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Sport-related concussion has garnered increasing scientific attention and research over the last decade. Collegiate student-athletes represent an important cohort in this field. As such, the Pac-12 CARE-Affiliated Program (CAP) was formed in 2017 as a regional hub of the Concussion Assessment, Research and Education (CARE) consortium. CAP is multisite, prospective, longitudinal study that aims to improve student-athlete health by identifying factors associated with concussion incidence and recovery and using this knowledge to inform best clinical practices and policy decisions. CAP employed a staggered rollout across the Pac-12, with the first four institutions enrolling in fall 2018. After receiving institutional review board (IRB) approval, these institutions began consenting student-athletes to share clinical concussion and baseline data for research purposes. Athletes completed baseline testing that included a medical questionnaire, concussion history and a battery for clinical concussion assessments. Concussed student-athletes were given the same battery of assessments in addition to full injury and return to play reports. Clinicians at each university worked with a data coordinator to ensure appropriate reporting, and the Pac-12 Concussion Coordinating Unit at the University of Colorado Boulder provided oversight for quality control of the data study wide. During year 1, CAP consented 2181 student-athletes and tracked 140 concussions. All research was conducted with the appropriate IRB approval across the participating Pac-12 institutions. Data security and dissemination are managed by the Presagia Sports Athlete Electronic Health Record software (Montreal, Quebec, Canada) and QuesGen Systems (San Francisco, California, USA).

Background Mild traumatic brain injury (mTBI) is a signature injury sustained by Veterans during recent conflicts. For some, mTBI/concussion is associated with disabling symptoms, including post-concussive headaches (PCH). However, there are limited evidence-based treatments for persistent PCH. Objective Investigators assessed the feasibility of design elements of a yoga-based interventional trial for PCH among Veterans, as well as the acceptability of the intervention. Methods This randomized controlled acceptability and feasibility trial was implemented using a waitlist-control design. Design elements of interest included: an exercise run-in class; recruitment and retention strategies; and, ecological momentary assessment (EMA) modalities to track headaches and yoga practice. Veteran satisfaction regarding the intervention was also evaluated. A descriptive analysis was conducted on candidate outcomes including PCH, post-concussive symptoms, pain, and daily functioning. Results Twenty-seven participants (out of 70 consented and eligible after Study Visit 1) completed each evaluation timepoint and regularly attended yoga sessions, with 89% of these Veterans reporting moderate to high levels of satisfaction with the intervention at study completion. Qualitatively, participants endorsed improvements in headaches, chronic pain, and mood. Feasibility results were mixed. Initial feasibility criterion regarding yoga attendance was not met; however, modifications, such as expansion to an additional clinic site and reduction of in-person yoga sessions with increased encouragement to use study-created online yoga videos improved feasibility of the study design. Participants most frequently used mobile and web-based EMA modalities to track yoga practice. Conclusions Although challenges with feasibility of the study design elements were noted, results suggested acceptability of the yoga-based intervention for Veterans with persistent PCH. Additional exploration regarding the frequency and modality of yoga delivery (e.g., in-person, telehealth) is warranted. Impact Veterans found the yoga-based intervention acceptable, however exploration of novel modalities of intervention delivery will likely be necessary to enhance the feasibility of intervention implementation during future trials.

Given the upsurge of research in posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI), much of which has focused on military samples who served in Iraq and Afghanistan, the purpose of this article is to review the literature published after September 11th, 2001 that addresses the epidemiology, pathophysiology, evaluation, and treatment of PTSD in the context of TBI. Language: en

Traumatic brain injury (TBI) is highly prevalent among a wide range of populations, including civilians, military personnel, and Veterans. TBI sequelae may be further exacerbated by symptoms associated with frequently occurring comorbid psychiatric conditions, including posttraumatic stress disorder (PTSD). This is particularly true among the population of military personnel from recent conflicts in Iraq and Afghanistan, with a history of mild TBI (mTBI) and PTSD. The need for efficacious treatments for TBI and comorbid PTSD is significant, and evidence-based interventions for these frequently co-occurring conditions are limited. Based on findings suggesting that inflammation may be an underlying mechanism of both conditions, anti-inflammatory/immunoregulatory agents, including probiotics, may represent a novel strategy to treat TBI and/or PTSD-related symptoms. The focus of this systematic review was to identify and evaluate existing research regarding prebiotic and probiotic interventions for the populations of individuals with a history of TBI and/or PTSD. Only 4 studies were identified (3 severe TBI, 1 PTSD, 0 co-occurring TBI and PTSD). Although findings suggested some promise, work in this area is nascent and results to date do not support some claims within the extensive coverage of probiotics in the popular press.

Identifying a non-pharmacological intervention to reduce the stress response could be particularly beneficial to college students, a group prone to considerable stress. Acupressure has shown some efficacy in reducing stress in adults following stroke or traumatic brain injury (TBI), but multiple treatments were required. Results from single treatments in healthy populations have been mixed.The current study used a randomised, placebo-controlled, single-blind design to investigate the use of a single acupressure treatment for stress reduction in healthy college students (n=109) during a stressor.Participants were randomly assigned to one of three single, 40-min interventions: active acupressure, placebo acupressure, or a relaxation CD control. A math task stressor administered before and after the intervention assessed intervention effects on stressor responsivity.Stress responses were measured by physiological (heart rate (HR), heart rate variability (HRV), skin conductance response (SCR)) and subjective measures (State Anxiety Inventory, nine-item Psychological Stress Measure) of anxiety and stress.All interventions were associated with the following changes during the post-intervention stressor compared to the pre-intervention stressor: reduced HR (p0.001), increased HRV (p0.024), reduced SCR (p0.001), reduced subjective stress scores (p0.001), and increased correct answers (p0.001). Although all groups demonstrated stress reduction, there were no significant group differences after a single treatment.All interventions significantly reduced the stress response, although not differently. The lack of active acupressure-associated treatment effects appears to be due to insufficient dosing.

