Population coding of strategic variables during foraging in freely moving macaques.

Until now, it has been difficult to examine the neural bases of foraging in naturalistic environments because previous approaches have relied on restrained animals performing trial-based foraging tasks. Here we allowed unrestrained monkeys to freely interact with concurrent reward options while we wirelessly recorded population activity in the dorsolateral prefrontal cortex. The animals decided when and where to forage based on whether their prediction of reward was fulfilled or violated. This prediction was not solely based on a history of reward delivery, but also on the understanding that waiting longer improves the chance of reward. The task variables were continuously represented in a subspace of the high-dimensional population activity, and this compressed representation predicted the animal's subsequent choices better than the true task variables and as well as the raw neural activity. Our results indicate that monkeys' foraging strategies are based on a cortical model of reward dynamics as animals freely explore their environment.

Visuo-frontal interactions during social learning in freely moving macaques.

Social interactions represent a ubiquitous aspect of our everyday life that we acquire by interpreting and responding to visual cues from conspecifics1. However, despite the general acceptance of this view, how visual information is used to guide the decision to cooperate is unknown. Here, we wirelessly recorded the spiking activity of populations of neurons in the visual and prefrontal cortex in conjunction with wireless recordings of oculomotor events while freely moving macaques engaged in social cooperation. As animals learned to cooperate, visual and executive areas refined the representation of social variables, such as the conspecific or reward, by distributing socially relevant information among neurons in each area. Decoding population activity showed that viewing social cues influences the decision to cooperate. Learning social events increased coordinated spiking between visual and prefrontal cortical neurons, which was associated with improved accuracy of neural populations to encode social cues and the decision to cooperate. These results indicate that the visual-frontal cortical network prioritizes relevant sensory information to facilitate learning social interactions while freely moving macaques interact in a naturalistic environment.

Endogenous fluctuations in cortical state selectively enhance different modes of sensory processing in human temporal lobe.

The degree of synchronized fluctuations in neocortical network activity can vary widely during alertness. One influential idea that has emerged over the past few decades is that perceptual decisions are more accurate when the state of population activity is desynchronized. This suggests that optimal task performance may occur during a particular cortical state - the desynchronized state. Here we show that, contrary to this view, cortical state can both facilitate and suppress perceptual performance in a task-dependent manner. We performed electrical recordings from surface-implanted grid electrodes in the temporal lobe while human subjects completed two perceptual tasks. We found that when local population activity is in a synchronized state, network and perceptual performance are enhanced in a detection task and impaired in a discrimination task, but these modulatory effects are reversed when population activity is desynchronized. These findings indicate that the brain has adapted to take advantage of endogenous fluctuations in the state of neural populations in temporal cortex to selectively enhance different modes of sensory processing during perception in a state-dependent manner.

The impact of childhood malnutrition on mortality from pneumonia: a systematic review and network meta-analysis.

INTRODUCTION: Childhood malnutrition is widespread in low-income and middle-income countries (LMICs) and increases the frequency and severity of infections such as pneumonia. We aimed to identify studies investigating pneumonia deaths in malnourished children and estimate mortality risk by malnutrition severity. METHODS: We conducted a systematic review of MEDLINE, EMBASE and Global Health databases to identify relevant studies. We used a network meta-analysis to derive ORs of death from pneumonia for moderately and severely underweight children using low weight-for-age, the most reported measure of malnutrition. We compared meta-estimates of studies conducted before and after 2000 to assess changes in mortality risk over time. We estimated the prevalence of underweight hospitalised children from hospital-based cohort studies and calculated the population attributable fraction of in-hospital pneumonia deaths from being underweight using our results. RESULTS: Our network meta-analysis included 33 544 underweight children from 23 studies. The estimated OR of death from pneumonia was 2.0 (95% CI 1.6 to 2.6) and 4.6 (95% CI 3.7 to 5.9) for children moderately and severely underweight, respectively. The OR of death from pneumonia for those severely underweight was 5.3 (95% CI 3.9 to 7.4) pre-2000 and remained high post-2000 at 4.1 (95% CI 3.0 to 6.0). Prevalence of underweight children hospitalised with pneumonia varied (median 40.2%, range 19.6-66.3) but was high across many LMIC settings. We estimated a median 18.3% (range 10.8-34.6) and 40.9% (range 14.7-69.9) of in-hospital pneumonia deaths were attributable to being moderately and severely underweight, respectively. CONCLUSIONS: The risk of death from childhood pneumonia dramatically increases with malnutrition severity. This risk has remained high in recent years with an estimated over half of in-hospital pneumonia deaths attributable to child malnutrition. Prevention and treatment of all child malnutrition must be prioritised to maintain progress on reducing pneumonia deaths.

