Selective Reduction of AMPA Currents onto Hippocampal Interneurons Impairs Network Oscillatory Activity

Reduction of excitatory currents onto GABAergic interneurons in the forebrain results in impaired spatial working memory and altered oscillatory network patterns in the hippocampus. Whether this phenotype is caused by an alteration in hippocampal interneurons is not known because most studies employed genetic manipulations affecting several brain regions. Here we performed viral injections in genetically modified mice to ablate the GluA4 subunit of the AMPA receptor in the hippocampus (GluA4HC−/− mice), thereby selectively reducing AMPA receptor-mediated currents onto a subgroup of hippocampal interneurons expressing GluA4. This regionally selective manipulation led to a strong spatial working memory deficit while leaving reference memory unaffected. Ripples (125–250 Hz) in the CA1 region of GluA4HC−/− mice had larger amplitude, slower frequency and reduced rate of occurrence. These changes were associated with an increased firing rate of pyramidal cells during ripples. The spatial selectivity of hippocampal pyramidal cells was comparable to that of controls in many respects when assessed during open field exploration and zigzag maze running. However, GluA4 ablation caused altered modulation of firing rate by theta oscillations in both interneurons and pyramidal cells. Moreover, the correlation between the theta firing phase of pyramidal cells and position was weaker in GluA4HC−/− mice. These results establish the involvement of AMPA receptor-mediated currents onto hippocampal interneurons for ripples and theta oscillations, and highlight potential cellular and network alterations that could account for the altered working memory performance

No advantage for remembering horizontal over vertical spatial locations learned from a single viewpoint

Previous behavioral and neurophysiological research has shown better memory for horizontal than for vertical locations. In these studies, participants navigated toward these locations. In the present study we investigated whether the orientation of the spatial plane per se was responsible for this difference. We thus had participants learn locations visually from a single perspective and retrieve them from multiple viewpoints. In three experiments, participants studied colored tags on a horizontally or vertically oriented board within a virtual room and recalled these locations with different layout orientations (Exp. 1) or from different room-based perspectives (Exps. 2 and 3). All experiments revealed evidence for equal recall performance in horizontal and vertical memory. In addition, the patterns for recall from different test orientations were rather similar. Consequently, our results suggest that memory is qualitatively similar for both vertical and horizontal two-dimensional locations, given that these locations are learned from a single viewpoint. Thus, prior differences in spatial memory may have originated from the structure of the space or the fact that participants navigated through it. Additionally, the strong performance advantages for perspective shifts (Exps. 2 and 3) relative to layout rotations (Exp. 1) suggest that configurational judgments are not only based on memory of the relations between target objects, but also encompass the relations between target objects and the surrounding room—for example, in the form of a memorized view

Non-invasive cardiac imaging techniques and vascular tools for the assessment of cardiovascular disease in type 2 diabetes mellitus

Cardiovascular disease is the major cause of mortality in type 2 diabetes mellitus. The criteria for the selection of those asymptomatic patients with type 2 diabetes who should undergo cardiac screening and the therapeutic consequences of screening remain controversial. Non-invasive techniques as markers of atherosclerosis and myocardial ischaemia may aid risk stratification and the implementation of tailored therapy for the patient with type 2 diabetes. In the present article we review the literature on the implementation of non-invasive vascular tools and cardiac imaging techniques in this patient group. The value of these techniques as endpoints in clinical trials and as risk estimators in asymptomatic diabetic patients is discussed. Carotid intima–media thickness, arterial stiffness and flow-mediated dilation are abnormal long before the onset of type 2 diabetes. These vascular tools are therefore most likely to be useful for the identification of ‘at risk’ patients during the early stages of atherosclerotic disease. The additional value of these tools in risk stratification and tailored therapy in type 2 diabetes remains to be proven. Cardiac imaging techniques are more justified in individuals with a strong clinical suspicion of advanced coronary heart disease (CHD). Asymptomatic myocardial ischaemia can be detected by stress echocardiography and myocardial perfusion imaging. The more recently developed non-invasive multi-slice computed tomography angiography is recommended for exclusion of CHD, and can therefore be used to screen asymptomatic patients with type 2 diabetes, but has the associated disadvantages of high radiation exposure and costs. Therefore, we propose an algorithm for the screening of asymptomatic diabetic patients, the first step of which consists of coronary artery calcium score assessment and exercise ECG

Assessing the queuing process using data envelopment analysis:an application in health centres

