Anhedonia is a core symptom of depression, but the underlying neurobiological mechanisms are unknown. Correlative neuroimaging studies implicate dysfunction within ventromedial prefrontal cortex, but ...the causal roles of specific subregions remain unidentified. We addressed these issues by combining intracerebral microinfusions with cardiovascular and behavioral monitoring in marmoset monkeys to show that over-activation of primate subgenual anterior cingulate cortex (sgACC, area 25) blunts appetitive anticipatory, but not consummatory, arousal, whereas manipulations of adjacent perigenual ACC (pgACC, area 32) have no effect. sgACC/25 over-activation also reduces the willingness to work for reward. 18F-FDG PET imaging reveals over-activation induced metabolic changes in circuits involved in reward processing and interoception. Ketamine treatment ameliorates the blunted anticipatory arousal and reverses associated metabolic changes. These results demonstrate a causal role for primate sgACC/25 over-activity in selective aspects of impaired reward processing translationally relevant to anhedonia, and ketamine’s modulation of an affective network to exert its action.
•Primate sgACC/25 over-activation blunts reward anticipation, but not consumption•Over-activation of sgACC/25 also blunts willingness to work for reward•Anticipatory blunting involves metabolic changes in reward-related circuits•Acute ketamine reverses blunted anticipatory arousal and metabolic changes
Using intracerebral microinfusions in marmosets, Alexander et al. demonstrate a causal role for sgACC/25 over-activity in specific aspects of impaired reward processing associated with anhedonia. Ketamine successfully ameliorates related impairments by modulating activity within a dysfunctional neural circuit involved in reward processing and interoception.
We have previously demonstrated that prefrontal serotonin depletion impairs orbitofrontal cortex (OFC)-mediated serial discrimination reversal (SDR) learning but not lateral prefrontal cortex ...(PFC)-mediated attentional set shifting. To address the neurochemical specificity of this reversal deficit, Experiment 1 compared the effects of selective serotonin and selective dopamine depletions of the OFC on performance of the SDR task. Whereas serotonin depletions markedly impaired performance, OFC dopamine depletions were without effect. The behavioral specificity of this reversal impairment was investigated in Experiment 2 by examining the effect of OFC serotonin depletion on performance of a modified SDR task designed to distinguish between 3 possible causes of the impairment. The results showed that the reversal deficit induced by prefrontal serotonin depletion was not due to a failure to approach a previously unrewarded stimulus (enhanced learned avoidance) or reduced proactive interference. Instead, it was due specifically to a failure to inhibit responding to the previously rewarded stimulus. The neurochemical and behavioral specificity of this particular form of cognitive inflexibility is of particular relevance to our understanding of the aetiology and treatment of inflexible behavior apparent in many neuropsychiatric and neurodegenerative disorders involving the PFC.
Serotonergic dysregulation within the prefrontal cortex (PFC) is implicated in many neuropsychiatric disorders, but the precise role of serotonin within the PFC is poorly understood. Using a serial ...discrimination reversal paradigm, we showed that upon reversal, selective serotonin depletion of the marmoset PFC produced perseverative responding to the previously rewarded stimulus without any significant effects on either retention of a discrimination learned preoperatively or acquisition of a novel discrimination postoperatively. These results highlight the importance of prefrontal serotonin in behavioral flexibility and are highly relevant to obsessive-compulsive disorder, schizophrenia, and the cognitive sequelae of drug abuse in which perseveration is prominent.
Recently, we have shown that serotonin (5-HT) depletion from the prefrontal cortex (PFC) of the marmoset monkey impairs performance on a serial discrimination reversal (SDR) task, resulting in ...perseverative responding to the previously correct stimulus (Clarke et al., 2004). This pattern of impairment is just one example of inflexible responding seen after damage to the PFC, with performance on the SDR task being dependent on the integrity of the orbitofrontal cortex. However, the contribution of 5-HT to other forms of flexible responding, such as attentional set shifting, an ability dependent on lateral PFC (Dias et al., 1996a), is unknown. The present study addresses this issue by examining the effects of 5,7-dihydroxytryptamine-induced PFC 5-HT depletions on the ability to shift attention between two perceptual dimensions of a compound visual stimulus (extradimensional shift). Monkeys with selective PFC 5-HT lesions, despite being impaired in their ability to reverse a stimulus-reward association, were unimpaired in their ability to make an extradimensional shift when compared with sham-operated controls. These findings suggest that 5-HT is critical for flexible responding at the level of changing stimulus-reward contingencies but is not essential for the higher-order shifting of attentional set. Thus, psychological functions dependent on different loci within the PFC are differentially sensitive to serotonergic modulation, a finding of relevance to our understanding of cognitive inflexibility apparent in disorders such as obsessive-compulsive disorder and schizophrenia.
Aims. A 2‐year project was carried out to evaluate the use of multi‐component, computer‐assisted strategies for implementing clinical practice guidelines. This paper describes the implementation of ...the project and lessons learned. The evaluation and outcomes of implementing clinical practice guidelines to prevent and treat pressure ulcers will be reported in a separate paper.
