The stable supply of cerebral blood flow (CBF) is crucial for maintaining the normal physiological function of the brain. This regulation relies on complex physiological mechanisms involving the collaboration between the basilar arteries and the microvascular network that penetrates the brain parenchyma. Although advances in non-invasive detection technology have provided new opportunities for cerebrovascular research, relevant studies remain limited. Numerous studies are confined to single-scale analyses of blood flow changes, lacking extensive investigations into the interaction between large arteries and microvascular blood flow. Additionally, there are relatively few comprehensive evaluations of cerebrovascular regulatory mechanisms and neurovascular coupling in response to dynamic stimulation conditions. Therefore, an in-depth investigation of the interaction between large arteries and microvascular blood flow patterns not only enhances understanding of the mechanisms governing cerebral blood flow regulation but also provides a critical basis for the early diagnosis, prevention, and treatment of cerebrovascular diseases. The aim of this study was to systematically assess the interaction of cerebral macrovascular and microvascular blood flow patterns under different physiological tasks by integrating transcranial Doppler ultrasound (TCD) and diffuse correlation spectroscopy (DCS) techniques. The outcomes of this study will contribute to current brain research, offering new concepts and methods to improve medical interventions for cerebrovascular diseases.

A total of 16 young, healthy participants (8 women and 8 men, ages 18 to 25) were recruited for this study. They were instructed to perform four tasks: the verbal fluency task (VFT), high-level cognitive task (HCT), voluntary breath-holding (VBH), and postural change task (PCT). Simultaneous changes in microvascular cerebral blood flow (F_cb) and middle cerebral artery blood flow velocity (V_m) during each task were measured using DCS and TCD, respectively. The experimental design adhered strictly to international ethical principles to ensure the safety of the subjects. Precise placement of the TCD probe and DCS optical probe on the subjects’ frontal heads allowed for real-time monitoring of blood flow dynamics in specific brain regions. During data analysis, slope (S), D-index (D_index), and response time (T_R) were defined, and a wide range of statistical variables, including analysis of variance (ANOVA) and Pearson correlation analysis, were utilized to comprehensively assess the correlation and asynchrony between V_m and F_cb across different tasks. The integration of multiple technical approaches ensures the accuracy and reliability of the research findings, providing robust data to reveal the mechanisms underlying cerebral blood flow regulation.

The results indicate that F_cb outperforms V_m in both initial response and response amplitude for all four tasks. Specifically, the initial slope and D-index of F_cb are higher, demonstratingits greater sensitivity to physiological changes (Figs. 5 and 6). During cognitive tasks (VFT and HCT), V_m exhibits a faster reaction time than F_cb (Fig. 5). Conversely, during the VBH and PCT tasks, the reaction time of V_m is slower than that of F_cb (Fig. 6). These outcomes suggest that distinct tasks exert different effects on the mechanisms of blood flow regulation, with F_cb showing a quicker response rate under hypoxia or fluctuations in blood pressure. ANOVA results reveal that in VFT and HCT, the mean slope of V_m is 0.26±0.07 and 0.21±0.06, respectively, while the mean slope of F_cb is 0.69±0.04 and 0.74±0.06, respectively, with significant differences (P<0.05). Similarly, the response time (T_R) for V_m is 23.68 s±0.90 s and 31.43 s±1.29 s for VFT and HCT, respectively, whereas the T_R for F_cb is 38.81 s±1.52 s and 48.38 s±1.48 s, respectively, also showing significant differences (P<0.01) (Table 1). Among the four tasks, V_m and F_cb demonstrate a significant correlation during the initial reaction stage; however, the correlation between other variables, such as reaction amplitude and reaction time, varies by task (Fig. 7).

This study investigated the influences of different physiological paradigms (active and passive stimulation) on cerebral hemodynamics at two scales: macrovascular (measured by TCD) and microvascular (measured by DCS). During the physiological tests, the VFT and HCT primarily triggered neuronal excitation at varying cognitive intensities and explored the rapid response of cerebral blood flow. In contrast, the VBH and PCT tasks challenged the brain’s ability to regulate itself automatically under hypoxic conditions. The asynchrony and correlation between the two measurements suggest that changes in major artery blood velocity support the maintenance of cerebral circulation at the microvascular level. The combination of TCD and DCS provides a comprehensive assessment of neurovascular coupling, demonstrating significant potential for diagnosing cerebrovascular diseases and psychiatric disorders. This study emphasizes the importance of examining hemodynamics in both large and microvessels of the brain to achieve a thorough understanding of neurovascular functions.