Lobule VI Research Articles

Characterization of central manifestations in patients with Niemann-Pick disease type C

PurposeNiemann-Pick disease type C (NPC) is a rare lysosomal storage disease characterized by progressive neurodegeneration and neuropsychiatric symptoms. This study investigated pathophysiological mechanisms underlying motor deficits, particularly speech production, and cognitive impairment. MethodsWe prospectively phenotyped 8 adults with NPC and age-sex-matched healthy controls using a comprehensive assessment battery, encompassing clinical presentation, plasma biomarkers, hand-motor skills, speech production, cognitive tasks, and (micro-)structural and functional central nervous system properties through magnetic resonance imaging. ResultsPatients with NPC demonstrated deficits in fine-motor skills, speech production timing and coordination, and cognitive performance. Magnetic resonance imaging revealed reduced cortical thickness and volume in cerebellar subdivisions (lobule VI and crus I), cortical (frontal, temporal, and cingulate gyri) and subcortical (thalamus and basal ganglia) regions, and increased choroid plexus volumes in NPC. White matter fractional anisotropy was reduced in specific pathways (intracerebellar input and Purkinje tracts), whereas diffusion tensor imaging graph theory analysis identified altered structural connectivity. Patients with NPC exhibited altered activity in sensorimotor and cognitive processing hubs during resting-state and speech production. Canonical component analysis highlighted the role of cerebellar-cerebral circuitry in NPC and its integration with behavioral performance and disease severity. ConclusionThis deep phenotyping approach offers a comprehensive systems neuroscience understanding of NPC motor and cognitive impairments, identifying potential central nervous system biomarkers.

FL-41 Tint Reduces Activation of Neural Pathways of Photophobia in Patients with Chronic Ocular Pain

To assess the therapeutic effect of tinted lenses (FL-41) on photophobia and light-evoked brain activity using functional magnetic resonance imaging (fMRI) in individuals with chronic ocular surface pain. Prospective case series. 25 subjects from the Miami veterans affairs (VA) eye clinic were recruited based on the presence of chronic ocular pain, dry eye symptoms, and photophobia. Using a 3T MRI scanner, subjects underwent 2 fMRI scans using an event-related design based on light stimuli: one scan while wearing FL-41 lenses and one without. Unpleasantness ratings evoked by the light stimuli were collected after each scan. With FL-41 lenses, subjects reported decreased (n = 19), maintained (n = 2), or increased (n = 4) light-evoked unpleasantness ratings. Group analysis at baseline (no lens) revealed significant light evoked responses in bilateral primary somatosensory (S1), bilateral secondary somatosensory (S2), bilateral insula, bilateral frontal pole, visual, precuneus, paracingulate, and anterior cingulate cortices (ACC) as well as cerebellar vermis, bilateral cerebellar hemispheric lobule VI, and bilateral cerebellar crus I and II. With FL-41 lenses, light-evoked responses were significantly decreased in bilateral S1, bilateral S2, bilateral insular, right temporal pole, precuneus, ACC, and paracingulate cortices as well as bilateral cerebellar hemispheric lobule VI. FL-41 lenses modulated photophobia symptoms in some individuals with chronic ocular pain. In conjunction, FL-41 lenses decreased activation in cortical areas involved in processing affective and sensory-discriminative dimensions of pain. Further research into these relationships will advance the ability to provide precision therapy for individuals with ocular pain.

Cognitive impairment associated with cerebellar volume loss in spinocerebellar ataxia type 3.

