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Highlights • A non-human primate protective head cap that promotes wound healing after cranial implants. • Use of the head cap reduced wound dehiscence and the need to re-suture surgical wounds. • The head cap is easily adjustable to cover most primate cranial implants. • The head cap facilitates primate cranial implant wound management in neuroscience., Background Neuroscience studies with macaque monkeys may require cranial implants to stabilize the head or gain access to the brain for scientific purposes. Wound management that promotes healing after the cranial implant surgery in non-human primates can be difficult as it is not necessarily possible to cover the wound margins. New method Here, we developed an easily modifiable head cap that protects the sutured skin margins after cranial implant surgery and contributes to wound healing. The protective head cap was developed in response to monkeys picking at sutured skin margins around an implant, complicating healing. The user-friendly protective cap, made from Klarity- R™ Sheet (3.2 mm thick with 36 % or 42 % perforation) is affixed to the implant post-surgically. Once secured and while the monkey is still anesthetized, the plastic sheeting is molded around the implant. The protective head cap restricts the monkey’s finger access to its’ wound margins while allowing air to circulate to promote wound healing. Results and comparison with existing methods Across two UK primate facilities, the protective head cap promoted wound healing. In monkeys that did not wear the head cap, re-suturing was necessary in ∼30 % of cases. In contrast, none of the monkeys that wore the head cap required re-suturing. The monkeys wearing the head cap also had reduced numbers of days of prescribed antibiotics and analgesia. Conclusion This bespoken, easily adaptable, protective head cap supports postoperative wound healing, and enhances the welfare of monkeys involved in neuroscience research.

Im Hinblick auf die gerichtliche Konfliktlosung und Streitbeilegung sind im EU-Raum das Recht der EU und der EMRK zu unterscheiden. Vor allem dem EU-Justizsystem mit dem EuGH an der Spitze kommt heute insoweit ein bedeutender Einfluss zu. Seit 1998 hat sich aber auch die Rolle des EGMR in nationalen Gerichtsverfahren ausgeweitet. Zentrale Forschungsfelder im Hinblick auf den ersten Bereich bilden die Reichweite des Vorrangs des Europarechts, die materiellen Vorgaben des Europarechts sowie die Ausgestaltung des europaischen Systems des Rechtsschutzes. Seit einigen Jahren wird auch vermehrt eine historische Betrachtung der europaischen Integration in Form einer „europaischen Rechtsgeschichte betrieben. Beim zweiten Bereich interessieren die Stellung der EMRK im nationalen Recht sowie die Wirkungen der vom EGMR getroffenen Entscheidungen.

SummaryPerception and cognition require the integration of feed-forward sensory information with feedback signals. Feed-forward and feedback signals have been associated with specific cortical laminae and specific oscillatory frequencies. We used stimuli of different sizes to isolate spectral signatures of feedforward and feedback signals, and their effect on communication between layers in primary visual cortex of male macaque monkeys. Small stimuli, centered on the neurons’ receptive fields elicited broad band gamma frequency oscillations predominantly in the superficial layers. These Granger causal originated in upper layer 4 and lower supragranular layers, in line with existing feed-forward models of oscillatory responses. However, large stimuli extending into the far surround of neurons’ receptive fields, generated strong narrow band gamma oscillatory activity across cortical layers. They Granger causal arose in layer 5, were conveyed through layer 6 to superficial layers, and violated existing models of feedback spectral signatures. Equally surprising, with large stimuli, alpha band oscillatory activity arose predominantly in granular and supragranular layers, and communicated in a feed-forward direction. This shows that oscillations in specific frequency bands can be dynamically modulated to serve feedback and feed-forward communication and are not restricted to specific cortical layers in V1

