Task-evoked pupil dilation and BOLD variance as indicators of locus coeruleus dysfunction

Area of Science:

• Neuroscience
• Biomarker Discovery
• Alzheimer's Disease Research

Background:

• The locus coeruleus (LC) is implicated in Alzheimer's disease (AD) pathophysiology due to early tau deposition.
• Pupillary responses to cognitive load changes may reflect LC functioning and serve as an early AD risk biomarker.
• LC dysfunction is hypothesized to cause sustained high tonic activity and impaired phasic responses.

Purpose of the Study:

• To investigate the association between pupillary responses and early locus coeruleus (LC) dysfunction.
• To determine if resting-state brain activity predicts pupillary responses during cognitive tasks in relation to LC function.

Main Methods:

• 358 middle-aged men underwent resting-state fMRI to measure low-frequency BOLD variance (LFBV) in ventral attention network (VAN) nodes.
• Pupil dilation during a digit span task was measured as an indicator of phasic LC activity.
• LFBV was used as a proxy for tonic LC activity.

Main Results:

• Higher LFBV in VAN nodes (indicating greater tonic brain activity) was associated with smaller increases in pupil dilation from low to moderate cognitive loads.
• Increased resting tonic activity correlated with reduced task-appropriate phasic pupillary responses.
• These findings support models of LC dysfunction leading to altered tonic and phasic activity.

Conclusions:

• Pupillary responses may serve as a sensitive index of early locus coeruleus (LC) dysfunction.
• The study supports pupillary measures as a potential biomarker for early Alzheimer's disease (AD) risk.
• Further research into pupillary responses for AD risk assessment is warranted.