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.

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.

Multi-Scale Heart Beat Entropy Measures for Mental Workload Assessment of Ambulant Users.

Mental workload assessment is crucial in many real life applications which require constant attention and where imbalance of mental workload resources may cause safety hazards. As such, mental workload and its relationship with heart rate variability (HRV) have been well studied in the literature. However, the majority of the developed models have assumed individuals are not ambulant, thus bypassing the issue of movement-related electrocardiography (ECG) artifacts and changing heart beat dynamics due to physical activity. In this work, multi-scale features for mental workload assessment of ambulatory users is explored. ECG data was sampled from users while they performed different types and levels of physical activity while performing the multi-attribute test battery (MATB-II) task at varying difficulty levels. Proposed features are shown to outperform benchmark ones and further exhibit complementarity when used in combination. Indeed, results show gains over the benchmark HRV measures of 24.41 % in accuracy and of 27.97 % in F1 score can be achieved even at high activity levels.

Defining a multimodal signature of remote sports concussions.

Sports-related concussions lead to persistent anomalies of the brain structure and function that interact with the effects of normal ageing. Although post-mortem investigations have proposed a bio-signature of remote concussions, there is still no clear in vivo signature. In the current study, we characterized white matter integrity in retired athletes with a history of remote concussions by conducting a full-brain, diffusion-based connectivity analysis. Next, we combined MRI diffusion markers with MR spectroscopic, MRI volumetric, neurobehavioral and genetic markers to identify a multidimensional in vivo signature of remote concussions. Machine learning classifiers trained to detect remote concussions using this signature achieved detection accuracies up to 90% (sensitivity: 93%, specificity: 87%). These automated classifiers identified white matter integrity as the hallmark of remote concussions and could provide, following further validation, a preliminary unbiased detection tool to help medical and legal experts rule out concussion history in patients presenting or complaining about late-life abnormal cognitive decline.

Palladium-catalyzed synthesis of monofluoroalkenes from 3,3-difluoropropenes using dimethylmalonate and derivatives as nucleophiles.

The synthesis of monofluoroalkenes bearing a malonate or its derivatives at the ß position is presented. The reaction can be performed with various 3,3-difluoropropenes. A preliminary result for an enantioselective variant is also reported. Further synthetic transformations of a monofluoroalkene were also accomplished.

Single-Trial Decoding of Visual Attention from Local Field Potentials in the Primate Lateral Prefrontal Cortex Is Frequency-Dependent.

Local field potentials (LFPs) are fluctuations of extracellular voltage that may reflect the physiological phenomena occurring within a volume of neural tissue. It is known that the allocation of spatial attention modulates the amplitude of LFPs in visual areas of primates. An issue that remains poorly investigated is whether and how attention modulates LFPs in executive brain areas, such as the lateral prefrontal cortex (LPFC), thought to be involved in the origins of attention. We addressed this issue by recording LFPs from multielectrode arrays implanted in the LPFC of two macaques. We found that the allocation of attention can be reliably decoded on a single-trial basis from ensembles of LFPs with frequencies >60 Hz. Using LFP frequencies <60 Hz, we could not decode the allocation of attention, but we could decode the location of a visual stimulus as well as the endpoint of saccades toward that stimulus. The information contained in the high-frequency LFPs was fully redundant with the information contained in the spiking activity of single neurons recorded from the same electrodes. Moreover, the decoding of attention using γ frequency LFPs was less accurate than using spikes, but it was twice more stable across time. Finally, decorrelating the LFP signals from the different electrodes increased decoding performance in the high frequencies by up to ∼14%. Our findings suggest that LFPs recorded from chronically implanted multielectrode arrays in the LPFC contain information about sensory, cognitive, and motor components of a task in a frequency-dependent manner.

Attitudes of pediatric intensive care unit physicians towards the use of cognitive aids: a qualitative study.

