Human Pupil Response Research Articles

Brightness illusions drive a neuronal response in the primary visual cortex under top-down modulation

Brightness illusions are a powerful tool in studying vision, yet their neural correlates are poorly understood. Based on a human paradigm, we presented illusory drifting gratings to mice. Primary visual cortex (V1) neurons responded to illusory gratings, matching their direction selectivity for real gratings, and they tracked the spatial phase offset between illusory and real gratings. Illusion responses were delayed compared to real gratings, in line with the theory that processing illusions requires feedback from higher visual areas (HVAs). We provide support for this theory by showing a reduced V1 response to illusions, but not real gratings, following HVAs optogenetic inhibition. Finally, we used the pupil response (PR) as an indirect perceptual report and showed that the mouse PR matches the human PR to perceived luminance changes. Our findings resolve debates over whether V1 neurons are involved in processing illusions and highlight the involvement of feedback from HVAs.

Role of the frontal eye field in human pupil and saccade orienting responses.

The appearance of a salient stimulus evokes a series of orienting responses including saccades and pupil size to prepare the body for appropriate action. The midbrain superior colliculus (SC) that receives critical control signals from the frontal eye field (FEF) is hypothesized to coordinate all components of orienting. It has shown recently that the FEF, together with the SC, is also importantly involved in the control of pupil size, in addition to its well-documented role in eye movements. Although the role of the FEF in pupil size is demonstrated in monkeys, its role in human pupil responses and the coordination between pupil size and saccades remains to be established. Through applying continuous theta-burst stimulation over the right FEF and vertex, we investigated the role of the FEF in human pupil and saccade responses evoked by a salient stimulus, and the coordination between pupil size and saccades. Our results showed that neither saccade reaction times (SRT) nor pupil responses evoked by salient stimuli were modulated by FEF stimulation. In contrast, the correlation between pupil size and SRTs in the contralateral stimulus condition was diminished with FEF stimulation, but intact with vertex stimulation. Moreover, FEF stimulation effects between saccade and pupil responses associated with salient stimuli correlated across participants. This is the first transcranial magnetic stimulation (TMS) study on the pupil orienting response, and our findings suggest that human FEF was involved in coordinating pupil size and saccades, but not involved in the control of pupil orienting responses.

Effects of Narrowband Light on Choroidal Thickness and the Pupil.

PurposeTo determine the effects of narrowband light exposure on choroidal thickness and the pupil response in humans.MethodsTwenty subjects, ages 21 to 43 years, underwent 1 hour of exposure to broadband, short wavelength “blue,” or long wavelength “red” light, or darkness. Choroidal thickness, imaged with spectral domain optical coherence tomography, axial length, determined from biometry, and rod/cone- and intrinsically photosensitive retinal ganglion cell-driven pupil responses were measured before and after exposure. Pupil stimuli were six 1 second alternating red (651 nm) and blue (456 nm) stimuli, 60 seconds apart. Pupil metrics included maximum constriction and the 6 second post-illumination pupil response (PIPR).ResultsCompared with before exposure, the choroid significantly thinned after broadband light, red light, and dark exposure (all P < 0.05), but not after blue light exposure (P = 0.39). The maximum constriction to 1 second red stimuli significantly decreased after all light exposures (all P < 0.001), but increased after dark exposure (P = 0.02), compared with before exposure. Maximum constriction and 6-second PIPR to 1 second blue stimuli significantly decreased after all light exposures compared with before exposure (all P < 0.005), with no change after dark exposure (P > 0.05). There were no differences in axial length change or 6-second PIPR to red stimuli between exposures.ConclusionsNarrowband blue and red light exposure induced differential changes in choroidal thickness. Maximum constriction, a function of rod/cone activity, and the intrinsically photosensitive retinal ganglion cell-mediated PIPR were attenuated after all light exposures. Findings demonstrate differing effects of short-term narrowband light and dark exposure on the choroid, rod/cone activity, and intrinsically photosensitive retinal ganglion cells.

Modulation of stimulus contrast on the human pupil orienting response.

The sudden appearance of a novel stimulus initiates a series of responses to orient the body for appropriate actions, including not only shifts of gaze and attention, but also transient pupil dilation. Modulation of pupil dynamics by stimulus properties is less understood, although its effects on other components of orienting have been extensively explored. Microstimulation of the superior colliculus evoked transient pupil dilation, and the initial component of pupil dilation evoked by microstimulation was similar to that elicited by the presentation of salient sensory stimuli, suggesting a coordinated role of the superior colliculus on this behavior, although evidence in humans is yet to be established. To examine pupil orienting responses in humans, we presented visual stimuli while participants fixated on a central visual spot. Transient pupil dilation in humans was elicited after presentation of a visual stimulus in the periphery. The evoked pupil responses were modulated systematically by stimulus contrast, with faster and larger pupil responses triggered by higher contrast stimuli. The pupil response onset latencies for high contrast stimuli were similar to those produced by the light reflex and significantly faster than the darkness reflex, suggesting that the initial component of pupil dilation is probably mediated by inhibition of the parasympathetic pathway. The contrast modulation was pronounced under different levels of baseline pupil size. Together, our results demonstrate visual contrast modulation on the orienting pupil response in humans.

