Neural signatures of natural behaviour in socializing macaques.

Our understanding of the neurobiology of primate behaviour largely derives from artificial tasks in highly controlled laboratory settings, overlooking most natural behaviours that primate brains evolved to produce1-3. How primates navigate the multidimensional social relationships that structure daily life4 and shape survival and reproductive success5 remains largely unclear at the single-neuron level. Here we combine ethological analysis, computer vision and wireless recording technologies to identify neural signatures of natural behaviour in unrestrained, socially interacting pairs of rhesus macaques. Single-neuron and population activity in the prefrontal and temporal cortex robustly encoded 24 species-typical behaviours, as well as social context. Male-female partners demonstrated near-perfect reciprocity in grooming, a key behavioural mechanism supporting friendships and alliances6, and neural activity maintained a running account of these social investments. Confronted with an aggressive intruder, behavioural and neural population responses reflected empathy and were buffered by the presence of a partner. Our findings reveal a highly distributed neurophysiological ledger of social dynamics, a potential computational foundation supporting communal life in primate societies, including our own.

The effect of augmented reality on preoperative anxiety in children and adolescents: A randomized controlled trial.

BACKGROUND AND AIMS: Virtual reality has been shown to be an effective non-pharmacological intervention for reducing anxiety of pediatric patients. A newer immersive technology, that of augmented reality, offers some practical advantages over virtual reality, and also seems to show beneficial effects on anxiety. The main objective of this study was to determine whether augmented reality could reduce preoperative anxiety in pediatric patients undergoing elective day surgeries. A secondary outcome was to document the level of satisfaction from pediatric patients toward augmented reality intervention. METHODS: Children and adolescents aged between 5 and 17 years old scheduled for elective day surgery under general anesthesia were randomly divided into two groups. Patients in the control group received standard care, whereas patients in the augmented reality group were accompanied by two virtual characters who taught them relaxation techniques and provided emotional and informational support. Anxiety was measured at the time of admission and at the time of induction using the short version of the modified Yale Preoperative Anxiety Scale. RESULTS: The analysis included 37 pediatric patients in the augmented reality group and 64 in the control group. Anxiety scores were statistically significantly lower in the augmented reality group than those in the control group at the time of admission (median difference [95% CI]: 6.3 [0-10.4], p = .01), while no difference was observed between groups at the time of induction (median difference [95% CI]: -4.2 [-5.2-4.2], p = .58). Most patients in the augmented reality group wished to wear the glasses again and reported to be very satisfied with the intervention. CONCLUSION: To our knowledge, this study is the first large randomized controlled trial to provide empirical evidence of reduction in anxiety for children and adolescents using augmented reality prior to induction of general anesthesia.

A single-cell multi-omic atlas spanning the adult rhesus macaque brain.

Cataloging the diverse cellular architecture of the primate brain is crucial for understanding cognition, behavior, and disease in humans. Here, we generated a brain-wide single-cell multimodal molecular atlas of the rhesus macaque brain. Together, we profiled 2.58 M transcriptomes and 1.59 M epigenomes from single nuclei sampled from 30 regions across the adult brain. Cell composition differed extensively across the brain, revealing cellular signatures of region-specific functions. We also identified 1.19 M candidate regulatory elements, many previously unidentified, allowing us to explore the landscape of cis-regulatory grammar and neurological disease risk in a cell type-specific manner. Altogether, this multi-omic atlas provides an open resource for investigating the evolution of the human brain and identifying novel targets for disease interventions.

Human OPRM1 and murine Oprm1 promoter driven viral constructs for genetic access to µ-opioidergic cell types.

