Dataset Information

Mapping BOLD Activation by Pharmacologically Evoked Tremor in Swine.

ABSTRACT: Harmaline-induced tremor is one of the most commonly utilized disease models for essential tremor (ET). However, the underlying neural networks involved in harmaline-induced tremor and the degree to which these are a representative model of the pathophysiologic mechanism of ET are incompletely understood. In this study, we evaluated the functional brain network effects induced by systemic injection of harmaline using pharmacological functional magnetic resonance imaging (ph-fMRI) in the swine model. With harmaline administration, we observed significant activation changes in cerebellum, thalamus, and inferior olivary nucleus (ION). In addition, inter-regional correlations in activity between cerebellum and deep cerebellar nuclei and between cerebellum and thalamus were significantly enhanced. These harmaline-induced effects gradually decreased with repeated administration of drug, replicating the previously demonstrated 'tolerance' effect. This study demonstrates that harmaline-induced tremor is associated with activity changes in brain regions previously implicated in humans with ET. Thus, harmaline-induction of tremor in the swine may be a useful model to explore the neurological effects of novel therapeutic agents and/or neuromodulation techniques for ET.

SUBMITTER: Lee J

PROVIDER: S-EPMC6759958 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Mapping BOLD Activation by Pharmacologically Evoked Tremor in Swine.

Lee Jeyeon J Jo Hang Joon HJ Kim Inyong I Lee Jihyun J Min Hoon-Ki HK In Myung-Ho MH Knight Emily J EJ Chang Su-Youne SY

Frontiers in neuroscience 20190918

Harmaline-induced tremor is one of the most commonly utilized disease models for essential tremor (ET). However, the underlying neural networks involved in harmaline-induced tremor and the degree to which these are a representative model of the pathophysiologic mechanism of ET are incompletely understood. In this study, we evaluated the functional brain network effects induced by systemic injection of harmaline using pharmacological functional magnetic resonance imaging (ph-fMRI) in the swine mo ...[more]

PMID: 31619955

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Project description:The exact neurophysiological basis of chronic tinnitus, which affects 10-15% of the population, remains unknown and is controversial at many levels. It is an open question whether phantom sound perception results from increased central neural gain or not, a crucial question for any future therapeutic intervention strategies for tinnitus. We performed a comprehensive study of mild hearing-impaired participants with and without tinnitus, excluding participants with co-occurrences of hyperacusis. A right-hemisphere correlation between tinnitus loudness and auditory perceptual difficulty was observed in the tinnitus group, independent of differences in hearing thresholds. This correlation was linked to reduced and delayed sound-induced suprathreshold auditory brain responses (ABR wave V) in the tinnitus group, suggesting subsided rather than exaggerated central neural responsiveness. When anatomically predefined auditory regions of interest were analysed for altered sound-evoked BOLD fMRI activity, it became evident that subcortical and cortical auditory regions and regions involved in sound detection (posterior insula, hippocampus), responded with reduced BOLD activity in the tinnitus group, emphasizing reduced, rather than increased, central neural gain. Regarding previous findings of evoked BOLD activity being linked to positive connectivities at rest, we additionally analysed r-fcMRI responses in anatomically predefined auditory regions and regions associated with sound detection. A profound reduction in positive interhemispheric connections of homologous auditory brain regions and a decline in the positive connectivities between lower auditory brainstem regions and regions involved in sound detection (hippocampus, posterior insula) were observed in the tinnitus group. The finding went hand-in-hand with the emotional (amygdala, anterior insula) and temporofrontal/stress-regulating regions (prefrontal cortex, inferior frontal gyrus) that were no longer positively connected with auditory cortex regions in the tinnitus group but were instead positively connected to lower-level auditory brainstem regions. Delayed sound processing, reduced sound-evoked BOLD fMRI activity and altered r-fcMRI in the auditory midbrain correlated in the tinnitus group and showed right hemisphere dominance as did tinnitus loudness and perceptual difficulty. The findings suggest that reduced central neural gain in the auditory stream may lead to phantom perception through a failure to energize attentional/stress-regulating networks for contextualization of auditory-specific information. Reduced auditory-specific information flow in tinnitus has until now escaped detection in humans, as low-level auditory brain regions were previously omitted from neuroimaging studies.Trial registrationGerman Clinical Trials Register DRKS0006332.

Project description:Investigations of between-person variability are enjoying a recent resurgence in functional magnetic resonance imaging (fMRI) research. Several recent studies have found persistent between-person differences in blood-oxygenated-level dependent (BOLD) activation patterns and resting-state functional connectivity. Conflicting findings have been reported regarding the extent to which (a) between-person or (b) within-person cognitive state differences explain differences in BOLD activation patterns. These discrepancies may arise due to statistical analysis choices, parcellation resolution, and limited sampling of task-fMRI datasets. We attempt to address these issues in a large-scale analysis of several task-fMRI paradigms. Using a novel application of multivariate distance matrix regression, we examine between-person and task-condition variability estimates across varying levels of "resolution", from a coarse region-of-interest level to the vertex-level, and across different distance metrics. These analyses revealed that under most circumstances, differences in task conditions explained a greater amount of variance in activation map differences than between-person differences. However, this finding was reversed when comparing activation maps at a "high-resolution" vertex level. More generally, we observed that when moving from "low" to "high" resolutions, the variance explained by between-person differences increased while variance explained by task conditions decreased. We further analyzed the relationships among subject-level activation maps across all task-conditions using an unsupervised clustering approach and identified a superordinate task structure. This structure went beyond conventional task labels and highlighted those experimental manipulations across task conditions that produce contrasting versus similar whole-brain activation patterns. Overall, these analyses suggest that the question of the subject- versus task-effects on BOLD activation patterns is nontrivial, and depends on the comparison "resolution," choice of distance metric, and the coding of task-conditions.

Dataset Information

Mapping BOLD Activation by Pharmacologically Evoked Tremor in Swine.

Publications

Mapping BOLD Activation by Pharmacologically Evoked Tremor in Swine.

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