3,970 research outputs found

    Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Signaling in The Prefrontal Cortex Modulates Cued Fear Learning, But Not Spatial Working Memory, in Female Rats

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    A genetic polymorphism within the gene encoding the pituitary adenylate cyclase- activating polypeptide (PACAP) receptor type I (PAC1R) has recently been associated with hyper-reactivity to threat-related cues in women, but not men, with post-traumatic stress disorder (PTSD). PACAP is a highly conserved peptide, whose role in mediating adaptive physiological stress responses is well established. Far less is understood about the contribution of PACAP signaling in emotional learning and memory, particularly the encoding of fear to discrete cues. Moreover, a neurobiological substrate that may account for the observed link between PAC1R and PTSD in women, but not men, has yet to be identified. Sex differences in PACAP signaling during emotional learning could provide novel targets for the treatment of PTSD. Here we investigated the contribution of PAC1R signaling within the prefrontal cortex to the acquisition of cued fear in female and male rats. We used a variant of fear conditioning called trace fear conditioning, which requires sustained attention to fear cues and depends on working-memory like neuronal activity within the prefrontal cortex. We found that cued fear learning, but not spatial working memory, was impaired by administration of a PAC1R antagonist directly into the prelimbic area of the prefrontal cortex. This effect was specific to females. We also found that levels of mRNA for the PAC1R receptor in the prelimbic cortex were greater in females compared with males, and were highest during and immediately following the proestrus stage of the estrous cycle. Together, these results demonstrate a sex-specific role of PAC1R signaling in learning about threat-related cues

    Combining reward and M1 transcranial direct current stimulation enhances the retention of newly learnt sensorimotor mappings

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    Background: Reward-based feedback given during motor learning has been shown to improve the retention of the behaviour being acquired. Interestingly, applying transcranial direct current stimulation (tDCS) during learning over the primary motor cortex (M1), an area associated with motor retention, also results in enhanced retention of the newly formed motor memories. However, it remains unknown whether combining these distinct interventions result in an additive benefit of motor retention. Methods: We investigated whether combining both interventions while participants learned to account for a visuomotor transformation results in enhanced motor retention (total n = 56; each group n = 14). To determine whether these interventions share common physiological mechanisms underpinning learning, we assessed motor cortical excitability and inhibition (i.e. SICI) on a hand muscle before and after all participants learned the visuomotor rotation using their entire arm and hand. Results: We found that both the Reward-Stim (i.e. reward + tDCS) and Reward-Sham (i.e. reward-only) groups had increased retention at the beginning of the retention phase, indicating an immediate effect of reward on behaviour. However, each intervention on their own did not enhance retention when compared to sham, but rather, only the combination of both reward and tDCS demonstrated prolonged retention. We also found that only the Reward-Stim group had a significant reduction in SICI after exposure to the perturbation. Conclusions: We show that combining both interventions are additive in providing stronger retention of motor adaptation. These results indicate that the reliability and validity of using tDCS within a clinical context may depend on the type of feedback individuals receive when learning a new motor pattern

    GALA: an international multicentre randomised trial comparing general anaesthesia versus local anaesthesia for carotid surgery

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    Background: Patients who have severe narrowing at or near the origin of the internal carotid artery as a result of atherosclerosis have a high risk of ischaemic stroke ipsilateral to the arterial lesion. Previous trials have shown that carotid endarterectomy improves long-term outcomes, particularly when performed soon after a prior transient ischaemic attack or mild ischaemic stroke. However, complications may occur during or soon after surgery, the most serious of which is stroke, which can be fatal. It has been suggested that performing the operation under local anaesthesia, rather than general anaesthesia, may be safer. Therefore, a prospective, randomised trial of local versus general anaesthesia for carotid endarterectomy was proposed to determine whether type of anaesthesia influences peri-operative morbidity and mortality, quality of life and longer term outcome in terms of stroke-free survival. Methods/design: A two-arm, parallel group, multicentre randomised controlled trial with a recruitment target of 5000 patients. For entry into the study, in the opinion of the responsible clinician, the patient requiring an endarterectomy must be suitable for either local or general anaesthesia, and have no clear indication for either type. All patients with symptomatic or asymptomatic internal carotid stenosis for whom open surgery is advised are eligible. There is no upper age limit. Exclusion criteria are: no informed consent; definite preference for local or general anaesthetic by the clinician or patient; patient unlikely to be able to co-operate with awake testing during local anaesthesia; patient requiring simultaneous bilateral carotid endarterectomy; carotid endarterectomy combined with another operation such as coronary bypass surgery; and, the patient has been randomised into the trial previously. Patients are randomised to local or general anaesthesia by the central trial office. The primary outcome is the proportion of patients alive, stroke free ( including retinal infarction) and without myocardial infarction 30 days post-surgery. Secondary outcomes include the proportion of patients alive and stroke free at one year; health related quality of life at 30 days; surgical adverse events, re-operation and re-admission rates; the relative cost of the two methods of anaesthesia; length of stay and intensive and high dependency bed occupancy

    Urban particulate pollution reduction by four species of green roof vegetation in a UK city

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    AbstractUrban particulate pollution in the UK remains at levels which have the potential to cause negative impacts on human health. There is a need, therefore, for mitigation strategies within cities, especially with regards to vehicular sources. The use of vegetation as a passive filter of urban air has been previously investigated, however green roof vegetation has not been specifically considered. The present study aims to quantify the effectiveness of four green roof species – creeping bentgrass (Agrostis stolonifera), red fescue (Festuca rubra), ribwort plantain (Plantago lanceolata) and sedum (Sedum album) – at capturing particulate matter smaller than 10 μm (PM10). Plants were grown in a location away from major road sources of PM10 and transplanted onto two roofs in Manchester city centre. One roof is adjacent to a major traffic source and one roof is characterised more by urban background inputs. Significant differences in metal containing PM10 capture were found between sites and between species. Site differences were explained by proximity to major sources. Species differences arise from differences in macro and micro morphology of the above surface biomass. The study finds that the grasses, A. stolonifera and F. rubra, are more effective than P. lanceolata and S. album at PM10 capture. Quantification of the annual PM10 removal potential was calculated under a maximum sedum green roof installation scenario for an area of the city centre, which totals 325 ha. Remediation of 2.3% (±0.1%) of 9.18 tonnes PM10 inputs for this area could be achieved under this scenario

    Physiology and Pathophysiology of the Swallowing Area of Human Motor Cortex

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    Swallowing problems can affect as many as one in three patients in the period immediately after stroke. Despite this, in the majority of cases, recovery usually occurs to a safe level after a month or two. In this review, we show. how the organization of the cortical projections to swallowing nuscles can account for many of the clinical observations on swallowing after stroke and explain why recovery is common in the long term. In addition, we examine approaches that may be useful in speeding up recovery of swallowing. Swallowing may be a useful model in which to study central nervous reorganization after injury
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