Transient Pupil Dilation after Subsaccadic Microstimulation of Primate Frontal Eye Fields.

Pupillometry provides a simple and noninvasive index for a variety of cognitive processes, including perception, attention, task consolidation, learning, and memory. The neural substrates by which such cognitive processes influence pupil diameter remain somewhat unclear, although cortical inputs to the locus coeruleus mediating arousal are likely involved. Changes in pupil diameter also accompany covert orienting; hence the oculomotor system may provide an alternative substrate for cognitive influences on pupil diameter. Here, we show that low-level electrical microstimulation of the primate frontal eye fields (FEFs), a cortical component of the oculomotor system strongly connected to the intermediate layers of the superior colliculus (SCi), evoked robust pupil dilation even in the absence of evoked saccades. The magnitude of such dilation scaled with increases in stimulation parameters, depending strongly on the intensity and number of pulses. Although there are multiple pathways by which FEF stimulation could cause pupil dilation, the timing and profile of dilation closely resembled that evoked by SCi stimulation. Moreover, pupil dilation evoked from the FEFs increased when presumed oculomotor activity was higher at the time of stimulation. Our findings implicate the oculomotor system as a potential substrate for how cognitive processes can influence pupil diameter. We suggest that a pathway from the frontal cortex through the SCi operates in parallel with frontal inputs to arousal circuits to regulate task-dependent modulation of pupil diameter, perhaps indicative of an organization wherein one pathway assumes primacy for a given cognitive process. SIGNIFICANCE STATEMENT: Pupillometry (the measurement of pupil diameter) provides a simple and noninvasive index for a variety of cognitive processes, offering a biomarker that has value in both health and disease. But how do cognitive processes influence pupil diameter? Here, we show that low-level stimulation of the primate frontal eye fields can induce robust pupil dilation without saccades. Pupil dilation scaled with the number and intensity of stimulation pulses and varied with endogenous oculomotor activity at the time of stimulation. The oculomotor system therefore provides a plausible pathway by which cognitive processes may influence pupil diameter, perhaps operating in conjunction with systems regulating arousal.