Altered Phase Interactions between Spontaneous Blood Pressure and Flow Fluctuations in Type 2 Diabetes Mellitus: Nonlinear Assessment of Cerebral Autoregulation.

Cerebral autoregulation (CA) is an important mechanism that involves dilation and constriction in arterioles to maintain relatively s cerebral blood flow in response to changes of systemic blood pressure. Traditional assessments of CA focus on the changes of cerebral blood flow velocity in response to large blood pressure fluctuations induced by interventions. This approach is not feasible for patients with impaired autoregulation or cardiovascular regulation. Here we propose a newly developed technique-the multimodal pressure-flow (MMPF) analysis, which assesses CA by quantifying nonlinear phase interactions between spontaneous oscillations in blood pressure and flow velocity during resting conditions. We show that CA in healthy subjects can be characterized by specific phase shifts between spontaneous blood pressure and flow velocity oscillations, and the phase shifts are significantly reduced in diabetic subjects. Smaller phase shifts between oscillations in the two variables indicate more passive dependence of blood flow velocity on blood pressure, thus suggesting impaired cerebral autoregulation. Moreover, the reduction of the phase shifts in diabetes is observed not only in previously-recognized effective region of CA (<0.1Hz), but also over the higher frequency range from ~0.1 to 0.4Hz. These findings indicate that Type 2 diabetes alters cerebral blood flow regulation over a wide frequency range and that this alteration can be reliably assessed from spontaneous oscillations in blood pressure and blood flow velocity during resting conditions. We also show that the MMPF method has better performance than traditional approaches based on Fourier transform, and is more sui for the quantification of nonlinear phase interactions between nonstationary biological signals such as blood pressure and blood flow.