BACKGROUND: Cognitive aids are increasingly recommended in clinical practice, yet little is known about the attitudes of physicians towards these tools. METHODS: We employed a qualitative, descriptive design to explore physician attitudes towards cognitive aids in pediatric intensive care units (PICUs). Semi-structured interviews elicited the opinions of a convenience sample of practicing PICU physicians towards the use of cognitive aids. We analyzed interview data for thematic content to examine the three factors of intention to use cognitive aids as defined by the Theory of Planned Behavior (TPB), attitudes, social norms, and perceived control. RESULTS: Analysis of 14 interviews suggested that in the PICU setting, cognitive aids are widely used. Discovered themes related to their use touched on all three TPB factors of intention and included: aids are perceived to improve team communication; aids may improve patient safety; aids may hinder clinician judgment; physicians may resist implementation if it occurs prior to demonstration of benefit; effective adoption requires cognitive aids to be integrated into local workplace culture; and implementation should take physician concerns into account. CONCLUSIONS: Our sample of PICU physicians were open to cognitive aids in their practice, as long as such aids preserve the primacy of clinical judgment, focus on team communication, demonstrate effectiveness through preliminary testing, and are designed and implemented with the local culture and work environment in mind. Future knowledge translation efforts to implement cognitive aids would benefit from consideration of these issues.

Diffuse white matter tract abnormalities in clinically normal ageing retired athletes with a history of sports-related concussions.

Sports-related concussions have been shown to lead to persistent subclinical anomalies of the motor and cognitive systems in young asymptomatic athletes. In advancing age, these latent alterations correlate with detectable motor and cognitive function decline. Until now, the interacting effects of concussions and the normal ageing process on white matter tract integrity remain unknown. Here we used a tract-based spatial statistical method to uncover potential white matter tissue damage in 15 retired athletes with a history of concussions, free of comorbid medical conditions. We also investigated potential associations between white matter integrity and declines in cognitive and motor functions. Compared to an age- and education-matched control group of 15 retired athletes without concussions, former athletes with concussions exhibited widespread white matter anomalies along many major association, interhemispheric, and projection tracts. Group contrasts revealed decreases in fractional anisotropy, as well as increases in mean and radial diffusivity measures in the concussed group. These differences were primarily apparent in fronto-parietal networks as well as in the frontal aspect of the corpus callosum. The white matter anomalies uncovered in concussed athletes were significantly associated with a decline in episodic memory and lateral ventricle expansion. Finally, the expected association between frontal white matter integrity and motor learning found in former non-concussed athletes was absent in concussed participants. Together, these results show that advancing age in retired athletes presenting with a history of sports-related concussions is linked to diffuse white matter abnormalities that are consistent with the effects of traumatic axonal injury and exacerbated demyelination. These changes in white matter integrity might explain the cognitive and motor function declines documented in this population.

Sports concussions and aging: a neuroimaging investigation.

Recent epidemiological and experimental studies suggest a link between cognitive decline in late adulthood and sports concussions sustained in early adulthood. In order to provide the first in vivo neuroanatomical evidence of this relation, the present study probes the neuroimaging profile of former athletes with concussions in relation to cognition. Former athletes who sustained their last sports concussion >3 decades prior to testing were compared with those with no history of traumatic brain injury. Participants underwent quantitative neuroimaging (optimized voxel-based morphometry [VBM], hippocampal volume, and cortical thickness), proton magnetic resonance spectroscopy ((1)H MRS; medial temporal lobes and prefrontal cortices), and neuropsychological testing, and they were genotyped for APOE polymorphisms. Relative to controls, former athletes with concussions exhibited: 1) Abnormal enlargement of the lateral ventricles, 2) cortical thinning in regions more vulnerable to the aging process, 3) various neurometabolic anomalies found across regions of interest, 4) episodic memory and verbal fluency decline. The cognitive deficits correlated with neuroimaging findings in concussed participants. This study unveiled brain anomalies in otherwise healthy former athletes with concussions and associated those manifestations to the long-term detrimental effects of sports concussion on cognitive function. Findings from this study highlight patterns of decline often associated with abnormal aging.

Attentional costs and failures in air traffic control notifications.

Large display screens are common in supervisory tasks, meaning that alerts are often perceived in peripheral vision. Five air traffic control notification designs were evaluated in their ability to capture attention during an ongoing supervisory task, as well as their impact on the primary task. A range of performance measures, eye-tracking and subjective reports showed that colour, even animated, was less effective than movement, and notifications sometimes went unnoticed. Designs that drew attention to the notified aircraft by a pulsating box, concentric circles or the opacity of the background resulted in faster perception and no missed notifications. However, the latter two designs were intrusive and impaired primary task performance, while the simpler animated box captured attention without an overhead cognitive cost. These results highlight the need for a holistic approach to evaluation, achieving a balance between the benefits for one aspect of performance against the potential costs for another. Practitioner summary: We performed a holistic examination of air traffic control notification designs regarding their ability to capture attention during an ongoing supervisory task. The combination of performance, eye-tracking and subjective measurements demonstrated that the best design achieved a balance between attentional power and the overhead cognitive cost to primary task performance.

