Network analysis of mesoscale optical recordings to assess regional, functional connectivity

Lim, Diana H.; LeDue, Jeffrey; Murphy, Timothy H.

doi:10.1117/1.nph.2.4.041405

Cited by 17 publications

(15 citation statements)

References 51 publications

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“…5 B ). Parietal cortex is widely regarded as a hub for integrating multisensory information in the mouse ( Kolb and Walkey 1987 ; Lim et al 2012 , 2015 ). It has been reported that sensory stimulation and photostimulation both induce propagated activity that terminates at a common sink in parietal association areas ( Mohajerani et al 2013 ).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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“…Cortical parcellation based on the spectral and spatial decomposition of the calcium signal resulted in 12 functional modules. 27,28…”

Section: Methodsmentioning

confidence: 99%

Longitudinal monitoring of mesoscopic cortical activity in a mouse model of microinfarcts reveals dissociations with behavioral and motor function

Balbi

Vanni

Vega

et al. 2018

J Cereb Blood Flow Metab

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Small vessel disease is characterized by sporadic obstruction of small vessels leading to neuronal cell death. These microinfarcts often escape detection by conventional magnetic resonance imaging and are identified only upon postmortem examination. Our work explores a brain-wide microinfarct model in awake head-fixed mice, where occlusions of small penetrating arterioles are reproduced by endovascular injection of fluorescent microspheres. Mesoscopic functional connectivity was mapped longitudinally in awake GCaMP6 mice using genetically encoded calcium indicators for transcranial wide-field calcium imaging. Microsphere occlusions were quantified and changes in cerebral blood flow were measured with laser speckle imaging. The neurodeficit score in microinfarct mice was significantly higher than in sham, indicating impairment in motor function. The novel object recognition test showed a reduction in the discrimination index in microinfarct mice compared to sham. Graph-theoretic analysis of functional connectivity did not reveal significant differences in functional connectivity between sham and microinfarct mice. While behavioral tasks revealed impairments following microinfarct induction, the absence of measurable functional alterations in cortical activity has a less straightforward interpretation. The behavioral alterations produced by this model are consistent with alterations observed in human patients suffering from microinfarcts and support the validity of microsphere injection as a microinfarct model.

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“…The temporal resolution is at the level of millisecond that is on par with electrophysiological recordings 19 – 23 The spatial resolution reaches 25 to 65 μm per pixel, and the size of imaged brain area is sufficient to record the signs of electrical activity over much of the dorsal mouse cortex, 24 1 cm2 area monkey’s cortex, 25 or 0.3 cm2 area over the cat cortex 26 . With these characteristics, voltage-sensitive dye imaging (VSDI) is an excellent technique to study neuronal dynamics over large cortical areas.…”

Section: Introductionmentioning

confidence: 99%

High-performance, inexpensive setup for simultaneous multisite recording of electrophysiological signals and mesoscale voltage imaging in the mouse cortex

et al. 2018

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Simultaneous recording of optical and electrophysiological signals from multiple cortical areas may provide crucial information to expand our understanding of cortical function. However, the insertion of multiple electrodes into the brain may compromise optical imaging by both restricting the field of view and interfering with the approaches used to stabilize the specimen. Existing methods that combine electrophysiological recording and optical imaging implement either multiple surface electrodes, silicon probes, or a single electrode for deeper recordings. To address such limitation, we built a microelectrode array (hyperdrive, patent US5928143 A) compatible with wide-field imaging that allows insertion of up to 12 probes into a large brain area (8 mm diameter). The hyperdrive is comprised of a circle of individual microdrives where probes are positioned at an angle leaving a large brain area unobstructed for wide-field imaging. Multiple tetrodes and voltage-sensitive dye imaging were used for acute simultaneous registration of spontaneous and evoked cortical activity in anesthetized mice. The electrophysiological signals were used to extract local field potential (LFP) traces, multiunit, and single-unit spiking activity. To demonstrate our approach, we compared LFP and VSD signals over multiple regions of the cortex and analyzed the relationship between single-unit and global cortical population activities. The study of the interactions between cortical activity at local and global scales, such as the one presented in this work, can help to expand our knowledge of brain function.

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Network analysis of mesoscale optical recordings to assess regional, functional connectivity

Cited by 17 publications

References 51 publications

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

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

Longitudinal monitoring of mesoscopic cortical activity in a mouse model of microinfarcts reveals dissociations with behavioral and motor function

High-performance, inexpensive setup for simultaneous multisite recording of electrophysiological signals and mesoscale voltage imaging in the mouse cortex

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