Resting‐state functional connectivity of the rat brain

Abstract

Regional-specific average time courses of spontaneous fluctuations in blood oxygen level dependent (BOLD) MRI contrast at 9.4T in lightly anesthetized resting rat brain are formed, and correlation coefficients between time course pairs are interpreted as measures of connectivity. A hierarchy of regional pairwise correlation coefficients (RPCCs) is observed, with the highest values found in the thalamus and cortex, both intra-and interhemisphere, and lower values between the cortex and thalamus. Independent sensory networks are distinguished by two methods: data driven, where task activation defines regions of interest (ROI), and hypothesis driven, where regions are defined by the rat histological atlas. Success in these studies is attributed in part to the use of medetomidine hydrochloride (Domitor) for anesthesia. Functional connectivity in the resting human brain using blood oxygen level dependent (BOLD) contrast is revealed by analysis of a series of MRI echo-planar images acquired over a period of several minutes with the subject at rest (1). In the present work, functional connectivity experiments are extended from human brain to rat brain and our central hypothesis is that the underlying physiology is conserved across all mammalian species.A reference time course obtained from a reference voxel (or, alternatively, an average over a cluster of voxel time courses in a region of interest [ROI]) is formed. Cross correlation of the reference time course with all voxel time courses in the slice provides a functional connectivity map. A strategy is required for selection of the reference time course, and performance of a task is commonly used to define ROIs in resting brain that can be used to form reference time courses.We have discovered that electrical stimulation using an implanted electrode on the radial nerve of the brachial plexus of a rat (2) results in activation of a network of sensorimotor brain regions, each of which is a suitable candidate for formation of a reference time course when analyzing resting-state data. Experiments not only in the sensorimotor system but also in the visual system provide further support for our central hypothesis. Functional connectivity was studied using reference waveforms obtained from areas that were found to be activated by light incident on the retina that was turned on and off in a block-trial functional MRI (fMRI) experiment.Anatomic images acquired in this experiment are of high quality, and it is possible to define anatomic regions purely by reference to the rat histological atlas (3). One can develop a reference waveform from each of these regions and test a specific hypothesis that functional connectivity to a second region is consistent with a known connectivity. We report here success in this hypothesis-driven approach to analysis of resting-state data. A total of 22 sensorimotor regions were identified, and connectivities between each of these regions and the other 21 regions were determined.Most functional connectivity studies have been in the awake human b...

Low-frequency hippocampal–cortical activity drives brain-wide resting-state functional MRI connectivity

“…Given the differences in anatomical and functional organization (7,8), the vHP may predominantly affect nonsensory-related regions through unknown mechanisms. Interhemispheric or homotopic rsfMRI connectivity networks are conserved across species (17,(68)(69)(70) and under distinct brain states (e.g., anesthesia, sleep, and wake) (71,72) and consistent among different human subjects (73). We (14,36) and others (16,17,68) have reliably measured interhemispheric rsfMRI connectivity in sensory cortices of rodents under light isoflurane (∼1.0%).…”

Dynamic Properties of Functional Connectivity in the Rodent

“…The sensory and motor areas are strongly connected across hemispheres via the corpus callosum and exhibit high BOLD correlation when typical ''steady-state'' analysis methods are used (Pawela et al, 2008;Williams et al, 2010;Zhao et al, 2008). In contrast, the left and right caudate putamen (CP) are only indirectly connected but still exhibit BOLD-based functional connectivity (Williams et al, 2010;Zhao et al, 2008).…”

Neural basis of global resting-state fMRI activity

“…These fluctuations typically exhibit their highest intervoxel coherence at low temporal frequencies (<0.1 Hz) and can be observed during alertness (12, 13), sleep (14, 15), light sedation (16), and general anesthesia (17,18). Experiments are beginning to address the spatiotemporal characteristics of these spontaneous fluctuations in animal models (19)(20)(21), with initial studies in macaques suggesting a human-like pattern of functional connectivity (7,22).In humans, spontaneous activity is typically investigated in the so-called resting state, a term that is only loosely defined and which typically amounts to a subject lying in the scanner without an explicit stimulus or task. Under these conditions, analysis of spatiotemporal coherence of fMRI activity reveals several distinct domains of correlated activity in the brain, sometimes described as networks (23)(24)(25).…”

“…These fluctuations typically exhibit their highest intervoxel coherence at low temporal frequencies (<0.1 Hz) and can be observed during alertness (12, 13), sleep (14, 15), light sedation (16), and general anesthesia (17,18). Experiments are beginning to address the spatiotemporal characteristics of these spontaneous fluctuations in animal models (19)(20)(21), with initial studies in macaques suggesting a human-like pattern of functional connectivity (7,22).…”