Acupressure is a complementary and alternative medicine (CAM) treatment using fingertips to stimulate acupoints on the skin. Although suggested to improve cognitive function, acupressure has not been previously investigated with a controlled design in traumatic brain injury (TBI) survivors, who could particularly benefit from a non-pharmacological intervention for cognitive impairment. A randomized, placebo-controlled, single-blind design assessed the effects of acupressure (eight treatments over 4 weeks) on cognitive impairment and state of being following TBI, including assessment of event-related potentials (ERPs) during Stroop and auditory oddball tasks. It was hypothesized that active acupressure treatments would confer greater cognitive improvement than placebo treatments, perhaps because of enhanced relaxation response induction and resulting stress reduction. Significant treatment effects were found comparing pre- to post-treatment change between groups. During the Stroop task, the active-treatment group showed greater reduction in both P300 latency (p = 0.010, partial η² = 0.26) and amplitude (p = 0.011, partial η² = 0.26), as well as a reduced Stroop effect on accuracy (p = 0.008, partial η² = 0.21) than did the placebo group. Additionally, the active-treatment group improved more than did the placebo group on the digit span test (p = 0.043, Cohen's d = 0.68). Together, these results suggest an enhancement in working memory function associated with active treatments. Because acupressure emphasizes self-care and can be taught to novice individuals, it warrants further study as an adjunct treatment for TBI.

Summary Objectives Acupressure, a complementary and alternative medicine (CAM) treatment, uses fingertips, rather than needles, to stimulate acupoints on the skin and has been implicated as a successful treatment for a variety of medical disorders. However, acupressure's underlying mechanisms remain unclear. One theory is that acupoint stimulation modulates autonomic nervous system activity. Previous studies have suggested that acupressure may positively affect heart rate and blood pressure. The current study investigated the effects of a type of acupressure, Jin Shin, on cardiovascular function in stroke survivors, a population that could especially benefit from a treatment promoting cardiovascular health. The study tested the hypothesis that active acupressure treatments would reduce heart rate and blood pressure (i.e., induce a greater relaxation response) above and beyond that seen during placebo acupressure treatments. Methods A randomised, placebo-controlled, single-blind crossover design was utilised, in which 16 participants received 8 weeks of either active or placebo acupressure followed by washout and crossover into the opposite treatment condition. Heart rate and blood pressure measurements were taken throughout treatments. Results Active acupressure treatments were associated with a significantly greater ( p =.043, partial η 2 =.30) and faster ( p =.002, partial η 2 =.76) reduction in heart rate compared to that seen during placebo treatments. No treatment effect on blood pressure was found. Conclusions Active acupressure reduced heart rate significantly more than did placebo acupressure during treatments. Although no treatment effect on blood pressure was found, this could be due to 67% of participants taking antihypertensive medications during the study.

It has been predicted that cervical arthroplasty will replace fusion and become the new “gold standard” in the near future. Although short-term clinical results associated with cervical artificial disc replacement are promising, longterm benefits of reduced stress on the adjacent levels or effectiveness of cervical arthroplasty compared with anterior cervical discectomy and fusion (ACDF) remain unknown. The advantage of preserved segmental mobility should be weighed against potential negative effects on the facet joints and the possibility of late implant failure or loosening. Strict patient selection based on clear indications and absence of exclusion criteria should heavily outweigh the marketing enthusiasm.

Joiner's (2005) interpersonal-psychological theory of suicide (IPTS) has become one of the most frequently studied in the field. Currently there are 2 primary measures designed to assess the 3 main constructs of the theory-the Interpersonal Needs Questionnaire (INQ; Van Orden, Witte, Gordon, Bender, & Joiner, 2008) and the Acquired Capability for Suicide Scale (ACSS; Van Orden et al., 2008). The psychometric properties of these 2 measures were evaluated in a sample of 477 U.S. military veterans. It was determined that the factor structure for both measures is consistent with the underlying theory and that all internal consistency reliability estimates are good. Acceptable convergent validity was found for the INQ, but not for the ACSS. Recommendations for refining the ACSS based on the results of the current analyses are provided. Comparisons of scale performance were made with data from participants with and without a history of 1 or more suicide attempts. Burdensomeness alone and the interaction between thwarted belongingness and burdensomeness were associated with prior suicide attempts. In conclusion, although some refinement may improve performance of the ACSS, both measures are appropriate and psychometrically sound for use in research and clinical applications with veterans of the U.S. military. (PsycINFO Database Record

Object The sport of triathlon is very physically demanding and has experienced rapid growth in recent years. The number of triathletes seen for spine disorders at neurosurgery clinics is increasing. Neck pain and overuse injuries have not been adequately studied in multisport athletes. The authors undertook an epidemiological study to establish the lifetime incidence of neck pain and the prevalence of possible discogenic pain, and to identify risk factors among triathletes in the Boulder, Colorado area. Methods An online questionnaire was developed to collect information about physical characteristics, training habits, athletic status, number of races completed, and neck pain among triathletes. The incidence of possible cervical discogenic pain was defined according to the duration of symptoms for the most recent pain episode. Results One hundred and sixty-four athletes responded to the questionnaire. The lifetime incidence of neck pain was 47.6% (78 athletes), with 15.4% possibly being of discogenic origin based on the duration of symptoms. Approximately 64% of responding athletes reported that their neck pain was sports related. Although the number of previous triathlons was not predictive of neck pain, total years in the sport (p = 0.029) and number of previous sports-related injuries (p < 0.0001) were. Conclusions Two major risk factors for long-term spinal problems in triathletes are sports-related injuries and overuse. This report is one of the first comprehensive studies of neck pain and overuse injury in multisport athletes.

Traumatic brain injury (TBI) is highly prevalent and occurs in a variety of populations. Because of the complexity of its sequelae, treatment strategies pose a challenge. Given this complexity, TBI provides a unique target of opportunity for complementary and alternative medicine (CAM) treatments. The present review describes and discusses current opportunitites and challenges associated with CAM research and clinical applications in civilian, veteran and military service populations. In addition to a brief overview of CAM, the translational capacity from basic to clinical research to clinical practice will be described. Finally, a systematic approach to developing an adoptable evidence base, with proof of effectiveness based on the literature will be discussed. Inherent in this discussion will be the methodological and ethical challenges associated with CAM research in those with TBI and associated comorbidities, specifically in terms of how these challenges relate to practice and policy issues, implementation and dissemination. This article is part of a Special Issue entitled SI:Brain injury and recovery.