Context affects the salience and visibility of image elements in visual scenes. Collinear flankers can enhance or decrease the perceptual and neuronal sensitivity to flanked stimuli. These effects are mediated through lateral interactions between neurons in the primary visual cortex (area V1), in conjunction with feedback from higher visual areas. The strength of lateral interactions is affected by cholinergic neuromodulation. Blockade of muscarinic receptors should increase the strength of lateral intracortical interactions, while nicotinic blockade should reduce thalamocortical feed-forward drive. Here we test this proposal through local iontophoretic application of the muscarinic receptor antagonist scopolamine and the nicotinic receptor antagonist mecamylamine, while recording single cells in parafoveal representations in awake fixating macaque V1. Collinear flankers generally reduced neuronal contrast sensitivity. Muscarinic and nicotinic receptor blockade equally reduced neuronal contrast sensitivity. Contrary to our hypothesis, flanker interactions were not systematically affected by either receptor blockade.

SummaryAchieving behavioral goals requires integration of sensory and cognitive information, across cortical laminae and cortical regions. How this computation is performed remains unknown. Using local field potential recordings and spectrally resolved conditional Granger causality (cGC) analysis, we mapped visual information flow, and its attentional modulation, between cortical layers within and between macaque areas V1 and V4. Stimulus induced inter-laminar information flow within V1 dominated upwardly, channeling information towards supragranular cortico-cortical output layers. Within V4, information flow dominated from granular to supragranular layers, but interactions between supragranular and infragranular layers dominated downwardly. Low-frequency across-area communication was stronger from V4 to V1, with little layer specificity. Gamma-band communication was stronger in the feedforward V1 to V4 direction. Attention to the receptive field of V1 decreased communication between all V1 layers, except for granular to supragranular layers interactions. Communication within V4, and from V1 to V4, increased with attention across all frequencies. While communication from V4 to V1 was stronger in lower frequency bands (4-25 Hz), attention modulated cGCs from V4 to V1 across all investigated frequencies. Our data show that top down cognitive processes result in reduced communication within cortical areas, increased feedforward communication across all frequency bands and increased gamma band feedback communication.

The historic financial crisis that began on the American housing market in 2007 and from there spread all over the globe had tremendous consequences for more or less every country worldwide, especially for their respective public finances. The overall public debt level skyrocketed due to the substantial economic downfall and the necessity to bail out hundreds of financial institutions that had suffered severe losses when the American subprime market collapsed and the money markets froze. Though the States were (with tremendous help by the European Central Bank) finally successful in preventing a complete breakdown of the major financial markets, their intervention left the national budgets and the balance of payments (BOP) of several of them in a devastating condition with insolvencies only being averted by massive external and mainly financial assistance by other States and institutions (especially the International Monetary Fund (IMF)). Some of these states facing such a financial calamity were Member States of the European Union (EU)—a fact having an important normative implication: Other Member States wanting to help financially were bound by the normative framework of the European Union Treaties. And the same was obviously true for the European Union itself where it wanted to initiate any form of (financial) assistance.

According to Article 127(1) TFEU, it is the core purpose of the European System of Central Banks (ESCB) (with the European Central Bank (ECB) at the top) to maintain price-stability within the European Monetary Union (EMU). It is this task that is usually referred to, where the ‘monetary mandate’ or the ‘monetary policy’ of the ECB is mentioned. However, though this monetary mandate is not only the most prominent but most certainly also the most disputed task of the ESCB–especially since the financial and euro crisis–it is by no means the only task transferred onto the ESCB (respectively the ECB) by the Member States. According to Article 127(2) TFEU, the basic tasks to be carried out by the ESCB in actual fact include the conduct of foreign-exchange operations and thus the ‘foreign policy’ relations of the euro area and the euro with other currency areas (mainly states) and currencies. When creating the EMU, however, it was highly disputed whether the ECB or the Council should be the competent authority to conduct or rather to decide on such operations.

