Post-Traumatic Headache is Associated with Worse Anxiety and Mood Symptoms in Adolescent Mild Traumatic Brain Injury.

This study examined the relationships between post-traumatic headache (PTH) and mental health symptoms after concussions to inform adolescent concussion management. Headache is the most common complaint following adolescent concussion. In this sample of 123 adolescents with concussion, there was a 5-fold increase in odds of clinically elevated anxiety, as well as increased mental health symptoms (anxiety, depression, anger, and disruptive behaviours), among adolescents with PTH relative to those without PTH. Adolescents with headache following concussions are vulnerable to worse mental health outcomes, particularly anxiety, and may benefit from routine monitoring of mental health symptoms for early detection and intervention.

Neurotoxicity and Chemoreception: A Systematic Review of Neurotoxicity Effects on Smell and Taste.

Several different types of exposure have the potential to produce olfactory and gustatory deficits related to neurotoxicity. Although the literature contains relatively few studies of such chemoreceptive dysfunction in the context of toxic exposure, this review explores the strength of such published associations. Several studies collectively demonstrated moderately strong evidence for an association between manganese dust exposure and olfactory deficits. Evidence of associations between individual chemicals, therapeutics, and composites, such as World Trade Center debris, and olfactory and gustatory deficits remains limited or mixed. Further need for controlled studies for clinical management, exposure limits, and policy development is identified.

Virtual reality gaming as a neurorehabilitation tool for brain injuries in adults: A systematic review.

OBJECTIVE: Evidence of the effectiveness of virtual reality (VR) in motor and cognitive rehabilitation for traumatic brain injury (TBI) continues to be mixed. Therefore, we conducted a systematic literature review in accordance with PRISMA guidelines to strategically evaluate the strength of evidence supporting the use of VR as a rehabilitation tool for motor function and cognition in patients with TBI. METHOD: The van Tulder criteria were modified to determine the quality of the outcomes of studies deemed eligible for inclusion in the review. OUTCOMES AND RESULTS: Twelve studies were considered eligible for inclusion in the systematic review. These studies utilized methods of varying quality such as case and quasi-experimental studies and found moderately positive support for the effectiveness of VR-enhanced rehabilitation for both motor skills and cognitive deficits. CONCLUSIONS AND IMPLICATIONS: The varying quality of the included studies provides moderate support for use of VR-enhanced rehabilitation techniques per the van Tulder criteria. This highlights the continued gap in the literature for robust studies that enable providers, policy makers, and the public to draw conclusions about the effectiveness of VR-enhanced rehabilitation for traumatic brain injury. Continued pursuit of analyses in the context of newer immersive VR-enhanced rehabilitation is recommended.

Impact of motor therapy with dynamic body-weight support on Functional Independence Measures in traumatic brain injury: An exploratory study.

BACKGROUND: Contemporary goals of rehabilitation after traumatic brain injury (TBI) aim to improve cognitive and motor function by applying concepts of neuroplasticity. This can be challenging to carry out in TBI patients with motor, balance, and cognitive impairments. OBJECTIVE: To determine whether use of dynamic body-weight support (DBWS) would allow safe administration of intensive motor therapy during inpatient rehabilitation and whether its use would yield greater improvement in functional recovery than standard-of-care (SOC) therapy in adults with TBI. METHODS: Data in this retrospective cohort study was collected from patients with TBI who receive inpatient rehabilitation incorporating DBWS (n = 6) and who received inpatient rehabilitation without DBWS (SOC, n = 6). The primary outcome measure was the change in Functional Independence Measures (FIM) scores from admission to discharge. RESULTS: There was significant improvement in total FIM scores at discharge compared to admission for both the DBWS (p = 0.001) and SOC (p = 0.005) groups. Overall, the DBWS group had greater improvement in total FIM score and FIM subscales compared to the SOC group. CONCLUSIONS: Our results suggest DBWS has the potential to allow a greater intensity of therapy during inpatient rehabilitation and yield better outcomes compared to SOC in patients with TBI.

Convergent and discriminant validity of the Immediate Postconcussion Assessment and Cognitive Testing Battery (ImPACT) in young athletes.