There are an estimated 2 million traumatic brain injuries (TBIs) each year in the United States, making the yearly incidence eight times greater than that of breast cancer and 34 times greater than HIV/AIDS. Still, it remains a "silent epidemic" because TBI results in persistent neurobehavioral impairment, without necessarily imparting a physical scar. The present review is a comparative analysis of TBI research, both basic and applied, outlining the evidence that at least one component of the brain's innate response to insult (e.g., post-traumatic neural depression) is sufficiently well understood to be the target of additional clinical studies and therapeutic strategy development.

Background: Acquired brain injury (e.g., stroke and traumatic brain injury or TBI) and associated sequelae are highly prevalent in the United States (U.S.), impacting both civilians and military populations. Because conventional treatments can be limited and functional recovery incomplete, complementary and alternative medicine (CAM) is often sought out. The popularity of CAM exists despite inconclusive research findings for CAM treatments for injuryassociated sequelae. Apparent methodological limitations in CAM studies include issues related to experimental design, control groups, sample size, blinding and disparities in outcome measures. Overcoming these limitations poses challenges, but not insurmountable ones. Objective: Delineate and describe the necessary evidence-based infrastructure so that efficacious CAM treatments can be identified and this information disseminated to individuals seeking CAM therapies. With the full information of both risks and benefits, there is a increased likelihood of resources being invested in treatments that will achieve outcomes of interest. Design: The present review of a published body of work will describe, step-by-step, the fundamental framework within which researching the CAM intervention acupressure for two types of acquired brain injury (traumatic brain injury/TBI and stroke), can be accomplished using the highest methodological rigor. Results: Included is a review and description of the "choice points" encountered in the decade-plus of published research from the CAIRR (Clinical Assessment of Injury, Recovery and Resilience) Neuroscience Laboratory, the methodological framework underlying these choice points, and how decisions at each choice point were made to optimize rigor. Conclusions: Cogent scientific research is essential for identifying effective treatments for acquired brain injury, regardless of whether the treatments are conventional or CAM-based. In terms of CAM, such work will provide the opportunity to characterize both efficacy and limitations of CAM treatments, so that CAM may be fully understood and accessed appropriately by both treatment teams and those engaged in rehabilitation.

Although Veterans utilize complementary and alternative medicine (CAM) at rates comparable with civilians, little is known about Veterans' attitudes and beliefs toward CAM. Measures to increase such knowledge may help to identify treatment preferences, particularly among those with signature conditions from the recent conflicts [ie, traumatic brain injury (TBI), posttraumatic stress disorder (PTSD)].This exploratory study aimed to: (1) determine the factors of the Complementary, Alternative, and Conventional Medicine Attitudes Scale (CACMAS); and to utilize the resulting factors to describe (2) attitudes and beliefs toward CAM; (3) their association with TBI, PTSD, and history of self-directed violence. Patterns of CAM use were also obtained.Factor analysis. Observational study.Participants were 97 Veterans seeking care at a Mountain State Veterans Affairs Medical Center.Participants completed the CACMAS, clinical interviews, and self-report measures during a single visit.CACMAS factors identified were: acceptability of (1) CAM and (2) conventional medicine; (3) mind-body integration; and (4) belief in CAM. Acceptability of CAM was significantly associated with history of mild TBI (mTBI) or PTSD symptom severity. Veterans endorsed a wide range of CAM use.Veterans in this sample were open to CAM and conventional medicine, believed in CAM, and believed that treatments should incorporate the mind and body. Veterans with a history of mTBI or PTSD symptoms may be more accepting of CAM. Understanding Veterans' beliefs and attitudes regarding CAM may help providers deliver patient-centered treatments, particularly among those with conditions for which evidence-based interventions are limited (eg, mTBI).

It is widely accepted that suicidal behavior often occurs with little planning. We propose, however, that suicidal behavior is rarely if ever impulsive—that it is too frightening and physically distressing to engage in without forethought—and that suicidal behavior in impulsive individuals is accounted for by painful and fearsome behaviors capable of enhancing their capacity for suicide. We conducted a meta-analysis of the association between trait impulsivity and suicidal behavior and a critical review of research considering the impulsiveness of specific suicide attempts. Meta-analytic results suggest the relationship between trait impulsivity and suicidal behavior is small. Furthermore, studies examining a mediating role of painful and provocative behaviors have uniformly supported our model. Results from our review suggest that researchers have been unable to adequately measure impulsivity of attempts and that measures sensitive to episodic planning must be developed to further our understanding of this phenomenon.

The anticonvulsant drug vigabatrin has not been found to be detrimental to the recovery process when administered following focal cortical insult. This finding is in contrast to the negative postinjury consequences of other anticonvulsant drugs (e.g., phenobarbital and diazepam) with more direct activation of the GABA/benzodiazepine receptor complex. Moreover, phenobarbital directed against kindled seizures affects functional recovery more adversely than either the drug or subconvulsive seizures alone. The purpose of the present study was to determine whether vigabatrin (150, 200, and 250 mg/kg) directed against kindled seizures would impact recovery from lesion-induced somatosensory deficits. Vigabatrin was coupled with daily electrical kindling of the amygdala during the first week after a unilateral anteromedial cortex (AMC) lesion. Somatosensory recovery was assessed using bilateral tactile stimulation tests. Animals receiving the highest dose of vigabatrin prior to electrical kindling (250 mg/kg vigabatrin/kindled) remained significantly impaired even after two months of testing relative to vehicle/kindled, kindled/250 mg/kg vigabatrin, which received vigabatrin after electrical kindling, and the 150, 200, and 250 mg/kg vigabatrin/nonkindled groups (p0.0001). In contrast, neither vigabatrin (at any of the doses tested) nor subconvulsive kindled seizures impacted the recovery process (p0.05) when administered alone (i.e., without the drug + seizure interaction). These data add to the accumulating experimental and clinical evidence suggesting that the neurobehavioral consequences of the interaction between anticonvulsant drugs and subclinical seizures after brain insult are detrimental to functional recovery.