Many neuroscience and neurology studies have forced a reconsideration of the traditional motor-related scope of cerebellar function, which has now expanded to include various cognitive functions. Spinocerebellar ataxia type 3 (SCA3; the most common hereditary ataxia) is neuropathologically characterized by cerebellar atrophy and frequently presents with cognitive impairment. To characterize cognitive impairment in SCA3 and investigate the cerebellum-cognition associations. This prospective, cross-sectional cohort study recruited 126 SCA3 patients and 41 healthy control individuals (HCs). Participants underwent a brain 3D T1-weighted images as well as neuropsychological tests. Voxel-based morphometry (VBM) and region of interest (ROI) approaches were performed on the 3D T1-weighted images. CERES was used to automatically segment cerebellums. Patients were grouped into cognitively impaired (CI) and cognitively preserved (CP), and clinical and MRI parameters were compared. Multivariable regression models were fitted to examine associations between cerebellar microstructural alterations and cognitive domain impairments. Compared to HCs, SCA3 patients showed cognitive domain impairments in information processing speed, verbal memory, executive function, and visuospatial perception. Between CI and CP subgroups, the CI subgroup was older and had lower education, as well as higher severity scores. VBM and ROI analyses revealed volume loss in cerebellar bilateral lobule VI, right lobule Crus I, and right lobule IV of the CI subgroup, and all these cerebellar lobules were associated with the above cognitive domain impairments. Our findings demonstrate the multiple cognitive domain impairments in SCA3 patients and indicate the responsible cerebellar lobules for the impaired cognitive domain(s).

The cerebellum plays more than one role in the dysregulation of appetite: Review of structural evidence from typical and eating disorder populations.

Dysregulated appetite control is characteristic of anorexia nervosa (AN), bulimia nervosa (BN), and obesity (OB). Studies using a broad range of methods suggest the cerebellum plays an important role in aspects of weight and appetite control, and is implicated in both AN and OB by reports of aberrant gray matter volume (GMV) compared to nonclinical populations. As functions of the cerebellum are anatomically segregated, specific localization of aberrant anatomy may indicate the mechanisms of its relationship with weight and appetite in different states. We sought to determine if there were consistencies in regions of cerebellar GMV changes in AN/BN and OB, as well as across normative (NOR) variation. Systematic review and meta-analysis using GingerALE. Twenty-six publications were identified as either case-control studies (nOB =277; nAN/BN =510) or regressed weight from NOR data against brain volume (total n=3830). AN/BN and OB analyses both showed consistently decreased GMV within Crus I and Lobule VI, but volume reduction was bilateral for AN/BN and unilateral for OB. Analysis of the NOR data set identified a cluster in right posterior lobe that overlapped with AN/BN cerebellar reduction. Sensitivity analyses indicated robust repeatability for NOR and AN/BN cohorts, but found OB-specific heterogeneity. Findings suggest that more than one area of the cerebellum is involved in control of eating behavior and may be differentially affected in normal variation and pathological conditions. Specifically, we hypothesize an association with sensorimotor and emotional learning via Lobule VI in AN/BN, and executive function via Crus I in OB.

Altered morphological characteristics and structural covariance connectivity associated with verbal working memory performance in ADHD children.

Deficits in verbal working memory (VWM) observed in attention deficit hyperactivity disorder (ADHD)children can persist into adulthood. Although previous studies have identified brain regions that are activated during VWM tasks, the neural mechanisms underlying the relationship between VWM deficits remain unclear. The objective of this study was to investigate the structural covariance network connectivity and brain morphology changes that are associated with VWM performance in ADHD children. For this study, we selected 26 ADHD children and 26 healthy control (HC) participants. Participants were instructed to perform a n-back VWM task and their accuracy and response times were subsequently recorded. This research utilized voxel-based morphometry to measure the grey matter (GM) volume, and conducted structural covariance connectivity network analysis to explore the changes of brain in ADHD. Voxel-based morphometry analysis showed that lower GM volume in the right cerebellum lobule VI and the left parahippocampal gryus in ADHD children. Moreover, a positive correlation was found between the GM volume in the right cerebellum lobule VI and the accuracy of 2-back VWM task with verbal, small reward, and delayed feedback (VSD). Structural covariance network analysis found decreased structural connectivity between right cerebellum lobule VI and right precentral gyrus, right postcentral gyrus, left paracentral lobule, right superior parietal gyrus, left hippocampus in ADHD children. The low GM volume and altered structural covariance connectivity in the right cerebellum lobule VI might potentially affect VWM performance in ADHD children. The innovation of this study lies in its more focused discussion on the morphological characteristics and structural covariance connectivity of verbal working memory deficits in ADHD children, and the innovative finding of a positive correlation between gray matter volume in the right cerebellum lobule VI and accuracy in completing the 2-back VWM task with verbal instructions, small reward, and delayed feedback(VSD). This expands upon previous research by elucidating the specific brain structures involved in verbal working memory deficits in ADHD children and highlights the potential importance of the cerebellum in this cognitive process. Overall, these innovative findings advance our understanding of the neural basis of ADHD and may have important implications for the development of targeted interventions for verbal working memory deficits.

