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The American College of Cardiology/American Heart Association guidelines recommend implantable cardioverter-defibrillator (ICD) implantation for patients with hypertrophic cardiomyopathy (HCM) with a wall thickness of ≥30 mm (class IIA), whereas they give a class IIB recommendation for the implantation of an ICD on the basis of extensive late gadolinium enhancement alone. In this analysis, we show that in a high-risk population with ICD implanted for primary prevention of sudden cardiac death (SCD) in the setting of HCM, the presence of massive left ventricular hypertrophy predicts a higher incidence of ICD therapy than other traditional SCD risk factors. The presence of extensive myocardial fibrosis, however, identifies a subgroup of patients without massive left ventricular hypertrophy who have an equally high incidence of receiving appropriate device therapy. These findings suggest that the presence of extensive late gadolinium enhancement on cardiac magnetic resonance can be used as a risk modifier for traditional SCD risk factors in patients with HCM to better understand their overall risk of ventricular arrhythmias.

Coastlines worldwide are coming under increasing pressure due to climate change and human activity. Data on shoreline change are essential for coastal managers and when no long-term monitoring programs are implemented and shoreline change is typically on the order of less than 1 m/yr., as observed in Ireland, aerial photography is the most valuable source of information. A well-established literature exists for automated vegetation extraction from digital images based on the near infrared reflectance, but there is less research available on spectrally limited colour photography. This study develops a methodology for automating vegetation line extraction from a series of historical aerial photography of the Cork coastline in the South-West of Ireland. The approach relies on the Normalised Green–Blue Difference Index (NGBDI), which is versatile enough to discriminate disparate coastal vegetation environments, at different resolutions and in various lighting and seasonal conditions. An iterative optimal threshold process and the use of LiDAR ancillary datasets resulted in an automated vegetation line measurement with uncertainties estimated to be between 0.6 and 1.2 m. Change rates derived from the vegetation lines extracted present uncertainties in the range of ±0.27 m/yr. This robust and repeatable method provides a valuable alternative to time-consuming and subjective manual digitisation.

Coarctation of the aorta (CoA) comprises 5–7% of congenital heart disease and can present as an isolated narrowing in the aortic arch just distal to the left subclavian artery or can be associated with cardiac abnormalities such as a bicuspid aortic valve, aortopathy, or ventricular septal defects. With the advances in the medical field, intervention on CoA can either be via surgical repair or endovascular stenting. Echocardiography is the mainstay in diagnosing CoA, with tomographic imaging such as magnetic resonance imaging (MRI) or computed tomography providing supplementary assessment of the aorta, valves, and collateral vessels. We present a case of a young hypertensive male who was noted to have a continuous cardiac murmur with diagnostic Doppler pattern of CoA on echocardiography that normalized soon after percutaneous stenting.

