Data-Driven Pupil Response Profiles as Transdiagnostic Readouts for the Detection of Neurocognitive Functioning in Affective and Anxiety Disorders

Neurocognitive functioning is a relevant transdiagnostic dimension in psychiatry. As pupil size dynamics track cognitive load during a working memory task, we aimed to explore if this parameter allows identification of psychophysiological subtypes in healthy participants and patients with affective and anxiety disorders. Our sample consisted of 226 participants who completed the n-back task during simultaneous functional magnetic resonance imaging and pupillometry measurements. We used latent class growth modeling to identify clusters based on pupil size in response to cognitive load. In a second step, these clusters were compared on affective and anxiety symptom levels, performance in neurocognitive tests, and functional magnetic resonance imaging activity. The clustering analysis resulted in two distinct pupil response profiles: one with a stepwise increasing pupil size with increasing cognitive load (reactive group) and one with a constant pupil size across conditions (nonreactive group). A larger increase in pupil size was significantly associated with better performance in neurocognitive tests in executive functioning and sustained attention. Statistical maps of parametric modulation of pupil size during the n-back task showed the frontoparietal network in the positive contrast and the default mode network in the negative contrast. The pupil response profile of the reactive group was associated with more thalamic activity, likely reflecting better arousal upregulation and less deactivation of the limbic system. Pupil measurements have the potential to serve as a highly sensitive psychophysiological readout for detection of neurocognitive deficits in the core domain of executive functioning, adding to the development of valid transdiagnostic constructs in psychiatry.