Psychostimulant Effects on Cognitive Flexibility and Risk-Based Decision-Making Behavior Following Repetitive Mild Traumatic Brain Injury
Abstract
Contribution to Understanding and Treatment of TBI: The proposal addresses the following focus areas of FY21 TBIHRP IIRA: (1) knowledge gaps in understanding the immediate and prolonged effects of repetitive mild traumatic brain injury (TBI) on higher order cognitive functions in male and female subjects and (2) pharmacologic intervention to treat cognitive dysfunction after repetitive brain injury. Military personnel frequently experience head injuries that range from mild to severe and can lead to acute and chronic problems with neurological functions, including slower processing speed and reaction time. Estimates of the prevalence of these injuries in military personnel range from 15.2-22.8%. Roughly 85% of these injuries are classified as mTBI, which are non-penetrative injuries and generally considered concussions. Furthermore, increasing evidence suggests that military personnel are subject to multiple mTBI events during the course of active duty. Such injuries can and often do negatively impact higher order executive functions, including the ability to attend or react with flexibility to dynamically changing environmental cues and the ability to evaluate options and make the most opportune decisions when faced with choices involving risk. These executive processes are critical for optimal performance of the tasks required of active duty military personnel who are engaged in mission critical operations. Moreover, the day-to-day health and well-being of TBI patients and their families can be severely affected by both short- and long-term executive dysfunction. Although overall women suffer TBI at a lower rate than men, recent reviews have reported that in both civilian and military populations; females suffer worse outcomes, demonstrate more neurocognitive impairments, and use more outpatient services than males. While the basic science of mTBI is advancing there is still a major gap in our understanding of the behavioral manifestations, underlying neurobiology, and treatment of mTBI and an even greater gap in knowledge regarding the consequences of repeated mTBI incidents. The goals of the current proposal are to understand the impact of multiple injury exposures on complex executive functions, assess sex differences in TBI-induced disruption of these processes, and create a platform to evaluate the potential for psychostimulant drug treatment to improve cognitive dysfunction following multiple mTBIs. Applicability of the Research: We will use an established rodent model of mTBI with proven translational validity to assess cognitive flexibility and risk-based decision making in male and female subjects exposed to repeated mild head impacts. Presently, neither cognitive flexibility nor risk-based decision-making are measured as part of the Military Acute Concussion Evaluation (MACE 2) standardized mental status exam used to evaluate the consequences of mTBI in military personnel. These two dimensions of executive function are critical for effective performance under active duty conditions. Cognitive flexibility will be tested using the automated strategy shifting task. Risk-based decision-making will be evaluated using the probability discounting task. Both tasks are established rodent tests of executive function that correspond to human clinical tests of executive function, i.e., the Wisconsin Card Sort Test (WCST) and Iowa Gambling Task (IGT), respectively. Our work will provide justification for use of WCST and IGT to evaluate higher order function in military personnel who experience mTBI, leading to a more comprehensive profile of their post-injury neurocognitive state and establishment of more sophisticated criteria for authorizing return to active duty and/or implementing treatment strategies. The same rodent assays will be used to identify an effective dose range of methylphenidate for treating short- and long-term TBI-induced deficits in executive function. Potential Clinical Applications
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210616
Entities
People
- Rachel L Navarra
Organizations
- UMDNJ – School of Osteopathic Medicine
- United States Army