With concurrent global epidemics of chronic pain and opioid use disorders, there is a critical need to identify, target and manipulate specific cell populations expressing the mu-opioid receptor (MOR). However, available tools and transgenic models for gaining long-term genetic access to MOR+ neural cell types and circuits involved in modulating pain, analgesia and addiction across species are limited. To address this, we developed a catalog of MOR promoter (MORp) based constructs packaged into adeno-associated viral vectors that drive transgene expression in MOR+ cells. MORp constructs designed from promoter regions upstream of the mouse Oprm1 gene (mMORp) were validated for transduction efficiency and selectivity in endogenous MOR+ neurons in the brain, spinal cord, and periphery of mice, with additional studies revealing robust expression in rats, shrews, and human induced pluripotent stem cell (iPSC)-derived nociceptors. The use of mMORp for in vivo fiber photometry, behavioral chemogenetics, and intersectional genetic strategies is also demonstrated. Lastly, a human designed MORp (hMORp) efficiently transduced macaque cortical OPRM1+ cells. Together, our MORp toolkit provides researchers cell type specific genetic access to target and functionally manipulate mu-opioidergic neurons across a range of vertebrate species and translational models for pain, addiction, and neuropsychiatric disorders.

Neural signatures of natural behavior in socializing macaques.

Our understanding of the neurobiology of primate behavior largely derives from artificial tasks in highly-controlled laboratory settings, overlooking most natural behaviors primate brains evolved to produce1. In particular, how primates navigate the multidimensional social relationships that structure daily life and shape survival and reproductive success remains largely unexplored at the single neuron level. Here, we combine ethological analysis with new wireless recording technologies to uncover neural signatures of natural behavior in unrestrained, socially interacting pairs of rhesus macaques within a larger colony. Population decoding of single neuron activity in prefrontal and temporal cortex unveiled robust encoding of 24 species-typical behaviors, which was strongly modulated by the presence and identity of surrounding monkeys. Male-female partners demonstrated near-perfect reciprocity in grooming, a key behavioral mechanism supporting friendships and alliances, and neural activity maintained a running account of these social investments. When confronted with an aggressive intruder, behavioral and neural population responses reflected empathy and were buffered by the presence of a partner. Surprisingly, neural signatures in prefrontal and temporal cortex were largely indistinguishable and irreducible to visual and motor contingencies. By employing an ethological approach to the study of primate neurobiology, we reveal a highly-distributed neurophysiological record of social dynamics, a potential computational foundation supporting communal life in primate societies, including our own.

A microworld simulation of dynamic cognition as a test of executive function.

INTRODUCTION: The lack of consensus regarding the nature or composition of executive functioning (EF) has led to a proliferation of executive tasks to assess the concept. Many do agree however that the theoretical concept of EF is a holistic one, leading us to consider whether it would be beneficial to assess EF in a more holistic manner. We explore how well a computerized simulation of dynamic cognition - that reproduces the context of real-world complex decision-making - can predict performance on nine classical neuropsychological tasks of EF. METHODS: A sample of 121 participants completed all tasks, and canonical correlations were used to assess the nine tasks as predictors of the three simulation performance metrics to evaluate the multivariate-shared relationship between the two variable sets: executive functions and dynamic cognition. RESULTS: Results show that a substantial amount of variance in two indices of dynamic cognition can be explained by a linear combination of three key types of neuropsychological tasks (planning, inhibition, working memory), with a larger contribution from the planning tasks. CONCLUSION: Our findings suggest that tasks of dynamic cognition could augment traditional, separate tests of EF, offering benefits in terms of parsimony, ecological validity, sensitivity, and computerized delivery.

68Ga-DOTATATE Prepared from Cyclotron-Produced 68Ga: An Integrated Solution from Cyclotron Vault to Safety Assessment and Diagnostic Efficacy in Neuroendocrine Cancer Patients.

