Abstract
BACKGROUND: Neurodevelopmental disorders (NDD) cause individuals to have difficulty in learning facts, procedures, or social skills. NDD has been linked to several genes, and several animal models have been used to identify potential therapeutic candidates based on specific learning paradigms for long-term and associative memory. In individuals with NDD, however, such testing has not been used so far, resulting in a gap in translating preclinical results to clinical practice. OBJECTIVE: We aim to assess if individuals with NDD could be tested for paired association learning and long-term memory deficit, as shown in previous animal models. METHODS: We developed an image-based paired association task, which can be performed at different time points using remote web-based testing, and evaluated its feasibility in children with typical development (TD), as well as NDD. We included 2 tasks: object recognition as a simpler task and paired association. Learning was tested immediately after training and also the next day for long-term memory. RESULTS: We found that children aged 5-14 years with TD (n=128) and with NDD of different types (n=57) could complete testing using the Memory Game. Children with NDD showed deficits in both recognition and paired association tasks on the first day of learning, in both 5-9-year old (P<.001 and P=.01, respectively) and 10-14-year old groups (P=.001 and P<.001, respectively). The reaction times to stimuli showed no significant difference between individuals with TD or NDD. Children with NDD exhibited a faster 24-hour memory decay for the recognition task than those with TD in the 5-9-year old group. This trend is reversed for the paired association task. Interestingly, we found that children with NDD had their retention for recognition improved and matched with typically developing individuals by 10-14 years of age. The NDD group also showed improved retention deficits in the paired association task at 10-14 years of age compared to the TD group. CONCLUSIONS: We showed that web-based learning testing using simple picture association is feasible for children with TD, as well as with NDD. We showed how web-based testing allows us to train children to learn the association between pictures, as shown in immediate test results and those completed 1 day after. This is important as many models for learning deficits in NDD target both short- and long-term memory for therapeutic intervention. We also demonstrated that despite potential confounding factors, such as self-reported diagnosis bias, technical issues, and varied participation, the Memory Game shows significant differences between typically developing children and those with NDD. Future experiments will leverage this potential of web-based testing for larger cohorts and cross-validation with other clinical or preclinical cognitive tasks.