Rhesus macaques ( Macaca mulatta) used in behavioural neuroscience are often required to complete cognitively complex tasks, for which a high level of motivation is essential. To induce motivation, researchers may implement fluid-restriction protocols, whereby freely available water is limited, such that fluid can be used as a reward in the laboratory. A variety of different rewards and schedules are used, but there exists a lack of data assessing their effectiveness. In this study, we aimed to quantify fluid preference in rhesus macaques and to use these preferences to compare the motivational quality of different reward schedules: the monkey's previous reward (i.e. the fluid used to reward them in past studies), their new preferred reward, a variable schedule of previous and preferred reward, and a choice between the previous and preferred rewards. We found that it may be possible to reduce the level of restriction if an adequately motivating preferred reward is identified, but that this is dependent on the animal. Each monkey responded differently to both the fluid-preference assessments and to the different reward schedules. As such, monkeys should not be subject to ‘blanket’ protocols but should be assessed individually to maintain adequate scientific data collection at the least severe level of fluid restriction.

Graphical abstract, Highlights • We created custom PEEK implants coated with hydroxylapatite to promote osseointegration. • Headposts and chambers were implanted with ceramic screws and the surgical incision was closed subcutaneously. • We prevented the animal from picking and scratching after surgery by using a head cap that protects the wound margin. • Implants integrated with the skull and remained robust after a year with no growth of granulation tissue. • MRI signal and contrast-to-noise ratio improved in NHPs implanted with our new methods., Background Neuroscientists commonly use permanently implanted headposts to stabilize the head of nonhuman primates (NHPs) during electrophysiology and functional magnetic resonance imaging (fMRI). Here, we present improved methodology for MRI-compatible implants without the use of acrylic for head stabilization in NHPs. New method MRI is used to obtain a 3D-reconstruction of NHP skulls, which are used to create customized implants by modeling intersections with the bone. Implants are manufactured from PEEK using computer numerical control machining and coated with hydroxyapatite to promote osseointegration. Surgically, implants are attached to the skull with ceramic screws, while the skin flap is pulled over the implant and closed subcutaneously. Results Quality of blood oxygen level dependent (BOLD) fMRI signal is improved in animals implanted with our method as compared to traditional acrylic implants. Additionally, implants are well-integrated with the skull, remain robust for more than a year and without granulation tissue around the skin margin. Comparison with existing method(s) Previous improvements on NHP implants (Chen et al., 2017; McAndrew et al., 2012; Mulliken et al., 2015; Overton et al., 2017) lacked fMRI-compatibility, as they relied on titanium headposts and/or titanium screws. Thus, most fMRI studies in NHPs today still rely on the use of acrylic-based headposts for stabilization and the use of contrast-enhanced agents to improve MRI signal. Conclusions Our method preserves fMRI-compatibility and results in measurable improvement in BOLD signal without the use of contrast-enhanced agents. Furthermore, the long-term stability of our implants contributes positively to the wellbeing of NHPs in neuroscience research.

Contains fulltext : 217200.pdf (Publisher’s version ) (Closed access) Nonhuman primate neuroimaging is on the cusp of a transformation, much in the same way its human counterpart was in 2010, when the Human Connectome Project was launched to accelerate progress. Inspired by an open data-sharing initiative, the global community recently met and, in this article, breaks through obstacles to define its ambitions. 4 p.

Neocortical activity is permeated with endogenously generated fluctuations, but how these dynamics affect goal-directed behavior remains a mystery. We found that ensemble neural activity in primate visual cortex spontaneously fluctuated between phases of vigorous (On) and faint (Off) spiking synchronously across cortical layers. These On-Off dynamics, reflecting global changes in cortical state, were also modulated at a local scale during selective attention. Moreover, the momentary phase of local ensemble activity predicted behavioral performance. Our results show that cortical state is controlled locally within a cortical map according to cognitive demands and reveal the impact of these local changes in cortical state on goal-directed behavior.

