Explicit and implicit learning and memory networks exist where each network can facilitate or inhibit memory. Clinical evidence suggests that implicit networks are relatively preserved after traumatic brain injury (TBI). Non-spatial pre-training (NSPT) in the Morris water maze (MWM) provides the necessary behavioral components to complete the task, while limiting the formation of spatial maps. Our study utilized NSPT in the MWM to assess implicit and explicit learning and memory system deficits in the controlled cortical impact (CCI) model of TBI. 76 adult male Sprague-Dawley rats were divided: CCI vs. sham surgery, NSPT vs. No-NSPT, and cued vs. non-cued groups. NSPT occurred for 4d prior to surgery (dynamic hidden platform location, extra-maze cues covered, static pool entry point). Acquisition (d14–18), Probe/Visible Platform (d19), and Reversal (d20–21) trials were conducted with or without extra-maze cues. Novel time allocation and search strategy selection metrics were utilized. Results indicated implicit and explicit learning/memory networks are distinguishable in the MWM. In the cued condition, NSPT reduced thigmotaxis, improved place learning, and largely eliminated the apparent injury-induced deficits typically observed between untrained CCI and sham rats. However, among NSPT groups, incorporation of cues into search strategy selection for CCI rats was relatively impaired compared to shams. Non-cued condition performance showed sham/NSPT and CCI/NSPT rats perform similarly, suggesting implicit memory networks are largely intact 2 weeks after CCI. Place learning differences between CCI/NSPT and sham/NSPT rats more accurately reflect spatial deficits in our CCI model compared to untrained controls. These data suggest NSPT as a clinically relevant construct for evaluating potential neurorestorative and neuroprotective therapies. These findings also support development of non-spatial cognitive training paradigms for evaluating rehabilitation relevant combination therapies.

Background Following traumatic brain injury (TBI), clinical cognitive training paradigms harness implicit and explicit learning and memory systems to improve function; however, these systems are differentially affected by TBI, highlighting the need for an experimental TBI model that can test efficacy of cognitive training approaches. Objectives To develop a clinically relevant experimental cognitive training model using the Morris water maze (MWM) wherein training on implicitly learned task components was provided to improve behavioral performance post-TBI. Methods: 81 adult male rats were divided by injury status [controlled cortical impact (CCI)/Sham], non-spatial cognitive training (CogTrained/No-CogTrained), and extra-maze cues (Cued/Non-Cued) during MWM testing. Platform latencies, thigmotaxis, and search strategies were assessed during MWM trials. Results Cognitive training was associated with improved platform latencies, reduced thigmotaxis, and more effective search strategy use for Sham and CCI rats. In the Cued and Non-Cued MWM paradigm, there were no differences between CCI/CogTrained and Sham/No-CogTrained groups. During novel testing conditions, CogTrained groups applied implicitly learned knowledge/skills; however, sham-cued CogTrained/rats better incorporated extramaze cues into their search strategy than the CCI-Cued group. Cognitive training had no effects on contusion size or hippocampal cell survival. Conclusions The results provide evidence that CCI-CogTrained rats that learned the non-spatial components of the MWM task applied these skills during multiple conditions of the place-learning task, thereby mitigating cognitive deficits typically associated with this injury model. The results show that a systematic application of clinically relevant constructs associated with cognitive training paradigms can be used with experimental TBI to affect place learning.

Objectives The primary outcome of this study was to assess the efficacy and safety of preventive treatment with amitriptyline on headache frequency and severity after mild traumatic brain injury (mTBI). Background Despite the fact that headache is the most common and persistent physical symptom after TBI, there has been little research on the longitudinal course or pharmacologic treatment of this disorder. Of those who have headache after injury, about 60% continue to complain of headache at 3 months post injury, with higher levels of disability than those without headache. There have been no prospective, randomized, controlled trials of a pharmacologic agent for headache after TBI. Additionally, a brain‐injured population may be more susceptible to side effects of medication. Design This is a single‐center phase II trial of amitriptyline to prevent persistent headache after an mTBI. Medication dose was gradually increased from 10 to 50 mg daily. Results Fifty participants were enrolled and 33 who completed the 90‐day assessment were included in the final analysis. In order to detect a possible cognitive impact of the study drug, 24 participants were randomly assigned to start amitriptyline immediately after study enrollment and 26 were assigned to start 30 days after enrollment. Forty‐nine percent (18/37) of those assigned to take medication took none throughout the study period, with less compliance in younger participants with mean ages of 32.7 in those who did not take any medication, 33.4 who were less than 80% compliant, and 42.3 who were compliant (P = .013). Compliance in keeping a daily headache diary was low, with 29/50 participants (58%) meeting daily entry completion, and only 10 participants maintaining 100% diary completion. No differences were found between those who started medication immediately vs at day 30 in headache frequency or severity. Conclusions While headache is the most common symptom following mTBI, current evidence does not support a specific treatment. No differences were noted in headache frequency compared to our prior study. However, the current sample had significantly lower headache severity (15% vs 36% with pain rating of 6 or above, P = .015) compared to our prior study. Our current study was not able to determine whether there is any benefit for the use of amitriptyline as a headache preventive because of difficulty with study recruitment and compliance. The challenges with recruitment and retention in the mTBI population were instructive, and future research in this area will need to identify strategies to improve recruitment, diary compliance, and medication adherence in this population.

Together with previous work assessing daily LEV treatment, these results suggest that longer-term therapy may be required to confer beneficial effects within these domains. These findings may guide (1) future experimental studies assessing minimal effective dosing for neuroprotection and anti-epileptogenesis and (2) treatment guideline updates for seizure prophylaxis post-TBI.

Purpose of Review Our goal is to provide a current review of health disparities in patients with dysvascular lower extremity amputation, so that we can better identify how disparities persist after an amputation and how to reduce these disparities. Recent Findings Health disparities in amputation risk, level, and outcomes exist in the USA based on race/ethnicity, gender, income, insurance, care provider, hospital, neighborhood, and US region. Summary While health disparities exist for patients with dysvascular lower extremity amputation, little is known about differences in function, rehabilitation, and prosthesis prescriptions. Future research in this area is important, so that we can better identify how disparities persist after an amputation.