Mortality and Causes of Death among Older Inpatients with Non-Severe Coronavirus Disease 2019 during the Omicron Era: A Retrospective Cohort Study in a Community Hospital.

Spontaneous fluctuations in hemodynamic signals, particularly at frequencies around 0.1 Hz, are commonly observed during so-called resting state imaging experiments. This term typically refers to a condition where a subject lies in the functional magnetic resonance imaging (fMRI) scanner without performing an explicit task or being exposed to a specific stimulus. Studies using fMRI and intrinsic optical imaging have revealed that these low-frequency fluctuations are present in animals and humans and they are strongly synchronized within similar networks and across distant, functionally connected regions. This phenomenon, known as “functional connectivity,” provides valuable insights into the brain’s functional organization and underscore the utility of hemodynamic-based imaging techniques for studying brain function. These hemodynamic low-frequency fluctuations are associated with neural activity in areas with known anatomical connections. To capture activity over slower hemodynamic timescales, which typically lag neural activity by a few seconds, researchers have used changes in band-limited power (BLP) derived from LFP measurements. These BLP changes not only reflect large-amplitude fluctuations over extended time scales but also show synchronization across distant cortical regions, linking local neuronal activity to broader network dynamics. In monkeys, concurrent LFP-fMRI recordings have revealed that spontaneous BOLD fluctuations strongly correlate with BLP in the gamma (30–100 Hz) frequency range. Similarly, in mice, low-frequency arterial oscillations have been found to phase-lock with slow variations in gamma BLP. Together, these findings highlight a robust relationship between neural gamma activity and spontaneous hemodynamic fluctuations, though the mechanisms underlying this link remain unclear. Gamma activity in the cortex is thought to have a strong contribution from parvalbumin (PV) interneuron activity. These interneurons provide strong inhibitory input to local populations of asynchronously firing principal cells, effectively suppressing their activity and generating synchronized gamma rhythms. Optogenetic studies have demonstrated the critical role of PV interneurons in gamma oscillation generation, where selective activation of PV cells induced gamma rhythms and their inhibition attenuated them significantly. Given the strong correlation between gamma BLP and spontaneous hemodynamic fluctuations, it is plausible that PV interneurons not only drive gamma activity but also play a key role in regulating resting-state cerebral blood flow (CBF) dynamics.