Pupillometry, the measurement of pupil diameter, provides a glimpse into the internal mechanisms that guide attention and focused states. Among a number of innervations within the cortex, locus coeruleus-norephinephrine (LC-NE) connections modulate brain regions involved in visual attention, and pupil response serves as a biomarker for activation within the LC-NE system. Due to its degree of influence, small mechanistic differences in LC-NE functioning may lead to cascading deficits across various neurological domains. Aberrant pupil/LC-NE response has been demonstrated in a variety of clinical populations, including individuals with autism spectrum disorder (ASD), in whom hyperphasic activity has been found to facilitate enhanced visual perception in visual search tasks1. While hyperfocused attention may be specific to ASD, repetitive behaviors and restricted interests (RBRI) are frequently observed in a variety of developmental brain disorders, as well as in typical development, and may be best described as a dimensional construct.
Vanessa Troiani and her colleagues at the Geisinger Autism & Developmental Medicine Institute propose that aberrant LC-NE responses and subsequent modulations of visual attention are a source of brain dysfunction that results in cascading and pervasive maladaptive behaviors and cognitive deficits. This study will quantitatively measure variable performance and task-related pupil dilation to demonstrate the relationship between hyperphasic LC-NE activity and enhanced performance during visual search.
The researchers will examine the association between the phasic pupillary response during visual search, standardized measures of attention, and measures of RBRI in children with and without neurodevelopmental disorders, including those with ASD. They will also use a spatial prediction task to examine learning in response to changing, dynamic stimuli, and test the hypothesis that aberrant LC-NE activity derails adaptive learning in these individuals. To investigate potential genetic contributions of pupil response and the link to RBRI, the team will recruit a subsample of children with 16p11.2 de novo deletions. The proposed study, focused on inherent mechanisms, aims to provide a global framework in which to interpret the role(s) of the LC-NE system in brain function and dysfunction.
References:
1. Blaser E. et al. Sci. Rep. 4, 4301 (2014) PubMed
Interagency Autism Coordinating Committee (IACC)
Autism Research Database (AFD)
