Altered phase interactions between spontaneous blood pressure and flow fluctuations in type 2 diabetes mellitus: Nonlinear assessment of cerebral autoregulation

Abstract

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.

Neurovascular Regulation in the Ischemic Brain

“…Similarly, patients with chronic diabetes have impaired cerebral autoregulatory capacity. Long-term diabetics have been shown to have impaired autoregulation in response to increases and decreases in blood pressure, with cerebral blood flow passively following pressure (12,36). Whereas the impairment of cerebral autoregulation in diabetic patients has been attributed to both microvascular disease and cardiovascular autonomic neuropathy, autoregulatory dysfunction has been demonstrated in type 2 diabetes patients without clinical indications of microvascular disease and may suggest that autoregulatory dysfunction is an early sign of developing microvascular damage (47).…”

Spurious cross-frequency amplitude–amplitude coupling in nonstationary, nonlinear signals

“…To illustrate the difficulties, we test a previously used AAC method that is based on spectral analysis or Fourier transform [22]. In addition, we propose a new analytical tool for the assessment of AAC that is based on the empirical mode decomposition (EMD) — a decomposition that can better extract nonlinear and nonstationary oscillatory components from noisy signals [23-30]. We examine and compare the performances of the two methods using synthetic signals without AAC that are nonstationary and nonlinear as often observed in EEG recordings.…”

Microvascular brain damage with aging and hypertension

“…Using multimodal pressureflow analysis, a new dimension with potential clinical implications is observed [51]. A characteristic phase lag between blood flow velocity and BP oscillations was found in healthy individuals, and this phase lag was reduced in patients with hypertension [52] and diabetes [53] indicating alteration in the autoregulation curve. The final consequence of this phase lag lost is the cerebral flow velocity was more passively dependent on BP, and microvascular territories are most exposed to systemic BP impact [33].…”