Kavli Affiliate: David Kleinfeld
| Authors: Sangcheon Choi, Gabriel Hoffmann, Sebastian Schneider, Stephan Kaczmarz, David Kleinfeld, Xin Yu, Christian Sorg and Christine Preibisch
| Summary:
Vasomotor dynamics at the infra-slow frequencies (~0.1 Hz), driven by synchronized oscillation of smooth muscle cells in vessel walls, play an important role in regulating cerebral perfusion and constitute a physiological basis for resting-state functional connectivity (FC). Invasive animal studies have demonstrated that vasomotor activity contributes to coherent blood oxygenation-dependent level (BOLD) signal fluctuations. However, in humans, it remains challenging to non-invasively detect this contribution due to the limited spatiotemporal sensitivity of functional magnetic resonance imaging (fMRI) to vasomotion. Leveraging internal carotid artery stenosis (ICAS) as a natural lesion model of impaired vasomotion, we examined whether impaired vasomotor activity influences inter-hemispheric BOLD coherence at ~0.1 Hz. Using a multi-modal fMRI framework that integrates resting-state fMRI with quantitative multi-parametric mapping of cerebral blood volume, blood flow, oxygen metabolism, and BOLD time lag, we compared BOLD coherence in patients with unliteral ICAS to healthy controls. Frequency-specific coherence analysis revealed significantly diminished inter-hemispheric BOLD coherence at the vasomotor frequency range (~0.1 Hz) across canonical resting-state networks in ICAS patients, whereas ultra-slow (<0.05 Hz) coherence remains largely preserved. This reduction was spatially widespread and particularly pronounced inside watershed areas, i.e., border zones between major vascular perfusion territories that are especially vulnerable to hypoperfusion, and associated with a significantly increased lateralization in cerebral blood volume (p < 0.01) inside watershed areas. Notably, coherence-based FC patterns at ~0.1 Hz were heterogeneous inside watershed areas and homogeneous outside watershed areas, suggesting an interplay between compensatory mechanisms and vasomotion impairment. Taken together, our findings demonstrate that frequency-resolved, region-specific analysis can capture presumably vasomotion-related oscillatory signals at ~0.1 Hz and detect subtle differences in inter-hemispheric FC, offering a non-invasive biomarker for early cerebrovascular dysfunction, particularly in patients with ICAS and other vasomotion-related neuropathologies.