Purpose: To characterize changes in subfoveal choroidal thickness in preterm infants from 30 to 60 weeks' postmenstrual age (PMA). Design: The prospective, observational Study of Eye Imaging in Preterm infantS (BabySTEPS) enrolled infants eligible for retinopathy of prematurity screening per the American Association of Pediatrics guidelines. Subjects: Infants imaged with an investigational, handheld OCT at ≥ 4 distinct imaging sessions between 30 to 60 weeks' PMA as part of BabySTEPS. Methods: Average choroidal thickness across the central subfoveal 1 mm in each eye at each time point was measured using custom segmentation software, and errors were manually corrected by a trained grader. We prospectively collected birth history data. A segmented mixed model was used to analyze the change in choroidal thickness as a function of PMA, birth weight, and gestational age (GA). Main Outcome Measures: Characterization of normative subfoveal choroidal thickness values and choroidal growth rate between 30 to 60 weeks' PMA. Results: We included 592 imaging sessions of 79 preterm infants (152 eyes). Mean (± standard deviation) GA was 27.5 ± 2.5 weeks. Mean choroidal thickness was 141.4 ± 34.5 μm at 30 weeks, 272.2 ± 83.9 μm at 38 weeks, and 306.2 ± 77.4 μm between 56 and 60 weeks. Between 30 and 60 weeks' PMA, choroidal growth followed a biphasic model, with a linear growth rate of 14.8 μm per week (95% confidence interval [CI], 13.6–16.0) from 30 until 38.4 weeks, then cessation of growth, with a growth rate of 0.3 μm per week (95% CI, −1.1 to 1.6) from 38.4 to 60 weeks. Infants with extremely low birth weight (ELBW; < 1000 g) and extremely preterm (GA < 28 weeks) infants had significantly slower initial growth rates compared with very low and low birth weight and very preterm and preterm infants (ELBW 13.0 vs. 21.0 μm per week; P < 0.0001 and extremely preterm 13.2 vs. 18.0 μm per week; P = 0.003). Conclusions: Preterm infant choroidal thickness experiences rapid linear growth from 30 to 38 weeks' PMA, at which time growth nearly stops. These foundational measurements and identification of the impact of extremes of low birth weight and prematurity on choroidal development will be essential as researchers begin to understand the role of choroidal development in ocular and retinal health in human infants. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Offshore anthropogenic activities such as the installation of Offshore Renewable Energy (ORE) developments and sediment extraction for marine aggregates have been shown to disrupt current flow, wave propagation, and sediment transport pathways, leading to potential environmental instability. Due to the complexity of the interconnected sediment transport pathways in the south-western Irish Sea combined with an increase in planned anthropogenic activities, the assessment of this risk is imperative for the development of a robust marine spatial plan. Subsequently, this study uses two-dimensional morphological modelling to build upon previous studies to assess the dependency of Arklow Bank’s local sediment transport regime on external sediment sources. Additionally, scenario modelling is used to identify vulnerable areas of this offshore linear sand bank to wind and wave-forcing and to examine the nature of this impact. A sediment budget is estimated for Arklow Bank, whereby seven source and nine sink pathways are identified. New evidence to support the exchange of sediment between offshore sand banks and offshore independent sand wave fields is also provided. The areas of the bank most vulnerable to changes in external sediment sources and the addition of wind- and wave-induced flow are analogous. These high vulnerability zones (HVZs) align with regions of residual cross-flow under pure current conditions. The restriction of sediment sources off the southern extent of Arklow Bank impacts erosion and accretion patterns in the mid- and northern sections of the bank after just one lunar month of simulation. Where tidal current is the primary driver of sand bank morphodynamics, wind- and wave-induced flow is shown to temporarily alter sediment distribution patterns. Wind and wave-induced flow can both accelerate and decelerate the east-west fluctuation of the upper slopes of the bank, yet the nature of this impact is inconsistent due to the misalignment of the directionality of these two forces. The methods and new knowledge derived from this study are directly applicable to tidally-dominated environments outside the Irish Sea.

Aims:Increased left ventricular (LV) wall thickness is frequently encountered in transthoracic echocardiography (TTE). While accurate and early diagnosis is clinically important, given the differences in available therapeutic options and prognosis, an extensive workup is often required to establish the diagnosis. We propose the first echo-based, automated deep learning model with a fusion architecture to facilitate the evaluation and diagnosis of increased left ventricular (LV) wall thickness. Methods and Results: Patients with an established diagnosis of increased LV wall thickness (hypertrophic cardiomyopathy (HCM), cardiac amyloidosis (CA), and hypertensive heart disease (HTN)/others) between 1/2015 and 11/2019 at Mayo Clinic Arizona were identified. The cohort was divided into 80%/10%/10% for training, validation, and testing sets, respectively. Six baseline TTE views were used to optimize a pre-trained InceptionResnetV2 model. Each model output was used to train a meta-learner under a fusion architecture. Model performance was assessed by multiclass area under the receiver operating characteristic curve (AUROC). A total of 586 patients were used for the final analysis (194 HCM, 201 CA, and 191 HTN/others). The mean age was 55.0 years, and 57.8% were male. Among the individual view-dependent models, the apical 4-chamber model had the best performance (AUROC: HCM: 0.94, CA: 0.73, and HTN/other: 0.87). The final fusion model outperformed all the view-dependent models (AUROC: HCM: 0.93, CA: 0.90, and HTN/other: 0.92). Conclusion: The echo-based InceptionResnetV2 fusion model can accurately classify the main etiologies of increased LV wall thickness and can facilitate the process of diagnosis and workup.

