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Research Article: State-dependent facial pulsation asymmetry and phase asynchrony measured by imaging photoplethysmography and their coupling with contingent negative variation in migraine

Date Published: 2026-06-04

Abstract:
To characterize imaging photoplethysmography (iPPG)-derived facial hemodynamic alterations across migraine states and examine their association with contingent negative variation (CNV), an electroencephalography-derived marker of anticipatory cortical activity. We enrolled 78 patients with migraine, including 60 assessed during the interictal phase (IP) and 18 assessed during the migraine attack phase (MAP), together with 72 healthy controls (HC). Short facial videos were analyzed across three facial angiosomes: the lateral forehead, mid-forehead, and cheek. Two peripheral pulsation metrics were derived: bilateral pulsation amplitude asymmetry (BPA) and bilateral pulsation phase difference (BPP). CNV recordings obtained during an S1–S2 paradigm were used to quantify initial CNV (iCNV), overall CNV (oCNV), and terminal CNV (tCNV) amplitudes and areas. Group effects and CNV–iPPG associations were evaluated using linear mixed-effects models adjusted for age and sex. Sensitivity analyses evaluated potential confounding by mood symptoms, headache impact, acute medication use, and unequal IP–MAP sample sizes. Exploratory receiver operating characteristic analyses were used to assess within-cohort separability before and after adjustment for age and sex. BPA and BPP were higher in patients with migraine than in HC across facial angiosomes. CNV metrics showed state-dependent differences: IP participants had higher iCNV, oCNV, and tCNV amplitudes and areas than both HC and MAP participants, whereas MAP participants were generally comparable to HC. CNV amplitudes were positively associated with BPA and BPP, with angiosome-dependent slopes and stronger group differences in iCNV-related models. Exploratory analyses showed high within-cohort separability for mid-forehead iPPG metrics in distinguishing migraine from HC and for central CNV metrics in distinguishing MAP from IP. Migraine is associated with increased facial pulsation asymmetry and phase asynchrony, state-dependent CNV alterations, and angiosome- and state-dependent central–peripheral coupling. These candidate markers require validation in larger, longitudinal, and external cohorts.

Introduction:
Migraine is a common primary headache disorder characterized by recurrent attacks of moderate to severe pulsating pain ( 1–3 ). It is often accompanied by nausea, photophobia, and phonophobia, and is typically aggravated by routine physical activity ( 4 ). Migraine can substantially impair social functioning and quality of life and imposes a sustained healthcare and socioeconomic burden. Currently, clinical diagnosis and disease monitoring rely largely on subjective information, including medical history,…

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