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

Temporal processing, including duration discrimination, is essential for survival and communication across species. Intellectual disability (ID), which can arise from diverse causes, including mutation in Cereblon (CRBN) gene, impairs duration discrimination. CRBN-related ID is associated with abnormal cognitive behaviors and may disrupt both perceptual and behavioral processes involved in duration discrimination. However, cross-species behavioral strategies, their variation with ID, and the behavioral indices underlying these strategies remain unclear. Here, humans and wild-type (WT) mice with typical intelligence and CRBN knockout (KO) mice with ID, all females across species, performed an auditory duration discrimination task involving 10-s and 2-s cues. All groups successfully distinguished the 10-s and 2-s cues, but their latency-based behavioral strategies diverged. In humans and WT mice, reaction time and latency for both stimuli clustered between 2 and 5 s, whereas in KO mice, they varied depending on the stimulus duration. WT mice and humans consistently delayed their responses by approximately 2 s relative to the 2-s cue length, reflecting response inhibition and alignment between group-level and individual-level responses. In contrast, KO mice exhibited more variable response patterns, consistent with impulsivity and misalignment between group-level and individual-level responses. These findings suggest that CRBN-related ID preserves duration discrimination while altering the behavioral response pattern associated with typical intelligence.