Open AccessPupil diameter covaries with BOLD activity in human locus coeruleus
Author(s) -
Murphy Peter R.,
O'Connell Redmond G.,
O'Sullivan Michael,
Robertson Ian H.,
Balsters Joshua H.
Publication year - 2014
Publication title -
human brain mapping
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.005
H-Index - 191
eISSN - 1097-0193
pISSN - 1065-9471
DOI - 10.1002/hbm.22466
Subject(s) - locus coeruleus , pupillometry , neuroscience , pupil , psychology , stimulus (psychology) , oddball paradigm , neuromelanin , habituation , cognition , cognitive psychology , central nervous system , event related potential , substantia nigra , dopamine , dopaminergic
The locus coeruleus‐noradrenergic (LC–NA) neuromodulatory system has been implicated in a broad array of cognitive processes, yet scope for investigating this system's function in humans is currently limited by an absence of reliable non‐invasive measures of LC activity. Although pupil diameter has been employed as a proxy measure of LC activity in numerous studies, empirical evidence for a relationship between the two is lacking. In the present study, we sought to rigorously probe the relationship between pupil diameter and BOLD activity localized to the human LC. Simultaneous pupillometry and fMRI revealed a relationship between continuous pupil diameter and BOLD activity in a dorsal pontine cluster overlapping with the LC, as localized via neuromelanin‐sensitive structural imaging and an LC atlas. This relationship was present both at rest and during performance of a two‐stimulus oddball task, with and without spatial smoothing of the fMRI data, and survived retrospective image correction for physiological noise. Furthermore, the spatial extent of this pupil/LC relationship guided a volume‐of‐interest analysis in which we provide the first demonstration in humans of a fundamental characteristic of animal LC activity: phasic modulation by oddball stimulus relevance. Taken together, these findings highlight the potential for utilizing pupil diameter to achieve a more comprehensive understanding of the role of the LC–NA system in human cognition. Hum Brain Mapp 35:4140–4154, 2014 . © 2014 Wiley Periodicals, Inc .