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INTRODUCTION: 3%-8% of newborns need positive pressure ventilation (PPV) after birth. Heart rate (HR) is considered the most sensitive indicator of the newborns' condition and response to resuscitative interventions. According to guidelines, HR should be assessed and PPV initiated within 60 s after birth in non-breathing newborns. Dry electrode ECG can provide accurate feedback on HR immediately after birth and continuously during resuscitation. The impact of early and continuous HR feedback is unknown. METHOD AND ANALYSIS: This single-centre randomised controlled trial seeks to determine if HR feedback by dry electrode ECG immediately after birth and continuously during newborn resuscitation results in more timely initiation of PPV, improved ventilation and short-term outcomes compared with standard HR assessment.In all newborns≥34 gestational weeks, the dry electrode ECG sensor is placed on the upper abdomen immediately after birth as an additional modality of HR assessment. The device records and stores HR signals. In intervention subjects, the HR display is visible to guide decision-making and further management, in control subjects the display is masked. Standard HR assessment is by stethoscope, gel-electrode ECG and/or pulse oximetry (PO).Time of birth is registered in the Liveborn app. Time of initiation and duration of PPV is calculated from video recordings. Ventilation parameters are retrieved from the ventilation monitor, oxygen saturation and HR from the PO and gel-electrode ECG monitors.The primary endpoint is proportion of resuscitated newborns who receive PPV within 60 s after birth. To detect a 50% increase with power of 90% using an overall significance level of 0.05 and 1 interim analysis, 169 newborns are needed in each group. ETHICS AND DISSEMINATION: Approval by the Norwegian National Research Ethics Committee West (2018/338). Parental consent is sought at routine screening early in pregnancy. The results will be published in peer-reviewed journ

DDeciding the best action in social settings requires decision-makers to consider their and others' preferences, since the outcome depends on the actions of both. Numerous empirical investigations have demonstrated variability of behavior across individuals in strategic situations. While prosocial, moral, and emotional factors have been intensively investigated to explain this diversity, neuro-cognitive determinants of strategic decision-making and their relation with intelligence remain mostly unknown. This study presents a new model of the process of strategic decision-making in repeated interactions, first providing a precise measure of the environment's complexity, and then analyzing how this complexity affects subjects' performance and neural response. The results confirm the theoretical predictions of the model. The frequency of deviations from optimal behavior is explained by a combination of higher complexity of the strategic environment and cognitive skills of the individuals. Brain response correlates with strategic complexity, but only in the subgroups with higher cognitive skills. Furthermore, neural effects were only observed in a fronto-parietal network typically involved in single-agent tasks (the Multiple Demand Network), thus suggesting that neural processes dealing with cognitively demanding individual tasks also have a central role in interactive decision-making. Our findings contribute to understanding how cognitive factors shape strategic decision-making and may provide the neural pathway of the reported association between strategic sophistication and fluid intelligence.

Describes the development of a mission statement for the biology department at Morehouse College, and discusses how mission statements at the departmental level can frame strategic planning and assessment efforts, build community, and focus teaching and research activities. (EV)

This article explores a small sample of musicians in two European musical contexts – the Netherlands and the UK. It examines the relationship between the conditions of national music industries and the strategies used to negotiate a career in music and the extent to which musicians frame their careers as entrepreneurs. Interview data from two projects with early-career musicians form the basis of our secondary comparative analysis. We argue that their strategizing can be framed as a set of responses to their local structural conditions. However, neither set of responses produces market advantage. Instead, traditional power and economic relations that reinforce the logic of the hegemonic mainstream industry tend to prevail, whereby only a very small fraction of the aspiring musicians can sustain themselves financially in music.

