Male mice are particularly vulnerable to cognitive impairment following mTBI

bioRxiv [Preprint]. 2026 Feb 23:2026.02.21.707169. doi: 10.64898/2026.02.21.707169.

Abstract

Traumatic brain injuries (TBIs) result from impact to or rapid displacement of the brain and can lead to various neurological deficits involving working memory, decision-making, and anxiety. While large-scale effects of brain damage are well-described for more severe TBIs, less is known about the extent and duration of cognitive deficits at the mild level. Interval timing can provide a helpful window into cognition in mice and humans. Interval-timing behavior is impaired in a wide range of neuropsychiatric disease states, such as Parkinson's disease. Furthermore, novel object recognition (NOR) and the Barnes maze (BM) tests are valuable assays for evaluating spatial learning, working memory, and anxiety-like behavior in mice. Here, we employed a weight-drop model of mild TBI (mTBI) to investigate changes in internal cognitive states resulting from mTBI treatment. mTBI mice were not significantly impaired in either interval timing or NOR, but they demonstrated impaired spatial memory in the Barnes Maze. Interestingly, within-sex comparisons revealed impairments in male mTBI mice in the interval-timing task and the NOR, suggesting that male and female mice may be differently affected by mTBIs.

Keywords: Barnes maze; behavioral flexibility; cognitive control; executive function; interval timing; mild traumatic brain injury; novel object recognition; radial arm maze; sex differences; working memory.

Publication types

  • Preprint