Covariations between pupil diameter and supplementary eye field activity suggest a role in cognitive effort implementation.

In both human and nonhuman primates (NHP), the medial prefrontal region, defined as the supplementary eye field (SEF), can indirectly influence behavior selection through modulation of the primary selection process in the oculomotor structures. To perform this oculomotor control, SEF integrates multiple cognitive signals such as attention, memory, reward, and error. As changes in pupil responses can assess these cognitive efforts, a better understanding of the precise dynamics by which pupil diameter and medial prefrontal cortex activity interact requires thorough investigations before, during, and after changes in pupil diameter. We tested whether SEF activity is related to pupil dynamics during a mixed pro/antisaccade oculomotor task in 2 macaque monkeys. We used functional ultrasound (fUS) imaging to examine temporal changes in brain activity at the 0.1-s time scale and 0.1-mm spatial resolution concerning behavioral performance and pupil dynamics. By combining the pupil signals and real-time imaging of NHP during cognitive tasks, we were able to infer localized cerebral blood volume (CBV) responses within a restricted part of the dorsomedial prefrontal cortex, referred to as the SEF, an area in which antisaccade preparation activity is also recorded. Inversely, SEF neurovascular activity measured by fUS imaging was found to be a robust predictor of specific variations in pupil diameter over short and long-time scales. Furthermore, we directly manipulated pupil diameter and CBV in the SEF using reward modulations. These results bring a novel understanding of the physiological links between pupil and SEF, but it also raises questions about the role of anterior cingulate cortex (ACC), as CBV variations in the ACC seems to be negligible compared to CBV variations in the SEF.