The differing effects of partial seizures on neurobehavioral recovery following anteromedial cortex (AMC) injury in rats have previously been reported. Specifically, convulsive Stage 1 seizures evoked ipsilateral to the lesion during the 6-day post-lesion critical period delayed recovery, while non-convulsive Stage 0 seizures were neutral. The present study was designed to elaborate on that research by examining several potential mechanisms for the seizure-associated difference observed in functional outcome. Anesthetized rats sustained unilateral AMC lesions followed by implantation of a stimulating electrode in the amygdala ipsilateral (Expt. 1) or contralateral (Expt. 2) to the lesion. Beginning 48 h after surgery, animals were kindled to evoke Stage 0 or Stage 1 seizure activity during the critical period. Kindling trials and afterdischarge (AD) were controlled to ascertain their role in functional outcome. Recovery from somatosensory deficits was assessed over a two-month period. The results revealed that (i) Stage 0 seizures did not impact recovery regardless of whether initiated ipsilateral or contralateral to the lesion, (ii) Stage 1 seizures prevented recovery only when initiated in the ipsilateral hemisphere during the post-lesion critical period, and (iii) the detrimental effect of Stage 1 seizures appears to be independent of the number of kindling trials provided and cumulative AD. Thus, to determine why Stage 1 seizures evoked in the hemisphere ipsilateral to the lesion impeded recovery, a separate group of animals (Expt. 3) were kindled accordingly and processed for c-Fos and basic fibroblast growth factor (bFGF) immunohistochemistry. It was hypothesized that Stage 1 seizures evoked in the injured hemisphere prevent recovery by blocking lesion-induced bFGF expression in structures shown to be important for recovery after cortex lesions (e.g., striatum). The results confirmed our hypothesis and suggest that the seizure-associated inhibition of lesion-induced bFGF may alter the growth factor-mediated plasticity necessary for functional recovery.

If the primary goal in the treatment of traumatic brain injury is the minimization of post-injury morbidity, treatment strategies that effectively prevent the development of post-traumatic epilepsy and have a beneficial (or at least neutral) impact on functional recovery are necessary. Here, Theresa Hernandez discusses the degree to which the current post-injury practice of anticonvulsant prophylaxis satisfies each of these criteria.

Mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) co-occur at a high rate in Soldiers and Veterans. Despite this, there is a paucity of evidence-based treatments for those dealing with mTBI/PTSD symptoms and their exacerbation by stress. Using a placebo-controlled, randomized, blinded design, the current study is testing the following hypothesis: active acupressure (more than Placebo) will reduce the adverse effects of stress in Veterans with co-occurring mTBI/PTSD, which will be evident in measures of anxiety, perceived stress, distress, psychiatric health, memory and in a laboratory stress task. Veterans have been recruited since regulatory approval was obtained (August 2012) and enrolled in the study in an ongoing manner, with several having already completed the study protocol or being in process. Because the study is ongoing, there are no data to report as of yet. The findings of the present study hold significant military significance: a safe, portable, low-cost, efficacious and accessible treatment strategy would benefit Veterans, family members and the military/VA health care systems. Results of the ongoing study will determine if acupressure is such a treatment strategy.

External stimuli may contribute to seizure occurrence in at least two ways. First, the aberrant neuronal activity that precipitates a seizure could be elicited by certain external events; and second, external events could cue the organism to an impending seizure and result in a compensatory response that is, in effect, ‘anti-convulsant’. While previous research has been aimed at addressing these issues, the results have been inconclusive. The present study was conducted to clarify and extend this prior work. Adult male Long-Evans hooded rats were chronically implanted with a kindling electrode and randomly assigned to one of two groups. The Tone group was presented with a 2-s auditory stimulus (Tone) beginning one second prior to and overlapping with the 1-s kindling stimulus. Animals in the No Tone group received only the kindling stimulus. Antecedent tone presentation significantly delayed the rate of amygdala kindling. The Tone group required significantly more stimulations to reach a Stage 5 seizure than did the No Tone group. The possibility of this phenomenon providing a means to study the mechanisms underlying anti-epileptogenesis is discussed.

Military personnel are returning from Iraq and Afghanistan and reporting non-specific physical (somatic), behavioral, psychological, and cognitive symptoms. Many of these symptoms are frequently associated with mild traumatic brain injury (mTBI) and/or post traumatic stress disorder (PTSD). Despite significant attention and advances in assessment and intervention for these two conditions, challenges persist. To address this, clinically relevant blast models are essential in the full characterization of this type of injury, as well as in the testing and identification of potential treatment strategies. In this publication, existing diagnostic challenges and current treatment practices for mTBI and/or PTSD will be summarized, along with suggestions regarding how what has been learned from existing models of PTSD and traditional mechanism (e.g., non-blast) traumatic brain injury can be used to facilitate the development of clinically relevant blast models.