Offshore sand banks are an important resource for coastal protection, marine aggregates, and benthic habitats and are the site of many offshore wind farms. Consequently, a comprehensive understanding of the baseline processes controlling sand bank morphodynamics is imperative. This knowledge will aid the development of a long-term robust marine spatial plan and help address the environmental instability arising from anthropogenic activities. This study uses a validated, dynamically coupled, two-dimensional hydrodynamic and sediment transport model to investigate the hydrodynamic processes controlling the highly mobile upper layer of Arklow Bank, while maintaining overall long-term bank base stability. The results reveal a flood and ebb tidal current dominance on the west and east side of the bank, respectively, ultimately generating a large anticlockwise residual current eddy encompassing the entire bank. This residual current flow distributes sediment along the full length of the sand bank. The positioning of multiple off-bank anticlockwise residual current eddies on the edge of this cell is shown to influence east–west fluctuations of the upper slopes of the sand bank and act as a control on long-term stability. These off-bank eddies facilitate this type of movement when the outer flows of adjacent eddies, located on both sides of the bank, flow in a general uniform direction. Whereas they inhibit this east–west movement when the outer flows of adjacent eddies, on either side of the bank, flow in converging directions towards the bank itself. These residual eddies also facilitate sediment transport in and out of the local sediment transport system. Within Arklow Bank’s morphological cell, eight morphodynamically and hydrodynamically unique bank sections or ‘sub-cells’ are identified, whereby a complex morphodynamic–hydrodynamic feedback loop is present. The local east–west fluctuation of the upper slopes of the bank is driven by migratory on-bank stationary and transient clockwise residual eddies and the development of ‘narrow’ residual current cross-flow zones. Together, these processes drive upper slope mobility but maintain long-term bank base stability. This novel understanding of sand bank morphodynamics is applicable to bedforms in tidally dominated continental shelf seas outside the Irish Sea.

With the recent push for a transition towards a climate-resilient economy, the demand on marine resources is accelerating. For many economic exploits, a comprehensive understanding of environmental parameters underpinning seabed morphodynamics in tidally-dominated shelf seas, and the relationship between local and regional scale sediment transport regimes as an entire system, is imperative. In this paper, high-resolution, time-lapse bathymetry datasets, hydrodynamic numerical modelling outputs and various theoretical parameters are used to describe the morphological characteristics of sediment waves and their spatio-temporal evolution in a hydrodynamically and morphodynamically complex region of the Irish Sea. Analysis reveals sediment waves in a range of sizes (height = 0.1 to 25.7 m, and wavelength = 17 to 983 m), occurring in water depths of 8.2 to 83 mLAT, and migrating at a rate of 1.1 to 79 m/yr. Combined with numerical modelling outputs, a strong divergence of sediment transport pathways from the previously understood predominantly southward flow in the south Irish Sea is revealed, both at offshore sand banks and independent sediment wave assemblages. This evidence supports the presence of a semi-closed circulatory hydrodynamic and sediment transport system at Arklow Bank (an open-shelf linear sand bank). Contrastingly, the Lucifer–Blackwater Bank complex and associated sediment waves are heavily influenced by the interaction between a dominant southward flow and a residual headland eddy, which also exerts a strong influence on the adjacent banner bank. Furthermore, a new sediment transfer system is defined for offshore independent sediment wave assemblages, whereby each sediment wave field is supported by circulatory residual current cells originating from offshore sand banks. These new data and results improve knowledge of seabed morphodynamics in tidally-dominated shelf seas, which has direct implications for offshore renewable developments and long-term marine spatial planning.

AimThe aim was to predict and understand variations in swimmer performance between individual and relay events, and develop a predictive model for the 4x200-m swimming freestyle relay event to help inform team selection and strategy.Data and methodsRace data for 716 relay finals (4 x 200-m freestyle) from 14 international competitions between 2010-2018 were analysed. Individual 200-m freestyle season best time for the same year was located for each swimmer. Linear regression and machine learning was applied to 4 x 200-m swimming freestyle relay events.ResultsCompared to the individual event, the lowest ranked swimmer in the team (-0.62 s, CI = [-0.94, -0.30]) and American swimmers (-0.48 s [-0.89, -0.08]) typically swam faster 200-m times in relay events. Random forest models predicted gold, silver, bronze and non-medal with 100%, up to 41%, up to 63%, and 93% sensitivity, respectively.DiscussionTeam finishing position was strongly associated with the differential time to the fastest team (mean decrease in Gini (MDG) when this variable was omitted = 31.3), world rankings of team members (average ranking MDG of 18.9), and the order of swimmers (MDG = 6.9). Differential times are based on the sum of individual swimmer's season's best times, and along with world rankings, reflect team strength. In contrast, the order of swimmers reflects strategy. This type of analysis could assist coaches and support staff in selecting swimmers and team orders for relay events to enhance the likelihood of success.