Responding to the invitation of this special issue of Childhood and Philosophy this paper considers the ethos of facilitation in philosophical enquiry with children, and the spatial-temporal order of the community of enquiry. Within the Philosophy with Children movement, there are differences of thinking and practice on ‘facilitation’ in communities of philosophical enquiry, and we suggest that these have profound implications for the political agency of children. Facilitation can be enacted as a chronological practice of progress and development that works against child, in terms of political agency. This paper theorises practices of facilitation grounded in philosophies of childhood that assume listening to child/ren as equals, as already able to philosophise, and against sameness. We explore the political and ethical implications of the radical posthumanist reconfiguration of the ‘zipped’ body in the light of including the disciplinary, imaginative and enabling energies of chronological time through the concept now/ness. We shift from ethics to ethos, and from ‘zipped’ to ‘unzipped’ bodies, through the notion of affect to explore the temporal and spatial dimensions of facilitation in Philosophy with Children and children’s political agency. We re-turn to David McKee’s Not Now Bernard (1980), getting ‘inside the text’, and attending to the postponement of equality in Philosophy with Children., Resumen Bajo nuestras propias narices : la postergación de la igualdad política de los niños y el ahora Respondiendo a la invitación de este número especial de Childhood and Philosophy este artículo pone en consideración el ethos de la facilitación en la investigación filosófica con niños y el orden espacio-temporal de la comunidad de investigación. Al interior del movimiento de Filosofía con Niños hay diferencias de pensamiento y práctica en relación a la “facilitación” en comunidades de investigación filosófica, y nosotros sugerimos que esas diferencias tienen profundas implicancias para con la agencia política de los y las niñas. La facilitación se puede representar como una práctica cronológica de progreso y desarrollo que opera en contra del niño, en términos de agencia política. Este artículo teoriza sobre prácticas de facilitación basadas en filosofías de la infancia que adoptan la postura de escuchar al/los niño/s como iguales, como ya capaces de filosofar, y en contra de la uniformidad. Exploramos las implicancias éticas y políticas de la reconfiguración posthumanista radical del cuerpo ‘zippeado’ [comprimido] a la luz de incluir las energías disciplinarias, imaginativas y habilitadoras del tiempo cronológico a través del concepto del ahora. Nos movemos de la ética al ethos y de los cuerpos ‘zippeados’ [comprimidos] a los ‘unzippeados’ [descomprimidos] a través de la noción de afecto para explorar las dimensiones temporales y espaciales de la facilitación en Filosofía con Niños y la agencia política de las y los niños. Re-tornamos al Not Now Bernard (1980) de David McKee, metiéndonos ‘adentro del texto’, y poniendo atención a la postergación de la igualdad en Filosofía con Niños., Resumo Bem debaixo de nossos narizes : o adiamento da igualdade política das crianças e o agora Respondendo ao convite desta edição especial da Infância e Filosofia, este artigo considera o ethos da facilitação na investigação filosófica com crianças e a ordem espaço-temporal da comunidade de investigação. Dentro do movimento Filosofia com Crianças, existem diferenças de pensamento e prática sobre ‘facilitação’ em comunidades de investigação filosófica, e sugerimos que isso tem implicações profundas para a agência política das crianças. A facilitação pode ser executada como uma prática cronológica de progresso e desenvolvimento que funciona contra a criança, em termos de agência política. Este artigo teoriza práticas de facilitação alicerçadas em filosofias da infância que pressupõem ouvir a criança / criança como iguais, já capazes de filosofar e contra a mesmice. Exploramos as implicações políticas e éticas da reconfiguração pós-humanista radical do corpo “fechado” à luz da inclusão das energias disciplinares, imaginativas e capacitadoras do tempo cronológico por meio do conceito agora / ness. Mudamos da ética para o ethos, e de corpos “compactados” para “descompactados”, por meio da noção de afeto para explorar as dimensões temporais e espaciais de facilitação em Filosofia com Crianças e a agência política infantil. Voltamos a Not Now Bernard de David McKee (1980), entrando “no texto” e tratando do adiamento da igualdade em Filosofia com Crianças.

This article explores a small sample of musicians in two European musical contexts – the Netherlands and the UK. It examines the relationship between the conditions of national music industries and the strategies used to negotiate a career in music and the extent to which musicians frame their careers as entrepreneurs. Interview data from two projects with early-career musicians form the basis of our secondary comparative analysis. We argue that their strategizing can be framed as a set of responses to their local structural conditions. However, neither set of responses produces market advantage. Instead, traditional power and economic relations that reinforce the logic of the hegemonic mainstream industry tend to prevail, whereby only a very small fraction of the aspiring musicians can sustain themselves financially in music.

For everyday communication, bilingual speakers need to face the complex task of rapidly choosing the most appropriate language given the context, maintaining this choice over the current communicative act, and shielding lexical selection from competing alternatives from non-target languages. Yet, speech production of bilinguals is typically flawless and fluent. Most of the studies available to date constrain speakers' language choice by cueing the target language and conflate language choice with language use. This left largely unexplored the neural mechanisms underlying free language choice, i.e., the voluntary situation of choosing the language to speak. In this study, we used fMRI and Multivariate Pattern Analysis to identify brain regions encoding the target language when bilinguals are free to choose in which language to name pictures. We found that the medial prefrontal cortex encoded the chosen language prior to speaking. By contrast, during language use, language control recruited a wider brain network including the left inferior frontal lobe, the basal ganglia, and the angular and inferior parietal gyrus bilaterally. None of these regions were involved in language choice. We argue that the control processes involved in language choice are different from those involved in language use. Furthermore, our findings confirm that the medial prefrontal cortex is a domain-general region critical for free choice and that bilingual language choice relies on domain general processes.

Discourses and relations of child/adult and early education are super-permeated with ideas and practices of authority and boundary-making. In early years’ practices, deeply important beliefs and assumptions about who or what has authority and who or what should create the boundaries of everyday activity often go unquestioned. This produces different kinds of epistemic injustice in respect of children and those who work with them, as well as through the materialities of early childhood and training settings, including higher education. These systems of authority both express and produce wider patterns of living associated with the wider society, including democracies. Posthumanism inspires questions about not only ways of knowing, but also about the privileging of dis/embodied knowing over feeling, intuiting, sensing, making, and moving. This paper thinks from the diffractive position that knowing is a direct material and moving engagement to explore possibilities for sympoietic pedagogies of enquiry-making-with (Haraway, 2016), and examines how these generate new ideas about early childhood practices and what professional knowledge might become. We illustrate this diffractive curriculum and pedagogy through an example from teacher education in South Africa to make important connections between authority, pedagogy, and an enlarged framework for democratic education; in this work, we explore sympoietic approaches to negotiation.

