The role of ongoing dendritic oscillations in single-neuron dynamics

The dendritic tree contributes significantly to the elementary computations a neuron performs while converting its synaptic inputs into action potential output. Traditionally, these computations have been characterized as temporally local, near-instantaneous mappings from the current input of the cell to its current output, brought about by somatic summation of dendritic contributions that are generated in spatially localized functional compartments. However, recent evidence about the presence of oscillations in dendrites suggests a qualitatively different mode of operation: the instantaneous phase of such oscillations can depend on a long history of inputs, and under appropriate conditions, even dendritic oscillators that are remote may interact through synchronization. Here, we develop a mathematical framework to analyze the interactions of local dendritic oscillations, and the way these interactions influence single cell computations. Combining weakly coupled oscillator methods with cable theoretic arguments, we derive phase-locking states for multiple oscillating dendritic compartments. We characterize how the phase-locking properties depend on key parameters of the oscillating dendrite: the electrotonic properties of the (active) dendritic segment, and the intrinsic properties of the dendritic oscillators. As a direct consequence, we show how input to the dendrites can modulate phase-locking behavior and hence global dendritic coherence. In turn, dendritic coherence is able to gate the integration and propagation of synaptic signals to the soma, ultimately leading to an effective control of somatic spike generation. Our results suggest that dendritic oscillations enable the dendritic tree to operate on more global temporal and spatial scales than previously thought

Accurate path integration in continuous attractor network models of grid cells

Grid cells in the rat entorhinal cortex display strikingly regular firing responses to the animal's position in 2-D space and have been hypothesized to form the neural substrate for dead-reckoning. However, errors accumulate rapidly when velocity inputs are integrated in existing models of grid cell activity. To produce grid-cell-like responses, these models would require frequent resets triggered by external sensory cues. Such inadequacies, shared by various models, cast doubt on the dead-reckoning potential of the grid cell system. Here we focus on the question of accurate path integration, specifically in continuous attractor models of grid cell activity. We show, in contrast to previous models, that continuous attractor models can generate regular triangular grid responses, based on inputs that encode only the rat's velocity and heading direction. We consider the role of the network boundary in the integration performance of the network and show that both periodic and aperiodic networks are capable of accurate path integration, despite important differences in their attractor manifolds. We quantify the rate at which errors in the velocity integration accumulate as a function of network size and intrinsic noise within the network. With a plausible range of parameters and the inclusion of spike variability, our model networks can accurately integrate velocity inputs over a maximum of ~10–100 meters and ~1–10 minutes. These findings form a proof-of-concept that continuous attractor dynamics may underlie velocity integration in the dorsolateral medial entorhinal cortex. The simulations also generate pertinent upper bounds on the accuracy of integration that may be achieved by continuous attractor dynamics in the grid cell network. We suggest experiments to test the continuous attractor model and differentiate it from models in which single cells establish their responses independently of each other

A grounded theory of female adolescents' dating experiences and factors influencing safety: the dynamics of the Circle

<p>Abstract</p> <p>Background</p> <p>This paper describes the nature and characteristics of the dating relationships of adolescent females, including any of their experiences of abuse.</p> <p>Methods</p> <p>A grounded theory approach was used with 22 theoretically sampled female adolescents ages 15–18.</p> <p>Results</p> <p>Several important themes emerged: Seven stages of dating consistently described the relationships of female adolescents. A circle consisting of two interacting same sex peer groups provided structure for each teen as they navigated the dating course. The circle was the central factor affecting a female adolescent's potential for risk or harm in dating relationships. Teens defined abuse as an act where the intention is to hurt. Having once succumbed to sexual pressure, teens felt unable to refuse sex in subsequent situations.</p> <p>Conclusion</p> <p>An awareness of both the stages of dating and the dynamics of the circle will assist health care providers to plan and implement interventions in the female adolescent population. Study findings on factors and influences that support non-abusive versus abusive relationship might help identify female teens at risk and/or support interventions aimed at preventing dating violence.</p

