Increased Pupil Size during Future Thinking in a Subject with Retrograde Amnesia

Recent research has assessed pupil size during past thinking in patients with retrograde amnesia. Building on this research, we assessed pupil size during future thinking in a retrograde amnesia patient. To this end, we measured pupil size during past and future thinking in L, a 19-year-old, right-handed man free of neurological/psychiatric disorders except for retrograde amnesia that occurred after an episode of fugue. During a past thinking condition, we invited L to retrieve retrograde events (i.e., events that occurred before amnesia) and anterograde events (i.e., events that occurred after amnesia). During a future thinking condition, we invited him to imagine events that might occur the following week, the following month, and in the new year. Past and future thinking occurred while L’s pupil size was monitored with eye-tracking glasses. L demonstrated higher specificity during future than during past thinking. Critically, the results demonstrated a larger pupil size during future than during past thinking. The larger pupil size during future thinking observed in L can be attributed to the high cognitive load involved in future thinking. Our study not only demonstrates preserved future thinking in a patient with dissociative retrograde amnesia, but also shows that pupillometry can be used for the physiological assessment of future thinking in retrograde amnesia patients.

Objective Eye Tracking Metrics of Vision and Autonomic Dysfunction Distinguish Adolescents With Acute Concussion and Those with Persistent Post-Concussion Symptoms from Uninjured Controls

ObjectiveTo explore the utility of an eye-tracking assessment in distinguishing binocular alignment, saccadic movement, and pupillary dynamics among uninjured adolescents, acute cases (= 28 days since concussion), and persistent cases (>28 days since concussion).BackgroundVisual and autonomic system disturbances are common sequelae of concussion. Quantification of visual and autonomic dysfunction via an eye tracking device could provide an objective method of acute diagnosis and subacute identification of ongoing injury.Design/MethodsWe compared 347 eye tracking metrics, derived from a 220 seconds eye-tracking assessment, among 132 uninjured adolescents (mean age: 15.3, 56.2% female), 110 acute cases (mean days since injury: 12.5, mean age: 15.4, 46.4% female), and 95 persistent cases (mean days since injury: 53.6, mean age: 15.4, 70.2% female) using Kruskal-Wallis tests with Bonferroni corrections to account for multiple comparisons.ResultsNine eye-tracking metrics were significantly associated with injury status. One measure of binocular alignment (acute v. control: p = 0.003, persistent v. control: p = 0.001) and one measure of saccadic movement (acute v. persistent: p = 0.03, acute v. control: p = 0.03, persistent v. control: p < 0.001) were worse in cases. Cases had larger left and right mean and median pupil size than uninjured adolescents (acute v. control, p < 0.001; persistent v. control, p < 0.001). Cases had greater differences in mean (acute v. control: p < 0.001, persistent v. control: p < 0.001), median (acute v. control, p < 0.001, persistent v. control, p = 0.003), and variance of (acute v. control: p < 0.001, persistent v. control: p < 0.001) left and right pupil size. Eight of these metrics distinguished female cases from uninjured adolescents, but similar differences were not observed in male participants.ConclusionsObjective eye tracking technology can identify vision and pupillary disturbances after concussion. These metrics could be integrated into clinical practice to monitor recovery in a heterogeneous adolescent concussion population and may identify sex-specific differences in autonomic dysfunction.

Chewing and Cognitive Improvement: The Side Matters

Chewing improves cognitive performance, which is impaired in subjects showing an asymmetry in electromyographic (EMG) masseter activity during clenching. In these subjects, the simultaneous presence of an asymmetry in pupil size (anisocoria) at rest indicates an imbalance in Ascending Reticular Activating System (ARAS) influencing arousal and pupil size. The aim of the present study was to verify whether a trigeminal EMG asymmetry may bias the stimulating effect of chewing on cognition. Cognitive performance and pupil size at rest were recorded before and after 1 min of unilateral chewing in 20 subjects with anisocoria, showing an EMG asymmetry during clenching. Unilateral chewing stimulated performance mainly when it occurred on the side of lower EMG activity (and smaller pupil size). Following chewing on the hypotonic side, changes in cognitive performance were negatively and positively correlated with those in anisocoria and pupil size, respectively. We propose that, following chewing on the hypotonic side, the arousing effects of trigeminal stimulation on performance are enhanced by a rebalancing of ARAS structures. At variance, following chewing on the hypertonic side, the arousing effect of trigeminal stimulation could be partially or completely prevented by the simultaneous increase in ARAS imbalance.