Correctly applied air source heat pumps (ASHPs) are a proven technology that can reliably and effectively replace fossil fuel heating systems and achieve targeted heating-related CO2 reductions. However, poor-quality system design, installation or commissioning can lead to higher than expected running costs and poorly-performing heating systems, thus resulting in lower than expected CO2 savings. The retrofit ASHP systems studied in this research in residential retrofits in Ireland had significant engineering input at design stage, and comprehensive oversight during the installation and commissioning stages by the engineering team. Following analysis, most of the systems performed in line with, or exceeded, predictions but further opportunities for optimisation were identified. The research highlights the need for increased focus and resources to be applied by commissioning engineers to ensure that all ASHP installations are successful, a point that is especially critical in the context of the Irish Climate Action Plan targets of 500,000 retrofitted homes and the installation of 400,000 retrofit heat pumps by 2030 (Government of Ireland, 2019). This paper presents recommendations on how the ASHP installation process can deliver systems that operate to their full potential in terms of energy efficiency and CO2 reductions.

Oxcarbazepine and carbamazepine cause hyponatremia by unknown mechanisms. We describe a patient with complete central diabetes insipidus and seizures who developed worsening hyponatremia when her dose of oxcarbazepine was increased. The patient maintained a normal serum sodium level and has had appropriately concentrated urine for 5 years on just oxcarbazepine, despite undetectable antidiuretic hormone (ADH) levels. This suggests that oxcarbazepine (or one of its metabolites) may stimulate collecting tubule V2 receptor-G protein complex independent of ADH, resulting in increased renal tubular water reabsorption. Oxcarbazepine may be useful as an alternative therapy for patients with central diabetes insipidus.

Marine renewable energy (MRE) is still an emerging technology. As such, there is still a lack of mature standards and guidance for the development and testing of these devices. The sector covers a wide range of disciplines, so there is a need for more comprehensive guidance to cover these. This paper builds on a study undertaken in the MaRINET2 project to summarise recommendations and guidance for testing MRE devices and components, by reviewing the recently published guidance. Perceived gaps in the guidance are then discussed, expanding on the previous study. Results from an industry survey are also used to help quantify and validate these gaps. The main themes identified can be summarised as: the development progression from concept to commercialisation, including more complex environmental conditions in testing, accurately modelling and quantifying the power generated, including grid integration, plus modelling and testing of novel moorings and foundation solutions. A pathway to a standardised approach to MRE testing is presented, building on recommendations learnt from the MaRINET2 round-robin testing, showing how these recommendations are being incorporated into the guidance and ultimately feeding into the development of international standards for the marine renewable energy sector.

This paper documents the round robin testing campaign carried out on a floating wind turbine as part of the EU H2020 MaRINET2 project. A 1/60th scale model of a 10 MW floating platform was tested in wave basins in four different locations around Europe. The tests carried out in each facility included decay tests, tests in regular and irregular waves with and without wind thrust, and tests to characterise the mooring system as well as the model itself. For the tests in wind, only the thrust of the turbine was considered and it was fixed to pre-selected levels. Hence, this work focuses on the hydrodynamic responses of a semi-submersible floating foundation. It was found that the global surge stiffness was comparable across facilities, except in one case where different azimuth angles were used for the mooring lines. Heave and pitch had the same stiffness coefficient and periods for all basins. Response Amplitude Operators (RAOs) were used to compare the responses in waves from all facilities. The shape of the motion RAOs were globally similar for all basins except around some particular frequencies. As the results were non-linear around the resonance and cancellation frequencies, the differences between facilities were magnified at these frequencies. Surge motions were significantly impacted by reflections leading to large differences in these RAOs between all basins.

