Pupil diameter covaries with BOLD activity in human locus coeruleus

Area of Science:

• Neuroscience
• Cognitive Science
• Neuroimaging

Background:

• The locus coeruleus-noradrenergic (LC-NA) system modulates cognition, but human studies are limited by a lack of non-invasive LC activity measures.
• Pupil diameter is proposed as a proxy for LC activity, but direct empirical evidence is lacking.

Purpose of the Study:

• To rigorously investigate the relationship between pupil diameter and blood-oxygen-level-dependent (BOLD) activity in the human LC.
• To establish pupil diameter as a reliable non-invasive measure for LC-NA system research.

Main Methods:

• Simultaneous pupillometry and functional magnetic resonance imaging (fMRI) were employed.
• Neuromelanin-sensitive structural imaging and an LC atlas localized the LC.
• fMRI data were analyzed at rest and during an oddball task, with and without spatial smoothing and physiological noise correction.

Main Results:

• A significant relationship was found between continuous pupil diameter and BOLD activity in a dorsal pontine cluster overlapping with the LC.
• This pupil-LC BOLD relationship persisted across resting and task conditions, and survived data processing variations.
• The study demonstrated phasic modulation of LC activity by stimulus relevance, mirroring findings in animal models.

Conclusions:

• Pupil diameter serves as a valid non-invasive proxy for human LC activity.
• This finding opens avenues for more comprehensive research into the LC-NA system's role in human cognition.