Robust training attenuates TBI-induced deficits in reference and working memory on the radial 8-arm maze

Abstract

Globally, it is estimated that nearly 10 million people sustain severe brain injuries leading to hospitalization and/or death every year. Amongst survivors, traumatic brain injury (TBI) results in a wide variety of physical, emotional and cognitive deficits. The most common cognitive deficit associated with TBI is memory loss, involving impairments in spatial reference and working memory. However, the majority of research thus far has characterized the deficits associated with TBI on either reference or working memory systems separately, without investigating how they interact within a single task. Thus, we examined the effects of TBI on short-term working and long-term reference memory using the radial 8-arm maze (RAM) with a sequence of four baited and four unbaited arms. Subjects were given 10 daily trials for 6 days followed by a memory retrieval test 2 weeks after training. Multiple training trials not only provide robust training, but also test the subjects' ability to frequently update short-term memory while learning the reference rules of the task. Our results show that TBI significantly impaired short-term working memory function on previously acquired spatial information but has little effect on long-term reference memory. Additionally, TBI significantly increased working memory errors during acquisition and reference memory errors during retention testing 2 weeks later. With a longer recovery period after TBI, the robust RAM training mitigated the reference memory deficit in retention but not the short-term working memory deficit during acquisition. These results identify the resiliency and vulnerabilities of short-term working and long-term reference memory to TBI in the context of robust training. The data highlight the role of cognitive training and other behavioral remediation strategies implicated in attenuating deficits associated with TBI.

Keywords: radial arm maze; reference memory; robust training; traumatic brain injury; working memory.

Figure 1

TBI post-training induces working memory deficits during retention testing. (A) Schematic diagram of the experimental design and timeline for experiment 1. (B,C) During training, there were no differences observed between groups during their pre-surgery assessment for acquisition of the RAM task. There was a significant improvement in percent correct and significant decreases in working and reference memory errors across training days for both groups (^***p < 0.001). (D,E) During retention testing, TBI impaired memory retrieval with a decrease in percent correct score and an increase in working memory errors (^*p < 0.05).

Figure 2

TBI induces differential memory deficits during training and retention testing 3 weeks post-injury. (A) Schematic diagram of the experimental design and timeline for experiment 2. (B,C) During training, there was a significant improvement in percent correct and a significant decrease in reference errors across training days for both groups (^***p < 0.001). There was also an overall increase in working memory errors over time (^*p < 0.05) and a deficit in working memory in the TBI group (^∧p < 0.05). (D,E) During retention testing, TBI impaired memory retrieval with a decrease in percent correct score and an increase in reference memory errors (^*p < 0.05).

Figure 3

TBI induces working memory deficits during training 6 weeks post-injury but does not impact memory retention. (A) Schematic diagram of the experimental design and timeline for experiment 3. (B,C) During training, there was a significant improvement in percent correct and significant decreases in working and reference memory errors across training days for both groups (^***p < 0.001). There was also a deficit in working memory in the TBI group (^∧∧p < 0.01). (D,E) During retention testing, there were no significant differences in performance between groups.