Postoperative cognitive impairment is among the most common medical complications associated with surgical interventions - particularly in elderly patients. In our aging society, it is an urgent medical need to determine preoperative individual risk prediction to allow more accurate cost-benefit decisions prior to elective surgeries. So far, risk prediction is mainly based on clinical parameters. However, these parameters only give a rough estimate of the individual risk. At present, there are no molecular or neuroimaging biomarkers available to improve risk prediction and little is known about the etiology and pathophysiology of this clinical condition. In this short review, we summarize the current state of knowledge and briefly present the recently started BioCog project (Biomarker Development for Postoperative Cognitive Impairment in the Elderly), which is funded by the European Union. It is the goal of this research and development (R&D) project, which involves academic and industry partners throughout Europe, to deliver a multivariate algorithm based on clinical assessments as well as molecular and neuroimaging biomarkers to overcome the currently unsatisfying situation. (C) 2017 Published by Elsevier Masson SAS.

BACKGROUND: Understanding the relative risks of maintenance treatment versus discontinuation of antipsychotics following remission in first episode psychosis (FEP) is an important area of practice. METHOD: A systematic review and meta-analysis. Prospective experimental studies including a parallel control group were identified to compare maintenance antipsychotic treatment with total discontinuation or medication discontinuation strategies following remission in FEP. RESULTS: Seven studies were included. Relapse rates were higher in the discontinuation group (53%; 95% CIs: 39%, 68%; N = 290) compared with maintenance treatment group (19%; 95% CIs: 0.05%, 37%; N = 230). In subgroup analyses, risk difference of relapse was lower in studies with a longer follow-up period, a targeted discontinuation strategy, a higher relapse threshold, a larger sample size, and samples with patients excluded for drug or alcohol dependency. Insufficient studies included psychosocial functioning outcomes for a meta-analysis. CONCLUSIONS: There is a higher risk of relapse for those who undergo total or targeted discontinuation strategies compared with maintenance antipsychotics in FEP samples. The effect size is moderate and the risk difference is lower in trials of targeted discontinuation strategies. DECLARATION OF INTEREST: A.T. has received honoraria and support from Janssen-Cilag and Otsuka Pharmaceuticals for meetings and has been has been an investigator on unrestricted investigator-initiated trials funded by AstraZeneca and Janssen-Cilag. He has also previously held a Pfizer Neurosciences Research Grant. S.M. has received sponsorship from Otsuka and Lundbeck to attend an academic congress and owns shares in GlaxoSmithKline and AstraZeneca. J.H. has attended meetings supported by Sunovion Pharmaceuticals.

© The Author(s) 2018. Background. Hyperactivation of phosphoinositide 3-kinase (PI3K) signaling is common in cancers, but the precise role of the pathway in glioma biology remains to be determined. Some understanding of PI3K signaling mechanisms in brain cancer comes from studies on neural stem/progenitor cells (NSPCs), where signals transmitted via the PI3K pathway cooperate with other intracellular pathways and downstream transcription factors to regulate critical cell functions. Methods. To investigate the role of the PI3K pathway in glioma initiation and development, we generated a mouse model targeting the inducible expression of a PIK3CAH1047A oncogenic mutant and deletion of the PI3K negative regulator, phosphatase and tensin homolog (PTEN), to NSPCs. Results. Expression of a Pik3caH1047A was sufficient to generate tumors with oligodendroglial features, but simultaneous loss of PTEN was required for the development of invasive, high-grade glioma. Pik3caH1047A-PTEN mutant NSPCs exhibited enhanced neurosphere formation which correlated with increased Wnt signaling, while loss of cAMP response element binding protein (CREB) in Pik3caH1047A-Pten mutant tumors led to longer symptom-free survival in mice. Conclusion. Taken together, our findings present a novel mouse model for glioma demonstrating that the PI3K pathway is important for initiation of tumorigenesis and that disruption of downstream CREB signaling attenuates tumor expansion.

Bilinguals require a high degree of cognitive control to select the language intended for speaking and inhibit the unintended. Previous neuroimaging studies have not teased apart brain regions for generating the intention to use a given language, and those for speaking in that language. Separating these two phases can clarify at what stage competition between languages occurs. In this fMRI study German-English bilinguals were first cued to use German or English. After a delay, they named a picture in the cued language. During the intention phase, the precuneus, right superior lateral parietal lobule, and middle temporal gyrus were more activated when participants had to update the currently active language. During language execution activation was higher for English compared to German in brain areas associated with cognitive control, most notably the anterior cingulate and the caudate. Our results suggest two different systems enabling cognitive control during bilingual language production.

