Dynamic effects of cholinergic blockade upon cerebral blood flow autoregulation in healthy adults

Background: Cerebral flow autoregulation (CFA) is a homeostatic mechanism critical for survival. The autonomic nervous system (ANS) plays a key role in maintaining proper CFA function. More quantitative studies of how the ANS influences CFA are desirable. Objective: To discover and quantify the dynamic effects of cholinergic blockade upon CFA in response to changes of arterial blood pressure and blood CO2 tension in healthy adults. Methods: We analyzed time-series data of spontaneous beat-to-beat mean arterial blood pressure (ABP) and cerebral blood flow velocity in the middle cerebral arteries (CFV), as well as breath-to-breath end-tidal CO2 (CO2), collected in 9 adults before and after cholinergic blockade, in order to obtain subject-specific predictive input-output models of the dynamic effects of changes in ABP and CO2 (inputs) upon CFV (output). These models are defined in convolutional form using "kernel" functions (or, equivalently, Transfer Functions in the frequency domain) that are estimated via the robust method of Laguerre expansions. Results: Cholinergic blockade caused statistically significant changes in the obtained kernel estimates (and the corresponding Transfer Functions) that define the linear dynamics of the ABP-to-CFV and CO2-to-CFV causal relations. The kernel changes due to cholinergic blockade reflect the effects of the cholinergic mechanism and exhibited, in the frequency domain, resonant peaks at 0.22 Hz and 0.06 Hz for the ABP-to-CFV and CO2-to-CFV dynamics, respectively. Conclusion: Quantitative estimates of the dynamics of the cholinergic component in CFA are found as average changes of the ABP-to-CFV and CO2-to-CFV kernels, and corresponding Transfer Functions, before and after cholinergic blockade.