Coupling between gamma-band power and cerebral blood volume during recurrent acute neocortical seizures

Characterization of neural and hemodynamic biomarkers of epileptic activity that can be measured using non-invasive techniques is fundamental to the accurate identification of the epileptogenic zone (EZ) in the clinical setting. Recently, oscillations at gamma-band frequencies and above (>30 Hz) have been suggested to provide valuable localizing information of the EZ and track cortical activation associated with epileptogenic processes. Although a tight coupling between gamma-band activity and hemodynamic-based signals has been consistently demonstrated in non-pathological conditions, very little is known about whether such a relationship is maintained in epilepsy and the laminar etiology of these signals. Confirmation of this relationship may elucidate the underpinnings of perfusion-based signals in epilepsy and the potential value of localizing the EZ using hemodynamic correlates of pathological rhythms. Here, we use concurrent multi-depth electrophysiology and 2-dimensional optical imaging spectroscopy to examine the coupling between multi-band neural activity and cerebral blood volume (CBV) during recurrent acute focal neocortical seizures in the urethane-anesthetized rat. We show a powerful correlation between gamma-band power (25-90 Hz) and CBV across cortical laminae, in particular layer 5, and a close association between gamma measures and multi-unit activity (MUA). Our findings provide insights into the laminar electrophysiological basis of perfusion-based imaging signals in the epileptic state and may have implications for further research using non-invasive multi-modal techniques to localize epileptogenic tissue

Comparison of stimulus-evoked cerebral hemodynamics in the awake mouse and under a novel anesthetic regime

Neural activity is closely followed by a localised change in cerebral blood flow, a process termed neurovascular coupling. These hemodynamic changes form the basis of contrast in functional magnetic resonance imaging (fMRI) and are used as a correlate for neural activity. Anesthesia is widely employed in animal fMRI and neurovascular studies, however anesthetics are known to profoundly affect neural and vascular physiology, particularly in mice. Therefore, we investigated the efficacy of a novel ‘modular’ anesthesia that combined injectable (fentanyl-fluanisone/midazolam) and volatile (isoflurane) anesthetics in mice. To characterize sensory-evoked cortical hemodynamic responses, we used optical imaging spectroscopy to produce functional maps of changes in tissue oxygenation and blood volume in response to mechanical whisker stimulation. Following fine-tuning of the anesthetic regime, stimulation elicited large and robust hemodynamic responses in the somatosensory cortex, characterized by fast arterial activation, increases in total and oxygenated hemoglobin, and decreases in deoxygenated hemoglobin. Overall, the magnitude and speed of evoked hemodynamic responses under anesthesia resembled those in the awake state, indicating that the novel anesthetic combination significantly minimizes the impact of anesthesia. Our findings have broad implications for both neurovascular research and longitudinal fMRI studies that increasingly require the use of genetically engineered mice

Abnormalities in whisking behaviour are associated with lesions in brain stem nuclei in a mouse model of amyotrophic lateral sclerosis

The transgenic SOD1G93A mouse is a model of human amyotrophic lateral sclerosis (ALS) and recapitulates many of the pathological hallmarks observed in humans, including motor neuron degeneration in the brain and the spinal cord. In mice, neurodegeneration particularly impacts on the facial nuclei in the brainstem. Motor neurons innervating the whisker pad muscles originate in the facial nucleus of the brain stem, with contractions of these muscles giving rise to “whisking” one of the fastest movements performed by mammals. A longitudinal study was conducted on SOD1G93A mice and wild-type litter mate controls, comparing: (i) whisker movements using high-speed video recordings and automated whisker tracking, and (ii) facial nucleus degeneration using MRI. Results indicate that while whisking still occurs in SOD1G93A mice and is relatively resistant to neurodegeneration, there are significant disruptions to certain whisking behaviours, which correlate with facial nuclei lesions, and may be as a result of specific facial muscle degeneration. We propose that measures of mouse whisker movement could potentially be used in tandem with measures of limb dysfunction as biomarkers of disease onset and progression in ALS mice and offers a novel method for testing the efficacy of novel therapeutic compounds