This paper introduces metrics developed for analysing irregular wave test results from the round robin testing campaign carried out on a floating wind turbine as part of the EU H2020 MaRINET2 project. A 1/60th scale model of a 10 MW floating platform was tested in wave basins in four different locations around Europe. The tests carried out in each facility included decay tests, tests in regular and irregular waves with and without wind thrust, and tests to characterise the mooring system as well as the model itself. While response amplitude operations (RAOs) are a useful tool for assessing device performance in irregular waves, they are not easy to interpret when performing an inter-facility comparison where there are many variables. Metrics that use a single value per test condition rather than an RAO curve are a means of efficiently comparing tests from different basins in a more heuristic manner. In this research, the focus is on using metrics to assess how the platform responds with varying wave height and thrust across different facilities. It is found that the metrics implemented are very useful for extracting global trends across different basins and test conditions.

The EU H2020 MaRINET2 project has a goal to improve the quality, robustness and accuracy of physical modelling and associated testing practices for the offshore renewable energy sector. To support this aim, a round robin scale physical modelling test programme was conducted to deploy a common wave energy converter at four wave basins operated by MaRINET2 partners. Test campaigns were conducted at each facility to a common specification and test matrix, providing the unique opportunity for intercomparison between facilities and working practices. A nonproprietary hinged raft, with a nominal scale of 1:25, was tested under a set of 12 irregular sea states. This allowed for an assessment of power output, hinge angles, mooring loads, and six-degree-of-freedom motions. The key outcome to be concluded from the results is that the facilities performed consistently, with the majority of variation linked to differences in sea state calibration. A variation of 5–10% in mean power was typical and was consistent with the variability observed in the measured significant wave heights. The tank depth (which varied from 2–5 m) showed remarkably little influence on the results, although it is noted that these tests used an aerial mooring system with the geometry unaffected by the tank depth. Similar good agreement was seen in the heave, surge, pitch and hinge angle responses. In order to maintain and improve the consistency across laboratories, we make recommendations on characterising and calibrating the tank environment and stress the importance of the device–facility physical interface (the aerial mooring in this case).

The advent of wireless sensors and internet of things connectivity combined with increased open source cloud based digital sharing among the architecture, engineering, and construction industry has helped expand the range of applications for building information modelling. As the rate of adoption of BIM as a standard practice for planning, designing, and constructing new infrastructure increases, the research focus is moving towards other applications. Utilizing BIM in innovative ways such as for building energy performance, carbon capture, and asset management are now being explored. An area which receives less focus is the application of BIM on existing structures. This study explores the potential for implementing BIM on an existing structure for asset management and structural health monitoring. A method of integrating sensors to enhance the visualisation of structural health monitoring through BIM is developed. The study describes how monitoring data can be integrated within the BIM of an offshore lighthouse.

This research presents a study on the morphodynamic evolution of the Rossbeigh coastal barrier and its dune system, located in Dingle Bay, County Kerry, Ireland. The study examines the evolution of the system over a 19-year period (2001–2019) through remote sensing, geographic information system (GIS) analysis, and field-based surveys. This research provides an ideal opportunity to examine a natural erosion event, referred to as cannibalization on a coastal barrier and its dune system. Since the beginning of this century, significant erosion has been visible on the coastal barrier, with the erosion eventually leading to a breaching event in the winter of 2008/2009. Over the study period, analysis has shown that the vegetated dunes decreased by more than 60 percent, the width of the breached area reached a maximum width of over 1 km and a change in orientation and appearance on the coastal barrier has been quantified. The analysis identifies a growing drift-aligned zone, contrasted with a reduction in the stable swash-aligned zone. Significantly, the point between these zones (i.e., the hinge point) has been shown to have moved by more than 1 km also. The migration of this hinge point and cannibalization of the dunes are illustrated. Finally, the potential mechanism for beach healing is identified, utilizing the rich datasets collected during the study, thus providing an insight into the long-term behavior of a dynamic coastal barrier system undergoing naturally driven cannibalization.