Humans use rules to organize their actions to achieve specific goals. Although simple rules that link a sensory stimulus to one response may suffice in some situations, often, the application of multiple, hierarchically organized rules is required. Recent theories suggest that progressively higher level rules are encoded along an anterior-to-posterior gradient within PFC. Although some evidence supports the existence of such a functional gradient, other studies argue for a lesser degree of specialization within PFC. We used fMRI to investigate whether rules at different hierarchical levels are represented at distinct locations in the brain or encoded by a single system. Thirty-seven male and female participants represented and applied hierarchical rule sets containing one lower-level stimulus-response rule and one higher-level selection rule. We used multivariate pattern analysis to investigate directly the representation of rules at each hierarchical level in absence of information about rules from other levels or other task-related information, thus providing a clear identification of low- and high-level rule representations. We could decode low- and high-level rules from local patterns of brain activity within a wide frontoparietal network. However, no significant difference existed between regions encoding representations of rules from both levels except for precentral gyrus, which represented only low-level rule information. Our findings show that the brain represents conditional rules regardless of their level in the explored hierarchy, so the human control system did not organize task representation according to this dimension. Our paradigm represents a promising approach to identifying critical principles that shape this control system.

Background. Previous studies have highlighted the role of the brain reward and cognitive control systems in the etiology of anorexia nervosa (AN). In an attempt to disentangle the relative contribution of these systems to the disorder, we used functional magnetic resonance imaging (fMRI) to investigate hemodynamic responses to reward-related stimuli presented both subliminally and supraliminally in acutely underweight AN patients and age-matched healthy controls (HC). Methods. fMRI data were collected from a total of 35 AN patients and 35 HC, while they passively viewed subliminally and supraliminally presented streams of food, positive social, and neutral stimuli. Activation patterns of the group × stimulation condition × stimulus type interaction were interrogated to investigate potential group differences in processing different stimulus types under the two stimulation conditions. Moreover, changes in functional connectivity were investigated using generalized psychophysiological interaction analysis. Results. AN patients showed a generally increased response to supraliminally presented stimuli in the inferior frontal junction (IFJ), but no alterations within the reward system. Increased activation during supraliminal stimulation with food stimuli was observed in the AN group in visual regions including superior occipital gyrus and the fusiform gyrus/parahippocampal gyrus. No group difference was found with respect to the subliminal stimulation condition and functional connectivity. Conclusion. Increased IFJ activation in AN during supraliminal stimulation may indicate hyperactive cognitive control, which resonates with clinical presentation of excessive self-control in AN patients. Increased activation to food stimuli in visual regions may be interpreted in light of an attentional food bias in AN.

Pluripotent stem cells (PSCs) are a valuable tool for interrogating development, disease modelling, drug discovery and transplantation. Despite the burgeoned capability to fate restrict human PSCs to specific neural lineages, comparative protocols for mouse PSCs have not similarly advanced. Mouse protocols fail to recapitulate neural development, consequently yielding highly heterogeneous populations, yet mouse PSCs remain a valuable scientific tool as differentiation is rapid, cost effective and an extensive repertoire of transgenic lines provides an invaluable resource for understanding biology. Here we developed protocols for neural fate restriction of mouse PSCs, using knowledge of embryonic development and recent progress with human equivalents. These methodologies rely upon naïve ground-state PSCs temporarily transitioning through LIF-responsive stage prior to neural induction and rapid exposure to regional morphogens. Neural subtypes generated included those of the dorsal forebrain, ventral forebrain, ventral midbrain and hindbrain. This rapid specification, without feeder layers or embryoid-body formation, resulted in high proportions of correctly specified progenitors and neurons with robust reproducibility. These generated neural progenitors/neurons will provide a valuable resource to further understand development, as well disorders affecting specific neuronal subpopulations.

Every day we need to plan and coordinate multiple future tasks. Previous studies have shown that rostral prefrontal cortex encodes individual future tasks across delays. However, so far it remains unclear how the brain encodes an ordered sequence of upcoming tasks across delays. Here, participants were scanned as they remembered to execute a single future task (single-task trials) or sequences of two tasks (sequence trials). A multivariate classifier was trained on patterns of BOLD activity that encode the single tasks, and was used to decode the identity of the same tasks when they were either first or second in a remembered sequence. The sequential order of tasks (e.g. AB vs. BA) was separately decoded. We found the following. (1) Both the first and the second upcoming tasks could be decoded from rostrolateral prefrontal and parietal cortices. (2) Sequence order was encoded in dorsomedial and dorsolateral PFC. (3) ROI analysis revealed that regions encoding the future tasks and regions encoding sequence order did not overlap. Our findings suggest that (a) the brain encodes future task sequences in a compositional fashion, and (b) there may be a segregation of task and order information in the PFC. Namely, while rostrolateral PFC encoded the identity of multiple future tasks, dorsomedial and dorsolateral PFC encoded information required for the orderly execution of abstract tasks.

