RESUMO
Introduction: Fragile X Syndrome (FXS) is a monogenic condition that leads to intellectual disability along with behavioral and learning difficulties. Among behavioral and learning difficulties, cognitive flexibility impairments are among the most commonly reported in FXS, which significantly impacts daily living. Despite the extensive use of the Fmr1 knockout (KO) mouse to understand molecular, synaptic and behavioral alterations related to FXS, there has been limited development of translational paradigms to understand cognitive flexibility that can be employed in both animal models and individuals with FXS to facilitate treatment development. Methods: To begin addressing this limitation, a parallel set of studies were carried out that investigated probabilistic reversal learning along with other behavioral and cognitive tests in individuals with FXS and Fmr1 KO mice. Fifty-five adolescents and adults with FXS (67% male) and 34 age- and sex-matched typically developing controls (62% male) completed an initial probabilistic learning training task and a probabilistic reversal learning task. Results: In males with FXS, both initial probabilistic learning and reversal learning deficits were found. However, in females with FXS, we only observed reversal learning deficits. Reversal learning deficits related to more severe psychiatric features in females with FXS, whereas increased sensitivity to negative feedback (lose:shift errors) unexpectedly appear to be adaptive in males with FXS. Male Fmr1 KO mice exhibited both an initial probabilistic learning and reversal learning deficit compared to that of wildtype (WT) mice. Female Fmr1 KO mice were selectively impaired on probabilistic reversal learning. In a prepotent response inhibition test, both male and female Fmr1 KO mice were impaired in learning to choose a non-preferred spatial location to receive a food reward compared to that of WT mice. Neither male nor female Fmr1 KO mice exhibited a change in anxiety compared to that of WT mice. Discussion: Together, our findings demonstrate strikingly similar sex-dependent learning disturbances across individuals with FXS and Fmr1 KO mice. This suggests the promise of using analogous paradigms of cognitive flexibility across species that may speed treatment development to improve lives of individuals with FXS.
RESUMO
The widespread adoption of smartphones has been associated with the emergence of problematic smartphone use. Problematic smartphone use is consistently associated with increased levels of depression and lower self-control, and pathological technology use more generally may be associated with reduced activity in the reward system, an effect that is also observed in depression and with poor self-control. The current study sought to examine the association between problematic smartphone use and event-related potentials (ERPs) related to reward processing, and to determine whether reward processing, depressive symptoms and self-control have shared or unique influences on problematic smartphone use. The sample was drawn from a university student population (N = 94, age M = 19.34, SD = 1.23 years, 67 female, 25 male, 1 gender non-conforming, 1 unidentified). Participants performed a gambling task while EEG was recorded and completed measures of smartphone pathology, depressive symptoms and self-control. The ERP data revealed that increasing problematic smartphone use was associated with reduced ERP amplitude for gains and losses when individuals were the agent of choice, but not when the computer chose. This may reflect a selective association between problematic smartphone use and neural prediction errors. Regression analyses revealed that reward processing, depressive symptoms and self-control were predictors of problematic smartphone use, possibly revealing multiple pathways to problematic smartphone use.
