Cereblon-related mild intellectual disability disrupts response inhibition and uniformity of group--individual strategies

Abstract

Temporal processing, including duration, is essential for survival and communication across species. Intellectual disability (ID), which has diverse causes, including Cereblon (CRBN), impairs duration discrimination. CRBN-related ID, link to abnormal cognitive behaviors, may disrupt both perception and behavior during duration discrimination. However, cross-species behavioral strategies, their variation with ID, and associated behavioral indices remain unclear. Here, humans and wild-type (WT) mice with typical intelligence, and CRBN knockout (KO) mice with ID, performed an auditory duration discrimination task with Long (10 s) and Short (2 s) cues. All groups distinguished stimulus durations, but latency-based strategies diverged. KO mice showed impulsivity and divergent responses at both individual and group levels, whereas WT mice and humans consistently delayed their responses by [~]2 s to the Short cue length, reflecting inhibition and convergent responses. In typical intelligence models, latencies for both stimuli clustered between 2-5 s, while in ID model depended on stimulus duration. Duration perception is a conserved cross-species capacity, while task-specific cognitive strategies are intrinsically preserved though variation emerges with ID. We suggest that latency indices dissociated inhibition from impulsivity, and convergence from divergence. We further suggest that CRBN-related ID preserves perceptual understanding but disrupts the shared behavioral language of typical intelligence.