Object The primary purpose of this study was to analyze what effect preoperative patient expectations and 36-Item Short Form Health Survey (SF-36) Mental Component Summary (MCS) scores have on clinical outcomes. To the authors' knowledge, there are no prospective studies that have examined the effects of both preoperative pain expectations and SF-36 MCS scores on clinical outcomes and satisfaction with results following anterior cervical discectomy and fusion (ACDF). Methods This study analyzed 79 patients (38 men, 41 women) undergoing 1- to 3-level ACDF surgery. Preoperatively, patients were divided into 2 groups for the expectation analyses: patients who expected complete resolution of pain postoperatively (44 total) and those who expected some residual pain (35 total) postoperatively. Preoperative SF-36 MCS scores were used to test the possible effects of mental health on clinical outcomes and satisfaction. Clinical outcomes were evaluated using visual analog scales (VASs) for neck/arm pain, Neck Disability Index (NDI), SF-36 Physical Component Summary (PCS)/MCS, and patient satisfaction with results scales. The mean follow-up duration was 38.8 months (range 7–59 months). Results All postoperative measures depicted significant improvement overall. Patients who expected no pain reported lower postoperative neck/arm pain scores (p < 0.02), higher SF-36 MCS scores (p = 0.04), and higher satisfaction with results scores (p = 0.01) compared with patients who expected some pain, after controlling for their respective preoperative scores. Higher preoperative SF-36 MCS scores predicted significantly lower postoperative neck pain (p = 0.003) and NDI (p = 0.004) scores, as well as higher postoperative SF-36 PCS (p = 0.002), SF-36 MCS (p = 0.001), and satisfaction (p = 0.03) scores, after controlling for their respective preoperative scores. Conclusions Patients who expected no pain postoperatively reported better scores on the nonstandardized outcome measure scales (VAS arm/neck, satisfaction with results), and higher SF-36 MCS scores. Higher preoperative MCS scores were related to better overall (standardized and nonstandardized) clinical outcomes (VAS neck, NDI, SF-36 PCS/MCS, and satisfaction with results). The results suggest that optimism in patients' expectations as well as mental well-being are related to improved clinical outcomes and higher patient satisfaction.

Our laboratory has previously reported a significant subsensitivity to iontophoretically applied GABA (gamma-aminobutyric acid) in dorsal raphe neurons of amygdala-kindled rats. This subsensitivity was selective for GABA and persisted at least 3 months after the last kindled seizure. In the present series of experiments, we explored mechanisms by which kindling could result in persistent GABA sensitivity changes, using in vivo microdialysis to quantitate neurotransmitter [including GABA and 5-hydroxytryptamine (5-HT)] release in the dorsal raphe nucleus of awake, unrestrained amygdala-kindled rats. Depolarization-induced release of GABA is markedly increased in the dorsal raphe nucleus in amygdala-kindled animals. This change in depolarization-induced GABA release appeared to be graded, dependent upon the stage to which the animal is kindled. Thus GABA release is increased in animals kindled to Stage 2 and even greater in animals kindled to Stage 5 seizures. The change in GABA release is also selective, since no consistent change in the release of other putative amino acid neurotransmitters or 5-HT was observed in these same animals. We hypothesize that this increase in depolarization-induced release of GABA in the amygdala-kindled animal underlies the development of subsensitivity to GABA in dorsal raphe neurons.

Previously we reported a long-term change in neuronal sensitivity to GABA following amygdala kindling. Dorsal raphe neurons of amygdala-kindled rats exhibited significant subsensitivity to GABA 4 weeks after the last fully generalized (Stage 5) seizure. We hypothesized that this alteration in GABA sensitivity might reflect neuronal changes corresponding to kindled seizure susceptibility and subsequent experiments have investigated this hypothesis. The progression towards neuronal subsensitivity to GABA during amygdala kindling can be correlated with the Stage to which an animal has been kindled. That is, when measured 4 weeks after the last kindled seizure, dorsal raphe neurons are supersensitive to GABA following a Stage 2 seizure, not different from controls following a Stage 3 seizure and subsensitive to GABA following a Stage 5 seizure. In addition, subsensitivity to GABA appears to be permanent in that it is still measurable 3 months after the last Stage 5 seizure. Thus, amygdala kindling produces long-term, perhaps permanent, changes in neuronal sensitivity to GABA and these changes reflect the Stage to which an animal has been kindled.

Objective The aim of this study was to explore how attitudes toward complementary and alternative medicine (CAM) and conventional medicine influence CAM use in a healthy population, and how health locus of control and exercise further affect CAM use. Design A cross-sectional survey design was used. Participants The sample consisted of 65 healthy graduate students. Main Outcome Measures Since previous studies have focused on the attitudes of medical providers toward CAM, there are currently no standard, widely used measures of attitudes toward CAM from the perspective of the healthcare recipient. Thus, a new measure, the Complementary, Alternative, and Conventional Medicine Attitudes Scale (CACMAS) was created to address how attitudes of healthcare recipients affect CAM use. The Multidimensional Health Locus of Control Scale (MHLC) was used to investigate effects of health locus of control on CAM use, and participants reported which of 17 listed CAM treatments they had used in the past, were currently using, or would likely use in the future. Participants also reported days of exercise in the past month to explore if those engaging in healthy behaviors might report more CAM use. Results Having a philosophical congruence with CAM and agreement with holistic balance was associated with increased CAM use. Dissatisfaction with conventional medicine was also related to increased CAM use, but to a lesser extent. Those attributing health to personal behaviors (an internal health locus of control) reported more CAM use, as did those engaging in more resistance training in the previous month.

The repeated, intraperitoneal administration of the benzodiazepine receptor inverse agonist, FG 7142 (β-carboline-3-carboxylic acid methylamide), leads to pharmacological kindling and an associated decrease in GABA-stimulataed influx of 36 Cl − into cortical membrane preparations. The chronic administration of benzodiazepine agonists results in the development of tolerance and also results in a decrease in GABA-stimulated uptake of 36 Cl − . The present study was designed to evaluate further the paradoxical reports that both chronic treatment with benzodiazepine receptor agonists and inverse agonists results in a decreased ability of GABA to stimulate uptake of 36 − into cortical membrane preparations. The effects of continuous administration of FG 7142 on GABA-stimulated uptake of 36 Cl − the threshold for bicuculline-induced seizures and the proconvulsant actions of acute administration FG 7142 were evaluated. The continuous administration of FG 7142 resulted in an increased capacity of GABA to stimulate the uptake of 36 Cl − into cortical membrane preparations and a significant increase in the seizure threshold for bicuculline following the acute administration of FG 7142. These data, therefore, indicate that changes in GABAergic function following chronic administration of FG 7142 are dependent on the regimen of administration of drug. The results also suggest that the GABA receptor homeostatically responds to continuous occupation by inverse agonists by an upregulation of its functional response to GABA.

