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Effective Connectivity Measured Using Optogenetically Evoked Hemodynamic Signals Exhibits Topography Distinct from Resting State Functional Connectivity in the Mouse.

ABSTRACT: Brain connectomics has expanded from histological assessment of axonal projection connectivity (APC) to encompass resting state functional connectivity (RS-FC). RS-FC analyses are efficient for whole-brain mapping, but attempts to explain aspects of RS-FC (e.g., interhemispheric RS-FC) based on APC have been only partially successful. Neuroimaging with hemoglobin alone lacks specificity for determining how activity in a population of cells contributes to RS-FC. Wide-field mapping of optogenetically defined connectivity could provide insights into the brain's structure-function relationship. We combined optogenetics with optical intrinsic signal imaging to create an efficient, optogenetic effective connectivity (Opto-EC) mapping assay. We examined EC patterns of excitatory neurons in awake, Thy1-ChR2 transgenic mice. These Thy1-based EC (Thy1-EC) patterns were evaluated against RS-FC over the cortex. Compared to RS-FC, Thy1-EC exhibited increased spatial specificity, reduced interhemispheric connectivity in regions with strong RS-FC, and appreciable connection strength asymmetry. Comparing the topography of Thy1-EC and RS-FC patterns to maps of APC revealed that Thy1-EC more closely resembled APC than did RS-FC. The more general method of Opto-EC mapping with hemoglobin can be determined for 100 sites in single animals in under an hour, and is amenable to other neuroimaging modalities. Opto-EC mapping represents a powerful strategy for examining evolving connectivity-related circuit plasticity.

SUBMITTER: Bauer AQ

PROVIDER: S-EPMC6057523 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Effective Connectivity Measured Using Optogenetically Evoked Hemodynamic Signals Exhibits Topography Distinct from Resting State Functional Connectivity in the Mouse.

Bauer Adam Q AQ Kraft Andrew W AW Baxter Grant A GA Wright Patrick W PW Reisman Matthew D MD Bice Annie R AR Park Jasmine J JJ Bruchas Michael R MR Snyder Abraham Z AZ Lee Jin-Moo JM Culver Joseph P JP

Cerebral cortex (New York, N.Y. : 1991) 20180101 1

Brain connectomics has expanded from histological assessment of axonal projection connectivity (APC) to encompass resting state functional connectivity (RS-FC). RS-FC analyses are efficient for whole-brain mapping, but attempts to explain aspects of RS-FC (e.g., interhemispheric RS-FC) based on APC have been only partially successful. Neuroimaging with hemoglobin alone lacks specificity for determining how activity in a population of cells contributes to RS-FC. Wide-field mapping of optogenetica ...[more]

PMID: 29136125

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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.

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Dataset Information

Effective Connectivity Measured Using Optogenetically Evoked Hemodynamic Signals Exhibits Topography Distinct from Resting State Functional Connectivity in the Mouse.

Publications

Effective Connectivity Measured Using Optogenetically Evoked Hemodynamic Signals Exhibits Topography Distinct from Resting State Functional Connectivity in the Mouse.

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