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      Repetitive Blast Exposure Increases Appetitive Motivation and Behavioral Inflexibility in Male Mice

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          Abstract

          Blast exposure ( via detonation of high explosives) represents a major potential trauma source for Servicemembers and Veterans, often resulting in mild traumatic brain injury (mTBI). Executive dysfunction (e.g., alterations in memory, deficits in mental flexibility, difficulty with adaptability) is commonly reported by Veterans with a history of blast-related mTBI, leading to impaired daily functioning and decreased quality of life, but underlying mechanisms are not fully understood and have not been well studied in animal models of blast. To investigate potential underlying behavioral mechanisms contributing to deficits in executive functioning post-blast mTBI, here we examined how a history of repetitive blast exposure in male mice affects anxiety/compulsivity-like outcomes and appetitive goal-directed behavior using an established mouse model of blast mTBI. We hypothesized that repetitive blast exposure in male mice would result in anxiety/compulsivity-like outcomes and corresponding performance deficits in operant-based reward learning and behavioral flexibility paradigms. Instead, results demonstrate an increase in reward-seeking and goal-directed behavior and a congruent decrease in behavioral flexibility. We also report chronic adverse behavioral changes related to anxiety, compulsivity, and hyperarousal. In combination, these data suggest that potential deficits in executive function following blast mTBI are at least in part related to enhanced compulsivity/hyperreactivity and behavioral inflexibility and not simply due to a lack of motivation or inability to acquire task parameters, with important implications for subsequent diagnosis and treatment management.

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          Most cited references46

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          Motivation concepts in behavioral neuroscience.

          Concepts of motivation are vital to progress in behavioral neuroscience. Motivational concepts help us to understand what limbic brain systems are chiefly evolved to do, i.e., to mediate psychological processes that guide real behavior. This article evaluates some major motivation concepts that have historic importance or have influenced the interpretation of behavioral neuroscience research. These concepts include homeostasis, setpoints and settling points, intervening variables, hydraulic drives, drive reduction, appetitive and consummatory behavior, opponent processes, hedonic reactions, incentive motivation, drive centers, dedicated drive neurons (and drive neuropeptides and receptors), neural hierarchies, and new concepts from affective neuroscience such as allostasis, cognitive incentives, and reward 'liking' versus 'wanting'. Copyright 2004 Elsevier Inc.
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            Mild traumatic brain injury in U.S. Soldiers returning from Iraq.

            An important medical concern of the Iraq war is the potential long-term effect of mild traumatic brain injury, or concussion, particularly from blast explosions. However, the epidemiology of combat-related mild traumatic brain injury is poorly understood. We surveyed 2525 U.S. Army infantry soldiers 3 to 4 months after their return from a year-long deployment to Iraq. Validated clinical instruments were used to compare soldiers reporting mild traumatic brain injury, defined as an injury with loss of consciousness or altered mental status (e.g., dazed or confused), with soldiers who reported other injuries. Of 2525 soldiers, 124 (4.9%) reported injuries with loss of consciousness, 260 (10.3%) reported injuries with altered mental status, and 435 (17.2%) reported other injuries during deployment. Of those reporting loss of consciousness, 43.9% met criteria for post-traumatic stress disorder (PTSD), as compared with 27.3% of those reporting altered mental status, 16.2% with other injuries, and 9.1% with no injury. Soldiers with mild traumatic brain injury, primarily those who had loss of consciousness, were significantly more likely to report poor general health, missed workdays, medical visits, and a high number of somatic and postconcussive symptoms than were soldiers with other injuries. However, after adjustment for PTSD and depression, mild traumatic brain injury was no longer significantly associated with these physical health outcomes or symptoms, except for headache. Mild traumatic brain injury (i.e., concussion) occurring among soldiers deployed in Iraq is strongly associated with PTSD and physical health problems 3 to 4 months after the soldiers return home. PTSD and depression are important mediators of the relationship between mild traumatic brain injury and physical health problems. Copyright 2008 Massachusetts Medical Society.
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              Mild Traumatic Brain Injury (mTBI) and chronic cognitive impairment: A scoping review

              Mild traumatic brain injury (mTBI), or concussion, is the most common type of traumatic brain injury. With mTBI comes symptoms that include headaches, fatigue, depression, anxiety and irritability, as well as impaired cognitive function. Symptom resolution is thought to occur within 3 months post-injury, with the exception of a small percentage of individuals who are said to experience persistent post-concussion syndrome. The number of individuals who experience persistent symptoms appears to be low despite clear evidence of longer-term pathophysiological changes resulting from mTBI. In light of the incongruency between these longer-term changes in brain pathology and the number of individuals with longer-term mTBI-related symptoms, particularly impaired cognitive function, we performed a scoping review of the literature that behaviourally assessed short- and long-term cognitive function in individuals with a single mTBI, with the goal of identifying the impact of a single concussion on cognitive function in the chronic stage post-injury. CINAHL, Embase, and Medline/Ovid were searched July 2015 for studies related to concussion and cognitive impairment. Data relating to the presence/absence of cognitive impairment were extracted from 45 studies meeting our inclusion criteria. Results indicate that, in contrast to the prevailing view that most symptoms of concussion are resolved within 3 months post-injury, approximately half of individuals with a single mTBI demonstrate long-term cognitive impairment. Study limitations notwithstanding, these findings highlight the need to carefully examine the long-term implications of a single mTBI.
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                Author and article information

                Contributors
                Journal
                Front Behav Neurosci
                Front Behav Neurosci
                Front. Behav. Neurosci.
                Frontiers in Behavioral Neuroscience
                Frontiers Media S.A.
                1662-5153
                22 December 2021
                2021
                : 15
                : 792648
                Affiliations
                [1] 1VA Northwest Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System , Seattle, WA, United States
                [2] 2Department of Psychiatry and Behavioral Sciences, University of Washington , Seattle, WA, United States
                [3] 3Graduate Program in Neuroscience, University of Washington , Seattle, WA, United States
                [4] 4VA Northwest Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System , Seattle, WA, United States
                [5] 5Department of Pharmacology, University of Washington , Seattle, WA, United States
                [6] 6Department of Medicine, University of Washington , Seattle, WA, United States
                Author notes

                Edited by: Christopher Olsen, Medical College of Wisconsin, United States

                Reviewed by: Fiona Harrison, Vanderbilt University Medical Center, United States; Serge Campeau, University of Colorado Boulder, United States

                *Correspondence: Abigail G. Schindler aschind@ 123456u.washington.edu

                Specialty section: This article was submitted to Pathological Conditions, a section of the journal Frontiers in Behavioral Neuroscience

                Article
                10.3389/fnbeh.2021.792648
                8727531
                ee956b2b-89a8-4a2b-9d4c-c37254db34a9
                Copyright © 2021 Baskin, Lee, Skillen, Wong, Rau, Hendrickson, Pagulayan, Raskind, Peskind, Phillips, Cook and Schindler.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 10 October 2021
                : 25 November 2021
                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 46, Pages: 10, Words: 7002
                Categories
                Behavioral Neuroscience
                Brief Research Report

                Neurosciences
                traumatic brain injury,executive function,veteran,motivation,blast,behavioral flexibility

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