Abstract
Previous studies revealed deficits in working memory among old macaques (> 20 years old) compared to younger macaques (< 14 years old) but have not thoroughly assessed these metrics in middle-aged macaques (14-19 years old). Here, we sought to develop a high-throughput adaptation of the 2-choice delayed response task of spatial working memory suitable to query middle-aged macaques in comparison to young-adult and very old rhesus macaques. We administered our manual 3-choice delayed response task to male and female monkeys ranging in age from 7 to 27 years, and included 3 choice locations to avoid floor effects and improve task sensitivity. Critically, Acquisition was limited to 15 blocks of 30 trials and used a short 1-second delay. Spatial memory was then probed using variable delays of 5, 10, 30, and 60 s. Retrieval accuracy (percent correct) significantly decreased with increasing delay length and age, as expected. In addition, we developed a new method to quantify the temporal and spatial distribution of responses and assess perseverative responding. The results identified age-dependent differences in memory, learning and perseveration, suggesting a decline in cognitive flexibility in late adulthood contributed to the memory deficits measured here. This task refinement therefore provides a novel approach to quantify errors in this age-sensitive short-term spatial memory task.