Alterations of interhemispheric functional homotopic connectivity and corpus callosum microstructure in bulimia nervosa.

Accumulating evidence indicates maladaptive neural information interactions between different brain regions underlie bulimia nervosa (BN). However, little is known about the alterations in interhemispheric communication of BN, which is facilitated by the corpus callosum (CC), the major commissural fiber connecting the two hemispheres. To shed light on the interhemispheric communications in BN, the present study aims to explore alterations of interhemispheric homotopic functional connectivity and the CC microstructure in BN. Based on magnetic resonance imaging (MRI) data collected from 42 BN patients and 38 healthy controls (HCs), the group differences of voxel-mirrored homotopic connectivity (VMHC) index and CC white matter microstructure were compared. Then brain regions with significant group differences in VMHC were selected as seeds for subsequent functional connectivity (FC) analysis. Seed-based fiber tracking and correlation analysis were used to analyze the relationship between VMHC and CC changes. And correlation analysis was used to reveal the correlation between abnormal imaging variables and the clinical features of BN. Compared with HCs, the BN group showed decreased fractional anisotropy (FA) in middle part of CC (CCMid) and increased VMHC in bilateral orbitofrontal cortex (OFC) and middle temporal gyrus (MTG) [false discovery rate (FDR) correction with a corrected threshold of P<0.05]. Subsequent FC analyses indicated increased FC between left OFC and right OFC, bilateral MTG, left middle occipital gyrus and right precuneus (PCUN); between right OFC and left cerebellum crus II and right PCUN; and between left MTG and right inferior temporal gyrus, right cerebellum lobule VI and right medial superior frontal gyrus (FDR correction with a corrected threshold of P<0.05). The VMHC values of OFC and MTG showed no correlations with FA values of the CCMid and the white fibers between the bilateral OFC and MTG were not through the CCMid. In addition, several regions with abnormal FC had a potential correlation trend with abnormal eating behaviors in BN patients (P<0.05, uncorrected). Aberrant interhemispheric homotopic functional connectivity and CC microstructure were observed in BN, and they may be independent of each other. Regions with aberrant interhemispheric homotopic functional connectivity showed hyperconnectivity with regions related to reward processing, body shape perception, and self-reference.

MRgFUS of the nucleus ventralis intermedius in essential tremor modulates functional connectivity within the classical tremor network and beyond

BackgroundMagnetic resonance-guided focused ultrasound (MRgFUS) of the thalamic ventral intermediate nucleus is an incisionless lesional treatment for essential tremor. ObjectiveTo examine relationships between tremor severity and functional connectivity in patients with essential tremor and to assess long-term changes in the tremor network after sonication of the ventral intermediate nucleus. MethodsTwenty-one patients with essential tremor (70.33 ± 11.32 years) were included in the final analysis and underwent resting state functional magnetic resonance imaging at 3 T before and 6 months after treatment. Tremor severity (Fahn-Tolosa-Marin Clinical Rating Scale) was evaluated and functional connectivity was investigated using independent component analysis. ResultsMRgFUS of the thalamic ventral intermediate nucleus reduced contralateral tremor effectively. Multiple regression analysis revealed exclusively negative correlations between FC and tremor severity, notably in the right cerebellar lobe VI and the left cerebellar lobe VIIIa (cerebellar network), in the left occipital fusiform gyrus (lateral visual network), the anterior division of the left superior temporal gyrus (fronto-parieto-temporal network), and in the posterior division of the left parahippocampal gyrus and the bilateral lingual gyri (default mode network). Six months after treatment, increased functional connectivity was observed in almost all tremor-associated clusters, except the cluster localized in the left cerebellum. ConclusionsOur findings suggest that tremor-related activity in essential tremor extends beyond the classical cerebellar network, additionally involving areas related to visual processing. Functional restoration of network activity after sonication of the ventral intermediate nucleus is observed within the classical tremor network (cerebellum) and notably also in visual processing areas.

