Person:

Hu, Kun

Cerebral autoregulation (CA) is an important vascular control mechanism responsible for relatively stable cerebral blood flow despite changes of systemic blood pressure (BP). Impaired CA may leave brain tissue unprotected against potentially harmful effects of BP fluctuations. It is generally accepted that CA is less effective or even inactive at frequencies >∼0.1 Hz. Without any physiological foundation, this concept is based on studies that quantified the coupling between BP and cerebral blood flow velocity (BFV) using transfer function analysis. This traditional analysis assumes stationary oscillations with constant amplitude and period, and may be unreliable or even invalid for analysis of nonstationary BP and BFV signals. In this study we propose a novel computational tool for CA assessment that is based on nonlinear dynamic theory without the assumption of stationary signals. Using this method, we studied BP and BFV recordings collected from 39 patients with chronic ischemic infarctions and 40 age-matched non-stroke subjects during baseline resting conditions. The active CA function in non-stroke subjects was associated with an advanced phase in BFV oscillations compared to BP oscillations at frequencies from ∼0.02 to 0.38 Hz. The phase shift was reduced in stroke patients even at > = 6 months after stroke, and the reduction was consistent at all tested frequencies and in both stroke and non-stroke hemispheres. These results provide strong evidence that CA may be active in a much wider frequency region than previously believed and that the altered multiscale CA in different vascular territories following stroke may have important clinical implications for post-stroke recovery. Moreover, the stroke effects on multiscale cerebral blood flow regulation could not be detected by transfer function analysis, suggesting that nonlinear approaches without the assumption of stationarity are more sensitive for the assessment of the coupling of nonstationary physiological signals.

The mammalian central circadian pacemaker (the suprachiasmatic nucleus, SCN) contains thousands of neurons that are coupled through a complex network of interactions. In addition to the established role of the SCN in generating rhythms of ∼24 hours in many physiological functions, the SCN was recently shown to be necessary for normal self-similar/fractal organization of motor activity and heart rate over a wide range of time scales—from minutes to 24 hours. To test whether the neural network within the SCN is sufficient to generate such fractal patterns, we studied multi-unit neural activity of in vivo and in vitro SCNs in rodents. In vivo SCN-neural activity exhibited fractal patterns that are virtually identical in mice and rats and are similar to those in motor activity at time scales from minutes up to 10 hours. In addition, these patterns remained unchanged when the main afferent signal to the SCN, namely light, was removed. However, the fractal patterns of SCN-neural activity are not autonomous within the SCN as these patterns completely broke down in the isolated in vitro SCN despite persistence of circadian rhythmicity. Thus, SCN-neural activity is fractal in the intact organism and these fractal patterns require network interactions between the SCN and extra-SCN nodes. Such a fractal control network could underlie the fractal regulation observed in many physiological functions that involve the SCN, including motor control and heart rate regulation.

Human aging into senescence diminishes the capacity of the postural control system to adapt to the stressors of everyday life. Diminished adaptive capacity may be reflected by a loss of the fractal-like, multiscale complexity within the dynamics of standing postural sway (i.e., center-of-pressure, COP). We therefore studied the relationship between COP complexity and adaptive capacity in 22 older and 22 younger healthy adults. COP magnitude dynamics were assessed from raw data during quiet standing with eyes open and closed, and complexity was quantified with a new technique termed empirical mode decomposition embedded detrended fluctuation analysis (EMD-DFA). Adaptive capacity of the postural control system was assessed with the sharpened Romberg test. As compared to traditional DFA, EMD-DFA more accurately identified trends in COP data with intrinsic scales and produced short and long-term scaling exponents (i.e., αShort, αLong) with greater reliability. The fractal-like properties of COP fluctuations were time-scale dependent and highly complex (i.e., αShort values were close to one) over relatively short time scales. As compared to younger adults, older adults demonstrated lower short-term COP complexity (i.e., greater αShort values) in both visual conditions (p>0.001). Closing the eyes decreased short-term COP complexity, yet this decrease was greater in older compared to younger adults (p<0.001). In older adults, those with higher short-term COP complexity exhibited better adaptive capacity as quantified by Romberg test performance (r2 = 0.38, p<0.001). These results indicate that an age-related loss of COP complexity of magnitude series may reflect a clinically important reduction in postural control system functionality as a new biomarker.