Vascular physiology drives functional brain networks

Abstract

<jats:title>ABSTRACT</jats:title><jats:p>We present the first evidence for vascular regulation driving fMRI signals in specific functional brain networks. Using concurrent neuronal and vascular stimuli, we collected 30 BOLD fMRI datasets in 10 healthy individuals: a working memory task, flashing checkerboard stimulus, and CO<jats:sub>2</jats:sub> inhalation challenge were delivered in concurrent but orthogonal paradigms. The resulting imaging data were averaged together and decomposed using independent component analysis, and three “neuronal networks” were identified as demonstrating maximum temporal correlation with the neuronal stimulus paradigms: Default Mode Network, Task Positive Network, and Visual Network. For each of these, we observed a second network component with high spatial overlap. Using dual regression in the original 30 datasets, we extracted the time-series associated with these network pairs and calculated the percent of variance explained by the neuronal or vascular stimuli using a normalized R<jats:sup>2</jats:sup> parameter. In each pairing, one network was dominated by the appropriate neuronal stimulus, and the other was dominated by the vascular stimulus as represented by the end-tidal CO<jats:sub>2</jats:sub> time-series recorded in each scan. We acquired a second dataset in 8 of the original participants, where no CO<jats:sub>2</jats:sub> challenge was delivered and CO<jats:sub>2</jats:sub> levels fluctuated naturally with breathing variations. Although splitting of functional networks was not robust in these data, performing dual regression with the network maps from the original analysis in this new dataset successfully replicated our observations. Thus, in addition to responding to localized metabolic changes, the brain’s vasculature may be regulated in a coordinated manner that mimics (and potentially supports) specific functional brain networks. Multi-modal imaging and advances in fMRI acquisition and analysis could facilitate further study of the dual nature of functional brain networks. It will be critical to understand network-specific vascular function, and the behavior of a coupled <jats:italic>vascular-neural network</jats:italic>, in future studies of brain pathology.</jats:p>

Physiological and head motion signatures in static and time-varying functional connectivity and their subject discriminability

“…However, in principle, nuisance fluctuations could give rise to similar spatial patterns as neurally-driven fluctuations. A recent study by (Bright et al, 2018) provided evidence that physiological fluctuations (end-tidal CO 2 ) give rise to networks that spatially resemble neurally-driven networks linked to working memory and visual stimuli. The authors suggested that this phenomenon may be due to the vasculature adapting to the neural network architecture, as vascular and neuronal growth processes evolve concurrently during development (Quaegebeur et al, 2011).…”

Physiological and motion signatures in static and time-varying functional connectivity and their subject identifiability

“…However, in principle, nuisance fluctuations could give rise to similar spatial patterns as neurally-driven fluctuations. A recent study by (Bright et al, 2018) provided evidence that physiological fluctuations (end-tidal CO 2 ) give rise to networks that spatially resemble neurallydriven networks linked to working memory and visual stimuli. The authors suggested that this phenomenon may be due to the vasculature adapting to the neural network architecture, as vascular and neuronal growth processes evolve concurrently during development (Quaegebeur et al, 2011).…”

Resting-state “Physiological Networks”

“…Bright MG, Whittaker JR, Driver ID, Murphy K. 2018. Vascular physiology drives functional brain networks.…”