Abstract Body (Do not enter title and authors here): Introduction: Heart rate fragmentation (HRF) is an inter-beat interval dynamics approach that enhances the analysis of short-term heart rate variability. HRF has been shown to reflect disruptions in the neuroautonomic-electrophysiologic control of the sino-atrial node. Migraine, the fifth leading cause of disability worldwide, is increasingly recognized as a neurovascular disorder with significant autonomic dysfunction. However, HRF signatures in the context of migraine remain unexplored. Here, we investigate HRF dynamics in a validated rodent model of chronic migraine to identify electrophysiological correlates of altered heart-brain connectivity.
Methods: We used a total number of n=20 Sprague-Dawley rats (50% female; 150-250g; 6-8 weeks), which were randomized into two groups: (1) Chronic migraine Group (n=10, 50% female): rats received repeated intraperitoneal (IP) administration of Nitroglycerin (NTG, 10 mg/kg), a well-established migraine trigger, every other day over a nine-day period (Fig1); (2) Control Group (n=10, 50% female): rats received an equivalent volume of saline at the same regime. At the last injection day, rats were anesthetized prior to NTG or saline injection for invasive electrocardiogram (ECG) recording via subcutaneous needle electrodes. HRF metrics were computed using a 2-minute ECG recording at 2 hours after NTG/saline administration. These included quantification of soft and hard inflection points (Soft: transitions between steady and accelerating/decelerating heart rate; Hard: abrupt switches between acceleration and deceleration).
Results: Significant differences were observed between the control and chronic migraine groups (Fig.2) for three HRF metrics. PIPH% (percentage of hard inflection points in heart rate acceleration sign throughout the ECG recording) was significantly increased in the migraine group. W1s% and W2s% (percentages of only one and only two soft inflection points, respectively, in sequences of five consecutive heart rate intervals) were both significantly decreased in the migraine group.
Conclusions: Our findings suggest alterations in heart-brain connectivity in rats with chronic migraine, as evidenced by distinct changes in the HRF. The results also indicate that HRF metrics may serve as novel, noninvasive biomarkers for detecting and monitoring migraine-related autonomic dysfunction. Future studies may explore the clinical utility of HRF-based techniques in management and monitoring of migraine patients.