“Blue Sky Effect”: Contextual Influences on Pupil Size During Naturalistic Visual Search

Pupil size is influenced by cognitive and non-cognitive factors. One of the strongest modulators of pupil size is scene luminance, which complicates studies of cognitive pupillometry in environments with complex patterns of visual stimulation. To help understand how dynamic visual scene statistics influence pupil size during an active visual search task in a visually rich 3D virtual environment (VE), we analyzed the correlation between pupil size and intensity changes of image pixels in the red, green, and blue (RGB) channels within a large window (~14 degrees) surrounding the gaze position over time. Overall, blue and green channels had a stronger influence on pupil size than the red channel. The correlation maps were not consistent with the hypothesis of a foveal bias for luminance, instead revealing a significant contextual effect, whereby pixels above the gaze point in the green/blue channels had a disproportionate impact on pupil size. We hypothesized this differential sensitivity of pupil responsiveness to blue light from above as a “blue sky effect,” and confirmed this finding with a follow-on experiment with a controlled laboratory task. Pupillary constrictions were significantly stronger when blue was presented above fixation (paired with luminance-matched gray on bottom) compared to below fixation. This effect was specific for the blue color channel and this stimulus orientation. These results highlight the differential sensitivity of pupillary responses to scene statistics in studies or applications that involve complex visual environments and suggest blue light as a predominant factor influencing pupil size.

Pupillometry and the vigilance decrement: Task-evoked but not baseline pupil measures reflect declining performance in visual vigilance tasks

Baseline and task-evoked pupil measures are known to reflect the activity of the nervous system's central arousal mechanisms. With the increasing availability, affordability and flexibility of video-based eye tracking hardware, these measures may one day find practical application in real-time biobehavioral monitoring systems to assess performance or fitness for duty in tasks requiring vigilant attention. But real-world vigilance tasks are predominantly visual in their nature and most research in this area has taken place in the auditory domain. Here we explore the relationship between pupil size—both baseline and task-evoked—and behavioral performance measures in two novel vigilance tasks requiring visual target detection: 1) a traditional vigilance task involving prolonged, continuous, and uninterrupted performance (n = 28), and 2) a psychomotor vigilance task (n = 25). In both tasks, behavioral performance and task-evoked pupil responses declined as time spent on task increased, corroborating previous reports in the literature of a vigilance decrement with a corresponding reduction in task-evoked pupil measures. Also in line with previous findings, baseline pupil size did not show a consistent relationship with performance measures. We discuss our findings considering the adaptive gain theory of locus coeruleus function and question the validity of the assumption that baseline (prestimulus) pupil size and task-evoked (poststimulus) pupil measures correspond to the tonic and phasic firing modes of the LC.

From pre-processing to advanced dynamic modeling of pupil data

The pupil of the eye provides a rich source of information for cognitive scientists, as it can index a variety of bodily states (e.g., arousal, fatigue) and cognitive processes (e.g., attention, decision-making). As pupillometry becomes a more accessible and popular methodology, researchers have proposed a variety of techniques for analyzing pupil data. Here, we provide recommendations and offer an up-to-date account of how pupil data can be analyzed in hypothesis-testing experiments. We first introduce pupillometry, its neural underpinnings, and the relation between pupil measurements, visual features (e.g., luminance), and other oculomotor behaviors (e.g., blinks, saccades), to stress the importance of understanding what is being measured and what can be inferred from changes in pupillary activity. We discuss pre-processing steps and contend that the insights gained from pupillometry are constrained by the analysis techniques available. Then, in addition to the traditional approach of analyzing mean pupil size within some epoch of interest, we focus on time series-based analyses, which enable one to relate dynamic changes in pupil size over time with dynamic changes in a stimulus series, task of interest, behavioral outcome measures, or other participants' pupil traces. Analytic techniques considered include: correlation (auto-, and cross-, reverse-, and inter/intra-subject-), regression (including temporal response functions), classification, dynamic time warping, phase clustering, magnitude squared coherence, detrended fluctuation analysis, and recurrence quantification analysis. Assumptions of these techniques, and examples of the scientific questions each can address, are outlined, with references to key papers and software packages.

Early phase of pupil dilation is mediated by the peripheral parasympathetic pathway

Pupil diameter fluctuates in association with changes in brain states induced by the neuromodulator systems. However, it remains unclear how the neuromodulator systems control the activity of the iris sphincter (constrictor) and dilator muscles to change the pupil size. The present study compared temporal patterns of pupil dilation during movement when each muscle was pharmacologically manipulated in the human eye. When the iris sphincter muscle was blocked with tropicamide, the latency of pupil dilation was delayed and the magnitude of pupil dilation was reduced during movement. In contrast, when the iris dilator muscle was continuously stimulated with phenylephrine, the latency and magnitude of rapid pupil dilation did not differ from the untreated control eye, but sustained pupil dilation was reduced until the end of movement. These results suggest that the iris sphincter muscle, which is under the control of the parasympathetic pathway, is quickly modulated by the neuromodulator system and plays a major role in rapid pupil dilation. However, the iris dilator muscle receives signals from the neuromodulator system with a slow latency and is involved in maintaining sustained pupil dilation.