Simultaneous mesoscopic Ca²⁺ imaging and fMRI: Neuroimaging spanning spatiotemporal scales

Abstract

To achieve a more comprehensive understanding of brain function requires simultaneous measurement of activity across a range of spatiotemporal scales. However, the appropriate tools to perform such studies are largely unavailable. Here, we present a novel approach for concurrent wide-field optical and functional magnetic resonance imaging (fMRI). By merging these two modalities, we are for the first time able to simultaneously acquire whole-brain blood-oxygen-leveldependent and whole-cortex calcium-sensitive fluorescent measures of brain activity. We describe the developments that allow us to combine these modalities without compromising the fidelity of either technique. In a transgenic murine model, we examine correspondences between activity measured using these modalities and identify unique and complementary features of each. Our approach links cell-type specific optical measurements of neural activity to the most widely used method for assessing human brain function. These data and approach directly establish the neural basis for the macroscopic connectivity patterns observed with fMRI.

Localized semi-nonnegative matrix factorization (LocaNMF) of widefield calcium imaging data

“…LocaNMF differs in the introduction of an atlas to localize the components; this directly enables across-subject comparisons and assigns region labels to the components (while still allowing the spatial footprints of the extracted components to shift slightly from brain to brain), which can be helpful for downstream analyses. Furthermore, recent studies have shown that the spatial and temporal activity recorded from WFCI and fMRI during spontaneous activity show considerable similarities 3,36 . Given these conceptual similarities, we believe there are opportunities to adapt the methods we introduced here to fMRI or other three-dimensional (3D) functional imaging modalities 37,38 , while using a 3D atlas of brain regions to aid in localization of the extracted demixed components.…”

Simultaneous mesoscopic and two-photon imaging of neuronal activity in cortical circuits

“…Finally, these studies have been carried out in the context of a larger collaboration to relate neural activity across a broad range of spatiotemporal scales. We have also established an approach for carrying out mesoscopic calcium imaging simultaneously with functional magnetic resonance imaging (fMRI) 16 . This method will enable us to link the activity of targeted cells to brain-wide activity measured by blood oxygenation level-dependent (BOLD) signaling in mice as well as relating such activity to analogous fMRI studies in humans.…”

“…For the individualized functional parcellation, we applied a multi-graph k-way spectral clustering algorithm, as is described in greater detail elsewhere 16 . For each mouse, the parcellation was determined using widefield-only imaging data collected prior to microprism implantation.…”

“…We also describe the diversity of cortex-wide network membership for individual cells in the primary somatosensory cortex (S1) of awake, juvenile mice. Using a novel functional parcellation for widefield calcium imaging data 16 , we find that activity-based segmentation of cortical networks is more effective than a commonly used anatomically-based approach. Finally, we leverage the cell-type specificity afforded by the use of genetically-encoded indicators to reveal the association of vasoactive intestinal peptide-expressing interneurons (VIP-INs) with distal cortical areas across behavioral state.…”

Localized semi-nonnegative matrix factorization (LocaNMF) of widefield calcium imaging data

“…LocaNMF differs in the introduction of an atlas to localize the components; this directly enables across-subject comparisons and assigns region labels to the components (while still allowing the spatial footprints of the extracted components to shift slightly from brain to brain), which can be helpful for downstream analyses. Furthermore, recent studies have shown that the spatial and temporal activity recorded from WFCI and fMRI during spontaneous activity show considerable similarities [3,36]. Given these conceptual similarities, we believe there are opportunities to adapt the methods we introduced here to fMRI or other three-dimensional (3D) functional…”