Impacts of climate change on aquaculture

• Aquaculture is a significant industry in UK coastal waters, with annual turnover valued at more than £1.8bn. It particularly important in western and northern Scotland. • Aquaculture is sensitive to the marine environment and changes therein. • The dominant contribution of a single species (Atlantic salmon) to production tonnage and value potentially increases vulnerability to climate change. • Temperature increase is expected to increase growth rates for most species farmed. • Increased problems associated with some diseases and parasites, notably sea lice and gill disease (which has emerged as a serious problem), are likely to increase in the short term and to get worse in the longer term. Impacts may be synergistic. • Harmful Algal Blooms (HABs) and jellyfish swarms/invasions may also get worse, however complex ecosystem interactions make responses uncertain. • The situation for shellfish is similar to finfish, although they are additionally at risk of accumulation of toxins from HABs, and recruitment failure, and, in the longer term, to sea-level rises and ocean acidification. • Technical and management changes in the rapidly evolving aquaculture industry make long-term impacts of climate change difficult to forecast

Contralateral dissociation between neural activity and cerebral blood volume during recurrent acute focal neocortical seizures

OBJECTIVE: Whether epileptic events disrupt normal neurovascular coupling mechanisms locally or remotely is unclear. We sought to investigate neurovascular coupling in an acute model of focal neocortical epilepsy, both within the seizure onset zone and in contralateral homotopic cortex. METHODS: Neurovascular coupling in both ipsilateral and contralateral vibrissal cortices of the urethane-anesthetized rat were examined during recurrent 4-aminopyridine (4-AP, 15 mm, 1 μl) induced focal seizures. Local field potential (LFP) and multiunit spiking activity (MUA) were recorded via two bilaterally implanted 16-channel microelectrodes. Concurrent two-dimensional optical imaging spectroscopy was used to produce spatiotemporal maps of cerebral blood volume (CBV). RESULTS: Recurrent acute seizures in right vibrissal cortex (RVC) produced robust ipsilateral increases in LFP and MUA activity, most prominently in layer 5, that were nonlinearly correlated to local increases in CBV. In contrast, contralateral left vibrissal cortex (LVC) exhibited relatively smaller nonlaminar specific increases in neural activity coupled with a decrease in CBV, suggestive of dissociation between neural and hemodynamic responses. SIGNIFICANCE: These findings provide insights into the impact of epileptic events on the neurovascular unit, and have important implications both for the interpretation of perfusion-based imaging signals in the disorder and understanding the widespread effects of epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here

The impact of habitat quality inside protected areas on distribution of the Dominican Republic’s last endemic non-volant land mammals

