Noradrenergic responsiveness supports selective attention across the adult lifespan

Abstract

AbstractBackgroundTheories of healthy and pathological aging assume a critical role of the locus coeruleus (LC), the main cortical norepinephrine (NE) supply, in shaping late‐life cognition. Postmortem analyses identified the LC as one of the first brain sites that accumulates tau pathology. However, in‐vivo research linking the noradrenergic system to senescent cognitive decline in humans is rare.Here we used a multimodal assessment to investigate whether individual differences in attention are related to the noradrenergic system.MethodIn younger (n = 39) and older adults (n = 38) we applied fear conditioning, an experimental manipulation known to modulate arousal‐related noradrenergic drive. Concurrently, we assessed pupil dilation, a non‐invasive proxy for noradrenergic activity, and the electroencephalogram (EEG) as indicators for successful NE manipulation. Reliable pupil and EEG signatures associated with elevated LC‐NE activity were identified in repeated conditioning sessions. We further evaluated participants’ general attention ability using a multimodal cognitive assessment. During one of the attention tasks (dichotic listening), fear‐conditioned (CS+) or perceptually matched control stimuli (CS–) were presented on a trial‐by‐trial basis to dynamically modulate arousal‐related noradrenergic drive.ResultRelative to younger adults, older adults demonstrated compromised performance across a variety of attention tasks. On a physiological level, presentation of fear‐conditioned stimuli during dichotic listening reinstated the acquired arousal response. Relative to control stimuli (CS–), conditioned stimuli (CS+) induced a multimodal response, consisting of pupil dilation and EEG desynchronization. Crucially, greater pupil dilation in response to the CS+ was associated with a stronger transient alpha–beta desynchronization (9–30 Hz), indicating a common dependence on phasic NE release. Using structural equation modeling, we integrated over EEG desynchronization and pupil dilation markers to derive a single index reflecting the responsiveness of the noradrenergic system to arousing stimuli. Combining behavioral and physiological data, we observed that a more responsive noradrenergic system was associated with better performance across attention tasks. Finally, we found that older age is associated with lower pupil‐ and EEG‐indexed noradrenergic responsiveness.ConclusionTaken together, our findings indicate that (1) noradrenergic neuromodulation dynamically sculpts low frequency oscillatory dynamics in posterior brain areas and (2) this interaction supports attention across the lifespan.