Queuing is one of the very important criteria for assessing the performance and efficiency of any service industry, including healthcare. Data Envelopment Analysis (DEA) is one of the most widely-used techniques for performance measurement in healthcare. However, no queue management application has been reported in the health-related DEA literature. Most of the studies regarding patient flow systems had the objective of improving an already existing Appointment System. The current study presents a novel application of DEA for assessing the queuing process at an Outpatients’ department of a large public hospital in a developing country where appointment systems do not exist. The main aim of the current study is to demonstrate the usefulness of DEA modelling in the evaluation of a queue system. The patient flow pathway considered for this study consists of two stages; consultation with a doctor and pharmacy. The DEA results indicated that waiting times and other related queuing variables included need considerable minimisation at both stages

Characteristics of therapeutic alliance in musculoskeletal physiotherapy and occupational therapy practice: A scoping review of the literature

© 2017 The Author(s). Background: Most conventional treatment for musculoskeletal conditions continue to show moderate effects, prompting calls for ways to increase effectiveness, including drawing from strategies used across other health conditions. Therapeutic alliance refers to the relational processes at play in treatment which can act in combination or independently of specific interventions. Current evidence guiding the use of therapeutic alliance in health care arises largely from psychotherapy and medicine literature. The objective of this review was to map out the available literature on therapeutic alliance conceptual frameworks, themes, measures and determinants in musculoskeletal rehabilitation across physiotherapy and occupational therapy disciplines. Methods: A scoping review of the literature published in English since inception to July 2015 was conducted using Medline, EMBASE, PsychINFO, PEDro, SportDISCUS, AMED, OTSeeker, AMED and the grey literature. A key search term strategy was employed using physiotherapy , occupational therapy , therapeutic alliance , and musculoskeletal to identify relevant studies. All searches were performed between December 2014 and July 2015 with an updated search on January 2017. Two investigators screened article title, abstract and full text review for articles meeting the inclusion criteria and extracted therapeutic alliance data and details of each study. Results: One hundred and thirty articles met the inclusion criteria including quantitative (33%), qualitative (39%), mixed methods (7%) and reviews and discussions (23%) and most data came from the USA (23%). Randomized trials and systematic reviews were 4.6 and 2.3% respectively. Low back pain condition (22%) and primary care (30.7%) were the most reported condition and setting respectively. One theory, 9 frameworks, 26 models, 8 themes and 42 subthemes of therapeutic alliance were identified. Twenty-six measures were identified; the Working Alliance Inventory (WAI) was the most utilized measure (13%). Most of the therapeutic alliance themes extracted were from patient perspectives. The relationship between adherence and therapeutic alliance was examined by 26 articles of which 57% showed some correlation between therapeutic alliance and adherence. Age moderated the relationship between therapeutic alliance and adherence with younger individuals and an autonomy support environment reporting improved adherence. Prioritized goals, autonomy support and motivation were facilitators of therapeutic alliance. Conclusion: Therapeutic Alliance has been studied in a limited extent in the rehabilitation literature with conflicting frameworks and findings. Potential benefits described for enhancing therapeutic alliance might include better exercise adherence. Several knowledge gaps have been identified with a potential for generating future research priorities for therapeutic alliance in musculoskeletal rehabilitation

Neural Correlates of Visual Motion Prediction

Predicting the trajectories of moving objects in our surroundings is important for many life scenarios, such as driving, walking, reaching, hunting and combat. We determined human subjects’ performance and task-related brain activity in a motion trajectory prediction task. The task required spatial and motion working memory as well as the ability to extrapolate motion information in time to predict future object locations. We showed that the neural circuits associated with motion prediction included frontal, parietal and insular cortex, as well as the thalamus and the visual cortex. Interestingly, deactivation of many of these regions seemed to be more closely related to task performance. The differential activity during motion prediction vs. direct observation was also correlated with task performance. The neural networks involved in our visual motion prediction task are significantly different from those that underlie visual motion memory and imagery. Our results set the stage for the examination of the effects of deficiencies in these networks, such as those caused by aging and mental disorders, on visual motion prediction and its consequences on mobility related daily activities

Once bitten, not necessarily shy? Determinants of foreign market re-entry commitment strategies

We investigate foreign market re-entry commitment strategies, namely the changes in the modes of operation (commitment) undertaken by multinational enterprises (MNEs) as they return to foreign markets from which they had previously exited. We combine organisational learning theory with the institutional change literature to examine the antecedents of re-entry commitment strategies. From an analysis of 1,020 re-entry events between 1980 and 2016, we find that operation mode prior to exit is a strong predictor of subsequent re-entry mode. Contrary to the predictions of learning theory, we did not find support for the effect of experience accumulated during the initial market endeavour on the re-entry commitment strategies of MNEs. In turn, exit motives significantly impact on the re-entrants' decision to re-enter via a different mode of operation, by either increasing or decreasing their commitment to the market. We show that re-entrants do not replicate unsuccessful operation mode strategies if they had previously underperformed in the market. When favourable host institutional changes occur during the time-out period re-entrants tend to increase commitment in the host market irrespective of the degree of prior experience accumulated in the market