European youth care sites serve different populations of adolescents with cannabis use disorder. Baseline and referral data from the INCANT trial

Background: MDFT (Multidimensional Family Therapy) is a family based outpatient treatment programme for adolescent problem behaviour. MDFT has been found effective in the USA in adolescent samples differing in severity and treatment delivery settings. On request of five governments (Belgium, France, Germany, the Netherlands, and Switzerland), MDFT has now been tested in the joint INCANT trial (International Cannabis Need of Treatment) for applicability in Western Europe. In each of the five countries, study participants were recruited from the local population of youth seeking or guided to treatment for, among other things, cannabis use disorder. There is little information in the literature if these populations are comparable between sites/countries or not. Therefore, we examined if the study samples enrolled in the five countries differed in baseline characteristics regarding demographics, clinical profile, and treatment delivery setting.Methods: INCANT was a multicentre phase III(b) randomized controlled trial with an open-label, parallel group design. It compared MDFT with treatment as usual (TAU) at and across sites in Berlin, Brussels, Geneva, The Hague and Paris.Participants of INCANT were adolescents of either sex, from 13 through 18 years of age, with a cannabis use disorder (dependence or abuse), and at least one parent willing to take part in the treatment. In total, 450 cases/families were randomized (concealed) into INCANT.Results: We collected data about adolescent and family demographics (age, gender, family composition, school, work, friends, and leisure time). In addition, we gathered data about problem behaviour (substance use, alcohol and cannabis use disorders, delinquency, psychiatric co-morbidity).There were no major differences on any of these measures between the treatment conditions (MDFT and TAU) for any of the sites. However, there were cross-site differences on many variables. Most of these could be explained by variations in treatment culture, as reflected by referral policy, i.e., participants' referral source. We distinguished 'self-determined' referral (common in Brussels and Paris) and referral with some authority-related 'external' coercion (common in Geneva and The Hague). The two referral types were more equally divided in Berlin. Many cross-site baseline differences disappeared when we took referral source into account, but not all.Conclusions: A multisite trial has the advantage of being efficient, but it also carries risks, the most important one being lack of equivalence between local study populations. Our site populations differed in many respects. This is not a problem for analyses and interpretations if the differences somehow can be accounted for. To a major extent, this appeared possible in INCANT. The most important factor underlying the cross-site variations in baseline characteristics was referral source. Correcting for referral source made most differences disappear. Therefore, we will use referral source as a covariate accounting for site differences in future INCANT outcome analyses

Evaluation of the Oscillatory Interference Model of Grid Cell Firing through Analysis and Measured Period Variance of Some Biological Oscillators

Models of the hexagonally arrayed spatial activity pattern of grid cell firing in the literature generally fall into two main categories: continuous attractor models or oscillatory interference models. Burak and Fiete (2009, PLoS Comput Biol) recently examined noise in two continuous attractor models, but did not consider oscillatory interference models in detail. Here we analyze an oscillatory interference model to examine the effects of noise on its stability and spatial firing properties. We show analytically that the square of the drift in encoded position due to noise is proportional to time and inversely proportional to the number of oscillators. We also show there is a relatively fixed breakdown point, independent of many parameters of the model, past which noise overwhelms the spatial signal. Based on this result, we show that a pair of oscillators are expected to maintain a stable grid for approximately t = 5µ3/(4πσ)2 seconds where µ is the mean period of an oscillator in seconds and σ2 its variance in seconds2. We apply this criterion to recordings of individual persistent spiking neurons in postsubiculum (dorsal presubiculum) and layers III and V of entorhinal cortex, to subthreshold membrane potential oscillation recordings in layer II stellate cells of medial entorhinal cortex and to values from the literature regarding medial septum theta bursting cells. All oscillators examined have expected stability times far below those seen in experimental recordings of grid cells, suggesting the examined biological oscillators are unfit as a substrate for current implementations of oscillatory interference models. However, oscillatory interference models can tolerate small amounts of noise, suggesting the utility of circuit level effects which might reduce oscillator variability. Further implications for grid cell models are discussed