Cyclotron production of 68Ga is a promising approach to supply 68Ga radiopharmaceuticals. To validate this capability, an integrated solution for a robust synthesis of 68Ga-DOTATATE prepared from cyclotron-produced 68Ga was achieved. A retrospective comparison analysis was performed on patients who underwent PET/CT imaging after injection of DOTATATE labeled with 68Ga produced by a cyclotron or eluted from a generator to demonstrate the clinical safety and diagnostic efficacy of the radiopharmaceutical as a routine standard-of-care diagnostic tool in the clinic. Methods: An enriched pressed 68Zn target was irradiated by a cyclotron with a proton beam set at 12.7 MeV for 100 min. The fully automated process uses an in-vault dissolution system in which a liquid distribution system transfers the dissolved target to a dedicated hot cell for the purification of 68GaCl3 and radiolabeling of DOTATATE using a cassette-based automated module. Quality control tests were performed on the resulting tracer solution. The internal radiation dose for 68Ga-DOTATATE was based on extrapolation from rat biodistribution experiments. A retrospective comparison analysis was performed on patients who underwent PET/CT imaging after injection of DOTATATE labeled with cyclotron- or generator-produced 68Ga. Results: The synthesis of 68Ga-DOTATATE (20.7 ± 1.3 GBq) with high apparent molar activity (518 ± 32 GBq/µmol at the end of synthesis) was completed in 65 min, and the radiopharmaceutical met the requirements specified in the European Pharmacopoeia monograph on 68Ga-chloride (accelerator-produced) solution for radiolabeling. 68Ga-DOTATATE was stable for at least 5 h after formulation. The dosimetry calculated with OLINDA for cyclotron- and generator-produced 68Ga-DOTATATE was roughly equivalent. The SUVmean or SUVmax of tumoral lesions with cyclotron-produced 68Ga-DOTATATE was equivalent to that with generator-produced 68Ga. Among physiologic uptake levels, a significant difference was found in kidneys, spleen, and stomach wall, with lower values in cyclotron-produced 68Ga-DOTATATE in all cases. Conclusion: Integrated cyclotron production achieves reliable high yields of clinical-grade 68Ga-DOTATATE. The clinical safety and imaging efficacy of cyclotron-produced 68Ga-DOTATATE in humans provide supporting evidence for its use in routine clinical practice.

Neural cognitive signals during spontaneous movements in the macaque.

The single-neuron basis of cognitive processing in primates has mostly been studied in laboratory settings where movements are severely restricted. It is unclear, therefore, how natural movements might affect neural signatures of cognition in the brain. Moreover, studies in mice indicate that body movements, when measured, account for most of the neural dynamics in the cortex. To examine these issues, we recorded from single-neuron ensembles in the prefrontal cortex in moving monkeys performing a cognitive task and characterized eye, head and body movements using video tracking. Despite considerable trial-to-trial movement variability, single-neuron tuning could be precisely measured and decision signals accurately decoded on a single-trial basis. Creating or abolishing spontaneous movements through head restraint and task manipulations had no measurable impact on neural responses. However, encoding models showed that uninstructed movements explained as much neural variance as task variables, with most movements aligned to task events. These results demonstrate that cognitive signals in the cortex are robust to natural movements, but also that unmeasured movements are potential confounds in cognitive neurophysiology experiments.

Comparing a Fitbit Wearable to an Electrocardiogram Gold Standard as a Measure of Heart Rate Under Psychological Stress: A Validation Study.

BACKGROUND: Wearable devices collect physiological and behavioral data that have the potential to identify individuals at risk of declining mental health and well-being. Past research has mainly focused on assessing the accuracy and the agreement of heart rate (HR) measurement of wearables under different physical exercise conditions. However, the capacity of wearables to sense physiological changes, assessed by increasing HR, caused by a stressful event has not been thoroughly studied. OBJECTIVE: This study followed 3 objectives: (1) to test the ability of a wearable device (Fitbit Versa 2) to sense an increase in HR upon induction of psychological stress in the laboratory; (2) to assess the accuracy of the wearable device to capture short-term HR variations caused by psychological stress compared to a gold-standard electrocardiogram (ECG) measure (Biopac); and (3) to quantify the degree of agreement between the wearable device and the gold-standard ECG measure across different experimental conditions. METHODS: Participants underwent the Trier Social Stress Test protocol, which consists of an oral phase, an arithmetic stress phase, an anticipation phase, and 2 relaxation phases (at the beginning and the end). During the stress protocol, the participants wore a Fitbit Versa 2 and were also connected to a Biopac. A mixed-effect modeling approach was used (1) to assess the effect of experimental conditions on HR, (2) to estimate several metrics of accuracy, and (3) to assess the agreement: the Bland-Altman limits of agreement (LoA), the concordance correlation coefficient, the coverage probability, the total deviation index, and the coefficient of an individual agreement. Mean absolute error and mean absolute percent error were calculated as accuracy indices. RESULTS: A total of 34 university students were recruited for this study (64% of participants were female with a mean age of 26.8 years, SD 8.3). Overall, the results showed significant HR variations across experimental phases. Post hoc tests revealed significant pairwise differences for all phases. Accuracy analyses revealed acceptable accuracy according to the analyzed metrics of accuracy for the Fitbit Versa 2 to capture the short-term variations in psychological stress levels. However, poor indices of agreement between the Fitbit Versa 2 and the Biopac were found. CONCLUSIONS: Overall, the results support the use of the Fitbit Versa 2 to capture short-term stress variations. The Fitbit device showed acceptable levels of accuracy but poor agreement with an ECG gold standard. Greater inaccuracy and smaller agreement were found for stressful experimental conditions that induced a higher HR. Fitbit devices can be used in research to measure HR variations caused by stress, although they cannot replace an ECG instrument when precision is of utmost importance.