Diazepam and other GABA-related agents can prevent or delay recovery from an otherwise short-term somatosensory asymmetry caused by unilateral cortical lesions. Postrecovery treatment does not affect behavior. One possible contributive site of action for these agents is remaining cortical tissue. In the present study, following unilateral anteromedial cortex (AMC) lesions or sham operations, the GABA agonist muscimol or saline was infused once a day for 7 days into the adjacent sensorimotor cortex (SMC) or, as a control, into the more remote occipital cortex (OC) of the ipsilateral hemisphere. Each day the animals were given somatosensory and motor coordination tests at 21 h postinfusion. The SMC-muscimol regimen, but not the SMC-saline or OC-muscimol, retarded recovery from somatosensory asymmetry. The disruptive effect on recovery was enduring, greatly outlasting the week of exposure to muscimol. In sham-operated animals, SMC-muscimoI did not yield a chronic effect on behavior, although during the first hour after each infusion, in which the muscimol presumably was still present in the SMC, somatosensory asymmetry could be observed. Although the AMC lesion created a vulnerability to muscimol in the SMC, no detectable difference in the extent of cortical damage in this group could account for the prolongation of behavioral asymmetry. SMC-muscimol (but not SMC-saline) led to atrophy of SMC projection areas in the ipsilateral thalamus. However, in sham-operated animals, SMC-muscimol did not affect thalamic size. These behavioral and anatomical data suggest that systemically delivered GABAergic drugs might interfere with restoration of function after AMC lesions in part by adversely influencing events in the SMC.

Object As the sport of triathlon has continued to grow, increasing numbers of triathletes have presented in the neurosurgery clinics with various spinal disorders. This epidemiological study was undertaken to establish the lifetime incidence of neck and back pain, to gauge the prevalence of discogenic pain, and to identify risk factors among triathletes in the Boulder, Colorado, area. Methods A live online questionnaire was developed that was used to collect information about physical characteristics, training habits, athletic status, number of races completed, and back pain among triathletes. The incidence of cervical and/or lumbar discogenic back pain was defined according to the duration of symptoms for the most recent pain episode. The lifetime incidence of low-back pain was 67.8%, with 23.7% of cases possibly being discogenic in origin. The number of triathlons in which the respondents had participated and the presence of previous sports-related injuries were predictive of low-back pain (p = 0.02 and p < 0.00001, respectively). The lifetime incidence of neck pain was 48.3%, with 21.4% of cases being consistent with intervertebral disc involvement. The number of previous sports-related injuries was predictive of neck pain (p < 0.00001), and a strong tendency toward neck pain was observed for athletes with more total years of participation in sports (p = 0.06). Conclusions The two main risk factors for long-term spinal problems include sports-related injuries and overuse. The study results definitely support the influence of both mechanisms for low-back pain. Neck pain was associated with an injury event, and a strong (although not statistically significant) tendency toward neck pain was observed in respondents with overuse injuries.

GABAergic drugs can positively or negatively influence recovery of neurobehavioral function following brain injury. Direct potentiation of GABA-mediated inhibition at the post-synaptic receptor (i.e., via GABA, muscimol, diazepam, phenobarbital) after brain damage has been associated with impaired functional recovery. What remains unclear, however, is whether the mechanism of action by which GABA is augmented contributes to a drug's impact on the recovery process. Vigabatrin, a novel anti-convulsant that inhibits GABA-transaminase, was administered chronically after unilateral anteromedial cortex lesions and recovery from somatosensory deficits assessed. In contrast to the direct GABA receptor agonists, vigabatrin did not adversely impact (i.e., was neutral) recovery from neurobehavioral deficits at any of the anti-convulsant doses tested. Measurable secondary drug effects like sedation and hypothermia diminished over time and were reversible upon drug discontinuation. These results suggest that the degree to which a GABAergic agent impacts the recovery process after brain injury is dependent on the drug's mechanism of action.

The effects of propentofylline, a xanthine derivative and adenosine transport inhibitor, were evaluated following anteromedial cortex lesion in the rat. Propentofylline (2×/10 mg/kg, intraperitoneally) was administered for 7 days post-insult and basic fibroblast growth factor (bFGF) immunoreactivity measured at designated time points in the peri-lesional cortex and ipsilateral dorsal striatum. The spatiotemporal pattern of bFGF expression was then compared to functional recovery patterns. Propentofylline-treated animals displayed increased bFGF expression in the peri-lesional cortex which may have contributed to the observed early facilitation of functional recovery. Drug administration did not, however, produce a change in bFGF expression in the ipsilateral dorsal striatum compared to saline-treated animals. These findings taken together with other positive findings regarding propentofylline, support the drug's therapeutic potential.

Following a unilateral anteromedial cortex lesion, a critical period of 12 h to 6 days exists during which the recovery process is exquisitely vulnerable to manipulation. Certain anti-convulsant drugs, as well as convulsive seizures impede recovery when administered during, but not after, the critical period. The mechanisms underlying these behavioral phenomena have not been delineated. Thus, the present study was designed to determine potential mechanisms underlying and responsible for the critical period. To this end, we measured the immunoreactivity of two important markers of the post-injury response cascade, c-Fos and bFGF, at designated times after a unilateral anteromedial cortex lesion. These temporal patterns of expression in the perilesional cortex and ipsilateral dorsal striatum were mapped onto functional recovery patterns. Within the critical period, c-Fos was dramatically elevated through 48 h after the lesion, while bFGF peaked later, on day 6. Upregulation of these markers preceded recovery from somatosensory deficits, which was most dramatic after post-operative day 9 and complete by day 23. Early post-lesion expression of c-Fos may contribute to lesion-induced bFGF expression, which through its neurotrophic properties could be responsible for subsequent functional recovery. Gaining a similar understanding of the critical period following human traumatic brain injury could be an important first step toward improved treatment strategies and neurobehavioral outcome.