In everyday life, humans use rules to organize their thoughts and actions in order to achieve specific goals (Bunge & Wallis, 2007). For simple situations, single rules can be used to link a sensory stimulus (the traffic light is green) to its appropriate response (cross the road). More complex situations, however, require the application of multiple rules organized in hierarchies, where high level rules influence the selection or application of lower level rules. Previous studies have demonstrated that Prefrontal Cortex (PFC) is one of the key areas underlying rule processing and control of action. However, it is still unclear whether distinct brain regions within PFC systematically encode qualitatively different task features. In the present study we investigated whether different features defining a complex rule set are represented in different brain areas depending on the level of control they enforce. To this purpose, we devised an experiment in which participants (N = 20) learnt complex rule sets composed by rules at two different levels of control: low (e.g., “if you see a banana, then press left”) and high (e.g., “If you see a star, then only consider red targets”). The task required participants to retrieve, maintain, and apply two rule sets (one low and one high level) to target stimuli. At the beginning of each trial two cues associated with low (or high) level rules were displayed, followed by a delay (delay 1). Then a second pair of cues standing for high (or low) level rules were presented followed by a second delay (delay 2), after which the target was shown. Participants had to apply all the rules to the target stimuli and respond accordingly. The paradigm allowed us to: (i) independently assess the encoding of high and low level rules, (ii) evaluate the difference between the encoding of the two types of rules (comparing high vs. low level rule representations during delay 1, when only one type of rule was maintained), and (iii) decode rule integrat

Humans are able to flexibly devise and implement rules to reach their desired goals. For simple situations, we can use single rules, such as "if traffic light is green then cross the street." In most cases, however, more complex rule sets are required, involving the integration of multiple layers of control. Although it has been shown that prefrontal cortex is important for rule representation, it has remained unclear how the brain encodes more complex rule sets. Here, we investigate how the brain represents the order in which different parts of a rule set are evaluated. Participants had to follow compound rule sets that involved the concurrent application of two single rules in a specific order, where one of the rules always had to be evaluated first. The rules and their assigned order were independently manipulated. By applying multivariate decoding to fMRI data, we found that the identity of the current rule was encoded in a frontostriatal network involving right ventrolateral prefrontal cortex, right superior frontal gyrus, and dorsal striatum. In contrast, rule order could be decoded in the dorsal striatum and in the right premotor cortex. The nonhomogeneous distribution of information across brain areas was confirmed by follow-up analyses focused on relevant regions of interest. We argue that the brain encodes complex rule sets by "decomposing" them in their constituent features, which are represented in different brain areas, according to the aspect of information to be maintained.

The advent of functional magnetic resonance imaging (fMRI) of brain function 20 years ago has provided a new methodology for non-invasive measurement of brain function that is now widely used in cognitive neuroscience. Traditionally, fMRI data has been analyzed looking for overall activity changes in brain regions in response to a stimulus or a cognitive task. Now, recent developments have introduced more elaborate, content-based analysis techniques. When multivariate decoding is applied to the detailed patterning of regionally-specific fMRI signals, it can be used to assess the amount of information these encode about specific task-variables. Here we provide an overview over several developments, spanning from applications in cognitive neuroscience (perception, attention, reward, decision making, emotional communication) to methodology (information flow, surface-based searchlight decoding) and medical diagnostics.

A defining trait of human cognition is the capacity to form compounds out of simple thoughts. This ability relies on the logical connectives AND, OR and IF. Simple propositions, e.g., 'There is a fork' and 'There is a knife', can be combined in alternative ways using logical connectives: e.g., 'There is a fork AND there is a knife', 'There is a fork OR there is a knife', 'IF there is a fork, there is a knife'. How does the brain represent compounds based on different logical connectives, and how are compounds evaluated in relation to new facts? In the present study, participants had to maintain and evaluate conjunctive (AND), disjunctive (OR) or conditional (IF) compounds while undergoing functional MRI. Our results suggest that, during maintenance, the left posterior inferior frontal gyrus (pIFG, BA44, or Broca's area) represents the surface form of compounds. During evaluation, the left pIFG switches to processing the full logical meaning of compounds, and two additional areas are recruited: the left anterior inferior frontal gyrus (aIFG, BA47) and the left intraparietal sulcus (IPS, BA40). The aIFG shows a pattern of activation similar to pIFG, and compatible with processing the full logical meaning of compounds, whereas activations in IPS differ with alternative interpretations of conditionals: logical vs conjunctive. These results uncover the functions of a basic cortical network underlying human compositional thought, and provide a shared neural foundation for the cognitive science of language and reasoning.