Sports concussions are recognized as significant injuries among young athletes. Research demonstrates that return-to-play prior to becoming asymptomatic has significant repercussions including sustained cognitive deficits. Many programs have begun to use computerized testing rather than traditional neuropsychological tests to (a) determine baseline performance, (b) track symptoms, and (c) measure symptoms following concussion. Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) is one such tool. The current study examined ImPACT's convergent and discriminant validity by comparing scores from sports-related concussion athletes (SRC) to those from nonconcussed controls (CTL). SRC included 29 athletes, ages 12-16, referred for neuropsychological assessment following sports-related concussions. CTL included 25 healthy athletes, ages 12-16, who were concussion-free in the past year. Overall, results showed general support for ImPACT, when used to screen cognition. In fact, all ImPACT domains successfully differentiated between SRC and CTL athletes. Evidence supporting appropriate convergent validity was best for the Visual Memory domain. Further, ImPACT domains demonstrated variable discriminant validity. Overall examination of validity demonstrated that ImPACT has some weaknesses but may have utility in detecting postconcussion cognitive impairment.

Examining the relationship and clinical management between traumatic brain injury and pain in military and civilian populations.

In this review, we discuss the comorbidity of traumatic brain injury (TBI) and pain among civilians and military members, the common causes of pain resulting from TBI, and offer insight about the therapeutic management of TBI symptoms and pain. Traumatic brain injury (TBI) is a debilitating health problem and one of the most common post-TBI symptoms is pain, which can contribute to psychological issues such as Post-traumatic stress disorder (PTSD) and depression. Headache pain appears to be the most common type of pain that results from TBI, yet pain can also be more widespread. Managing TBI symptoms and pain simultaneously is difficult because extensive randomized control and clinical studies assessing the effectiveness of therapeutic approaches are lacking. Pharmacological agents such as antidepressants and Triptans and nonpharmacological therapies such as cognitive rehabilitation and physical therapies are commonly used yet it is unknown how effective these therapies are in the long-term. A combination of pharmacological and non-pharmacological therapies is often more effective for managing TBI symptoms and pain than either treatment alone. However, future research is needed to determine the most therapeutic approaches for managing the comorbidity of pain and TBI symptoms in the long term. This review offers suggestions for such future studies.

Reward loss and the basolateral amygdala: A function in reward comparisons.

The neural circuitry underlying behavior in reward loss situations is poorly understood. We considered two such situations: reward devaluation (from large to small rewards) and reward omission (from large rewards to no rewards). There is evidence that the central nucleus of the amygdala (CeA) plays a role in the negative emotion accompanying reward loss. However, little is known about the function of the basolateral nucleus (BLA) in reward loss. Two hypotheses of BLA function in reward loss, negative emotion and reward comparisons, were tested in an experiment involving pretraining excitotoxic BLA lesions followed by training in four tasks: consummatory successive negative contrast (cSNC), autoshaping (AS) acquisition and extinction, anticipatory negative contrast (ANC), and open field testing (OF). Cell counts in the BLA (but not in the CeA) were significantly lower in animals with lesions vs. shams. BLA lesions eliminated cSNC and ANC, and accelerated extinction of lever pressing in AS. BLA lesions had no effect on OF testing: higher activity in the periphery than in the central area. This pattern of results provides support for the hypothesis that BLA neurons are important for reward comparison. The three affected tasks (cSNC, ANC, and AS extinction) involve reward comparisons. However, ANC does not seem to involve negative emotions and it was affected, whereas OF activity is known to involve negative emotion, but it was not affected. It is hypothesized that a circuit involving the thalamus, insular cortex, and BLA is critically involved in the mechanism comparing current and expected rewards.

Dorsomedial striatum lesions affect adjustment to reward uncertainty, but not to reward devaluation or omission.

The dorsomedial striatum (DMS) has been implicated in the acquisition of reward representations, a proposal leading to the hypothesis that it should play a role in situations involving reward loss. We report the results of an experiment in which the effects of DMS excitotoxic lesions were tested in consummatory successive negative contrast (reward devaluation), autoshaping training with partial vs. continuous reinforcement (reward uncertainty), and appetitive extinction (reward omission). Animals with DMS lesions exhibited reduced lever pressing responding, but enhanced goal entries, during partial reinforcement training in autoshaping. However, they showed normal negative contrast, acquisition under continuous reinforcement (CR), appetitive extinction, and response facilitation in early extinction trials. Open-field testing also indicated normal motor behavior. Thus, DMS lesions selectively affected the behavioral adjustment to a situation involving reward uncertainty, producing a behavioral reorganization according to which goal tracking (goal entries) became predominant at the expense of sign tracking (lever pressing). This pattern of results shows that the function of the DMS in situations involving reward loss is not general, but restricted to reward uncertainty. We suggest that a nonassociative, drive-related process induced by reward uncertainty requires normal output from DMS neurons.