Multiregion transcriptomic profiling of the primate brain reveals signatures of aging and the social environment.

Aging is accompanied by a host of social and biological changes that correlate with behavior, cognitive health and susceptibility to neurodegenerative disease. To understand trajectories of brain aging in a primate, we generated a multiregion bulk (N = 527 samples) and single-nucleus (N = 24 samples) brain transcriptional dataset encompassing 15 brain regions and both sexes in a unique population of free-ranging, behaviorally phenotyped rhesus macaques. We demonstrate that age-related changes in the level and variance of gene expression occur in genes associated with neural functions and neurological diseases, including Alzheimer's disease. Further, we show that higher social status in females is associated with younger relative transcriptional ages, providing a link between the social environment and aging in the brain. Our findings lend insight into biological mechanisms underlying brain aging in a nonhuman primate model of human behavior, cognition and health.

Understanding the Influence of Web-Based Information, Misinformation, Disinformation, and Reinformation on COVID-19 Vaccine Acceptance: Protocol for a Multicomponent Study.

BACKGROUND: The COVID-19 pandemic has generated an explosion in the amount of information shared on the internet, including false and misleading information on SARS-CoV-2 and recommended protective behaviors. Prior to the pandemic, web-based misinformation and disinformation were already identified as having an impact on people's decision to refuse or delay recommended vaccination for themselves or their children. OBJECTIVE: The overall aims of our study are to better understand the influence of web-based misinformation and disinformation on COVID-19 vaccine decisions and investigate potential solutions to reduce the impact of web-based misinformation and disinformation about vaccines. METHODS: Based on different research approaches, the study will involve (1) the use of artificial intelligence techniques, (2) a web-based survey, (3) interviews, and (4) a scoping review and an environmental scan of the literature. RESULTS: As of September 1, 2022, data collection has been completed for all objectives. The analysis is being conducted, and results should be disseminated in the upcoming months. CONCLUSIONS: The findings from this study will help with understanding the underlying determinants of vaccine hesitancy among Canadian individuals and identifying effective, tailored interventions to improve vaccine acceptance among them. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/41012.

Adaptive Filtering for Improved EEG-Based Mental Workload Assessment of Ambulant Users.

Recently, due to the emergence of mobile electroencephalography (EEG) devices, assessment of mental workload in highly ecological settings has gained popularity. In such settings, however, motion and other common artifacts have been shown to severely hamper signal quality and to degrade mental workload assessment performance. Here, we show that classical EEG enhancement algorithms, conventionally developed to remove ocular and muscle artifacts, are not optimal in settings where participant movement (e.g., walking or running) is expected. As such, an adaptive filter is proposed that relies on an accelerometer-based referential signal. We show that when combined with classical algorithms, accurate mental workload assessment is achieved. To test the proposed algorithm, data from 48 participants was collected as they performed the Revised Multi-Attribute Task Battery-II (MATB-II) under a low and a high workload setting, either while walking/jogging on a treadmill, or using a stationary exercise bicycle. Accuracy as high as 95% could be achieved with a random forest based mental workload classifier with ambulant users. Moreover, an increase in gamma activity was found in the parietal cortex, suggesting a connection between sensorimotor integration, attention, and workload in ambulant users.

