Instructions for use Title Developmental hypothyroidism disrupts visual signal detection performance in rats

1 Thyroid hormones (THs) are essential for proper brain development in mammals. TH insufficiency 2 during early development causes structural and functional abnormalities in brain leading to cognitive 3 dysfunction. The specific effects of developmental hypothyroidism on attention have not been well 4 characterized in animal models. The present study was conducted to characterize the effects of 5 developmental hypothyroidism on attention in rats, and tested the hypothesis that the hypothyroidism has 6 adverse impacts on attention by means of a visual signal detection task. Pregnant rats were exposed to the 7 anti-thyroid drug, methimazole (0.02% w/v) via drinking water from gestational day 15 through postnatal 8 day (PND) 21 to induce maternal and neonatal hypothyroidism. Male offspring served as subjects for the 9 task started on PND 90. A light stimulus (500ms, 250ms or 50ms) was presented in signal trials and not 10 in blank trials. The offspring were required to discriminate these signal events, and subsequently press the 11 correct lever. The correct response for signal and non-signal events was considered as hit and correct 12 rejection, respectively. The hypothyroid offspring exhibited a decreased hit response for short signals 13 (250ms and 50ms) which requires the higher attentional demand. The total number of lever responses 14 during inter-trial interval (ITI) was also increased in the hypothyroid group. The number of lever 15 responses was negatively correlated with a hit response at 50ms, not at 250ms. These results suggest that 16 developmental hypothyroidism disrupts signal detection performance via impairment of visual attention 17 and the altered lever response behavior. 18 19 Keyword 20 attention; thyroid hormone; developmental hypothyroidism; signal detection task; rat 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36