Complex effects of reward upshift on consummatory behavior.

Exposing rats to an upshift from a small reward to a larger reward sometimes yields evidence of consummatory successive positive contrast (cSPC), an effect that could be a suitable animal model of positive emotion. However, cSPC is an unreliable effect. Ten experiments explored the effects of an upshift in sucrose or saccharin concentration on consummatory behavior under several conditions. There was occasional evidence of cSPC, but mostly a combination of increased consummatory behavior relative to preshift reward concentrations and a reduced behavioral level relative to unshifted controls. Such a pattern is consistent with processes causing opposite changes on behavior. Reward upshift may induce processes that suppress behavior, such as taste neophobia (induced by an intense sucrose taste) and generalization decrement (induced by novelty in reward conditions after the upshift). An experiment tested the role of such novelty-related effects by preexposing animals to either the upshift concentration (12% sucrose) or water during three days before the start of the experiment. Sucrose-preexposed animals drank significantly more than water-preexposed animals during the upshift, but just as much as unshifted controls (i.e., no evidence of cSPC). These results suggest that cSPC may be difficult to obtain reliably because reward upshift induces opposing processes. However, they also seriously question the ontological status of cSPC.

Threats from the past: Barbados green monkeys (Chlorocebus sabaeus) fear leopards after centuries of isolation.

Ability to recognize and differentiate between predators and non-predators is a crucial component of successful anti-predator behavior. While there is evidence that both genetic and experiential mechanisms mediate anti-predator behaviors in various animal species, it is unknown to what extent each of these two mechanisms are utilized by the green monkey (Chlorocebus sabaeus). Green monkeys on the West Indies island of Barbados offer a unique opportunity to investigate the underpinnings of anti-predator behaviors in a species that has been isolated from ancestral predators for over 350 years. In the first experiment, monkeys in two free-ranging troops were presented with photographs of an ancestral predator (leopard, Panthera pardus) and a non-predator (African Buffalo, Syncerus caffer). Relative to non-predator stimuli, images of a leopard elicited less approach, more alarm calls, and more escape responses. Subsequent experiments were conducted to determine whether the monkeys were responding to a leopard-specific feature (spotted fur) or a general predator feature (forward facing eyes). The monkeys showed similar approach to images of an unfamiliar non-predator regardless of whether the image had forward facing predator eyes or side facing non-predator eyes. However, once near the images, the monkeys were less likely to reach for peanuts near the predator eyes than the non-predator eyes. The monkeys avoided an image of spotted leopard fur but approached the same image of fur when the dark spots had been removed. Taken together, the results suggest that green monkey anti-predator behavior is at least partially mediated by genetic factors.

Brain expression of pCREB in rats exposed to consummatory successive negative contrast.

A 32-to-4% sucrose devaluation leads to suppression of consummatory behavior relative to unshifted 4% sucrose controls. This is accompanied by an emotional response inducing memory consolidation. Expression levels of phosphorylated cyclic adenosine monophosphate response element-binding protein (pCREB, a marker of synaptic plasticity) were higher after the first devaluation session than after the second in prelimbic cortex, anterior cingulate cortex, and dorso-medial striatum. The central nucleus of the amygdala showed a tendency to differential pCREB expression. This evidence contributes to identifying the brain circuit for one form of traumatic memory involving reward loss.

