TY - JOUR
T1 - Uncharacteristic task-evoked pupillary responses implicate atypical locus ceruleus activity in autism
AU - Granovetter, Michael C.
AU - Burlingham, Charlie S.
AU - Blauch, Nicholas M.
AU - Minshew, Nancy J.
AU - Heeger, David J.
AU - Behrmann, Marlene
N1 - Funding Information:
This work was supported by National Institute of General Medical Sciences Awards T32GM008208 and T32GM081760 to M.C.G., and Simons Foundation Autism Research Initiative Grant to M.B. and D.J.H. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institute of General Medical Sciences or the National Institutes of Health. We thank Drs. Yael Niv and Eran Eldar for initial discussions that stimulated the early framework of this study; Dr. Shaun E. Eack, Patricia J. McCarroll, and Michelle Perrin for assisting with recruitment; John J. Markiewicz for organization of the neuropsychological testing data; Drs. Ilan Dinstein and Eran Eldar for input on the study design; Drs. Ilan Dinstein and Sarah M. Haigh, whose experiment code was adapted for the study task; Dr. Timothy Verstynen and Madhumita Harish for input on the analyses; and the participants for making this research possible. Correspondence should be addressed to Michael C. Granovetter at granovetter@cmu.edu. https://doi.org/10.1523/JNEUROSCI.2680-19.2020 Copyright © 2020 the authors
Publisher Copyright:
Copyright © 2020 the authors
PY - 2020/5/6
Y1 - 2020/5/6
N2 - Autism spectrum disorder (ASD) is characterized partly by atypical attentional engagement, reflected in exaggerated and variable responses to sensory stimuli. Attentional engagement is known to be regulated by the locus ceruleus (LC). Moderate baseline LC activity globally dampens neural responsivity and is associated with adaptive deployment and narrowing of attention to task-relevant stimuli. In contrast, increased baseline LC activity enhances neural responsivity across cortex and widening of attention to environmental stimuli regardless of their task relevance. Given attentional atypicalities in ASD, this study is the first to evaluate whether, under different attentional task demands, individuals with ASD exhibit a different profile of LC activity compared with typically developing controls. Males and females with ASD and age- and gender-matched controls participated in a one-back letter detection test while task-evoked pupillary responses, an established correlate for LC activity, were recorded. Participants completed this task in two conditions, either in the absence or presence of distractor auditory tones. Compared with controls, individuals with ASD evinced atypical pupillary responses in the presence versus absence of distractors. Notably, this atypical pupillary profile was evident despite the fact that both groups exhibited equivalent task performance. Moreover, between-group differences in pupillary responses were observed specifically in response to task-relevant events, providing confirmation that the group differences most likely were specifically associated with distinctions in LC activity. These findings suggest that individuals with ASD show atypical modulation of LC activity with changes in attentional demands, offering a possible mechanistic and neurobiological account for attentional atypicalities in ASD.
AB - Autism spectrum disorder (ASD) is characterized partly by atypical attentional engagement, reflected in exaggerated and variable responses to sensory stimuli. Attentional engagement is known to be regulated by the locus ceruleus (LC). Moderate baseline LC activity globally dampens neural responsivity and is associated with adaptive deployment and narrowing of attention to task-relevant stimuli. In contrast, increased baseline LC activity enhances neural responsivity across cortex and widening of attention to environmental stimuli regardless of their task relevance. Given attentional atypicalities in ASD, this study is the first to evaluate whether, under different attentional task demands, individuals with ASD exhibit a different profile of LC activity compared with typically developing controls. Males and females with ASD and age- and gender-matched controls participated in a one-back letter detection test while task-evoked pupillary responses, an established correlate for LC activity, were recorded. Participants completed this task in two conditions, either in the absence or presence of distractor auditory tones. Compared with controls, individuals with ASD evinced atypical pupillary responses in the presence versus absence of distractors. Notably, this atypical pupillary profile was evident despite the fact that both groups exhibited equivalent task performance. Moreover, between-group differences in pupillary responses were observed specifically in response to task-relevant events, providing confirmation that the group differences most likely were specifically associated with distinctions in LC activity. These findings suggest that individuals with ASD show atypical modulation of LC activity with changes in attentional demands, offering a possible mechanistic and neurobiological account for attentional atypicalities in ASD.
KW - Attention
KW - Autism
KW - Excitation-inhibition
KW - Locus ceruleus
KW - Neural gain
KW - Pupillometry
UR - http://www.scopus.com/inward/record.url?scp=85084379654&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85084379654&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.2680-19.2020
DO - 10.1523/JNEUROSCI.2680-19.2020
M3 - Article
C2 - 32253362
AN - SCOPUS:85084379654
VL - 40
SP - 3815
EP - 3826
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 19
ER -