Background. The prevalence and incidence rates of pressure ulcers, coupled with the cost of treatment, constitute a substantial burden for our health care system. It is estimated that treating a pressure ulcer can increase nursing time up to 50%, and that treatment costs per ulcer can range from US$10,000 to $86,000, with median costs of $27,000. Although evidence‐based guidelines for prevention and optimum treatment of pressure ulcers have been developed, there is little empirical evidence about the effectiveness of implementation strategies.
Method. The study was conducted across the continuum of care (primary, secondary and tertiary) in a Canadian urban Health Region involving seven health care organizations (acute, home and extended care). Trained surveyors (Registered Nurses) determined the prevalence and incidence of pressure ulcers among patients in these organizations. The use of a computerized decision‐support system assisted staff to select optimal, evidence‐based care strategies, record information and analyse individual and aggregate data.
Results. Evaluation indicated an increase in knowledge relating to pressure ulcer prevention, treatment strategies, resources required, and the role of the interdisciplinary team. Lack of visible senior nurse leadership; time required to acquire computer skills and to implement new guidelines; and difficulties with the computer system were identified as barriers.
Conclusions. There is a need for a comprehensive, supported and sustained approach to implementation of evidence‐based practice for pressure ulcer prevention and treatment, greater understanding of organization‐specific barriers, and mechanisms for addressing the barriers.
It is well established that the NMDA receptor antagonists block hippocampal long-term potentiation and impair acquisition in the Morris watermaze task, although the role of individual NMDA receptor ...subtypes is largely unknown. In the present study, we compared the effects of (±)-CP-101,606, an antagonist selective for NMDA receptor NR1/NR2B subunit-containing receptors and the nonselective NMDA receptor antagonist MK-801, on acquisition in the Morris watermaze. Male hooded Lister rats were given 4 trials/day to find a fixed hidden platform submerged beneath the opaque water of the Morris watermaze. Twenty-four hours after the last acquisition trial, a ‘probe trial’ was conducted to assess the rat's spatial memory for the location of the hidden platform. Those rats treated with MK-801 (0.1 mg/kg, i.p.) 60 min prior to the acquisition and probe trials took significantly longer to find the hidden platform during training and spent significantly less time searching the platform's location during the probe trial than vehicle-treated rats. In contrast, 60-min pretreatment with (±)-CP-101,606 (60 mg/kg, p.o.), a dose that fully occupied hippocampal NR1/NR2B subunit-containing receptors, as determined by ex vivo NMDA receptor-specific
3Hifenprodil binding immediately following watermaze experiments, had no effect on acquisition or the probe trial. These results suggest that antagonists selective for NR1/NR2B subunit-containing receptors may not impair spatial memory in rats in the Morris watermaze.
The provision of informatics content in the basic education programs for Canadian nurses has been limited to date. In previous years, efforts to engage nurse educators in discussions regarding the ...significance of informatics for tomorrow's nurses had been met with limited interest and understanding. There was an obvious need to heighten the awareness and active participation of nurse leaders in the development of strategies to attend to the informatics education needs of Canadian nurses. This paper describes the findings of a national study to understand the current state of informatics integration within basic nursing curricula
By using specific key words, clinicians can use an Internet database service to identify federally funded grant and scholarship opportunities--opportunities more frequently sought by basic ...scientists. The authors hypothesized that such an Internet service could be used as a research tool to examine and compare the clinical research preferences of potential medical and bioscience investigators. The authors selected 577 key words from an online key word thesaurus used by both the federal government and ScienceWise.com. These key words formed a survey instrument to measure the research interests of 40 family medicine academic faculty members of a college of osteopathic medicine. The findings were compared to a survey by ScienceWise.com of its 102,578 subscribers and to previous surveys of nonacademic clinicians. Results indicate an efficient means of determining research interests as well as a method of alerting academic clinicians/nonclinicians and basic scientists to current funding opportunities.
The Comox Valley Nursing Centre was initiated as a two year demonstration project by the Registered Nurses Association of British Columbia (RNABC) and funded by the Ministry of Health. The purpose of ...the project was to demonstrate innovative nursing practice in a primary health care context. Findings from the project were expected to inform provincial health care planning, nursing scope of practice, and health and nursing policy development. A free standing nursing center was planned and implemented through a collaborative effort by RNABC, nurses and community residents. An external team of researchers evaluated the project using a variety of methods, including participatory action research. During the project an innovative nursing practice, based on principles of collaboration, developed and has continued during the extended provincial and regional funding of the Centre. Drawing from the evaluation findings, case studies and using Henneman, Lee and Cohen's (1995) concept analysis of collaboration, this paper describes how the principles of collaboration were actualized or suppressed. The paper examines how collaboration impacted empowerment for nurses, clients and the community. Lessons learned about the reciprocal relationships between collaboration and empowerment, implications for nursing practice, and how the approach can contribute to a better understanding of the impact of collaborative practice approaches on health care delivery are discussed.
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