Browsing by Subject "Cerebellum"

Now showing 1 - 10 of 30
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    A magnetic resonance imaging-safe method for the study of human eyeblink conditioning
    (Elsevier, 2013) Kent, Jerillyn S.; Bailey, D. Michael; Vollmer, Jennifer M.; Newman, Sharlene D.; Bolbecker, Amanda R.; O’Donnell, Brian F.; Hetrick, William P.; Psychiatry, School of Medicine
    Eyeblink conditioning (EBC) is a widely used translational probe of cerebellar function in both humans and non-human animals. Decades of animal research have identified the cerebellum as critical for EBC. While there is evidence for the involvement of the cerebellum in human EBC, the neural circuitry of EBC in healthy humans has yet to be fully elucidated. The purpose of this study was to design and validate a highly customisable system for EBC stimulus presentation and response recording using infrared (IR) reflectance suitable for use in magnetic resonance imaging (MRI) environments; in this way, the neural activity of EBC could be investigated using fMRI in humans. Four participants underwent delay EBC and simultaneous fMRI. The results indicate (1) a high signal-to-noise ratio in the IR reflectance data that effectively quantifies the eyeblink morphology and timing and (2) evidence of conditioning in the fMRI environment. The quality of the data, the feasibility of conducting EBC experiments in the fMRI environment, and the customisability of the current system to fit a variety of EBC experimental design parameters are discussed.
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    Altered cerebellar-cortical resting-state functional connectivity in cannabis users
    (Sage, 2021) Schnakenberg Martin, Ashley M.; Kim, Dae-Jin; Newman, Sharlene D.; Cheng, Hu; Hetrick, William P.; Mackie, Ken; O’Donnell, Brian F.; Psychiatry, School of Medicine
    Background: Cannabis use has been associated with abnormalities in cerebellar mediated motor and non-motor (i.e. cognition and personality) phenomena. Since the cerebellum is a region with high cannabinoid type 1 receptor density, these impairments may reflect alterations of signaling between the cerebellum and other brain regions. Aims: We hypothesized that cerebellar-cortical resting-state functional connectivity (rsFC) would be altered in cannabis users, relative to their non-using peers. It was also hypothesized that differences in rsFC would be associated with cannabis use features, such as age of initiation and lifetime use. Methods: Cerebellar-cortical and subcortical rsFCs were computed between 28 cerebellar lobules, defined by a spatially unbiased atlas template of the cerebellum, and individual voxels in the cerebral regions, in 41 regular cannabis users (20 female) and healthy non-using peers (N = 31; 18 female). We also investigated associations between rsFC and cannabis use features (e.g. lifetime cannabis use and age of initiation). Results: Cannabis users demonstrated hyperconnectivity between the anterior cerebellar regions (i.e. lobule I-IV) with the posterior cingulate cortex, and hypoconnectivity between the rest of the cerebellum (i.e. Crus I and II, lobule VIIb, VIIIa, VIIIb, IX, and X) and the cortex. No associations were observed between features of cannabis use and rsFC. Conclusions: Cannabis use was associated with altered patterns of rsFC from the cerebellum to the cerebral cortex which may have a downstream impact on behavior and cognition.
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    Cerebellar Activation Deficits in Schizophrenia During an Eyeblink Conditioning Task
    (Oxford University Press, 2021-08-28) Lundin, Nancy B.; Kim, Dae-Jin; Tullar, Rachel L.; Moussa-Tooks, Alexandra B.; Kent, Jerillyn S.; Newman, Sharlene D.; Purcell, John R.; Bolbecker, Amanda R.; O’Donnell, Brian F.; Hetrick, William P.; Psychiatry, School of Medicine
    The cognitive dysmetria theory of psychotic disorders posits that cerebellar circuit abnormalities give rise to difficulties coordinating motor and cognitive functions. However, brain activation during cerebellar-mediated tasks is understudied in schizophrenia. Accordingly, this study examined whether individuals with schizophrenia have diminished neural activation compared to controls in key regions of the delay eyeblink conditioning (dEBC) cerebellar circuit (eg, lobule VI) and cerebellar regions associated with cognition (eg, Crus I). Participants with schizophrenia-spectrum disorders (n = 31) and healthy controls (n = 43) underwent dEBC during functional magnetic resonance imaging (fMRI). Images were normalized using the Spatially Unbiased Infratentorial Template (SUIT) of the cerebellum and brainstem. Activation contrasts of interest were "early" and "late" stages of paired tone and air puff trials minus unpaired trials. Preliminary whole brain analyses were conducted, followed by cerebellar-specific SUIT and region of interest (ROI) analyses of lobule VI and Crus I. Correlation analyses were conducted between cerebellar activation, neuropsychological test scores, and psychotic symptom scores. In controls, the largest clusters of cerebellar activation peaked in lobule VI during early dEBC and Crus I during late dEBC. The schizophrenia group showed robust cortical activation to unpaired trials but no significant conditioning-related cerebellar activation. Crus I ROI activation during late dEBC was greater in the control than schizophrenia group. Greater Crus I activation correlated with higher working memory scores in the full sample and lower positive psychotic symptom severity in schizophrenia. Findings indicate functional cerebellar abnormalities in schizophrenia which relate to psychotic symptoms, lending direct support to the cognitive dysmetria framework.
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    Cerebellar Structure and Function in Autism Spectrum Disorder
    (Hapres, 2022) Bloomer, Bess F.; Morales, Jaime J.; Bolbecker, Amanda R.; Kim, Dae-Jin; Hetrick, William P.; Psychiatry, School of Medicine
    Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by early-onset repetitive behaviors, restricted interests, sensory and motor difficulties, and impaired social interactions. Converging evidence from neuroimaging, lesion and postmortem studies, and rodent models suggests cerebellar involvement in ASD and points to promising targets for therapeutic interventions for the disorder. This review elucidates understanding of cerebellar mechanisms in ASD by integrating and contextualizing recent structural and functional cerebellar research.
