ENVIRONMENTAL CONTEXT SHAPES SEX-SPECIFIC RESILIENCE TO ADHD-LIKE PHENOTYPES FOLLOWING EARLY SENSORY OVERSTIMULATION

Early-life exposure to excessive sensory stimulation (ESS), such as continuous audiovisual input from digital media, has been linked to attention-deficit/hyperactivity disorder (ADHD). However, the consequences of sensory overload are complex: ESS differentially affects males and females, and many individuals remain resilient. Here, we use a mouse model to examine how sex and environmental context shape vulnerability and resilience to early-life ESS. For that, juvenile female and male CD-1 mice were exposed to six hours of daily audiovisual overstimulation for 42 days. Behavioral outcomes were assessed under low- and high-light testing conditions, representing low- and high-anxiogenic contexts. Under low anxiogenic contexts, ESS did not uniformly induce an ADHD-like behavioral phenotype. Locomotor activity and cognitive functions remained largely intact; however, ESS was associated with sex-dependent divergence in anxiety-related behavior, risk-taking, and spatial memory, accompanied by pronounced interindividual variability. Variability in anxiety-related measures was particularly increased in females, whereas males showed more uniform cognitive performance.
By contrast, exposure to a high anxiogenic context unmasked robust ADHD-like phenotypes in ESS-exposed mice of both sexes, characterized by hyperactivity, increased risk-taking behavior, and impairments in object recognition memory. Behavioral variability under these conditions shifted in a sex-dependent manner, with greater divergence observed in males.
Together, these findings demonstrate that early-life sensory overstimulation biases neurobehavioral trajectories in a sex- and context-dependent manner. Environmental demand critically determines whether ESS-related vulnerability is buffered or expressed, highlighting the importance of considering sex, context, and behavioral heterogeneity when modeling ADHD-relevant phenotypes and resilience.