Dataset Information

Using Pupillometry to Assess the Atypical Pupillary Light Reflex and LC-NE System in ASD.

ABSTRACT: With recent advances in technology, there has been growing interest in use of eye-tracking and pupillometry to assess the visual pathway in autism spectrum disorder (ASD). Within emerging literature, an atypical pupillary light reflex (PLR) has been documented, holding potential for use as a clinical screening biomarker for ASD. This review outlines dominant theories of neuropathology associated with ASD and integrates underlying neuroscience associated with the atypical PLR through a reciprocal model of brainstem involvement and cortical underconnectivity. This review draws from animal models of ASD demonstrating disruption of cranial motor nuclei and brain imaging studies examining arousal and the influence of the locus coeruleus norepinephrine (LC-NE) system on the pupillary response. Pupillometry methods are explained in relation to existing data examining the PLR in ASD and pupillary parameters of constriction latency and tonic pupil diameter as key parameters for investigation. This focused review provides preliminary data toward future work developing pupillometry metrics and offers direction for studies aimed at rigorous study replication using pupillometry with the ASD population. Experimental conditions and testing protocol for capturing pupil parameters with this clinical population are discussed to promote clinical research and translational application.

SUBMITTER: Lynch G

PROVIDER: S-EPMC6262612 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Using Pupillometry to Assess the Atypical Pupillary Light Reflex and LC-NE System in ASD.

Lynch Georgina G

Behavioral sciences (Basel, Switzerland) 20181121 11

With recent advances in technology, there has been growing interest in use of eye-tracking and pupillometry to assess the visual pathway in autism spectrum disorder (ASD). Within emerging literature, an atypical pupillary light reflex (PLR) has been documented, holding potential for use as a clinical screening biomarker for ASD. This review outlines dominant theories of neuropathology associated with ASD and integrates underlying neuroscience associated with the atypical PLR through a reciprocal ...[more]

PMID: 30469373

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Project description:Non-visual photoreceptors (ipRGCs) and rods both exert a strong influence on the human pupil, yet pupil models regularly use cone-derived sensitivity as their basis. This inconsistency is further exacerbated by the fact that circadian effects can modulate the wavelength sensitivity. We assessed the pupillary reaction to narrowband light stimuli in the mesopic range. Pupil size for eighty-three healthy participants with normal color vision was measured in nine experimental protocols with varying series of continuous or discontinuous light stimuli under Ganzfeld conditions, presented after 90 seconds of dark adaptation. One hundred and fifty series of stimulation were conducted across three experiments, and were analyzed for wavelength-dependency on the normalized pupillary constriction (nPC), conditional on experimental settings and individual traits. Traits were surveyed by questionnaire; color vision was tested by Ishihara plates or the Lanthony D15 test. Data were analyzed with generalized additive mixed models (GAMM). The normalized pupillary constriction response is consistent with L+M-cone derived sensitivity when the series of light stimuli is continuous, i.e., is not interrupted by periods of darkness, but not otherwise. The results also show that a mesopic illuminance weighing led to an overall best prediction of pupillary constriction compared to other types of illuminance measures. IpRGC influence on nPC is not readily apparent from the results. When we explored the interaction of chronotype and time of day on the wavelength dependency, differences consistent with ipRGC influence became apparent. The models indicate that subjects of differing chronotype show a heightened or lowered sensitivity to short wavelengths, depending on their time of preference. IpRGC influence is also seen in the post-illumination pupil reflex if the prior light-stimulus duration is one second. However, shorter wavelengths than expected become more important if the light-stimulus duration is fifteen or thirty seconds. The influence of sex on nPC was present, but showed no interaction with wavelength. Our results help to define the conditions, under which the different wavelength sensitivities in the literature hold up for narrowband light settings. The chronotype effect might signify a mechanism for strengthening the individual´s chronotype. It could also be the result of the participant's prior exposure to light (light history). Our explorative findings for this effect demand replication in a controlled study.

Project description:ImportanceConcussion diagnosis remains clinical, without objective diagnostic tests available for adolescents. Known deficits in visual accommodation and autonomic function after concussion make the pupillary light reflex (PLR) a promising target as an objective physiological biomarker for concussion.ObjectiveTo determine the potential utility of PLR metrics as physiological biomarkers for concussion.Design, setting, and participantsProspective cohort of adolescent athletes between ages 12 and 18 years recruited between August 1, 2017, and December 31, 2018. The study took place at a specialty concussion program and private suburban high school and included healthy control individuals (n = 134) and athletes with a diagnosis of sport-related concussion (SRC) (n = 98). Analysis was completed June 30, 2020.ExposuresSports-related concussion and pupillometry assessments.Main outcomes and measuresPupillary light reflex metrics (maximum and minimum pupillary diameter, peak and average constriction/dilation velocity, percentage constriction, and time to 75% pupillary redilation [T75]).ResultsPupillary light reflex metrics of 134 healthy control individuals and 98 athletes with concussion were obtained a median of 12.0 days following injury (interquartile range [IQR], 5.0-18.0 days). Eight of 9 metrics were significantly greater among athletes with concussion after Bonferroni correction (maximum pupil diameter: 4.83 mm vs 4.01 mm; difference, 0.82; 99.44% CI, 0.53-1.11; minimum pupil diameter: 2.96 mm vs 2.63 mm; difference, 0.33; 99.4% CI, 0.18-0.48; percentage constriction: 38.23% vs 33.66%; difference, 4.57; 99.4% CI, 2.60-6.55; average constriction velocity: 3.08 mm/s vs 2.50 mm/s; difference, 0.58; 99.4% CI, 0.36-0.81; peak constriction velocity: 4.88 mm/s vs 3.91 mm/s; difference, 0.97; 99.4% CI, 0.63-1.31; average dilation velocity, 1.32 mm/s vs 1.22 mm/s; difference, 0.10; 99.4% CI, 0.00-0.20; peak dilation velocity: 1.83 mm/s vs 1.64 mm/s; difference, 0.19; 99.4% CI, 0.07-0.32; and T75: 1.81 seconds vs 1.51 seconds; difference, 0.30; 0.10-0.51). In exploratory analyses, sex-based differences were observed, with girls with concussion exhibiting longer T75 (1.96 seconds vs 1.63 seconds; difference, 0.33; 99.4% CI, 0.02-0.65). Among healthy control individuals, diminished PLR metrics (eg, smaller maximum pupil size 3.81 mm vs 4.22 mm; difference, -0.41; 99.4% CI, -0.77 to 0.05) were observed after exercise.Conclusions and relevanceThese findings suggest that enhancement of PLR metrics characterize acute adolescent concussion, while exercise produced smaller pupil sizes and overall slowing of PLR metrics, presumably associated with fatigue. Quantifiable measures of the PLR may serve in the future as objective physiologic biomarkers for concussion in the adolescent athlete.

Dataset Information

Using Pupillometry to Assess the Atypical Pupillary Light Reflex and LC-NE System in ASD.

Publications

Using Pupillometry to Assess the Atypical Pupillary Light Reflex and LC-NE System in ASD.

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