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    Cerebellar tDCS consistency and metabolite changes: A recommendation to decrease barriers to replicability
    (Elsevier, 2020-11) Moussa-Tooks, Alexandra B.; Burroughs, Leah P.; Rejimon, Abinand C.; Cheng, Hu; Hetrick, William P.; Psychiatry, School of Medicine
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    Congenital disorder of glycosylation – one size does not fit all: a parent’s perspective
    (Sage, 2022-08-22) Feinberg, Konstantin; Surgery, School of Medicine
    This article is written by the parent of a child living with PMM2-congenital disorder of glycosylation (abbreviated to PMM2-CDG). It provides a parental perspective of the journey taken from diagnosis to present day and details the effect of off-label treatment with epalrestat.
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    Different Patterns of Regional Purkinje Cell Loss in the Cerebellar Vermis as a Function of the Timing of Prenatal Ethanol Exposure in an Ovine Model
    (Elsevier, 2013) Sawant, Onkar B.; Lunde, Emilie R.; Washburn, Shannon E.; Chen, Wei-Jung A.; Goodlett, Charles R.; Cudd, Timothy A.; Psychology, School of Science
    Studies in rat models of fetal alcohol spectrum disorders have indicated that the cerebellum is particularly vulnerable to ethanol-induced Purkinje cell loss during the third trimester-equivalent, with striking regional differences in vulnerability in which early-maturing regions in the vermis show significantly more loss than the late-maturing regions. The current study tested the hypothesis that the sheep model will show similar regional differences in fetal cerebellar Purkinje cell loss when prenatal binge ethanol exposure is restricted to the prenatal period of brain development equivalent to the third trimester and also compared the pattern of loss to that produced by exposure during the first trimester-equivalent. Pregnant Suffolk sheep were assigned to four groups: first trimester-equivalent saline control group, first trimester-equivalent ethanol group (1.75 g/kg/day), third trimester-equivalent saline control group, and third trimester-equivalent ethanol group (1.75 g/kg/day). Ethanol was administered as an intravenous infusion on 3 consecutive days followed by a 4-day ethanol-free interval, to mimic a weekend binge drinking pattern. Animals from all four groups were sacrificed and fetal brains were harvested on gestation day 133. Fetal cerebellar Purkinje cell counts were performed in an early-maturing region (lobules I-X) and a late-maturing region (lobules VIc-VII) from mid-sagittal sections of the cerebellar vermis. As predicted, the third trimester-equivalent ethanol exposure caused a significant reduction in the fetal cerebellar Purkinje cell volume density and Purkinje cell number in the early-maturing region, but not in the late-maturing region. In contrast, the first trimester-equivalent ethanol exposure resulted in significant reductions in both the early and late-maturing regions. These data confirmed that the previous findings in rat models that third trimester-equivalent prenatal ethanol exposure resulted in regionally-specific Purkinje cell loss in the early-maturing region of the vermis, and further demonstrated that first trimester ethanol exposure caused more generalized fetal cerebellar Purkinje cell loss, independent of the cerebellar vermal region. These findings support the idea that prenatal ethanol exposure in the first trimester interferes with the genesis of Purkinje cells in an unselective manner, whereas exposure during the third trimester selectively kills post-mitotic Purkinje cells in specific vermal regions during a vulnerable period of differentiation and synaptogenesis.
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    Gray matter density loss in essential tremor: a lobule by lobule analysis of the cerebellum
    (BMC, 2017-07-03) Dyke, Jonathan P.; Cameron, Eric; Hernandez, Nora; Dydak, Ulrike; Louis, Elan D.; Radiology and Imaging Sciences, School of Medicine
    BACKGROUND: The pathophysiological basis for essential tremor (ET) remains unclear, although evidence increasingly links it to a disordered and perhaps degenerative cerebellum. Prior imaging studies have treated the cerebellum en bloc. Our hypothesis was that regional differences in cerebellar gray matter (GM) density may better distinguish ET cases from controls. Forty-seven ET cases and 36 control subjects were imaged using magnetic resonance imaging (MRI). The cerebellum was segmented into 34 lobes using a Spatially Unbiased Infra-Tentorial Template (SUIT) atlas within the Statistical Parametric Mapping (SPM) analysis package. Age, gender and Montreal Cognitive Assessment (MoCA) scores were regressed out from the statistical models to isolate group effects. ET cases were further stratified into phenotypically-defined subgroups. The Benjamini-Hochberg False Discovery Rate procedure (BH FDR) (α = 0.1) was used to correct for multiple comparisons. RESULTS: When all ET cases and controls were compared, none of the regions met the BH FDR criteria for significance. When compared with controls, ET cases with head or jaw tremor (n = 27) had significant changes in GM density in nine cerebellar lobules, with a majority in the left cerebellar region, and each meeting the BH FDR criteria. Likewise, ET cases with voice tremor (n = 22) exhibited significant changes in 11 lobules in both left and right regions and the vermis. These analyses, in sum, indicated decreases in GM density in lobules I-IV, V, VI, VII and VIII as well as the vermis. ET cases with severe tremor (n = 20) did not show regions of change that survived the BH FDR procedure when compared to controls. CONCLUSIONS: We showed that ET cases with various forms of cranial tremor differed from controls with respect to cerebellar GM density, with evidence of GM reduction across multiple cerebellar regions. Additional work, using a lobule-by-lobule approach, is needed to confirm these results and precisely map the regional differences in ET cases, subgroups of ET cases, and controls.