Cross-Frequency Coupling Between Cerebral Blood Flow Velocity and EEG in Ischemic Stroke Patients With Large Vessel Occlusion

Background: Neurovascular coupling enables a rapid adaptation of cerebral blood flow (CBF) to support neuronal activities. Whether this mechanism is compromised during the acute phase after ischemic stroke remains unknown. In this study, we applied a phase-amplitude cross-frequency coupling (PAC) algorithm to investigate multimodal neuro signals including CBF velocity (CBFV), and electroencephalography (EEG). Methods: Acute ischemic stroke patients admitted to the Neurointensive Care Unit, Tiantan Hospital, Capital Medical University (Beijing, China) with continuous monitoring of 8-lead EEG (F3-C3, T3-P3, P3-O1, F4-C4, T4-P4, P4-O2), non-invasive arterial blood pressure (ABP), and bilateral CBFV of the middle cerebral arteries or posterior cerebral arteries were retrospectively analyzed. PAC was calculated between the phase of CBFV in frequency bands (0–0.05 and 0.05–0.15 Hz) and the EEG amplitude in five bands (δ, θ, α, β, γ). The global PAC was calculated as the sum of all PACs across the six EEG channels and five EEG bands for each patient. The hemispherical asymmetry of cross-frequency coupling (CFC) was calculated as the difference between left and right PAC. Results: Sixteen patients (3 males) met our inclusion criteria. Their age was 60.9 ± 7.9 years old. The mean ABP, mean left CBFV, and mean right CBFV were 90.2 ± 31.2 mmHg, 57.3 ± 20.6 cm/s, and 68.4 ± 20.9 cm/s, respectively. The PAC between CBFV and EEG was significantly higher in β and γ bands than in the other three bands. Occipital region (P3-O1 and P4-O2 channels) showed stronger PAC than the other regions. The deceased group tended to have smaller global PAC than the survival group (the area under the receiver operating characteristic curve [AUROC] was 0.81, p = 0.57). The unfavorable outcome group showed smaller global PAC than the favorable group (AUROC = 0.65, p = 0.23). The PAC asymmetry between the two brain hemispheres correlates with the degree of stenosis in stroke patients (p = 0.01). Conclusion: We showed that CBFV interacts with EEG in β and γ bands through a phase-amplitude CFC relationship, with the strongest PAC found in the occipital region and that the degree of hemispherical asymmetry of CFC correlates with the degree of stenosis.