Smouldering European debt crisis: overall public debt ratio as problem – Haircut as possible solution – Greece’s current creditors: public institutions (Member States and European Central Bank) – Insuring a sound budgetary policy as main goal of Article 125 TFEU – Consequences for a haircut by the Member States – The mandate of the European Central Bank and the prohibition of direct purchases of Member State bonds – Consequences for a haircut by the European Central Bank – Haircut as political question open for democratic debate

Summary Spontaneous fluctuations in cortical excitability influence sensory processing and behavior. These fluctuations, long thought to reflect global changes in cortical state, were recently found to be modulated locally within a retinotopic map during spatially selective attention. We report that periods of vigorous (On) and faint (Off) spiking activity, the signature of cortical state fluctuations, are coordinated across brain areas with retinotopic precision. Top-down attention enhanced interareal local state coordination, traversing along the reverse cortical hierarchy. The extent of local state coordination between areas was predictive of behavioral performance. Our results show that cortical state dynamics are shared across brain regions, modulated by cognitive demands and relevant for behavior., Highlights • Cortical excitability fluctuations are coordinated across visual areas • During selective attention, these fluctuations are driven in a top-down manner • The degree of coordination depends on shared spatial representation • Increased cortical state coordination predicts better behavioral performance, How do fluctuations in ongoing brain activity interact with cognitive functions? In this study, van Kempen et al. show that fluctuations in neural excitability are coordinated between visual areas with retinotopic precision. Top-down attention drives interareal coordination along the reverse cortical hierarchy, predicting better behavioral performance with increased coordination.

Optogenetics has revolutionized neuroscience in small laboratory animals, but its effect on animal models more closely related to humans, such as non-human primates (NHPs), has been mixed. To make evidence-based decisions in primate optogenetics, the scientific community would benefit from a centralized database listing all attempts, successful and unsuccessful, of using optogenetics in the primate brain. We contacted members of the community to ask for their contributions to an open science initiative. As of this writing, 45 laboratories around the world contributed more than 1,000 injection experiments, including precise details regarding their methods and outcomes. Of those entries, more than half had not been published. The resource is free for everyone to consult and contribute to on the Open Science Framework website. Here we review some of the insights from this initial release of the database and discuss methodological considerations to improve the success of optogenetic experiments in NHPs. ispartof: NEURON vol:108 issue:6 ispartof: location:United States status: published

Rhesus macaques (

The timing and accuracy of perceptual decision-making is exquisitely sensitive to fluctuations in arousal. Although extensive research has highlighted the role of various neural processing stages in forming decisions, our understanding of how arousal impacts these processes remains limited. Here we isolated electrophysiological signatures of decision-making alongside signals reflecting target selection, attentional engagement and motor output and examined their modulation as a function of tonic and phasic arousal, indexed by baseline and task-evoked pupil diameter, respectively. Reaction times were shorter on trials with lower tonic, and higher phasic arousal. Additionally, these two pupil measures were predictive of a unique set of EEG signatures that together represent multiple information processing steps of decision-making. Finally, behavioural variability associated with fluctuations in tonic and phasic arousal, indicative of neuromodulators acting on multiple timescales, was mediated by its effects on the EEG markers of attentional engagement, sensory processing and the variability in decision processing., eLife digest Driving along a busy street requires you to constantly monitor the behavior of other road users. You need to be able to spot and avoid the car that suddenly changes lane, or the pedestrian who steps out in front of you. How fast you can react to such events depends in part on your brain's level of alertness, or 'arousal'. This in turn depends on chemicals within the brain called neuromodulators. Neuromodulators are a type of neurotransmitter. But whereas other neurotransmitters enable brain cells to signal to each other, neuromodulators turn the volume of these signals up or down. The activity of brain regions that produce neuromodulators varies over time, leading to changes in brain arousal. These changes take place over different time scales. Sudden unexpected events, such as those on the busy street above, trigger sub-second changes in arousal. But arousal levels also show spontaneous fluctuations over minutes to hours. We can follow these changes in real-time by looking into a participant’s eyes. This is because the brain regions that produce neuromodulators also control pupil size. Van Kempen et al. have now combined measurements of pupil size with recordings of electrical brain activity. Healthy volunteers learned to press a button as soon as a target appeared on a screen. The larger a volunteer’s pupils were before the target appeared, the more slowly the volunteer responded on that trial. Large baseline pupil size is thought to indicate a high baseline level of brain arousal. By contrast, the larger the increase in pupil size in response to the target, the faster the volunteer responded on that trial. This increase in pupil size is thought to reflect an increase in brain arousal. The recordings of brain activity provided clues to the underlying mechanisms. In trials with large baseline pupil size – and therefore high baseline arousal – the volunteers’ brains showed more variable responses to the target. But in trials with a large increase in pupil size – and a large increase in arousal – the volunteers’ brains showed less variable responses, as well as stronger signals related to attention. Neuromodulators thus act on different timescales to influence different aspects of cognitive performance, including attention and target detection. Fluctuating levels of neuromodulator activity may help explain the variability in our behavior. Monitoring pupil size is one way to gain insights into the mechanisms that bring about these changes in neuromodulator activity.

