Synchronization of intrinsic 0.1-Hz blood-oxygen-level-dependent oscillations in amygdala and prefrontal cortex in subjects with increased state anxiety

Abstract

Low-frequency oscillations with a dominant frequency at 0.1 Hz are one of the most influential intrinsic blood-oxygen-level-dependent (BOLD) signals. This raises the question if vascular BOLD oscillations (originating from blood flow in the brain) and intrinsic slow neural activity fluctuations (neural BOLD oscillations) can be differentiated. In this study, we report on two different approaches: first, on computing the phase-locking value in the frequency band 0.07-0.13 Hz between heart beat-to-beat interval (RRI) and BOLD oscillations and second, between multiple BOLD oscillations (functional connectivity) in four resting states in 23 scanner-naïve, anxious healthy subjects. The first method revealed that vascular 0.1-Hz BOLD oscillations preceded those in RRI signals by 1.7 ± 0.6 s and neural BOLD oscillations lagged RRI oscillations by 0.8 ± 0.5 s. Together, vascular BOLD oscillations preceded neural BOLD oscillations by ~90° or ~2.5 s. To verify this discrimination, connectivity patterns of neural and vascular 0.1-Hz BOLD oscillations were compared in 26 regions involved in processing of emotions. Neural BOLD oscillations revealed significant phase-coupling between amygdala and medial frontal cortex, while vascular BOLD oscillations showed highly significant phase-coupling between amygdala and multiple regions in the supply areas of the anterior and medial cerebral arteries. This suggests that not only slow neural and vascular BOLD oscillations can be dissociated but also that two strategies may exist to optimize regulation of anxiety, that is increased functional connectivity between amygdala and medial frontal cortex, and increased cerebral blood flow in amygdala and related structures.

Keywords: 0.1-Hz oscillations; amygdala; blood-oxygen-level-dependent signal; heart rate variability; state anxiety.