Temporary epicardial cardiac resynchronisation versus conventional right ventricular pacing after cardiac surgery: study protocol for a randomised control trial

Background: Heart failure patients with stable angina, acute coronary syndromes and valvular heart disease may benefit from revascularisation and/or valve surgery. However, the mortality rate is increased- 5-30%. Biventricular pacing using temporary epicardial wires after surgery is a potential mechanism to improve cardiac function and clinical endpoints. Method/design: A multi-centred, prospective, randomised, single-blinded, intervention-control trial of temporary biventricular pacing versus standard pacing. Patients with ischaemic cardiomyopathy, valvular heart disease or both, an ejection fraction ≤ 35% and a conventional indication for cardiac surgery will be recruited from 2 cardiac centres. Baseline investigations will include: an electrocardiogram to confirm sinus rhythm and measure QRS duration; echocardiogram to evaluate left ventricular function and markers of mechanical dyssynchrony; dobutamine echocardiogram for viability and blood tests for renal function and biomarkers of myocardial injury- troponin T and brain naturetic peptide. Blood tests will be repeated at 18, 48 and 72 hours. The principal exclusions will be subjects with permanent atrial arrhythmias, permanent pacemakers, infective endocarditis or end-stage renal disease. After surgery, temporary pacing wires will be attached to the postero-lateral wall of the left ventricle, the right atrium and right ventricle and connected to a triple chamber temporary pacemaker. Subjects will be randomised to receive either temporary biventricular pacing or standard pacing (atrial inhibited pacing or atrial-synchronous right ventricular pacing) for 48 hours. The primary endpoint will be the duration of level 3 care. In brief, this is the requirement for invasive ventilation, multi-organ support or more than one inotrope/vasoconstrictor. Haemodynamic studies will be performed at baseline, 6, 18 and 24 hours after surgery using a pulmonary arterial catheter. Measurements will be taken in the following pacing modes: atrial inhibited; right ventricular only; atrial synchronous-right ventricular; atrial synchronous-left ventricular and biventricular pacing. Optimisation of the atrioventricular and interventricular delay will be performed in the biventricular pacing group at 18 hours. The effect of biventricular pacing on myocardial injury, post operative arrhythmias and renal function will also be quantified

Grid Cells, Place Cells, and Geodesic Generalization for Spatial Reinforcement Learning

Reinforcement learning (RL) provides an influential characterization of the brain's mechanisms for learning to make advantageous choices. An important problem, though, is how complex tasks can be represented in a way that enables efficient learning. We consider this problem through the lens of spatial navigation, examining how two of the brain's location representations—hippocampal place cells and entorhinal grid cells—are adapted to serve as basis functions for approximating value over space for RL. Although much previous work has focused on these systems' roles in combining upstream sensory cues to track location, revisiting these representations with a focus on how they support this downstream decision function offers complementary insights into their characteristics. Rather than localization, the key problem in learning is generalization between past and present situations, which may not match perfectly. Accordingly, although neural populations collectively offer a precise representation of position, our simulations of navigational tasks verify the suggestion that RL gains efficiency from the more diffuse tuning of individual neurons, which allows learning about rewards to generalize over longer distances given fewer training experiences. However, work on generalization in RL suggests the underlying representation should respect the environment's layout. In particular, although it is often assumed that neurons track location in Euclidean coordinates (that a place cell's activity declines “as the crow flies” away from its peak), the relevant metric for value is geodesic: the distance along a path, around any obstacles. We formalize this intuition and present simulations showing how Euclidean, but not geodesic, representations can interfere with RL by generalizing inappropriately across barriers. Our proposal that place and grid responses should be modulated by geodesic distances suggests novel predictions about how obstacles should affect spatial firing fields, which provides a new viewpoint on data concerning both spatial codes