From the field to the lab and back: neuroethology of primate social behavior.

Social mammals with more numerous and stronger social relationships live longer, healthier lives. Despite the established importance of social relationships, our understanding of the neurobiological mechanisms by which they are pursued, formed, and maintained in primates remains largely confined to highly controlled laboratory settings which do not allow natural, dynamic social interactions to unfold. In this review, we argue that the neurobiological study of primate social behavior would benefit from adopting a neuroethological approach, that is, a perspective grounded in natural, species-typical behavior, with careful selection of animal models according to the scientific question at hand. We highlight macaques and marmosets as key animal models for human social behavior and summarize recent findings in the social domain for both species. We then review pioneering studies of dynamic social behaviors in small animals, which can inspire studies in larger primates where the technological landscape is now ripe for an ethological overhaul.

PASS: A Multimodal Database of Physical Activity and Stress for Mobile Passive Body/ Brain-Computer Interface Research.

With the burgeoning of wearable devices and passive body/brain-computer interfaces (B/BCIs), automated stress monitoring in everyday settings has gained significant attention recently, with applications ranging from serious games to clinical monitoring. With mobile users, however, challenges arise due to other overlapping (and potentially confounding) physiological responses (e.g., due to physical activity) that may mask the effects of stress, as well as movement artifacts that can be introduced in the measured signals. For example, the classical increase in heart rate can no longer be attributed solely to stress and could be caused by the activity itself. This makes the development of mobile passive B/BCIs challenging. In this paper, we introduce PASS, a multimodal database of Physical Activity and StresS collected from 48 participants. Participants performed tasks of varying stress levels at three different activity levels and provided quantitative ratings of their perceived stress and fatigue levels. To manipulate stress, two video games (i.e., a calm exploration game and a survival game) were used. Peripheral physical activity (electrocardiography, electrodermal activity, breathing, skin temperature) as well as cerebral activity (electroencephalography) were measured throughout the experiment. A complete description of the experimental protocol is provided and preliminary analyses are performed to investigate the physiological reactions to stress in the presence of physical activity. The PASS database, including raw data and subjective ratings has been made available to the research community at http://musaelab.ca/pass-database/. It is hoped that this database will help advance mobile passive B/BCIs for use in everyday settings.

WAUC: A Multi-Modal Database for Mental Workload Assessment Under Physical Activity.

Assessment of mental workload is crucial for applications that require sustained attention and where conditions such as mental fatigue and drowsiness must be avoided. Previous work that attempted to devise objective methods to model mental workload were mainly based on neurological or physiological data collected when the participants performed tasks that did not involve physical activity. While such models may be useful for scenarios that involve static operators, they may not apply in real-world situations where operators are performing tasks under varying levels of physical activity, such as those faced by first responders, firefighters, and police officers. Here, we describe WAUC, a multimodal database of mental Workload Assessment Under physical aCtivity. The study involved 48 participants who performed the NASA Revised Multi-Attribute Task Battery II under three different activity level conditions. Physical activity was manipulated by changing the speed of a stationary bike or a treadmill. During data collection, six neural and physiological modalities were recorded, namely: electroencephalography, electrocardiography, breathing rate, skin temperature, galvanic skin response, and blood volume pulse, in addition to 3-axis accelerometry. Moreover, participants were asked to answer the NASA Task Load Index questionnaire after each experimental section, as well as rate their physical fatigue level on the Borg fatigue scale. In order to bring our experimental setup closer to real-world situations, all signals were monitored using wearable, off-the-shelf devices. In this paper, we describe the adopted experimental protocol, as well as validate the subjective, neural, and physiological data collected. The WAUC database, including the raw data and features, subjective ratings, and scripts to reproduce the experiments reported herein will be made available at: http://musaelab.ca/resources/.

An Open Resource for Non-human Primate Optogenetics.

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.

Prediction of Stress and Mental Workload during Police Academy Training Using Ultra-Short-Term Heart Rate Variability and Breathing Analysis.

