Multimodal measures of spontaneous brain activity reveals both common and divergent patterns of cortical functional organization

Abstract

Understanding the organization of large-scale brain networks remains a central problem in neuroscience. Work in both humans and rodents shows that the brain can be decomposed in terms of several networks (e.g., "default network"). Whereas the bulk of what we know is based on the blood-oxygenation level-dependent (BOLD) signal, the relationship between BOLD and neuronal activity is complex, which poses several challenges to interpreting networks revealed by this technique. To resolve these challenges, here we employed wide-field Ca2+imaging simultaneously recorded with fMRI-BOLD in a highly-sampled group of GCaMP6f-expressing mice. This allowed us to determine the relationship between networks discovered by BOLD and Ca2+signals both at the group level and in individual animals. Network partition used a mixed-membership stochastic blockmodel algorithm, which allows networks to be overlapping, such that a brain region may be assigned to multiple networks with varying strengths. Here, we tested the hypothesis that functional networks of the mouse brain are organized in an overlapping manner for both BOLD and Ca2+data. Our findings demonstrate that BOLD large-scale networks can be detected via Ca2+signals. In addition: (1) Overlapping networks were reliably estimated at the group level via random-effects statistical analysis. (2) Functional organization was generally similar for BOLD and Ca2+; e.g., with seven networks, cosine similarity was very high in five instances (values between 0.82-0.90; max possible value of 1), moderate in one case (0.73) and different in one case (0.26). (3) We discovered overlapping network organization in both data modalities, which was quantified in multiple ways; e.g., the proportion of regions that belonged to multiple networks was 75\% for BOLD and 60\% for Ca2+. (4) The large-scale functional organization of the mouse cortex as determined by Ca2+signals is considerably more similar to that with BOLD when both signal modalities are considered in the low temporal frequency range (0.01 to 0.5 Hz). (5) Although many similarities were observed between data modalities, finer characterization uncovered key differences related to functional hubs believed to play important roles in the integration and/or segregation of signals. In particular, the spatial distribution of membership diversity (i.e., the extent to which a region affiliates with multiple networks), differed for the two types of signals. In conclusion, Ca2+mesoscale signals revealed that the mouse cortex is functionally organized in terms of large-scale networks in a manner that reflects many of the properties observed using BOLD. Despite many similarities, important differences were also uncovered, suggesting that mesoscale Ca2+has a strong potential to uncover additional properties of the large-scale organization of the mouse brain.

Disparity in temporal and spatial relationships between resting-state electrophysiological and fMRI signals

“…al. revealed notable differences in functional connectivity strength measured by fMRI and calcium imaging, despite an overlapping spatial pattern of cortical networks identified by both modalities (Vafaii et al, 2024). These findings collectively suggest that while the temporal correlation between electrophysiology and rsfMRI signals is significant, the effect size of this correlation might be small.…”

“…Moreover, voltagesensitive dye imaging in mice has unveiled comparable sensory-evoked and hemisphere-wide activity motifs represented in spontaneous activity in both lightly anesthetized and awake states (Mohajerani et al, 2013). Furthermore, in a more recent study by Vafaii and colleagues, overlapping cortical networks were identified using both fMRI and calcium imaging modalities, suggesting that networks observable in fMRI studies exhibit corresponding neural activity spatial patterns (Vafaii et al, 2024). These results align well with the notion that RSN spatial patterns are highly consistent with known functional systems and activation patterns observed in task-based studies (Biswal et al, 1995;Glasser et al, 2016;Hampson et al, 2002;Lowe et al, 1998;Smith et al, 2009), as well as patterns of structural networks (Andrews-Hanna et al, 2010;Greicius et al, 2009;Lowe et al, 2008).…”

Aging-Dependent Loss of Connectivity in Alzheimer’s Model Mice with Rescue by mGluR5 Modulator

“…Prior to imaging, all animals undergo a minimally invasive surgical procedure [31][32][33] , where a head-plate is affixed to the skull a month prior to any imaging (timeline, Fig. 1).…”

“…Thirty-minutes of resting-state BOLD-fMRI data, together with structural images for data registration, are collected at each timepoint under low-dose isoflurane (0.5-0.75%). Data are processed and registered to a common space 31,33,34 . A small fraction of the fMRI data (9%) are excluded based on quality control standards 16,[34][35][36] .…”

“…In the first experiment, N=27 animals undergo transverse sinus injections on postnatal day zero (P0) to induce whole-brain fluorescence. These mice then undergo head-post surgery at 3M and multimodal imaging at 4, 6, and 9M where wide-field calcium (WF-Ca 2+ ) and fMRI data are collected simultaneously 33,74 . The WF-Ca 2+ imaging data are the subject matter of a separate publication.…”