BACKGROUND: Maternal cigarette smoking during pregnancy (MSDP) is associated with numerous adverse health outcomes in infants and children with potential lifelong consequences. Negative effects of MSDP on placental DNA methylation (DNAm), placental structure, and function are well established. OBJECTIVE: Our aim was to develop biomarkers of MSDP using DNAm measured in placentas (N =96), collected as part of the Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function double-blind, placebo-controlled randomized clinical trial conducted between 2012 and 2016. We also aimed to develop a digital polymerase chain reaction (PCR) assay for the top ranking cytosine--guanine dinucleotide (CpG) so that large numbers of samples can be screened for exposure at low cost. METHODS: We compared the ability of four machine learning methods [logistic least absolute shrinkage and selection operator (LASSO) regression, logistic elastic net regression, random forest, and gradient boosting machine] to classify MSDP based on placental DNAm signatures. We developed separate models using the complete EPIC array dataset and on the subset of probes also found on the 450K array so that models exist for both platforms. For comparison, we developed a model using CpGs previously associated with MSDP in placenta. For each final model, we used model coefficients and normalized beta values to calculate placental smoking index (PSI) scores for each sample. Final models were validated in two external datasets: the Extremely Low Gestational Age Newborn observational study, N = 426; and the Rhode Island Children's Health Study, N = 237. RESULTS: Logistic LASSO regression demonstrated the highest performance in cross-validation testing with the lowest number of input CpGs. Accuracy was greatest in external datasets when using models developed for the same platform. PSI scores in smokers only (n = 72) were moderately correlated with maternal plasma cotinine levels. One CpG (cg27402634), with the largest coefficient in two models, was measured accurately by digital PCR compared with measurement by EPIC array ([R.sup.2] = 0.98). DISCUSSION: To our knowledge, we have developed the first placental DNAm-based biomarkers of MSDP with broad utility to studies of prenatal disease origins. https://doi.org/10.1289/EHP13838, Introduction Maternal cigarette smoking during pregnancy (MSDP) is associated with increased risk of low birth weight, prematurity, and perinatal mortality. (1-4) MSDP is also associated with greater risk of cardiovascular, [...]

The occurrence of contaminated materials encountered during harbour dredging is becoming increasingly problematic for harbour and port authorities. The risks to human health, wildlife and port infrastructure of exposure to such contaminants necessitates the removal or containment of such risks. As with contaminated terrestrial sites the solidification and stabilization (S/S) of this material has been proven to be an effective alternative to disposing of contaminants off-site, typically via dumping at sea or in a landfill. Research, to date, on S/S has been focused on heavily contaminated sediments in large industrial ports. However, with tightening environmental regulations, the limits of acceptable contamination are generally decreasing. This means the number of port dredging projects requiring contaminant remediation is increasing. There is now a need to examine the effectiveness of S/S on harbour sites that are mildly contaminated from both an environmental and project feasibility viewpoint. To that end, this study examines the effectiveness of various S/S mix percentages of ordinary Portland cement (OPC) and ground granulated blast furnace slag (GGBS) in retarding the leaching of contaminants from a mildly contaminated harbour site.

Several methods of monitoring sediment transport exist and have varying degrees of success depending on the study sites characteristics. Grain Size Trend Analysis (GSTA) is an experimental method based on identifying transport trends from the variation of sediment grain characteristics within a defined study area. The parameters examined when performing GSTA are mean grain size, sorting coefficient and skewness, the most common cases found in field studies being; finer, better sorted and negatively skewed (FB−) or coarser, better sorted and positively skewed (CB+), as most transport trends follow one or the other trend. However, on Rossbeigh beach, Co. Kerry, Ireland, a coarser poorer and more negatively skewed (CP−) trend case gave the most realistic plot of sediment transport trend when compared with sediment transport calculation, bathymetry surveys, hydrodynamic monitoring and morphological modelling.

Oscillating neuronal circuits, known as central pattern generators (CPGs), are responsible for generating rhythmic behaviours such as walking, breathing and chewing. The CPG model alone however does not account for the ability of animals to adapt their future behaviour to changes in the sensory environment that signal reward. Here, using multi-electrode array (MEA) recording in an established experimental model of centrally generated rhythmic behaviour we show that the feeding CPG of Lymnaea stagnalis is itself associated with another, and hitherto unidentified, oscillating neuronal population. This extra-CPG oscillator is characterised by high population-wide activity alternating with population-wide quiescence. During the quiescent periods the CPG is refractory to activation by food-associated stimuli. Furthermore, the duration of the refractory period predicts the timing of the next activation of the CPG, which may be minutes into the future. Rewarding food stimuli and dopamine accelerate the frequency of the extra-CPG oscillator and reduce the duration of its quiescent periods. These findings indicate that dopamine adapts future feeding behaviour to the availability of food by significantly reducing the refractory period of the brain's feeding circuitry.