Rewards obtained from specific behaviors can and do change across time. To adapt to such conditions, humans need to represent and update associations between behaviors and their outcomes. Much previous work focused on how rewards affect the processing of specific tasks. However, abstract associations between multiple potential behaviors and multiple rewards are an important basis for adaptation as well. In this experiment, we directly investigated which brain areas represent associations between multiple tasks and rewards, using time-resolved multivariate pattern analysis of functional magnetic resonance imaging data. Importantly, we were able to dissociate neural signals reflecting task–reward associations from those related to task preparation and reward expectation processes, variables that were often correlated in previous research. We hypothesized that brain regions involved in processing tasks and/or rewards will be involved in processing associations between them. Candidate areas included the dorsal anterior cingulate cortex, which is involved in associating simple actions and rewards, and the parietal cortex, which has been shown to represent task rules and action values. Our results indicate that local spatial activation patterns in the inferior parietal cortex indeed represent task–reward associations. Interestingly, the parietal cortex flexibly changes its content of representation within trials. It first represents task–reward associations, later switching to process tasks and rewards directly. These findings highlight the importance of the inferior parietal cortex in associating behaviors with their outcomes and further show that it can flexibly reconfigure its function within single trials.

Many daily behaviors require us to actively focus on the current task and ignore all other distractions. Yet, ignoring everything else might hinder the ability to discover new ways to achieve the same goal. Here, we studied the neural mechanisms that support the spontaneous change to better strategies while an established strategy is executed. Multivariate neuroimaging analyses showed that before the spontaneous change to an alternative strategy, medial prefrontal cortex (MPFC) encoded information that was irrelevant for the current strategy butnecessary for the later strategy. Importantly, this neural effect was related to future behavioralchanges: information encoding in MPFC was changed only in participants who eventually switched their strategy and started before the actual strategy change. This allowed us to predict spontaneous strategy shifts ahead of time. These findings suggest that MPFC might internally simulate alternative strategies and shed new light on the organization of PFC.

In recent years multivariate decoding has allowed to test where and how mental representations can be decoded from neuroimaging signals, which sheds light on how these representations are encoded in the brain. In one line of experiments, we investigated how intentions are encoded in fMRI signals, thus revealing information in medial and lateral prefrontal regions. These informative neural representations were even present prior to the person's awareness of their chosen intention. In comparison, for cued intentions we found information predominantly in lateral, but not medial prefrontal cortex. Intention coding in prefrontal cortex followed a compositional code and could also be observed across extended delays during which participants were busy performing other tasks. Taken together, our results suggest a systematic, compositional and hierarchical code in prefrontal cortex which intentions are encoded across delays while the mind is busy working on other tasks.

When choosing actions, humans have to balance carefully between different task demands. On the one hand, they should perform tasks repeatedly to avoid frequent and effortful switching between different tasks. On the other hand, subjects have to retain their flexibility to adapt to changes in external task demands such as switching away from an increasingly difficult task. Here, we developed a difficulty-based choice task to investigate how subjects voluntarily select task-sets in predictably changing environments. Subjects were free to choose 1 of the 3 task-sets on a trial-by-trial basis, while the task difficulty changed dynamically over time. Subjects self-sequenced their behavior in this environment while we measured brain responses with functional magnetic resonance imaging (fMRI). Using multivariate decoding, we found that task choices were encoded in the medial prefrontal cortex (dorso-medial prefrontal cortex, dmPFC, and dorsal anterior cingulate cortex, dACC). The same regions were found to encode task difficulty, a major factor influencing choices. Importantly, the present paradigm allowed us to disentangle the neural code for task choices and task difficulty, ensuring that activation patterns in dmPFC/dACC independently encode these 2 factors. This finding provides new evidence for the importance of the dmPFC/dACC for task-selection and motivational functions in highly dynamic environments.

LysR-type transcriptional regulators (LTTRs) are emerging as key circuit components in regulating microbial stress responses and are implicated in modulating oxidative stress in the human opportunistic pathogen Pseudomonas aeruginosa. The oxidative stress response encapsulates several strategies to overcome the deleterious effects of reactive oxygen species. However, many of the regulatory components and associated molecular mechanisms underpinning this key adaptive response remain to be characterised. Comparative analysis of publically available transcriptomic datasets led to the identification of a novel LTTR, PA2206, whose expression was altered in response to a range of host signals in addition to oxidative stress. PA2206 was found to be required for tolerance to H2O2 in vitro and lethality in vivo in the Zebrafish embryo model of infection. Transcriptomic analysis in the presence of H2O2 showed that PA2206 altered the expression of 58 genes, including a large repertoire of oxidative stress and iron responsive genes, independent of the master regulator of oxidative stress, OxyR. Contrary to the classic mechanism of LysR regulation, PA2206 did not autoregulate its own expression and did not influence expression of adjacent or divergently transcribed genes. The PA2214-15 operon was identified as a direct target of PA2206 with truncated promoter fragments revealing binding to the 5’-ATTGCCTGGGGTTAT-3’ LysR box adjacent to the predicted -35 region. PA2206 also interacted with the pvdS promoter suggesting a global dimension to the PA2206 regulon, and suggests PA2206 is an important regulatory component of P. aeruginosa adaptation during oxidative stress.

