Blink-related arousal network surges are shaped by cortical vigilance states

Author:

Demiral Sukru1ORCID,Lildharrie Christina1,Lin Esther1,Benveniste Helene2ORCID,Volkow Nora3ORCID

Affiliation:

1. National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health,

2. Yale School of Medicine

3. National Institute of Drug Abuse

Abstract

Abstract

The vigilance state and the excitability of cortical networks impose wide-range effects on brain dynamics that arousal surges could promptly modify. We previously reported an association between spontaneous eye-blinks and BOLD activation in the brain arousal ascending network (AAN) and in thalamic nuclei based on 3T MR resting state brain images. Here we aimed to replicate our analyses using 7T MR images in a larger cohort of participants collected from the Human Connectome Project (HCP), which also contained simultaneous eye-tracking recordings, and to assess the interaction between the blink-associated arousal surges and the vigilance states. For this purpose, we compared blink associated BOLD activity under a vigilant versus a drowsy state, a classification made based on the pupillary data obtained during the fMRI scans. We conducted two main analyses: i) Cross-correlation analysis between the BOLD signal and blink events (eye blink time-series were convolved with the canonical and also with the temporal derivative of the Hemodynamic Response Function, HRF) within preselected regions of interests (ROIs) (i.e., brainstem AAN, thalamic and cerebellar nuclei) together with an exploratory voxel-wise analyses to assess the whole-brain, and ii) blink-event analysis of the BOLD signals to reveal the signal changes onset to the blinks in the preselected ROIs. Consistent with our prior findings on 3T MRI, we showed significant positive cross correlations between BOLD peaks in brainstem and thalamic nuclei that preceded or were overlapping with blink moments and that sharply decreased post-blink. Whole brain analysis revealed blink-related activation that was strongest in cerebellum, insula, lateral geniculate nucleus (LGN) and visual cortex. Drowsiness impacted HRF BOLD (enhancing it), time-to-peak (delaying it) and post-blink BOLD activity (accentuating decreases). Responses in the drowsy state could be related to the differences in the excitability of cortical, subcortical and cerebellar tissue, such that cerebellar and thalamic regions involved in visual attention processing were more responsive for the vigilant state, but AAN ROIs, as well as cerebellar and thalamic ROIs connected to pre-motor, frontal, temporal and DMN regions were less responsive. Such qualitative and quantitative differences in the blink related BOLD signal changes could reflect delayed cortical processing and the ineffectiveness of arousal surges during states of drowsiness. Future studies that manipulate arousal are needed to corroborate a mechanistic interaction of arousal surges with vigilance states and cortical excitability.

Publisher

Research Square Platform LLC

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