Technologies, strategies and approaches for testing populations at risk of sexually transmitted infections: a systematic review protocol to inform prevention and control in EU/EEA countries.

OBJECTIVES: This protocol outlines a systematic review methodology, aiming to assess the recent evidence-base for the impact of testing strategies and approaches on access to testing, testing coverage, and linkage to care for populations at risk for specific curable sexually transmitted infections (STIs) (chlamydia, gonorrhoea, syphilis, trichomoniasis, and Mycoplasma genitalium infections). DATA SOURCES: These include MEDLINE, Embase, PsycINFO, Global Health, Cochrane Database, Epistemonikos, CINAHL Plus, and Web of Science Core Collection. REVIEW METHODS: Papers reporting primary data from 1 January 2012 onwards will be included. Titles, abstracts, and full texts will be reviewed for inclusion, and data will be extracted using a pre-specified and piloted data extraction form, by two independent reviewers. Experts in the field will be contacted and interviewed for further information about ongoing or unpublished studies. A narrative synthesis of the findings will be conducted. DISCUSSION: Outcomes of this study will inform policy makers, national and international programme coordinators, public health and clinical experts, and civil society organisations involved in STI prevention and control in EU/EEA countries and elsewhere. The review will provide a direction for future researchers and programmers seeking to improve STI testing services among key populations at high risk for STIs. SYSTEMATIC REVIEW REGISTRATION: In accordance with guidelines outlined in the PRISMA-P methodology, this protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 30 January 2019: CRD42019118261.

The utility of peripheral blood leucocyte ratios as biomarkers in infectious diseases: A systematic review and meta-analysis.

OBJECTIVES: To assess the utility of the neutrophil:lymphocyte (NLR), lymphocyte:monocyte (LMR) and platelet:lymphocyte ratios (PLR) as infection biomarkers. METHODS: PubMed/MEDLINE, Embase and Cochrane databases were searched to identify eligible articles. Studies of diagnosis, severity or outcome were included. PROSPERO systematic review registration CRD42017075032. RESULTS: Forty studies were included, reporting on bacterial and viral infections, malaria, and critical illness due to sepsis. Ten studies reported an association of higher NLR with bacteraemia, supported by meta-analysis of patient-level data (five studies, n = 3320; AUC 0.72, p<0.0001) identifying a cut-off of >12.65. Two studies reported an association with lower LMR and diagnosis of influenza virus infection in patients with respiratory tract infection. Meta-analysis of patient-level data (n = 85; AUC 0.66, p = 0.01) identified a cut-off of ≤2.06. The directionality of associations between NLR and outcomes in heterogeneous cohorts of critically ill adults with sepsis varied. Potential clinical utility was also demonstrated in pneumonia (NLR), pertussis (NLR), urinary tract infection (NLR), diabetic foot infections (NLR) and Crimean Congo Haemorrhagic Fever (PLR). Longitudinal measurement of LMR during respiratory virus infection reflected symptoms and NLR during sepsis and bacteraemia predicted mortality. CONCLUSIONS: Peripheral blood leucocyte ratios are useful infection biomarkers, with the most evidence related to diagnosis of bacteraemia and influenza virus infection. In critical illness due to sepsis, a signal towards an association with NLR and outcomes exists, and NLR should be evaluated in future stratification models. Longitudinal measurement of ratios during infection could be informative. Overall, these biomarkers warrant further recognition and study in infectious diseases.

A wireless transmission neural interface system for unconstrained non-human primates.

