Home-cage monitoring as a sensitive tool for detecting subtle behavioral alterations following mild traumatic brain injury.

Home-cage monitoring (HCM) has emerged as a powerful approach for detecting subtle and context-dependent behavioral alterations in rodent models. In this mini-review, we integrate clinical observations and preclinical data from the closed-head weight-drop model, emphasizing studies from our laboratory, to argue that mTBI should be conceptualized as a disorder of behavioral regulation rather than of basic behavioral capacity. We first outline the limitations of short, novelty-driven gold-standard assays (e.g., Open Field, Elevated Plus Maze, Rotarod), which often indicate intact motor function and no robust anxiety-like behavior in mTBI mice, despite converging evidence of neural and clinical dysfunction. We then summarize the converging HCM findings, demonstrating circadian disruption, altered habituation trajectories, residual avoidance, and changes in the microstructure of wheel-running. These long-duration, stress-free measures uncover fine-grained temporal signatures that closely parallel post-concussion syndrome in humans, including disturbed sleep-wake regulation, heightened stress sensitivity, and cognitive inflexibility. Finally, we propose practical recommendations for integrating HCM with standard behavioral assays and highlight candidate digital behavioral biomarkers relevant to mTBI. Taken together, the evidence supports a conceptual shift toward adopting continuous HCM-derived metrics as core outcome measures.