The timing and accuracy of perceptual decision making is exquisitely sensitive to fluctuations in arousal. Although extensive research has highlighted the role of neural evidence accumulation in forming decisions, our understanding of how arousal impacts these processes remains limited. Here we isolated electrophysiological signatures of evidence accumulation alongside signals reflecting target selection, attentional engagement and motor output and examined their modulation as a function of both tonic and phasic arousal, indexed by baseline and task-evoked pupil diameter, respectively. For both pupillometric measures, the relationship with reaction time was best described by a second-order, U-shaped, polynomial. Additionally, the two pupil measures were predictive of a unique set of EEG signatures that together represent multiple information processing steps of perceptual decision-making, including evidence accumulation. Finally, we found that behavioural variability associated with fluctuations in both tonic and phasic arousal was largely mediated by variability in evidence accumulation.

Summary Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience. Unfortunately, the technological and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMatE Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI). Here, we present the rationale, design, and procedures for the PRIME-DE consortium, as well as the initial release, consisting of 25 independent data collections aggregated across 22 sites (total = 217 non-human primates). We also outline the unique pitfalls and challenges that should be considered in the analysis of non-human primate MRI datasets, including providing automated quality assessment of the contributed datasets., Highlights • Openly shared, large non-human primate neuroimaging data resource • Multiple imaging modalities contributed from investigators around the world • Quality assessments of the dataset • Discussed pitfalls and challenges in analyzing the non-human primate MRI data, The PRIMatE Data Exchange (PRIME-DE) consortium is an open science resource for the neuroimaging community aiming to facilitate efforts to map the non-human primate connectome. It aggregates and shares anatomical, functional, and diffusion MRI datasets from laboratories throughout the world.

Zusammenfassung Die von der EZB im Zusammenhang mit der Eurokrise ergriffenen Maßnahmen bilden aktuell auch den Gegenstand einiger gerichtlicher Verfahren. Der Beitrag erläutert die Hintergründe dieser Verfahren und legt dar, dass der Streit um die „richtige“ Geldpolitik von diesen letztlich nicht entschieden werden kann.

Next to taxes, public debt has always been one of the most important funding sources of modern states. Until the beginning of the 19th century, however, it was mainly used in emergency situations, especially (though not only) for the financing of war. Since then, public borrowing has become more and more a regular way of funding state activities and this growing importance can be explained mainly by two developments. First, the number of state-tasks has constantly expanded, and this has automatically led to growing financial demands on the state. Due to the intentions of the politicians (who want to be re-elected, and therefore spend more money to please the public), as well as the requirements of the social welfare state, these demands could not be fully satisfied by taxes only. Both the debt brake and the Fiscal Compact therefore are the result of considerable fear of public borrowing amongst the German public and politicians. Against this background, this article takes a closer look at these two German instruments for curbing public debt (including the incorporation of the Fiscal Compact into German law)