Recently, we demonstrated using functional magnetic resonance imaging (fMRI) that the outcome of free decisions can be decoded from brain activity several seconds before reaching conscious awareness. Activity patterns in anterior frontopolar cortex (BA 10) were temporally the first to carry intention-related information and thus a candidate region for the unconscious generation of free decisions. In the present study, the original paradigm was replicated and multivariate pattern classification was applied to functional images of frontopolar cortex, acquired using ultra-high field fMRI at 7 Tesla. Here, we show that predictive activity patterns recorded before a decision was made became increasingly stable with increasing temporal proximity to the time point of the conscious decision. Furthermore, detailed questionnaires exploring subjects' thoughts before and during the decision confirmed that decisions were made spontaneously and subjects were unaware of the evolution of their decision outcomes. These results give further evidence that FPC stands at the top of the prefrontal executive hierarchy in the unconscious generation of free decisions.

In changing environments we need to dynamically re-organize our behavior in order to reach desired goals. This requires strategic switches between different tasks. However, little is known about the neural basis of such adaptation processes. We developed a novel, motivated choice paradigm and used multivariate pattern analysis of fMRI data (MVPA) to investigate this. Subjects chose between three different tasks on a trial-by-trial basis. Task difficulty varied independently for all three tasks, increasing for the chosen task set and decreasing for the non-chosen task sets. This created an exploration-exploitation dilemma for which subjects needed to find a solution. To keep difficulty and error rates low, they had to produce a motivated decision on which task to perform next, based on their estimation of the changing environmental variables. Using MVPA, we were able to predict subjects’ choices from medial PFC, and parietal cortex. Furthermore, we could predict the current difficulty level – the motivational factor driving choices – from reward related areas. Interestingly, the ventro-medial PFC (vmPFC) encoded both the choices and the diffi- culty. This area was previously associated with the processing of stimu- lus-values. Our results suggest that vmPFC is also involved in encoding motivated choices. Further planned analyses will investigate the interaction between areas encoding choices and areas encoding motivational factors in more detail. This should provide important clues on how humans endogenously adapt their behavior to cope with changing environments.

The multiple antigen peptide (MAP} approach is an elfective method to chemically synthesize and deliver multiple T-cell and 8-cell epitopes as the constituents of a single immunogen. Here we report on the design, chemical synthesis, and immunogenicity of three PIDsmodium falcipamm MAP vaccines that incorporated antigenic epitopes from the sporozoite, liver, and blood stages of the life cycle. Antibody and cellular responses were determined in three inbred (C5781)6, BALB/c, and AJJ) strains, one congenic (HLA-Al on the CS7BU6 background) strain, and one outbred strain (CD!} of mice. All three MAPs were immunogenic and induced both antibody and cellular responses, albeit in a somewhat genetically restricted manner. Antibodies against MAP-1, MAP-2, and MAP-3 had an antiparasite effect that was also dependent on the mouse major histocompatibility complex background. Anti-MAP-1 (CSP-based} antibodies blocked the invasion of HepG2 liver cells by P.falciparum sporozoites (highest, 95.16% in HLA-Al CS781)6; lowest, ll.21% in BALD/c). Furthermore, antibodies generated following immunizations with the MAP-2 (Pf'CSP, PfLSA-1, PfMSP-141, and PfMSP-3h} and MAP-3 (PfRAP-1, PfRAP-2, PfSERA, and PfMSP-141} vaccines were able to reduce the growth of blood stage parasites in erythrocyte cultures to various degrees. Thus, MAP-based vaccines remain a viable option to induce effective antibody and cellular responses. These results warrant further development and preclinical and clinical testing of the next generation of candidate MAP vaccines that are based on the conserved protective epitopes from PIDsmodium antigens that are widely recognized by populations of divergent HLA types from around the world., Pub. in Infection and Immunity, v78 n11, p4613-4624, Nov 2010.

In constantly changing environments, we are forced to dynamically re-organize our behavior in order to reach desired goals. Often, there is no obvious way to adapt to these environments, so different alternative courses of action have to be explored. Once a successful strategy is found, it is exploited until the environment changes and the need for behavioral adaptation arises again. This type of behavior requires endogenous and strategic switches between different behavioral sets. However, the neural implementation of these processes remains unclear. We use multivariate pattern classification of functional MRI data to investigate endogenous adaptations to external task demands in a modified task switching paradigm. More specifically, subjects were free to choose between three different task sets on a trial-by-trial basis. Difficulty varied independently in the three tasks, increasing for the chosen task set and decreasing for the non-chosen task sets. This created an exploration-exploitation dilemma in which subjects had to find the time point at which it is optimal to leave the current task set and switch to a different, possibly easier, one. Strategic choices lead to constantly low difficulty while poor choices lead to high difficulty. Therefore, to keep difficulty low, subjects were forced to constantly monitor the task environment and adapt their behavior accordingly. Behavioral results show that subjects cope efficiently with the task after some training. They track the task environment, keeping difficulty low through strategically placed switches between task sets. Crucially, potential confounds such as task preferences or learning effects do not influence choice behavior. While subjects performed the task we acquired functional MRI data. Using a time resolved decoding approach, we are able to decode whether subjects will stay in the current task or switch away from it from frontopolar cortex. This area is known to be involved in free choice processes. Furthe

