10 Pupil Dilation During the Stroop Task Offers a Sensitive and Scalable Biomarker of Locus Coeruleus Integrity

• Published in: Journal of the International Neuropsychological Society 2023-11, Vol.29 (s1), p.802-803
• Main Authors: Weigand, Alexandra J, Elman, Jeremy A, Solders, Seraphina K, Macomber, Alyssa J, Frank, Lawrence R, Granholm, Eric L, Bondi, Mark W
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Biomarkers; Cognitive ability; Cognitive Neuroscience; Dementia disorders; Locus coeruleus; Magnetic resonance imaging; Neurodegenerative diseases; Neuroimaging; Norepinephrine; Poster Session 09: Psychiatric Disorders | Mood & Anxiety Disorders | Addiction | Social Cognition | Cognitive Neuroscience | Emotional and Social Processing; Reaction time task
• ISSN: 1355-6177; 1469-7661
• DOI: 10.1017/S1355617723009967

Objective:Neuronal dysfunction of the locus coeruleus (LC), the primary producer of norepinephrine, has been identified as a biomarker of early Alzheimer's disease (AD) pathophysiology. Norepinephrine has been implicated in attentional control, and its reduced cortical circulation in AD may be associated with selective attentional difficulties. Additionally, greater pupil dilation indicates greater effort needed to perform a cognitive task, and greater compensatory effort to perform the digit span task has been found in individuals at risk for AD. In this study, we examined associations between a neuroimaging biomarker of the LC and pupil dilation during the Stroop task as a sensitive measure of attentional control.Participants and Methods:64 older adults without dementia were recruited from the San Diego community (mean [SD] age = 74.3 [6.3]; 39 cognitively unimpaired and 25 with mild cognitive impairment). All participants underwent magnetic resonance imaging of the LC and generated behavioral data from a computerized Stroop task that included 36 incongruent trials (e.g., GREEN presented in red ink), 36 congruent trials (e.g., GREEN presented in green ink), and 32 neutral trials (e.g., LEGAL presented in green ink) in a randomized presentation. Mean pupil dilation for each trial (change relative to baseline at the start of each trial) was measured at 30 Hz using the Tobii X2-30 system (Tobii, Stockholm, Sweden) and averaged within each Stroop condition. Paired t-tests assessed for differences in mean pupil dilation across incongruent and congruent Stroop conditions. Iterative re-weighted least squares regression was used to assess the association between a rostral LC contrast ratio measure derived from manually marked ROIs and mean pupil dilation during incongruent trials divided by congruent trials, adjusting for age, sex, and education. Follow-up analyses also assessed the association of these variables with mean reaction time (RT) for incongruent trials divided by congruent trials.Results:Mean pupil dilation significantly differed across conditions (t = 3.74, mean difference = .13, 95% CI [.06, .20]) such that dilation was higher during the incongruent condition (mean [SD] dilation = .18 [.38] mm) relative to the congruent condition (mean [SD] dilation = .05 [.35] mm). A significant association was observed between pupil dilation and LC contrast ratio, such that increased levels of mean dilation during incongruent trials relative to congruent trials w