Heart rate variability (HRV) has been studied in the context of human behavior analysis and many features have been extracted from the inter-beat interval (RR) time series and tested as correlates of constructs such as mental workload, stress and anxiety. Such constructs are crucial in assessing quality-of-life of individuals, as well as their overall performance when doing critical tasks. Most studies, however, have been conducted in controlled laboratory environments with artificially-induced psychological responses. While this assures that high quality data are collected, the amount of data is limited and the transferability of the findings to more ecologically-appropriate settings remains unknown. Additionally, it is desirable for such mental state monitoring systems to have high temporal resolution, thus allowing for quick feedback and adaptive decision making. In this article, we explore the use of features computed from time windows much shorter than typically reported in the literature. More specifically, we evaluate the potential of HRV and breathing features computed over so-called ultra-short-term segments (i.e., < 5 minutes) for stress and mental workload prediction. Experiments with 27 police academy trainees show that short time windows as low as 60 seconds can provide useful insights, in particular for mental workload assessment. Moreover, the fusion of HRV and breathing features showed to be an important aspect for reliable behavioural assessment in highly ecological settings.

Automated radiosynthesis of 68Ga for large-scale routine production using 68Zn pressed target.

Gallium-68 (68Ga) has attracted increasing interest in recent years due to the expanding clinical applications of 68Ga-based radiopharmaceuticals (Rahbar et al., 2017). 68Ga is mainly produced via 68Ge/68Ga generators that are limited in yield by the 68Ge activity (typically up to 1.85 GBq at calibration time). With the increased-demand of 68Ga in nuclear medicine for positron emission tomography (PET) imaging, there is a need for more efficient and robust production methods to obtain larger amounts of [68Ga]GaCl3 with high radionuclidic and radiochemical purity and apparent molar activity (AMA) for facilitating the distribution of 68Ga-based radiopharmaceuticals. The objectives of this study were to develop a fast and efficient process for the preparation of 68Zn-based solid targets and to optimize the critical parameters for the automated radiosynthesis of [68Ga]GaCl3 for large-scale routine production.

Monofluoroalkene-Isostere as a 19 F†NMR Label for the Peptide Backbone: Synthesis and Evaluation in Membrane-Bound PGLa and (KIGAKI)3.

Solid-state 19 F NMR is a powerful method to study the interactions of biologically active peptides with membranes. So far, in labelled peptides, the 19 F-reporter group has always been installed on the side chain of an amino acid. Given the fact that monofluoroalkenes are non-hydrolyzable peptide bond mimics, we have synthesized a monofluoroalkene-based dipeptide isostere, Val-Ψ[(Z)-CF=CH]-Gly, and inserted it in the sequence of two well-studied antimicrobial peptides: PGLa and (KIGAKI)3 are representatives of an α-helix and a ß-sheet. The conformations and biological activities of these labeled peptides were studied to assess the suitability of monofluoroalkenes for 19 F NMR structure analysis.

The diagnosticity of psychophysiological signatures: Can we disentangle mental workload from acute stress with ECG and fNIRS?

The ability to identify reliable and sensitive physiological signatures of psychological dimensions is key to developing intelligent adaptive systems that may in turn help to mitigate human error in complex operations. The challenge of this endeavor lies with diagnosticity. Despite different underlying causes, the physiological correlates of workload and acute psychological stress manifest in rather similar ways and can be easily confounded. The current work aimed to build a diagnostic model of mental state through the simultaneous classification of mental workload (varied through three levels of the n-back task) and acute stress (the presence/absence of aversive sounds) with machine learning. Using functional near infrared spectroscopy (fNIRS) and electrocardiography (ECG), the model's classifiers was above-chance to disentangle variations of mental workload from variations of acute stress. Both ECG and fNIRS could predict mental workload level, the best accuracy resulted from the two measures in combination. Stress level could not be accurately diagnosed through ECG alone, only with fNIRS or ECG and fNIRS combined. Individual calibration may be important since stress classification was more accurate for those with higher subjective state anxiety, perhaps due to a greater sensitivity to stress. Mental workload and stress were both better classified with activity in lateral prefrontal regions of the cortex than the medial areas, and the HbO2 signal generally lead to better classification than HHB. The current model represents a step forward to finely discriminate different mental states despite their rather analog physiological correlates.