OBJECTIVE: Studying the brain in large animal models in a restrained laboratory rig severely limits our capacity to examine brain circuits in experimental and clinical applications. APPROACH: To overcome these limitations, we developed a high-fidelity 96-channel wireless system to record extracellular spikes and local field potentials from the neocortex. A removable, external case of the wireless device is attached to a titanium pedestal placed in the animal skull. Broadband neural signals are amplified, multiplexed, and continuously transmitted as TCP/IP data at a sustained rate of 24 Mbps. A Xilinx Spartan 6 FPGA assembles the digital signals into serial data frames for transmission at 20 kHz though an 802.11n wireless data link on a frequency-shift key-modulated signal at 5.7-5.8 GHz to a receiver up to 10 m away. The system is powered by two CR123A, 3 V batteries for 2 h of operation. MAIN RESULTS: We implanted a multi-electrode array in visual area V4 of one anesthetized monkey (Macaca fascicularis) and in the dorsolateral prefrontal cortex (dlPFC) of a freely moving monkey (Macaca mulatta). The implanted recording arrays were electrically stable and delivered broadband neural data over a year of testing. For the first time, we compared dlPFC neuronal responses to the same set of stimuli (food reward) in restrained and freely moving conditions. Although we did not find differences in neuronal responses as a function of reward type in the restrained and unrestrained conditions, there were significant differences in correlated activity. This demonstrates that measuring neural responses in freely moving animals can capture phenomena that are absent in the traditional head-fixed paradigm. SIGNIFICANCE: We implemented a wireless neural interface for multi-electrode recordings in freely moving non-human primates, which can potentially move systems neuroscience to a new direction by allowing one to record neural signals while animals interact with their environment.

The Representation of Orientation in Macaque V2: Four Stripes Not Three.

Area V2 of macaque monkeys is traditionally thought to consist of 3 distinct functional compartments with characteristic cortical connections and functional properties. Orientation selectivity is one property that has frequently been used to distinguish V2 stripes, however, this receptive field property has been found in a high percentage of neurons across V2 compartments. Using quantitative intrinsic cortical imaging, we derived maps of preferred orientation, orientation selectivity, and orientation gradient in thin stripes, thick stripes, and interstripes in area V2. Orientation-selective responses were found in each V2 stripe, but the magnitude and organization of orientation selectivity differed significantly from stripe to stripe. Remarkably, the 2 pale stripes flanking each cytochrome oxidase dense stripe differed significantly in their representation of orientation resulting in their distinction as type-I and type-II interstripes. V2 orientation maps are characterized by clockwise and anticlockwise "orientation pinwheels", but unlike V1, they are not homogeneously distributed across V2. Furthermore, V2 stripes contain large-scale sequences of preferred orientation. These analyses demonstrate that V2 consists of 4 distinct functional compartments; thick stripes and type-II interstripes, which are strongly orientation selective and thin stripes and type-I interstripes, which are significantly less selective for orientation and exhibit larger orientation gradient magnitudes.

Mutual information of local field potentials distinguishes area-V2 stripe compartments.

PURPOSE: Determining how information is represented by populations of neurons in different cortical areas is critical to our understanding of the brain mechanisms of visual perception. Recently, information-theoretical approaches have been applied to the analysis of spike trains of multiple neurons. However, other neurophysiological signals, such as local field potentials (LFPs), offer a different source of information worthy of investigating in this way. In this study, we investigate how the modular organization of area V2 of macaque monkeys impacts the information represented in LFPs. MATERIALS AND METHODS: LFPs were recorded from a 32-channel microelectrode array implanted in area V2 of an anesthetized macaque monkey. The electrode positions were recovered in histological tissue stained for cytochrome oxidase (CO) to reveal the modular organization of V2. Visual stimuli consisted of a variety of moving gratings that differed in orientation, direction, spatial frequency, and chromatic content. RESULTS: LFPs were separated into different frequency bands for analysis of mutual information as a function of stimulus type and CO-stripe location. High-γ-band LFPs revealed the highest information content across the electrode array. The distributions of total mutual information as well as mutual information due to correlations varied greatly by CO stripe. This analysis indicates that local correlations within each CO stripe generally reduce mutual information, whereas correlations between stripes greatly increase mutual information. CONCLUSION: The decomposition mutual information based on the power of different frequency bands of LFPs provides new insight into the impact of modular architecture on population coding in area V2. Unlike other cortical areas, such as V1, where mutual information based on LFP correlations is largely determined by cortical separation, mutual information in V2 is also fundamentally determined by the CO-stripe architecture.