Testing usability and trainability of indirect touch interaction: perspective for the next generation of air traffic control systems.

This study aims to determine whether indirect touch device can be used to interact with graphical objects displayed on another screen in an air traffic control (ATC) context. The introduction of such a device likely requires an adaptation of the sensory-motor system. The operator has to simultaneously perform movements on the horizontal plane while assessing them on the vertical plane. Thirty-six right-handed participants performed movement training with either constant or variable practice and with or without visual feedback of the displacement of their actions. Participants then performed a test phase without visual feedback. Performance improved in both practice conditions, but accuracy was higher with visual feedback. During the test phase, movement time was longer for those who had practiced with feedback, suggesting an element of dependency. However, this 'cost' of feedback did not extend to movement accuracy. Finally, participants who had received variable training performed better in the test phase, but accuracy was still unsatisfactory. We conclude that continuous visual feedback on the stylus position is necessary if tablets are to be introduced in ATC.

Motor system alterations in retired former athletes: the role of aging and concussion history.

BACKGROUND: Retired athletes with a history of sports concussions experience cognitive and motor declines with aging, and the risk of severe neurodegenerative conditions is magnified in this population. The present study investigated the effects of aging on motor system metabolism and function in former university-level athletes who sustained their last concussion several decades prior to testing. METHODS: To test the hypothesis that age and remote concussions induce functional as well as metabolic alterations of the motor system, we used proton magnetic resonance spectroscopy to detect metabolic abnormalities in the primary motor cortex and the serial reaction time task (SRTT) to evaluate motor learning. RESULTS: Our results indicate that motor learning is significantly reduced in former concussed athletes relative to controls. In addition, glutamate/H2O ratio in M1 was disproportionately reduced in concussed athletes with advancing age and was found to strongly correlate with motor learning impairments. CONCLUSION: Findings from this study provide evidence that the acquisition of a repeated motor sequence is compromised in the aging concussed brain and that its physiological underpinnings could implicate disproportionate reductions of M1 glutamate concentrations with advancing age.

Altered bidirectional plasticity and reduced implicit motor learning in concussed athletes.

Persistent motor/cognitive alterations and increased prevalence of Alzheimer's disease are known consequences of recurrent sports concussions, the most prevalent cause of mild traumatic brain injury (TBI) among youth. Animal models of TBI demonstrated that impaired learning was related to persistent synaptic plasticity suppression in the form of long-term potentiation (LTP) and depression (LTD). In humans, single and repeated concussive injuries lead to lifelong and cumulative enhancements of gamma-aminobutyric acid (GABA)-mediated inhibition, which is known to suppress LTP/LTD plasticity. To test the hypothesis that increased GABAergic inhibition after repeated concussions suppresses LTP/LTD and contributes to learning impairments, we used a paired associative stimulation (PAS) protocol to induce LTP/LTD-like effects in primary motor cortex (M1) jointly with an implicit motor learning task (serial reaction time task, SRTT). Our results indicate that repeated concussions induced persistent elevations of GABA(B)-mediated intracortical inhibition in M1, which was associated with suppressed PAS-induced LTP/LTD-like synaptic plasticity. This synaptic plasticity suppression was related to reduced implicit motor learning on the SRTT task relative to normal LTP/LTD-like synaptic plasticity in unconcussed teammates. These findings identify GABA neurotransmission alterations after repeated concussions and suggest that impaired learning after multiple concussions could at least partly be related to compromised GABA-dependent LTP/LTD synaptic plasticity.

Asymmetric binding in serial memory for verbal and spatial information.

As the number of studies showing that items can be retained as bound representations in memory increases, researchers are beginning to investigate how the different features are bound together. In the present study, we examined the relative importances of the verbal and spatial features in serial memory for visual stimuli. Participants were asked to memorize the order of series of letters presented visually in different locations on the computer screen. The results showed that manipulating the phonological similarity of the letters affected recall of their spatial locations, but that increasing the complexity of the spatial pattern had no effect on recall of the letters. This finding was observed in both order reconstruction (Exps. 1 and 2) and probe serial recall (Exps. 3 and 4), suggesting that verbal-spatial binding in serial memory for visual information is asymmetric.

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.

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.

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.

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.

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.