Anti-convulsant drug administration or recurrent seizures can impact functional recovery following brain insult. The nature of that impact depends on a variety of factors, including timing of drug administration and drug mechanism of action, as well as seizure number, timing, and severity. The objective of this study was to determine the functional consequences of anti-convulsant administration directed against seizure activity in brain-damaged animals. To this end, phenobarbital was coupled with daily electrical kindling of the amygdala beginning 48 h after a unilateral anteromedial cortex lesion. Recovery from somatosensory deficits was assessed, as was regional atrophy and basic fibroblast growth factor (bFGF) expression. Animals receiving phenobarbital prior to daily kindling failed to recover within 2 months of testing. In contrast, animals receiving saline prior to kindling as well as phenobarbital-treated non-kindled animals recovered within 2 months after the lesion. Though the exact mechanisms underlying these behavioral phenomena remain uncertain, patterns of bFGF expression among the groups provide some insight. Taken together, results from the present study suggest that anti-convulsant drug administration directed against subclinical seizure activity can be more detrimental to functional recovery than seizures alone or anti-convulsant drug treatment after seizure activity has occurred.

Diverse neural alterations are responsible for and a consequence of seizures, epileptogenesis and epilepsy. Many of these changes are transient and tied to the seizures, themselves, while others are more permanent in nature and thought to reflect the long-term epileptogenic state. Seizures are characterized by the sudden and excessive discharge of neuronal activity [42]; epileptogenesis is the process by which distinct seizure events increase the likelihood of recurrence; epilepsy is the resulting disorder of recurrent seizures. The behavioral disturbances that are associated with each of these in certain measures of learning, memory and cognition have been fairly well characterized [9, 10, 22, 49, 52, 54, 55, 60]. The bulk of the data, however, has been collected from non-brain injured subjects with epilepsy (in the case of humans) or experimentally-induced models of epilepsy (in the case of animals). Much scarcer are studies assessing the neurobehavioral consequences of seizures or epileptogenesis following brain damage [3, 19], and their impact on functional recovery [20, 24, 39, 40]. Depending upon the severity, brain injuries carry a degree of risk for post-traumatic seizures (i.e., non-recurrent seizure(s) following brain injury) and post-traumatic epilepsy (i.e., recurrent seizures that cannot be linked to causes other than the brain injury). These issues are significant given the high incidence of brain injury each year, 1.5–2 million [44, 69] and the overall increase in survival rates following brain injury [70]. At the same time, fire-arm associated mortal injuries now surpass those of motor vehicles [70]. This increase in the type of brain injuries (e.g., penetrating missile type) that carry the highest risk for post-traumatic epilepsy translates into more individuals with both brain damage-associated morbidity and a high propensity for post-traumatic epilepsy.

Recently we reported that antecedent tone presentation significantly delays the rate of amygdala kindling when it precedes and overlaps with every kindling trial. The goal of the present study was to determine if there is a minimal number of pairings required for the tone to exert its effects or if continued exposure is required. To investigate this, male Long-Evans hooded rats were implanted with a bipolar electrode in the right amygdala and assigned to a Tone, No Tone, or Tone Discontinued group and kindled once daily. The Tone group was exposed to the auditory stimulus on every kindling trial, while the Tone Discontinued group received it for only the first 5 days and subsequently was kindled in the same manner as the No Tone group (i.e., not exposed to the tone while receiving the kindling stimulation). In agreement with our earlier report, antecedent tone presentation significantly delayed seizure progression for subjects kindled in the central nucleus. However, the antecedent tone also significantly accelerated epileptogenesis for rats kindled in the amygdalostriatal transition area and produced no significant difference for those kindled in the basolateral nucleus. Furthermore, presentation of the tone was not required with every kindling trial in order for these effects to be seen, suggesting that a critical period might exist early in the kindling process during which epileptogenesis is acutely vulnerable to intervention. Additional research is necessary to determine the nature of these interventions and what effects they may have on seizure genesis.

The present study was undertaken to assess the effects of amygdala kindling on behavioral recovery following unilateral frontal cortex damage in rats. Daily electrical stimulation of the amygdala began 48 h after lesion and continued until all animals had a single Stage 5 seizure. When amygdala kindled seizure activity ratable as Stage 0 occurred within the first 6 days after lesion, animals recovered from somatosensory asymmetries in approximately 3 weeks. In contrast, kindled animals that experienced Stage 1 seizure activity within the first 6 days after lesion failed to recover from somatosensory deficits in 4 months of testing. Differences in rate of recovery could not be accounted for by lesion size or placement. These data support the notion that not only is there a ‘critical period’ after brain damage during which the recovery process is vulnerable to seizure activity, but the type of kindled seizure that is experienced during that time ultimately determines how recovery is affected.

The effects of the anti-convulsant phenobarbital on recovery of function was assessed. Phenobarbital, which is frequently administered to humans after brain injury, was injected for 7 days beginning 48 h after unilateral cortex lesions in rats. Recovery from somatosensory deficits was significantly delayed in phenobarbital treated animals. These results provide additional evidence that anti-convulsants interfere with recovery when administered after brain damage.

Kindling induces long-term adaptations in neuronal function that lead to a decreased threshold for induction of seizures. In the present study, the influence of amygdala kindling on levels of mRNA for the immediate-early genes (lEGs) c-fos, c-jun, and NGFI-A were examined both before and after an acute electroconvulsive seizure (ECS). Although amygdala kindling did not significantly influence resting levels of c-fos mRNA in cerebral cortex, ECS-stimulated levels of c-fos mRNA (examined 45 min after ECS) were approximately twofold greater in the cerebral cortex of kindled rats relative to sham-treated controls. The influence of kindling on IEG expression was dependent on the time course of kindling, as ECS-stimulated levels of c-fos mRNA were not significantly increased in stage 2 kindled animals. ECS-stimulated levels ofc-jun and NGFI-A mRNA were also significantly increased in cerebral cortex of kindled rats relative to sham-treated controls. The influence of kindling on IEG expression was long-lasting because an acute ECS stimulus significantly elevated levels of c-fos and c-jun mRNA in the cerebral cortex of animals that were kindled 5 months previously. In contrast to these effects in cerebral cortex, kindling did not influence ECS-stimulated levels of c-fos mRNA in hippocampus. Finally, immunohistochemical studies revealed lamina-specific changes in the cerebral cortex. In sham-treated controls, acute ECS resulted in an increase in the number of Fos-like immunoreactive (Fos-li) neurons in layers II + III and V of prefrontal cortex, which approached significance; ECS did not influence the number of Fos-li neurons in layer VI. However, in kindled animals acute ECS significantly increased the number of Fos-li neurons in layers II + III and V of prefrontal cortex. These results suggest that kindling increases the responsiveness of cerebral cortical neurons to certain stimuli and that regulation of IEG expression could be involved in the molecular adaptations that underlie kindling.

