Mesoscale Functional Reorganization of Cortical Networks After Cortical Spreading Depression
Abstract
Background: Resting-state functional imaging is increasingly used to understand how cortical networks modulate and respond to pain. Awake imaging with a minimally invasive approach is key to observe the natural state of the brain. As migraine with aura, a common headache disorder, can be experimentally modeled by cortical spreading depressions (CSD) in rodents, it is essential to understand the impact of CSD on functional connectivity and network topology to find imaging cues of trigeminovascular activation and headache.
Methods: We used awake widefield intrinsic optical-signal imaging (IOSI) on optically cleared windows to non-invasively characterize the impact of CSDs on bihemispheric resting-state static and dynamic functional connectivity patterns and network topology. A subset of mice was chronically treated with amitriptyline to examine the effect of susceptibility to CSD on connectivity. After baseline imaging, CSD was triggered optogenetically and confirmed by laser speckle contrast imaging. A group of mice received intraperitoneal naproxen after CSD to suppress headache. IOSI was repeated at 30 minutes, 60 minutes, 4 hours, and 24 hours after CSD. The mouse grimace scale was scored at each time point for behavioral headache documentation.
Results: We observed time-dependent changes in resting-state functional connectivity that were reversed by naproxen. Amitriptyline, a prophylactic migraine medication, decreased susceptibility to CSD and modified resting-state…
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