The Hispaniolan solenodon, Solenodon paradoxus, and Hispaniolan hutia, Plagiodontia aedium, are the Dominican Republic’s only surviving endemic non-volant land mammals, and are high priorities for conservation. The country has an extensive protected area (PA) network designed to maintain habitats and benefit biodiversity, but which faces significant anthropogenic threats likely to detrimentally impact both species. We examined how differences in habitats, forest structure, topography, and human activity influence presence of solenodons and hutias across the Dominican Republic. Systematic surveys of seven PAs were undertaken to record indirect signs, with presence-absence data analyzed using a multi-model inference approach incorporating ecological variables from both field and GIS data. Solenodons were detected relatively frequently, whereas detections of hutias were uncommon. Lower elevations, increased surrounding tree cover, canopy closure, and reduced levels of low vegetation are all associated with increased probability of detecting solenodons, whereas agriculture and mangrove represent poor-quality habitat. Increased canopy closure, tree basal area (indicating older-growth forest), and increased rock substrate (providing more den sites) are associated with increased probability of detecting hutias. Our findings indicated that human activities within PAs are likely to negatively affect both species, and conservation activities should focus on preventing encroachment and conversion of forest to agriculture to maintain high-quality forest habitats. El solenodonte de la Hispaniola, Solenodon paradoxus, y la hutia de la Hispaniola, Plagiodontia aedium, son los únicos mamíferos endémicos terrestres no voladores que sobreviven en la República Dominicana, su conservación es de alta prioridad. El país tiene una extensa red de áreas protegidas (AP) diseñada para mantener hábitats y beneficiar la biodiversidad, pero se enfrenta a amenazas antropogénicas. Sin embargo, no existen datos cuantitativos para evaluar las presiones antropogénicas que amenazan a los solenodontes y las hutias. Examinamos cómo las diferencias en los hábitats, la estructura del bosque, la topografía y la actividad humana influyen la presencia de solenodontes y hutias en toda la República Dominicana. Se realizaron encuestas sistemáticas de siete AP para registrar los signos indirectos de ambas especies, los datos de presencia/ausencia fueron analizados mediante inferencia multimodelo que incorpora variables ecológicas de los datos de campo y Sistema de Información Geográfica. Los Solenodontes se detectaron relativamente frecuentemente, mientras que las detecciones de hutias fueron menos comunes. Las elevaciones más bajas, el aumento de la cubierta arbórea circundante, el cierre del dosel y los niveles reducidos de vegetación baja se asocian con una mayor probabilidad de detectar solenodones. Mientras que la agricultura y los manglares representan un hábitat de mala calidad para el solenodonte. Aumento del cierre del dosel, área basal del árbol (que indica un bosque más antiguo) y un sustrato con mayor proporcion de roca (que proporciona más sitios para madrigueras) se asocian con una mayor probabilidad de detectar hutias. Nuestros hallazgos indican que las actividades humanas dentro de las AP pueden afectar negativamente a ambas especies. Las actividades de conservación deberían enfocarse en mantener hábitats forestales de alta calidad por medio de prevenir la invasión y la conversión de los bosques a agricultura

A dynamic model of neurovascular coupling: implications for blood vessel dilation and constriction

Neurovascular coupling in response to stimulation of the rat barrel cortex was investigated using concurrent multichannel electrophysiology and laser Doppler flowmetry. The data were used to build a linear dynamic model relating neural activity to blood flow. Local field potential time series were subject to current source density analysis, and the time series of a layer IV sink of the barrel cortex was used as the input to the model. The model output was the time series of the changes in regional cerebral blood flow (CBF). We show that this model can provide excellent fit of the CBF responses for stimulus durations of up to 16 s. The structure of the model consisted of two coupled components representing vascular dilation and constriction. The complex temporal characteristics of the CBF time series were reproduced by the relatively simple balance of these two components. We show that the impulse response obtained under the 16-s duration stimulation condition generalised to provide a good prediction to the data from the shorter duration stimulation conditions. Furthermore, by optimising three out of the total of nine model parameters, the variability in the data can be well accounted for over a wide range of stimulus conditions. By establishing linearity, classic system analysis methods can be used to generate and explore a range of equivalent model structures (e.g., feed-forward or feedback) to guide the experimental investigation of the control of vascular dilation and constriction following stimulation. (C) 2010 Elsevier Inc. All rights reserved

Neural computations underlying action-based decision making in the human brain

Action-based decision making involves choices between different physical actions to obtain rewards. To make such decisions the brain needs to assign a value to each action and then compare them to make a choice. Using fMRI in human subjects, we found evidence for action-value signals in supplementary motor cortex. Separate brain regions, most prominently ventromedial prefrontal cortex, were involved in encoding the expected value of the action that was ultimately taken. These findings differentiate two main forms of value signals in the human brain: those relating to the value of each available action, likely reflecting signals that are a precursor of choice, and those corresponding to the expected value of the action that is subsequently chosen, and therefore reflecting the consequence of the decision process. Furthermore, we also found signals in the dorsomedial frontal cortex that resemble the output of a decision comparator, which implicates this region in the computation of the decision itself

