Phase coupling between eye and brain pulsations is bidirectional and modulated by the parasympathetic system – An <scp>fMREye</scp> study

PURPOSE: Physiological pulsations driven by cardiac, respiratory, and vasomotor activity are essential for solute transport within perivascular and perineural cerebrospinal fluid (CSF) pathways that support brain and eye clearance systems. Previous studies have shown that parasympathetic blockade significantly reduces ocular pulsation power and induces systemic alterations in cerebral pulsations, but the connecting mechanism has been uncertain. METHODS: We first investigated classical cross-correlation (CC) strength and lag values between brain and eye regions of interest (ROIs) and then examined the phase-based relationship between their physiological pulsations. We further assessed how this relationship is affected by topical parasympathetic blockade using tropicamide. Functional magnetic resonance eye imaging (fMREye) data were analysed from 46 healthy volunteers, with and without topical tropicamide. Static correlation analysis and dynamic phase transfer entropy (dPTE) served to quantify directional interactions across three physiological frequency bands: very-low-frequency (VLF), respiratory (RESP), and cardiac (CARD). RESULTS: At baseline, CC analysis revealed the strongest correlations in the CARD and RESP bands, particularly between peri-optic CSF and interpeduncular cisterns. With tropicamide, CC values were significantly higher in most connections. VLF correlations were weaker and remained mostly unchanged. Constant lag analysis revealed unphysiologically long lags. However, the deeper dynamic phase analysis revealed previously unforeseen low-frequency oscillations in the phases between the pulsations. The directional dPTE showed a near-zero net information transfer and a faint predilection for CARD pulsation directed from the eye towards the brain. Tropicamide administration significantly reduced bidirectional brain-eye information flow, with a visually greater reduction in the eye-to-brain direction. This was accompanied by significant alterations in phase dynamics, including a reversal in CARD-RESP directionality, indicating a shift in temporal precedence between frequency components, and higher CARD-VLF coupling. CONCLUSION: The brain-eye pulsation connections express highly dynamic bi-directionality with frequency dependent net information transfer partly modulated by (para)sympathetic activity.