Cortical and Cerebellar Contributions to Pupillary Light Reflex in Individuals with and without Autism Spectrum Disorder

Background: Accumulating evidence suggests that autism spectrum disorder (ASD) has its roots in early development, however diagnosis is not made until at least two years of age. Thus research in this field has mainly focused on the identification of behavioral, cognitive and neurophysiological markers that may serve as indicators for increased risk and also provide more insight into the neurophysiological mechanisms of ASD. Pupillary light reflex (PLR) which represents a stimulus-driven phenomenon whereby the pupil automatically dilates in response to the presentation of a bright luminance change is one such potential marker. Findings from previous studies suggest that PLR may be abnormal in individuals with ASD. Although the basis for ASD-related PLR is unclear, one possibility is that atypical PLR may arise from damage or disruption of other cortical and cerebellar areas not directly associated with modulation of the autonomic nervous system (ANS).

Objectives: We sought to further elucidate the neural basis for atypical PLR in individuals with ASD.

Methods: Twelve adolescents aged 13-18 years (M =16.1 yrs) with ASD and comparison sample of 12 neurologically uncompromised individuals without ASD aged 12-19 years (M =16.1 yrs) participated. We utilized a MRI-compatible eye monitoring system in concert with functional MRI (fMRI) to evaluate pupillary response and associated neural activity. Participants performed a passive viewing task in which they were shown a series of red-filtered, emotionally-neutral images that changed every 5 s. Every 20s the imperative stimulus (bright, dim, or black intensity levels) was superimposed over the red-filtered background. For each participant, PLR and neural responses were recorded for a total of 96 light stimulus trials (32 per condition). Trials were intermixed and presented over the course of 8 bold runs.

Results: Analysis of the eye tracking data revealed a main effect of condition (dim, bright) for constriction amplitude and time but not for latency. Greater constriction amplitude (18.3 ± 8.1 vs 10.4 ± 5.6) and time (469.4 ± 49.8 vs. 439 ± 49.1) were observed for the bright compared to the dim condition [F (1, 22) > 6.0, p < .05 in both instances]. There was no main effect of group (ASD, non-ASD) nor interaction effect of group and condition for any of the three PLR parameters. For the fMRI analyses, we found a group-by-PLR condition interaction for several regions including left cerebellum (-46, -64, -22), right ventral PFC (22, 32, -2), and right superior parietal lobule (30, -72, 46). In all cases, the activation contrast (Bright+Dim > Black) was greater for the ASD group as compared to the non-ASD group [t > 2.6, p < .05 in all instances].

Conclusions: Findings are consistent with previous studies (e.g., Nowinski et al, 2005) that have found that secondary regions such as cerebellum which project to the primary PLR circuitry are compromised in individuals with ASD and may possibly contribute to abnormal PLR.