Conditional rules of the form "if x then y" are of vital importance for our everyday life. Recent research has started to investigate the neural substrate underlying conditional rule processing. A critical aspect of rule processing that has so far been neglected is that many situations require the rules to be executed in a specific order. For example, it might be wise to apply the rule “If you don't have any money, go to the ATM machine” BEFORE the rule “If you want ice-cream, go to the ice-cream shop”, instead of applying them vice versa. Here, we present the results from a functional magnetic resonance imaging (fMRI) study in which we successfully decoded the identity of two simultaneously active rules as well as their application order from local patterns of fMRI data. A modified cued task-switching paradigm was administered during fMRI scanning. Participants were required to retrieve, maintain, and apply two conditional rules (e.g. “First, if there is a musical instrument, press left. Second, if there is a food item, press right”) to a set of target stimuli. We identified regions containing representations of rule identity and application order by applying multivariate pattern classifiers on local patterns of activation during the delay period between cue presentation and task execution. Using a redundant coding scheme for the rules (each rule was alternatively represented by one of two visual cues in different trials), we were able to disentangle representations of rules and representations of visual features of the cue. Representations of rule identity were found in bilateral supero-lateral parietal cortices, right dorso-lateral prefrontal cortex (dlPFC), and right anterior cingulate cortex (ACC). Representations of application order were found in bilateral supero-lateral parietal cortices and right ACC. In ACC, we found an overlap between regions that contained representations of rules and rule order. In contrast, a dissociation between both regions was found

Efficient recognition of odorous objects universally shapes animal behavior and is crucial for survival. To distinguish kin from nonkin, mate from nonmate and food from nonfood, organisms must be able to create meaningful perceptual representations of odor qualities and categories. It is currently unknown where and in what form the brain encodes information about odor quality. By combining functional magnetic resonance imaging (fMRI) with multivariate (pattern-based) techniques, we found that spatially distributed ensemble activity in human posterior piriform cortex (PPC) coincides with perceptual ratings of odor quality, such that odorants with more (or less) similar fMRI patterns were perceived as more (or less) alike. We did not observe these effects in anterior piriform cortex, amygdala or orbitofrontal cortex, indicating that ensemble coding of odor categorical perception is regionally specific for PPC. These findings substantiate theoretical models emphasizing the importance of distributed piriform templates for the perceptual reconstruction of odor object quality.

This paper is concerned with examining and recognizing aesthetics in an Information System (an organization incorporating both humans and information technology). Aesthetics emerge from the wholeness of things, not from specific parts or components. As such, aesthetics may naturally be considered in “systems”, and we propose that an effective manner of thinking of aesthetics is to think in terms of “themes”. Humans have an extraordinary capacity to capture events thematically. In other words, human beings have a natural sense of aesthetics. To examine aesthetics in an information systems context, we argue that one must consider not only aesthetics that may be perceived by the senses (a passive dimension), but also aesthetics that may be conceived in the mind (an active dimension). This paper draws the conclusion that the benefits of aesthetics in relation to the study of Information Systems, has characteristics similar to the nature and importance of ethics in IS. Also, the study of aesthetics in IS has greater implications than simply recognizing and appreciating beauty and art. The very human capacity for recognizing and appreciating beauty and art is also the same capacity for effective creativity and happiness: the active aesthetic dimension. It follows that if an information system encouraged and provided the enabling circumstances for the human capacity of thematic recognition (as found in the human appreciation of art and beauty) it thereby also provides the ground and the necessary thematically recognizable stimulus for effective creative and visionary organizational management.

Nitric oxide (NO) is known to regulate contractility and proliferation of cells within the prostate, however, the mechanism by which this occurs is unknown. The cGMP-dependent protein kinase (PKG) signalling pathway may be involved, and recent work has shown that activation of this pathway can be assessed by analysis of phosphorylation of vasodilator-stimulated phosphoprotein (VASP). The aim of the current study is to characterise the expression of VASP in the human prostate and human cultured prostatic stromal cells (HCPSCs), and to investigate whether NO activates PKG in these cells. Our studies revealed that VASP is expressed, and that incubation of HCPSCs with PKG-activating cGMP-analogues or the NO-donor, SNP, caused a significant PKG-dependent increase in VASP serine-239 phosphorylation. In addition, SNP elicited a reduction in intracellular K+ in a time frame consistent with the phosphorylation of VASP and activation of PKG. These data demonstrate that VASP can be used to assess the NO/cGMP/PKG signalling pathway in HCPSCs. In addition, we demonstrate for the first time that SNP, probably via NO release, leads to phosphorylation of VASP in a manner consistent with PKG activation.