Since the discovery of place cells – single pyramidal neurons that encode spatial location – it has been hypothesised that the hippocampus may act as a cognitive map of known environments. This putative function has been extensively modelled using auto-associative networks, which utilise rate-coded synaptic plasticity rules in order to generate strong bi-directional connections between concurrently active place cells that encode for neighbouring place fields. However, empirical studies using hippocampal cultures have demonstrated that the magnitude and direction of changes in synaptic strength can also be dictated by the relative timing of pre- and post- synaptic firing according to a spike-timing dependent plasticity (STDP) rule. Furthermore, electrophysiology studies have identified persistent ‘theta-coded’ temporal correlations in place cell activity in vivo, characterised by phase precession of firing as the corresponding place field is traversed. It is not yet clear if STDP and theta-coded neural dynamics are compatible with cognitive map theory and previous rate-coded models of spatial learning in the hippocampus. Here, we demonstrate that an STDP rule based on empirical data obtained from the hippocampus can mediate rate-coded Hebbian learning when pre- and post- synaptic activity is stochastic and has no persistent sequence bias. We subsequently demonstrate that a spiking recurrent neural network that utilises this STDP rule, alongside theta-coded neural activity, allows the rapid development of a cognitive map during directed or random exploration of an environment of overlapping place fields. Hence, we establish that STDP and phase precession are compatible with rate-coded models of cognitive map development.

Changes in the strength of excitatory synaptic connections are known to underlie associative memory formation in the molluscan nervous system but less is known about the role of synaptic inhibition. Tonic or maintained synaptic inhibition has an important function in controlling the Lymnaea feeding system and is known to suppress feeding in the absence of food or in satiated animals. Tonic inhibition to the feeding network is provided by the N3t interneuron that has inhibitory monosynaptic connection with the central pattern generator interneuron, the N1M. Here we asked whether a reduction in the level of tonic inhibition provided by the N3t cell could play a role in reward conditioning? Semi-intact preparations made from hungry snails were conditioned using a previously-developed one-trail chemical conditioning paradigm. We recorded electrical activity in a feeding motoneuron, the B3, at various time-points after conditioning. This allowed us to measure the frequency of spike activity in the N3t interneuron and monitor fictive feeding patterns that generate the rhythmic movements involved in food ingestion. We show that there is a reduction in N3t spiking at 1, 2, 3 and 4 hours after conditioning but not at 10 minutes and 30 minutes and the reduction in N3t firing inversely correlates with an increase in the conditioned fictive feeding response. Computer simulation of N3t-N1M interactions suggests that changes in N3t firing are sufficient to explain the increase in the fictive feeding activity produced by conditioning. A network model is presented that summarizes evidence suggesting that reward conditioning in Lymnaea is due to the combined effects of reduced tonic inhibition and enhanced excitatory synaptic connections between the CS pathway and feeding command neurons.

The firing rate of single neurons in the mammalian hippocampus has been demonstrated to encode for a range of spatial and non-spatial stimuli. It has also been demonstrated that phase of firing, with respect to the theta oscillation that dominates the hippocampal EEG during stereotype learning behaviour, correlates with an animal's spatial location. These findings have led to the hypothesis that the hippocampus operates using a dual (rate and temporal) coding system. To investigate the phenomenon of dual coding in the hippocampus, we examine a spiking recurrent network model with theta coded neural dynamics and an STDP rule that mediates rate-coded Hebbian learning when pre- and post-synaptic firing is stochastic. We demonstrate that this plasticity rule can generate both symmetric and asymmetric connections between neurons that fire at concurrent or successive theta phase, respectively, and subsequently produce both pattern completion and sequence prediction from partial cues. This unifies previously disparate auto- and hetero-associative network models of hippocampal function and provides them with a firmer basis in modern neurobiology. Furthermore, the encoding and reactivation of activity in mutually exciting Hebbian cell assemblies demonstrated here is believed to represent a fundamental mechanism of cognitive processing in the brain.