S-, M- and L-cone contributions to human pupil responses under dim illumination conditions

Cones, rods and melanopsin contribute to pupillary responses. However, how each type of cones contributes to pupil responses has been rarely studied. In our study, we investigated pupil responses to S-, M- and L-cone flicker inputs under dim illumination conditions. A four-primary Ganzfeldphotostimulator (DiagnosysColorDome) controlled rod and cone stimulations at −0.9 log cd/m2, which is below the melanopsin threshold but above the cone detection threshold. Four types of sinusoidally modulated stimuli (1 Hz, 20% contrast) were used: 1) rod stimuli (modulated rod excitation with a constant S- M- and L-cone excitation); 2) S-cone stimuli (modulated S-cone excitation; constant rod, M- and L-cone excitation); 3) M-cone stimuli (modulated M-cone excitation; constant rod, S- and L-cone excitation); and 4) L-cone stimuli (modulated L-cone excitation; constant rod, S- and M-cone excitation). Pupil sizes were measured using an Eyelink II eyetracker (SR Research) with a 250 Hz sampling rate. Pupil amplitudes and phases were derived by Fourier analysis. The results showed that, overall, the cone (S-, M- or L-) stimuli produced smaller responses than rod stimuli, suggesting rod dominance at −0.9 cd/m2. On the other hand, pupil responses to the M-cone stimuli were larger than for S- or L-cone stimuli. While the M- and L-cone stimuli produced similar response phases (between 0 deg and −50 deg), the S-cone stimuli had a response phase of approximately 180 deg. These results are consistent with L/M-On and S-OFF response characteristics of ipRGCs measured in primate retinas (Dacey et al., 2005).

Toward a Clinical Protocol for Assessing Rod, Cone, and Melanopsin Contributions to the Human Pupil Response

PURPOSE. To better understand the relative contributions of rod, cone, and melanopsin to the human pupillary light reflex (PLR) and to determine the optimal conditions for assessing the health of the rod, cone, and melanopsin pathways with a relatively brief clinical protocol. METHODS. PLR was measured with an eye tracker, and stimuli were controlled with a Ganzfeld system. In experiment 1, 2.5 log cd/m(2) red (640 ± 10 nm) and blue (467 ± 17 nm) stimuli of various durations were presented after dark adaptation. In experiments 2 and 3, 1-second red and blue stimuli were presented at different intensity levels in the dark (experiment 2) or on a 0.78 log cd/m(2) blue background (experiment 3). Based on the results of experiments 1 to 3, a clinical protocol was designed and tested on healthy control subjects and patients with retinitis pigmentosa and Leber's congenital amaurosis. RESULTS. The duration for producing the optimal melanopsin-driven sustained pupil response after termination of an intense blue stimulus was 1 second. PLR rod- and melanopsin-driven components are best studied with low- and high-intensity flashes, respectively, presented in the dark (experiment 2). A blue background suppressed rod and melanopsin responses, making it easy to assess the cone contribution with a red flash (experiment 3). With the clinical protocol, robust melanopsin responses could be seen in patients with few or no contributions from the rods and cones. CONCLUSIONS. It is possible to assess the rod, cone, and melanopsin contributions to the PLR with blue flashes at two or three intensity levels in the dark and one red flash on a blue background.

The trigemino-pupillary reflex: a model of sensory-vegetative integration

Trigeminal stimulation can induce pupillary changes. In vivo and in vitro studies have demonstrated that electrical impulses applied at the trigeminal level can provoke a miotic response, whose nature has been ascribed to the anti-dromic release of neuropeptides (substance P in particular). In order to better define the pupil response to trigeminal stimulation, we investigated the human pupil response to quantified (painless and painful) corneal stimuli by means of a combined (neurophysiological and pharmacological) technique. The response to corneal stimulation was bilateral, direct and consensual. It had a biphasic progression with an initial mydriasis (which directly correlated with the stimulus intensity), followed by a miotic phase. The mydriatic phase disappeared after thymoxamine application, while homatropine pre-treatment prevented occurrence of the miotic phase. The data obtained indicate that the pupillary response to corneal stimulation (trigemino-pupillary reflex) is a multisynaptic reflex with an afferent branch involving the trigeminal system, and an afferent branch involving both the sympathetic and the parasympathetic system. Other pathways, such as the SP-mediated release of acetylcholine, cannot be excluded. Thus the reflex appears to be a potentially useful tool for investigating pain/vegetative interactions in various clinical conditions. In turn, the description of its changes in pathologies characterized by a sympathetic/parasympathetic deficit or by a SP-ergic imbalance will allow us to better describe its inner mechanisms.

Instrumentation for automated study of human pupil responses.

Instrumentation has been developed for studying the responses of the human pupil to different kinds of visual stimuli. This involves stimulating the eye visually, acquiring pupillary diameter data samples, analyzing them, and displaying and storing the results All of these functions are controlled by a minicomputer. The apparatus is a convenient research tool for studying the visual system of color-normals and color-defectives by observing pupillary behavior.