Both stronger and weaker cerebro-cerebellar functional connectivity patterns during processing of spoken sentences in autism spectrum disorder.

Cerebellar differences have long been documented in autism spectrum disorder (ASD), yet the extent to which such differences might impact language processing in ASD remains unknown. To investigate this, we recorded brain activity with magnetoencephalography (MEG) while ASD and age-matched typically developing (TD) children passively processed spoken meaningful English and meaningless Jabberwocky sentences. Using a novel source localization approach that allows higher resolution MEG source localization of cerebellar activity, we found that, unlike TD children, ASD children showed no difference between evoked responses to meaningful versus meaningless sentences in right cerebellar lobule VI. ASD children also had atypically weak functional connectivity in the meaningful versus meaningless speech condition between right cerebellar lobule VI and several left-hemisphere sensorimotor and language regions in later time windows. In contrast, ASD children had atypically strong functional connectivity for in the meaningful versus meaningless speech condition between right cerebellar lobule VI and primary auditory cortical areas in an earlier time window. The atypical functional connectivity patterns in ASD correlated with ASD severity and the ability to inhibit involuntary attention. These findings align with a model where cerebro-cerebellar speech processing mechanisms in ASD are impacted by aberrant stimulus-driven attention, which could result from atypical temporal information and predictions of auditory sensory events by right cerebellar lobule VI.

Reduced volume of the left cerebellar lobule VIIb and its increased connectivity within the cerebellum predict more general psychopathology one year later via worse cognitive flexibility in children

Predicting the risk for general psychopathology (the p factor) requires the examination of multiple factors ranging from brain to cognitive skills. While an increasing number of findings have reported the roles of the cerebral cortex and executive functions, it is much less clear whether and how the cerebellum and cognitive flexibility (a core component of executive function) may be associated with the risk for general psychopathology. Based on the data from more than 400 children aged 6–12 in the Children School Functions and Brain Development (CBD) Project, this study examined whether the left cerebellar lobule VIIb and its connectivity within the cerebellum may prospectively predict the risk for general psychopathology one year later and whether cognitive flexibility may mediate such predictions in school-age children. The reduced gray matter volume in the left cerebellar lobule VIIb and the increased connectivity of this region to the left cerebellar lobule VI prospectively predicted the risk for general psychopathology and was partially mediated by worse cognitive flexibility. Deficits in cognitive flexibility may play an important role in linking cerebellar structure and function to the risk for general psychopathology.

Cortico-Cerebellar Monitoring of Speech Sequence Production.

In a functional magnetic resonance imaging study, we examined speech error monitoring in a cortico-cerebellar network for two contrasts: (a) correct trials with high versus low articulatory error probability and (b) overtly committed errors versus correct trials. Engagement of the cognitive cerebellar region Crus I in both contrasts suggests that this region is involved in overarching performance monitoring. The activation of cerebellar motor regions (superior medial cerebellum, lobules VI and VIII) indicates the additional presence of a sensorimotor driven implementation of control. The combined pattern of pre-supplementary motor area (active across contrasts) and anterior cingulate cortex (only active in the contrast involving overt errors) activations suggests sensorimotor driven feedback monitoring in the medial frontal cortex, making use of proprioception and auditory feedback through overt errors. Differential temporal and parietal cortex activation across contrasts indicates involvement beyond sensorimotor driven feedback in line with speech production models that link these regions to auditory target processing and internal modeling-like mechanisms. These results highlight the presence of multiple, possibly hierarchically interdependent, mechanisms that support the optimizing of speech production.

Disability and persistent motor deficits are linked to structural crossed cerebellar diaschisis in chronic stroke.

