regional brain atrophy in RIS prior to the development of a seminal attack related to inflammatory demyelination.

Cerebellar parcellation in schizophrenia and bipolar disorder.

The cerebellum is involved in cognitive processing and emotion control. Cerebellar alterations could explain symptoms of schizophrenia spectrum disorder (SZ) and bipolar disorder (BD). In addition, literature suggests that lithium might influence cerebellar anatomy. Our aim was to study cerebellar anatomy in SZ and BD, and investigate the effect of lithium. Participants from 7 centers worldwide underwent a 3T MRI. We included 182 patients with SZ, 144 patients with BD, and 322 controls. We automatically segmented the cerebellum using the CERES pipeline. All outputs were visually inspected. Patients with SZ showed a smaller global cerebellar gray matter volume compared to controls, with most of the changes located to the cognitive part of the cerebellum (Crus II and lobule VIIb). This decrease was present in the subgroup of patients with recent-onset SZ. We did not find any alterations in the cerebellum in patients with BD. However, patients medicated with lithium had a larger size of the anterior cerebellum, compared to patients not treated with lithium. Our multicenter study supports a distinct pattern of cerebellar alterations in SZ and BD.

Responding to Sensorimotor Suggestions: From Endothelial Nitric Oxide to the Functional Equivalence Between Imagery and Perception

The reduced cerebellar gray matter (GM) volume observed in highly hypnotizable individuals (highs) is likely due to the excessive release of endothelial nitric oxide in the brain and could account for their behavioral (postural and visuomotor control) and physiological (paradoxical pain control after cerebellar anodal stimulation) characteristics. Reduced cerebellar GM can induce low inhibition of the cerebral cortex, thus stronger functional equivalence (FE) between imagery and perception and greater proneness to respond to sensorimotor suggestions. In fact, stronger FE suggested in highs by behavioral studies has been confirmed by topological data analysis of EEG signals recorded during sensorimotor and imagery tasks. The authors’ hypothesis cannot be applied to obstructive suggestions likely sustained by mechanisms related to socio-cognitive factors, i.e., oxytocin availability.

Cerebellar Gray Matter and Olfactory Performance.

The role of the cerebellum in the chemical senses is still poorly understood. This voxel-based morphometry (VBM) study investigated associations between gray matter volume (GMV) in subregions of the cerebellum and olfactory performance. VBM data from 48 men were analyzed. The participants were tested with a standardized olfactory test that measured olfactory threshold, discrimination, and identification ability. The investigated sample covered a wide range of olfactory performance, including individuals with a reduced sense of smell (anosmia and hyposmia) and normosmia. The computed regression analyses revealed a positive association between olfactory identification performance and GMV in lobule VI. This cerebellar subregion is involved in higher-order cognitive functions (language and memory), which are necessary prerequisites for correct odor labeling. Odor detection and discrimination were unrelated to cerebellar GMV.

Neuroplasticity Modifications Following a Lower-Limb Amputation: A Systematic Review.

Although there are studies that have examined brain functional reorganization following upper-limb amputation, understanding of the brain changes that occur in people with lower-limb amputation is limited. To investigate modifications in the brain following lower-limb amputation. We included case-control studies that evaluate neuroplasticity in the central nervous system using neuroimaging techniques. A literature search was conducted using MEDLINE, CINAHL, Web of Science, Scopus, and Cochrane. Eleven articles were included (total n = 204 people with unilateral lower-limb amputation). These studies showed an increase in cerebellar gray matter volume in prosthesis users, as well as a decrease in thickness of the premotor cortex, orbitofrontal cortex, temporo-occipital junction, precentral gyrus, visual areas, and somatosensory cortex. Regarding white matter, the trials observed a decrease in the integrity at the corona radiata, the connections between the premotor areas, the fronto-occipital fasciculus and the corpus callosum. In addition, a decreased functional connectivity between cortical and subcortical areas has been described. Lower-limb amputation causes changes in several brain structures that may occur in the absence of pain and regardless of prosthesis use. The modifications observed include thinning or loss of gray matter volume, decrease in the integrity of the white matter connections between brain structures and changes in the functional connectivity between cortical and subcortical areas. I.

Atrophy of cerebellar peduncles in essential tremor: a machine learning-based volumetric analysis.

Subtle cerebellar signs are frequently observed in essential tremor (ET) and may be associated with cerebellar dysfunction. This study aims to evaluate the macrostructural integrity of the superior, middle, and inferior cerebellar peduncles (SCP, MCP, ICP) and cerebellar gray and white matter (GM, WM) volumes in patients with ET, and compare these volumes between patients with and without cerebellar signs (ETc and ETnc). Forty patients with ET and 37 age- and gender-matched healthy controls were recruited. Atlas-based region-of-interest analysis of the SCP, MCP, and ICP and automated analysis of cerebellar GM and WM volumes were performed. Peduncular volumes were employed in a multi-variate classification framework to attempt discrimination of ET from controls. Significant atrophy of bilateral MCP and ICP and bilateral cerebellar GM was observed in ET. Cerebellar signs were present in 20% of subjects with ET. Comparison of peduncular and cerebellar volumes between ETnc and ETc revealed atrophy of right SCP, bilateral MCP and ICP, and left cerebellar WM in ETc. The multi-variate classifier could discriminate between ET and controls with a test accuracy of 86.66%. Patients with ET have significant atrophy of cerebellar peduncles, particularly the MCP and ICP. Additional atrophy of the SCP is observed in the ETc group. These abnormalities may contribute to the pathogenesis of cerebellar signs in ET. • Patients with ET have significant atrophy of bilateral middle and inferior cerebellar peduncles and cerebellar gray matter in comparison with healthy controls. • Patients of ET with cerebellar signs have significant atrophy of right superior cerebellar peduncle, bilateral middle and inferior cerebellar peduncle, and left cerebellar white matter in comparison with ET without cerebellar signs. • A multi-variate classifier employing peduncular volumes could discriminate between ET and controls with a test accuracy of 86.66%.