Real-Time High-Sensitivity Reaction Monitoring of Important Nitrogen-Cycle Synthons by 15N Hyperpolarized Nuclear Magnetic Resonance

Here, we show how signal amplification by reversible exchange hyperpolarization of a range of 15N-containing synthons can be used to enable studies of their reactivity by 15N nuclear magnetic resonance (NO 2 - (28% polarization), ND 3 (3%), PhCH 2NH 2 (5%), NaN 3 (3%), and NO 3 - (0.1%)). A range of iridium-based spin-polarization transfer catalysts are used, which for NO 2 - work optimally as an amino-derived carbene-containing complex with a DMAP- d 2 coligand. We harness long 15N spin-order lifetimes to probe in situ reactivity out to 3 × T 1. In the case of NO 2 - ( T 1 17.7 s at 9.4 T), we monitor PhNH 2 diazotization in acidic solution. The resulting diazonium salt ( 15N- T 1 38 s) forms within 30 s, and its subsequent reaction with NaN 3 leads to the detection of hyperpolarized PhN 3 ( T 1 192 s) in a second step via the formation of an identified cyclic pentazole intermediate. The role of PhN 3 and NaN 3 in copper-free click chemistry is exemplified for hyperpolarized triazole ( T 1 < 10 s) formation when they react with a strained alkyne. We also demonstrate simple routes to hyperpolarized N 2 in addition to showing how utilization of 15N-polarized PhCH 2NH 2 enables the probing of amidation, sulfonamidation, and imine formation. Hyperpolarized ND 3 is used to probe imine and ND 4 + ( T 1 33.6 s) formation. Furthermore, for NO 2 -, we also demonstrate how the 15N-magnetic resonance imaging monitoring of biphasic catalysis confirms the successful preparation of an aqueous bolus of hyperpolarized 15NO 2 - in seconds with 8% polarization. Hence, we create a versatile tool to probe organic transformations that has significant relevance for the synthesis of future hyperpolarized pharmaceuticals

Direct effects of climate change on productivity of European aquaculture

Aquaculture managers and industry must take into account the impact of climate change on production and environmental quality to ensure that sector growth is sustainable over the coming decades, a key requirement for food security. The potential effects of climate change on aquaculture range from changes to production capacity in existing cultivation areas to changes in the areas themselves, which may become unsuitable for particular species, but also suitable for new species. The prediction of where and how such changes may occur is challenging, not least because the cultivated species may themselves exhibit plasticity, which makes it difficult to forecast the degree to which different locations and culture types may be affected. This work presents a modelling approach used to predict the potential effects of climate change on aquaculture, considering six key finfish and shellfish species of economic importance in Europe: Atlantic salmon (Salmo salar), gilthead seabream (Sparus aurata), sea bass (Dicentrarchus labrax), Pacific oyster (Crassostrea gigas), blue mussel (Mytilus edulis) and Mediterranean mussel (Mytilus galloprovincialis). The focus is on effects on physiology, growth performance and environmental footprint, and the resultant economic impact at the farm scale. Climate projections for present-day conditions; mid-century (2040–2060) and end-of-century (2080–2100) were extracted from regionally downscaled global climate models and used to force bioenergetic models. For each of those time periods, two different carbon concentration scenarios were considered: a moderate situation (IPCC RCP 4.5) and an extreme situation (IPCC RCP 8.5). Projected temperature changes will have variable effects on growth depending on the species and geographic region. From the case studies analysed, gilthead bream farmed in sea cages in the western Mediterranean was the most vulnerable, whereas offshore-suspended mussel culture in SW Portugal was least affected. Most of the marine finfish simulated were projected to have decreased feeding efficiency in both mid-century and end-of-century climate scenarios. Bivalve shellfish showed a decreasing trend with respect to most productivity parameters as climate change progresses, under both emission scenarios. As a general trend across species and regions, economic uncertainty is expected to increase under all future projections