Brain imaging has significantly contributed to our understanding of the cerebellum being involved in recovery after non-cerebellar stroke. Due to its connections with supratentorial brain networks, acute stroke can alter the function and structure of the contralesional cerebellum, known as crossed cerebellar diaschisis (CCD). Data on the spatially precise distribution of structural CCD and their implications for persistent deficits after stroke are notably limited. In this cross-sectional study, structural MRI and clinical data were analyzed from 32 chronic stroke patients, at least 6 months after the event. We quantified lobule-specific contralesional atrophy, as a surrogate of structural CCD, in patients and healthy controls. Volumetric data were integrated with clinical scores of disability and motor deficits. Diaschisis-outcome models were adjusted for the covariables age, lesion volume, and damage to the corticospinal tract. We found that structural CCD was evident for the whole cerebellum, and particularly for lobules V and VI. Lobule VI diaschisis was significantly correlated with clinical scores, that is, volume reductions in contralesional lobule VI were associated with higher levels of disability and motor deficits. Lobule V and the whole cerebellum did not show similar diaschisis-outcome relationships across the spectrum of the clinical scores. These results provide novel insights into stroke-related cerebellar plasticity and might thereby promote lobule VI as a key area prone to structural CCD and potentially involved in recovery and residual motor functioning.

Sex Differences and Behavioral Associations with Typically Developing Pediatric Regional Cerebellar Gray Matter Volume.

The cerebellum contributes to motor and higher-order control throughout neurodevelopment, with marked growth during childhood. Few studies have investigated differential associations of cerebellar morphometry with function in males and females. The present study examines sex differences in regional cerebellar gray matter volume (GMV) and the moderating effect of sex on the relationship between GMV and motor, cognitive, and emotional functions in a large cohort of typically developing (TD) children. Participants included 371 TD children (123 females, age 8-12 years). A convolutional neural network-based approach was employed for cerebellar parcellation. Volumes were harmonized using ComBat to adjust for hardware-induced variations. Regression analyses examined the effect of sex on GMV and whether sex moderated the relationship between GMV and motor, cognitive, and emotional functions. Males showed larger GMV in right lobules I-V, bilateral lobules VI, crus II/VIIb, and VIII, left lobule X, and vermis regions I-V and VIII-X. Greater motor function correlated with less vermis VI-VII GMV in females. Greater cognitive function correlated with greater left lobule VI GMV in females and less left lobule VI GMV in males. Finally, greater internalizing symptoms correlated with greater bilateral lobule IX GMV in females but less in males. These findings reveal sexually dimorphic patterns of cerebellar structure and associations with motor, cognitive, and emotional functions. Males generally show larger GMV than females. Larger GMV was associated with better cognitive functioning for females and better motor/emotional functioning for males.

Botulinum toxin A decreases neural activity in pain-related brain regions in individuals with chronic ocular pain and photophobia.

To examine the effect of botulinum toxin A (BoNT-A) on neural mechanisms underlying pain and photophobia using functional magnetic resonance imaging (fMRI) in individuals with chronic ocular pain. Twelve subjects with chronic ocular pain and light sensitivity were recruited from the Miami Veterans Affairs eye clinic. Inclusion criteria were: (1) chronic ocular pain; (2) presence of ocular pain over 1 week recall; and (3) presence of photophobia. All individuals underwent an ocular surface examination to capture tear parameters before and 4-6 weeks after BoNT-A injections. Using an event-related fMRI design, subjects were presented with light stimuli during two fMRI scans, once before and 4-6 weeks after BoNT-A injection. Light evoked unpleasantness ratings were reported by subjects after each scan. Whole brain blood oxygen level dependent (BOLD) responses to light stimuli were analyzed. At baseline, all subjects reported unpleasantness with light stimulation (average: 70.8 ± 32.0). Four to six weeks after BoNT-A injection, unpleasantness scores decreased (48.1 ± 33.6), but the change was not significant. On an individual level, 50% of subjects had decreased unpleasantness ratings in response to light stimulation compared to baseline ("responders," n = 6), while 50% had equivalent (n = 3) or increased (n = 3) unpleasantness ("non-responders"). At baseline, several differences were noted between responders and non-responders; responders had higher baseline unpleasantness ratings to light, higher symptoms of depression, and more frequent use of antidepressants and anxiolytics, compared to non-responders. Group analysis at baseline displayed light-evoked BOLD responses in bilateral primary somatosensory (S1), bilateral secondary somatosensory (S2), bilateral anterior insula, paracingulate gyrus, midcingulate cortex (MCC), bilateral frontal pole, bilateral cerebellar hemispheric lobule VI, vermis, bilateral cerebellar crus I and II, and visual cortices. BoNT-A injections significantly decreased light evoked BOLD responses in bilateral S1, S2 cortices, cerebellar hemispheric lobule VI, cerebellar crus I, and left cerebellar crus II. BoNT-A responders displayed activation of the spinal trigeminal nucleus at baseline where non-responders did not. BoNT-A injections modulate light-evoked activation of pain-related brain systems and photophobia symptoms in some individuals with chronic ocular pain. These effects are associated with decreased activation in areas responsible for processing the sensory-discriminative, affective, dimensions, and motor responses to pain.