The present experiments were undertaken to evaluate GABA sensitivity in dorsal raphe neurons following amygdala-kindled seizures. Dorsal raphe neurons of amygdala-kindled rats exhibited significant subsensitivityto GABA as measured electrophysiologically 3 or 4 weeks after the last stage 5 seizure. Amygdala stimulation with currents which did not produce kindled seizures did not produce subsensitivity to GABA. The subsensitivity observed after kindling was equivalent in magnitude to that observed following chronic diazepam treatment. However, exposure of fully kindled rats to chronic diazepam did not further decrease the sensitivity of dorsal raphe neurons to GABA. Additionally, while subsensitivity to GABA was reversed by bath application of the benzodiazepine antagonist, Ro 15-1788, in chronic diazepam-treated rats, it had no effect on GABA subsensitivity in fully kindled rats. These findings suggest a decrease in GABA sensitivity within the dorsal raphe might reflect long-term neuronal changes associated with kindled seizures. These data also suggest that the decrease in GABA sensitivity of dorsal raphe neurons following chronic diazepam may involve different mechanisms from those observed after amygdala kindling.

Following unilateral damage to the anterior-medial region of the neocortex (AMC) in rats a sensory asymmetry appeared, but recovered within a week. In a separate group of rats with AMC lesions daily 3-week exposure to diazepam (Valium, 5 mg/kg) beginning 12 h after surgery caused recovery to be delayed indefinitely. The efficiency and speed (as opposed to symmetry) of behavior was not impaired. More than 9 weeks after discontinuation of diazepam (12 weeks postsurgery), recovery was still not apparent. Postmortem analysis ruled out lesion size as a contributing factor. In a second experiment undrugged animals with AMC lesions were allowed to recover for at least 3 weeks before being exposed to diazepam. These animals showed only a transient (2-day) reinstatement of asymmetry despite continuous drug treatment. We conclude that important mechanisms serving recovery of function may be vulnerable during a short period soon after brain damage.

Following unilateral lesions of the anteromedial cortex, recovery from somatosensory asymmetry reliably occurs within about 10 days. Chronic exposure to diazepam significantly delays this recovery. In the present study, co-administration of Ro 15-1788, a benzodiazepine antagonist (i.e. it blocks the negative and positive allosteric modulation of GABA), prevented diazepam-induced retardation of recovery from somatosensory asymmetry. Nocturnal ambulatory (motor) activity was not different between rats receiving diazepam-alone and those receiving Ro 15-1788 in combination with diazepam. These data suggest that the benzodiazepine receptor is importantly involved in the detrimental effects of diazepam on recovery, and that non-specific behavior sedation plays little or no role.

Benzodiazepine ligands of differing efficacy including the agonist, diazepam, the partial agonist, Ro 16–6028 and the antagonist, Ro 15–1788, were administered in vivo to rats continuously for 3 weeks. The magnitude of change in various measures of GABA sensitivity could be correlated directly with increasing agonist efficacy: maximal changes were seen following chronic treatment with diazepam, intermediate changes were seen following the partial agonist Ro 16–6028 and no changes were observed following chronic Ro 15–1788 administration. The magnitude of change could also be correlated with increasing potential for tolerance development to anticonvulsant efficacy following chronic exposure to these benzodiazepine ligands.

The effects of the gamma-aminobutyric acid antagonist, pentylenetetrazol (PTZ), on recovery from somatosensory and motor asymmetries after unilateral sensorimotor cortex lesions were investigated. Behavior was assessed using a bilateral tactile stimulation test and a measure of forelimb motor coordination. Immediately after surgery, the PTZ-treated and saline (SAL) control groups both exhibited severe ipsilateral behavioral asymmetries. Rats receiving PTZ recovered significantly faster from somatosensory asymmetry than those receiving SAL. Recovery was complete in the PTZ group within 3 postoperative weeks, while the SAL group failed to reach a comparable level until 2 months after surgery. There was no difference between PTZ and SAL groups on recovery of forelimb motor coordination. No difference in lesion size between the SAL and the PTZ groups could be found. These data are consistent with the hypothesis that post-traumatic neuronal depression may contribute to the severity of sensorimotor deficits observed after brain damage.

A series of experiments have been conducted to assess the specificity of recovery from motor asymmetries that is provided by dopamine-rich grafts in the neostriatum of rats with unilateral dopamine-depleting lesions produced by injection of 6-hydroxydopamine into the ascending nigrostriatal pathway. Grafts of embryonic tissue taken from the substantia nigra (rich in dopamine neurons could provide a complete recovery of methamphetamine-induced rotation and a partial recovery of apomorphine-induced rotation, whereas no recovery was seen in rats with grafts of tissue rich in another monoamine (serotonin, dissected from the mesencephalic raphe) or of tissue appropriate to the target (dissected from the striatal eminence). 6-Hydroxydopamine lesions of dopamine cells in the grafts of recovered animals reinstated the initial lesion-induced asymmetry. Dopamine-rich grafts implanted into the intact neostriatum did not induce any "supernormal" asymmetry in the rats, but did provide a "prophylactic" protection against subsequent lesions of the intrinsic ipsilateral dopamine nigrostriatal system. Post-mortem biochemical assays indicated that the extent of dopamine depletion in the neostriatum of lesioned rats correlated highly with both methamphetamine and apomorphine turning rates. Similarly, both drug rotation tests correlated significantly with the extent of dopamine restoration in the dorsal striatum of rats with dopamine-rich grafts, the correlation being significantly higher for the methamphetamine than for the apomorphine test.