Interventions aimed at increasing research use in nursing: a systematic review

<p>Abstract</p> <p>Background</p> <p>There has been considerable interest recently in developing and evaluating interventions to increase research use by clinicians. However, most work has focused on medical practices; and nursing is not well represented in existing systematic reviews. The purpose of this article is to report findings from a systematic review of interventions aimed at increasing research use in nursing.</p> <p>Objective</p> <p>To assess the evidence on interventions aimed at increasing research use in nursing.</p> <p>Methods</p> <p>A systematic review of research use in nursing was conducted using databases (Medline, CINAHL, Healthstar, ERIC, Cochrane Central Register of Controlled Trials, and Psychinfo), grey literature, ancestry searching (Cochrane Database of Systematic Reviews), key informants, and manual searching of journals. Randomized controlled trials and controlled before- and after-studies were included if they included nurses, if the intervention was explicitly aimed at increasing research use or evidence-based practice, and if there was an explicit outcome to research use. Methodological quality was assessed using pre-existing tools. Data on interventions and outcomes were extracted and categorized using a pre-established taxonomy.</p> <p>Results</p> <p>Over 8,000 titles were screened. Three randomized controlled trials and one controlled before- and after-study met the inclusion criteria. The methodological quality of included studies was generally low. Three investigators evaluated single interventions. The most common intervention was education. Investigators measured research use using a combination of surveys (three studies) and compliance with guidelines (one study). Researcher-led educational meetings were ineffective in two studies. Educational meetings led by a local opinion leader (one study) and the formation of multidisciplinary committees (one study) were both effective at increasing research use.</p> <p>Conclusion</p> <p>Little is known about how to increase research use in nursing, and the evidence to support or refute specific interventions is inconclusive. To advance the field, we recommend that investigators: (1) use theoretically informed interventions to increase research use, (2) measure research use longitudinally using theoretically informed and psychometrically sound measures of research use, as well as, measuring patient outcomes relevant to the intervention, and (3) use more robust and methodologically sound study designs to evaluate interventions. If investigators aim to establish a link between using research and improved patient outcomes they must first identify those interventions that are effective at increasing research use.</p

Brief Exposure to Sensory Cues Elicits Stimulus-Nonspecific General Sensitization in an Insect

The effect of repeated exposure to sensory stimuli, with or without reward is well known to induce stimulus-specific modifications of behaviour, described as different forms of learning. In recent studies we showed that a brief single pre-exposure to the female-produced sex pheromone or even a predator sound can increase the behavioural and central nervous responses to this pheromone in males of the noctuid moth Spodoptera littoralis. To investigate if this increase in sensitivity might be restricted to the pheromone system or is a form of general sensitization, we studied here if a brief pre-exposure to stimuli of different modalities can reciprocally change behavioural and physiological responses to olfactory and gustatory stimuli. Olfactory and gustatory pre-exposure and subsequent behavioural tests were carried out to reveal possible intra- and cross-modal effects. Attraction to pheromone, monitored with a locomotion compensator, increased after exposure to olfactory and gustatory stimuli. Behavioural responses to sucrose, investigated using the proboscis extension reflex, increased equally after pre-exposure to olfactory and gustatory cues. Pheromone-specific neurons in the brain and antennal gustatory neurons did, however, not change their sensitivity after sucrose exposure. The observed intra- and reciprocal cross-modal effects of pre-exposure may represent a new form of stimulus-nonspecific general sensitization originating from modifications at higher sensory processing levels

Representing 3D Space in Working Memory: Spatial Images from Vision, Hearing, Touch, and Language

The chapter deals with a form of transient spatial representation referred to as a spatial image. Like a percept, it is externalized, scaled to the environment, and can appear in any direction about the observer. It transcends the concept of modality, as it can be based on inputs from the three spatial senses, from language, and from long-term memory. Evidence is presented that supports each of the claimed properties of the spatial image, showing that it is quite different from a visual image. Much of the evidence presented is based on spatial updating. A major concern is whether spatial images from different input modalities are functionally equivalent— that once instantiated in working memory, the spatial images from different modalities have the same functional characteristics with respect to subsequent processing, such as that involved in spatial updating. Going further, the research provides some evidence that spatial images are amodal (i.e., do not retain modality-specific features)