Cerebellar contributions to a brainwide network for flexible behavior in mice

The cerebellum regulates nonmotor behavior, but the routes of influence are not well characterized. Here we report a necessary role for the posterior cerebellum in guiding a reversal learning task through a network of diencephalic and neocortical structures, and in flexibility of free behavior. After chemogenetic inhibition of lobule VI vermis or hemispheric crus I Purkinje cells, mice could learn a water Y-maze but were impaired in ability to reverse their initial choice. To map targets of perturbation, we imaged c-Fos activation in cleared whole brains using light-sheet microscopy. Reversal learning activated diencephalic and associative neocortical regions. Distinctive subsets of structures were altered by perturbation of lobule VI (including thalamus and habenula) and crus I (including hypothalamus and prelimbic/orbital cortex), and both perturbations influenced anterior cingulate and infralimbic cortex. To identify functional networks, we used correlated variation in c-Fos activation within each group. Lobule VI inactivation weakened within-thalamus correlations, while crus I inactivation divided neocortical activity into sensorimotor and associative subnetworks. In both groups, high-throughput automated analysis of whole-body movement revealed deficiencies in across-day behavioral habituation to an open-field environment. Taken together, these experiments reveal brainwide systems for cerebellar influence that affect multiple flexible responses.

The neural signature of reality-monitoring: A meta-analysis of functional neuroimaging studies.

Distinguishing imagination and thoughts from information we perceived from the environment, a process called reality-monitoring, is important in everyday situations. Although reality monitoring seems to overlap with the concept of self-monitoring, which allows one to distinguish self-generated actions or thoughts from those generated by others, the two concepts remain largely separate cognitive domains and their common brain substrates have received little attention. We investigated the brain regions involved in these two cognitive processes and explored the common brain regions they share. To do this, we conducted two separate coordinate-based meta-analyses of functional magnetic resonance imaging studies assessing the brain regions involved in reality- and self-monitoring. Few brain regions survived threshold-free cluster enhancement family-wise multiple comparison correction (p < .05), likely owing to the small number of studies identified. Using uncorrected statistical thresholds recommended by Signed Differential Mapping with Permutation of Subject Images, the meta-analysis of reality-monitoring studies (k = 9 studies including 172 healthy subjects) revealed clusters in the lobule VI of the cerebellum, the right anterior medial prefrontal cortex and anterior thalamic projections. The meta-analysis of self-monitoring studies (k = 12 studies including 192 healthy subjects) highlighted the involvement of a set of brain regions including the lobule VI of the left cerebellum and fronto-temporo-parietal regions. We showed with a conjunction analysis that the lobule VI of the cerebellum was consistently engaged in both reality- and self-monitoring. The current findings offer new insights into the common brain regions underlying reality-monitoring and self-monitoring, and suggest that the neural signature of the self that may occur during self-production should persist in memories.