Anisomycin Disrupts Consummatory Behavior after Incentive Downshift via Conditioned Taste Aversion

The protein synthesis inhibitor anisomycin was tested in the consummatory successive negative contrast paradigm (cSNC). The cSNC effect involves suppression of consummatory behavior induced by 4% sucrose in animals that previously received 32% sucrose (downshifted), relative to animals that always received 4% sucrose (unshifted). Systemic anisomycin (25 mg/kg, ip) induced suppression in both downshifted and unshifted groups when injected before the first or second downshift trial (Experiment 1) or after the first downshift trial (50 mg/kg, ip; Experiment 2). The effect of anisomycin (50 mg/kg, sc) administration after the first downshift trial was observed only in downshifted animals in Experiment 3, but the same dose and route of administration induced significant conditioned taste aversion in Experiment 4. It was concluded that a conditioned taste aversion to the 4% sucrose solution accounts most parsimoniously for all the results. Implications for other experiments involving posttrial anisomycin administration are discussed (AU)

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Memory interfering effects of chlordiazepoxide on consummatory successive negative contrast.

Long-Evans rats downshifted from 32% to 4% sucrose solution exhibit lower consummatory behavior during downshift trials than rats exposed only to 4% sucrose. In Experiment 1, this effect, called consummatory successive negative contrast (cSNC), was attenuated by administration of the benzodiazepine anxiolytic chlordiazepoxide (CDP, 5mg/kg, ip) before the second downshift trial (Trial 12), but was not affected when CDP was administered before the first downshift trial (Trial 11). In Experiment 2, CDP administered after Trial 11 actually enhanced the cSNC effect on Trial 12. This posttrial effect of CDP was reduced by delayed administration (Experiment 3). This CDP effect was not present in the absence of incentive downshift (Experiments 4-5), or when animals were tested with the preshift incentive (Experiment 6) or after complete recovery from cSNC (Experiment 7). The posttrial CDP effect was observed after an 8-day interval between Trials 11 and 12 (Experiment 8) and when administered after Trial 12, rather than Trial 11 (Experiment 9). Experiment 10 extended the effect to Wistar rats. Because CDP is a memory interfering drug, it was hypothesized that its posttrial administration interferes with the consolidation of the memory of the downshifted incentive, thus prolonging the mismatch between expected (32% sucrose) and obtained (4% sucrose) incentives that leads to the cSNC effect.

Barbados green monkeys (Chlorocebus sabaeus) recognize ancestral alarm calls after 350 years of isolation.

Vervet monkeys (Chlorocebus pygerythrus) produce alarm calls and anti-predator behaviors that are specific to a threatening predator's mode of attack. Upon hearing a leopard alarm, the monkeys will run up trees where they are relatively safe. In contrast, eagle alarms prompt the monkeys to run under bushes and snake alarms stimulate bipedal standing. Early researchers proposed that the meaning of each alarm call is conveyed by observational learning. If this true then absence of the predator that elicits the alarm call may lead to alteration or decay of the alarm's meaning since there is no longer opportunity for observational learning to occur. The present study tested this hypothesis by presenting alarm calls to a closely related species of monkeys (Chlorocebus sabaeus) that have been isolated from their ancestral predators for more than 350 years. The monkeys ran up trees in response to a leopard alarm, but not when the same alarm was played backwards and not in response to a snake alarm. Snake alarms failed to reliably elicit bipedal standing. These results suggest that the leopard alarm call conveys the same information to Barbados green monkeys as West African green monkeys despite generations of isolation from leopards.

Role of the ventrolateral orbital cortex and medial prefrontal cortex in incentive downshift situations.

The present research evaluated the role of two prefrontal cortex areas, the ventrolateral orbital cortex (VLO) and the medial prefrontal cortex (mPFC), on two situations involving incentive downshifts, consummatory successive negative contrast (cSNC) with sucrose solutions and Pavlovian autoshaping following continuous vs. partial reinforcement with food pellets. Animals received electrolytic lesions and then were tested on cSNC, autoshaping, open-field activity, and sucrose sensitivity. Lesions of the VLO reduced suppression of consummatory behavior after the incentive downshift, but only during the first downshift trial, and also eliminated the enhancement of anticipatory behavior during partial reinforcement, relative to continuous reinforcement, in autoshaping. There was no evidence of specific effects of mPFC lesions on incentive downshifts. Open-field activity was also reduced by VLO lesions, but only in the central area, whereas mPFC lesions had no observable effects on activity. Animals with mPFC lesions exhibited decreased consumption of the lowest sucrose concentration, whereas no effects were observed in animals with VLO lesions. These results suggest that the VLO may exert nonassociative (i.e., motivational, emotional) influences on behavior in situations involving incentive downshifts. No clear role on incentive downshift was revealed by mPFC lesions.