Dystonia is Associated with Macro and Microstructural Abnormalities of the Cerebellum: Analysis of Volumetric and Diffusion-Weighted MRI Data in the UK Biobank (P11-11.004)

<h3>Objective:</h3> To determine whether subjects with dystonia in the UK Biobank exhibit MRI-based cerebellar pathology. <h3>Background:</h3> Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal movements and/or postures. Although classically considered a basal-ganglia disorder, neuroimaging studies of dystonia have revealed physiologic, structural, and functional changes in both the (1) pallido-thalamic and (2) cerebello-thalamic networks. Diffusion-weighted-MRI (DWI) analyses of both networks in dystonia have revealed differences in non-specific Diffusion-Tensor metrics such as Fractional Anisotropy. However newer DWI models, such as Neurite Orientation Dispersion and Density Imaging (NODDI), assess more specific and biologically relevant white-matter properties. <h3>Design/Methods:</h3> Using the UK Biobank, 23 subjects with isolated dystonia and diffusion-MRI data were identified, along with 69 control subjects without neurologic (ICD10 G-coded) diagnoses, matched (1:3) on age, sex, imaging site, and medical comorbidities relevant to white-matter integrity (hypertension, hyperlipidemia, and diabetes). Two DTI metrics (mean diffusivity and fractional anisotropy) and three NODDI metrics (intracellular volume fraction, isotropic volume fraction, and orientation dispersion) were extracted from each of four tracts (inferior, middle, and superior cerebellar peduncles, and superior thalamic radiations). Volumetric data consisted of cerebellar (15 regions), basal ganglia (3 regions), and whole-brain grey and white-matter volumes. <h3>Results:</h3> After correcting for multiple-comparisons (40 volumetric and 35 diffusion-related) using the Benjamini-Hochberg procedure (FDR = 0.05), intracellular-volume-fraction (ICVF) of the middle- and superior-cerebellar peduncles was significantly lower in subjects with dystonia, suggesting reduced axon density; volumetric analysis showed significantly reduced volumes of the motor cerebellum (lobules VI and VIII). There were no differences in basal ganglia, cortical, or whole-brain volumes. <h3>Conclusions:</h3> These findings support the hypothesis that abnormalities of cerebellar networks contribute to the pathogenesis of dystonia. <b>Disclosure:</b> Dr. Mason has nothing to disclose. Miss Haddad has nothing to disclose. The institution of Neda Jahanshad has received research support from Biogen Inc.

Cerebellar Structural Abnormality in Autism Spectrum Disorder: A Magnetic Resonance Imaging Study.

This study uses structural magnetic resonance imaging to explore changes in the cerebellar lobules in patients with autism spectrum disorder (ASD) and further analyze the correlation between cerebellar structural changes and clinical symptoms of ASD. A total of 75 patients with ASD and 97 typically developing (TD) subjects from Autism Brain Imaging Data Exchange dataset were recruited. We adopted an advanced automatic cerebellar lobule segmentation technique called CEREbellum Segmentation to segment each cerebellar hemisphere into 12 lobules. Normalized cortical thickness of each lobule was recorded, and group differences in the cortical measures were evaluated. Correlation analysis was also performed between the normalized cortical thickness and the score of Autism Diagnostic Interview-Revised. Results from analysis of variance showed that the normalized cortical thickness of the ASD group differed significantly from that of the TD group; specifically, the ASD group had lower normalized cortical thickness than the TD group. Post-hoc analysis revealed that the differences were more predominant in the left lobule VI, left lobule Crus I and left lobule X, and in the right lobule VI and right lobule Crus I. Lowered normalized cortical thickness in the left lobule Crus I in the ASD patients correlated positively with the abnormality of development evident at or before 36 months subscore. These results suggest abnormal development of cerebellar lobule structures in ASD patients, and such abnormality might significantly influence the pathogenesis of ASD. These findings provide new insights into the neural mechanisms of ASD, which may be clinically relevant to ASD diagnosis.

273 Dystonia is associated with macro and microstructural abnormalities of the cerebellum: A nested case-control study

OBJECTIVES/GOALS: Dystonia is a brain disorder which causes excessive muscle activation, manifesting as abnormal movements. Neuroimaging studies of dystonia have revealed changes in a network involving the cerebellum. We sought out to determine whether subjects with dystonia in the UK Biobank exhibit MRI-based cerebellar pathology. METHODS/STUDY POPULATION: This nested case-control study drew from the UK Biobank, a cohort of &gt;500,000 subjects in the United Kingdom, aged 40-69, enrolled 2006-2010. Eligible subjects must have undergone diffusion-weighted brain MRI. Dystonia cases were ascertained using ICD10 codes. We selected controls without neurologic diagnoses, matched (1:3) on age, sex, imaging site, and medical comorbidities. Mean diffusivity, fractional anisotropy, intracellular and isotropic volume fractions, and orientation dispersion were extracted from four white-matter tracts (inferior, middle, superior cerebellar peduncles; superior thalamic radiations) along with cerebellum, basal ganglia, and whole-brain grey and white-matter volumes. Means were compared using two-tailed t-tests and the Benjamini-Hochberg procedure (FDR = 0.05). RESULTS/ANTICIPATED RESULTS: 23 cases of dystonia and 69 control subjects were selected and ascertained. After correcting for multiple-comparisons (40 volumetric and 35 diffusion-related), intracellular-volume-fraction (ICVF) of the middle- and superior-cerebellar peduncles was significantly lower in subjects with dystonia, suggesting reduced axon density. Volumetric analysis showed significantly reduced volumes of the motor cerebellum (lobules VI and VIII). There were no differences in basal ganglia, cortical, or whole-brain volumes. DISCUSSION/SIGNIFICANCE: These findings support the hypothesis that abnormalities of cerebellar networks contribute to dystonia. In future we will use similar techniques to assess these tracts in subjects with dystonia who are undergoing Deep Brain Stimulation, with the goal of guiding stimulation targeting, and predicting therapeutic outcomes.

Abnormalities of regional spontaneous brain activity in poststroke aphasia: a meta-analysis.

Poststroke aphasia is an acquired language disorder and has been proven to have adverse effects on patients' social skills and quality of life. However, there are some inconsistencies in the neuroimaging studies investigating poststroke aphasia from the perspective of regional alterations. A meta-analysis has been employed to examine the common pattern of abnormal regional spontaneous brain activity in poststroke aphasia in the current study. Specifically, the Anisotropic effect-size version of seed-based d mapping was utilized, and 237 poststroke aphasia patients and 242 healthy controls (HCs) from 12 resting-state functional magnetic resonance imaging studies using amplitude of low-frequency fluctuations (ALFF), fractional ALFF, or regional homogeneity were included. The results showed that compared with HCs, patients with poststroke aphasia demonstrated increased regional spontaneous brain activity in the right insula, right postcentral gyrus, left cerebellar lobule IX, left angular gyrus, right caudate nucleus, left parahippocampal gyrus, and right supplementary motor area, and decreased regional spontaneous brain activity in the left cerebellar lobule VI, left median cingulate and paracingulate gyri, right cerebellar crus I, and left supplementary motor area. The study could provide further evidence for pathophysiological mechanism of poststroke aphasia and help find targets for treatment.

Reduced likelihood of the Poggendorff illusion in cerebellar strokes: a clinical and neuroimaging study.

This study aimed to test our hypothesis that the cerebellum plays an important role in the generation of the optical-geometric illusion known as the Poggendorff illusion, the mechanism of which has been explained by accumulated experience with natural scene geometry. A total of 79 participants, comprising 28 patients with isolated cerebellar stroke, 27 patients with isolated cerebral stroke and 24 healthy controls, performed Poggendorff illusion tasks and 2 different control tasks. We also investigated core brain regions underpinning changes in the experience of the illusion effect using multivariate lesion-symptom mapping. Our results indicate that patients with isolated cerebellar stroke were significantly less likely to experience the Poggendorff illusion effect than patients with isolated cerebral stroke or healthy controls (74.6, 90.5 and 89.8%, respectively; F(2,76) = 6.675, P = 0.002). However, there were no inter-group differences in the control tasks. Lesion-symptom mapping analysis revealed that the brain lesions associated with the reduced frequency of the Poggendorff illusion effect were mainly centred on the right posteromedial cerebellar region, including the right lobules VI, VII, VIII, IX and Crus II. Our findings demonstrated, for the first time, that patients with cerebellar damage were significantly less likely to experience the Poggendorff illusion effect and that right posteromedial cerebellar lesions played an important role in this effect. These results provide new insight into alterations of a geometric illusion effect in patients with cerebellar disorders and pave the way for future clinical use of the illusion task to detect cerebellar abnormalities.