Silencing hippocampal CA2 reduces behavioral flexibility in spatial learning.

The hippocampus is a key structure involved in learning and remembering spatial information. However, the extent to which hippocampal region CA2 is involved in these processes remains unclear. Here, we show that chronically silencing dorsal CA2 impairs reversal learning in the Morris water maze. After platform relocation, CA2-silenced mice spent more time in the vicinity of the old platform location and less time in the new target quadrant. Accordingly, behavioral strategy analysis revealed increased perseverance in navigating to the old location during the first day and an increased use of non-spatial strategies during the second day of reversal learning. Confirming previous indirect indications, these results demonstrate that CA2 is recruited when mice must flexibly adapt their behavior as task contingencies change. We discuss how these findings can be explained by recent theories of CA2 function and outline testable predictions to understand the underlying neural mechanisms. Demonstrating a direct involvement of CA2 in spatial learning, this work lends further support to the notion that CA2 plays a fundamental role in hippocampal information processing.

Impact of Time to Intervention on Catheter-Directed Therapy for Pulmonary Embolism.

Cather-directed therapies (CDTs) are an evolving therapeutic option for patients with intermediate-risk pulmonary embolism (PE). Although many techniques have been studied, there is limited evidence for the impact of timing of intervention on patient outcomes. Our objective was to assess the association between time to CDT in patients presenting with PE on patient-related outcomes such as length of stay (LOS) and mortality. DESIGN: Retrospective cohort study. SETTING: Single academic center. PATIENTS: We identified patients for which the PE response team had been activated from January 2014 to October 2021. Patients were split into two cohorts depending on whether they went to CDT less than 24 hours from admission (early) versus greater than 24 hours (late). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data on demographics, timing of interventions, pulmonary hemodynamics, and outcomes were collected. Sixty-four patients were included in analysis. Thirty-nine (63.8%) underwent their procedure less than 24 hours from admission, whereas 25 (36.2%) underwent the procedure after 24 hours. The time from admission to CDT was 15.9 hours (9.1-20.3 hr) in the early group versus 33.4 (27.9-41) in the late group (p ≤ 0.001). There was a greater decrease in pulmonary artery systolic pressure after intervention in the early cohort (14 mm Hg [6-20 mm Hg] vs 6 mm Hg [1-10 mm Hg]; p = 0.022). Patients who received earlier intervention were found to have shorter hospital LOS (4 vs 7 d; p = 0.038) and ICU LOS (3 vs 5 d; p = 0.004). There was no difference in inhospital mortality between the groups (17.9% vs 12%; p = 0.523). CONCLUSIONS: Patients who underwent CDT within 24 hours of admission were more likely to have shorter hospital and ICU LOS. The magnitude of change in LOS between the two cohorts was not fully explained by the difference in time to CDT. There were modest improvements in pulmonary hemodynamics in the patients who underwent CDT earlier.

Brian2Loihi: An emulator for the neuromorphic chip Loihi using the spiking neural network simulator Brian.

Developing intelligent neuromorphic solutions remains a challenging endeavor. It requires a solid conceptual understanding of the hardware's fundamental building blocks. Beyond this, accessible and user-friendly prototyping is crucial to speed up the design pipeline. We developed an open source Loihi emulator based on the neural network simulator Brian that can easily be incorporated into existing simulation workflows. We demonstrate errorless Loihi emulation in software for a single neuron and for a recurrently connected spiking neural network. On-chip learning is also reviewed and implemented, with reasonable discrepancy due to stochastic rounding. This work provides a coherent presentation of Loihi's computational unit and introduces a new, easy-to-use Loihi prototyping package with the aim to help streamline conceptualization and deployment of new algorithms.

Neuromodulator-dependent synaptic tagging and capture retroactively controls neural coding in spiking neural networks.

Events that are important to an individual's life trigger neuromodulator release in brain areas responsible for cognitive and behavioral function. While it is well known that the presence of neuromodulators such as dopamine and norepinephrine is required for memory consolidation, the impact of neuromodulator concentration is, however, less understood. In a recurrent spiking neural network model featuring neuromodulator-dependent synaptic tagging and capture, we study how synaptic memory consolidation depends on the amount of neuromodulator present in the minutes to hours after learning. We find that the storage of rate-based and spike timing-based information is controlled by the level of neuromodulation. Specifically, we find better recall of temporal information for high levels of neuromodulation, while we find better recall of rate-coded spatial patterns for lower neuromodulation, mediated by the selection of different groups of synapses for consolidation. Hence, our results indicate that in minutes to hours after learning, the level of neuromodulation may alter the process of synaptic consolidation to ultimately control which type of information becomes consolidated in the recurrent neural network.

Impact of pulmonary embolism response teams on acute pulmonary embolism: a systematic review and meta-analysis.

BACKGROUND: The impact of pulmonary embolism response teams (PERTs) on treatment choice and outcomes of patients with acute pulmonary embolism (PE) is still uncertain. OBJECTIVE: To determine the effect of PERTs in the management and outcomes of patients with PE. METHODS: PubMed, Embase, Web of Science, CINAHL, WorldWideScience and MedRxiv were searched for original articles reporting PERT patient outcomes from 2009. Data were analysed using a random effects model. RESULTS: 16 studies comprising 3827 PERT patients and 3967 controls met inclusion criteria. The PERT group had more patients with intermediate and high-risk PE (66.2%) compared to the control group (48.5%). Meta-analysis demonstrated an increased risk of catheter-directed interventions, systemic thrombolysis and surgical embolectomy (odds ratio (OR) 2.10, 95% confidence interval (CI) 1.74-2.53; p<0.01), similar bleeding complications (OR 1.10, 95% CI 0.88-1.37) and decreased utilisation of inferior vena cava (IVC) filters (OR 0.71, 95% CI 0.58-0.88; p<0.01) in the PERT group. Furthermore, there was a nonsignificant trend towards decreased mortality (OR 0.87, 95% CI 0.71-1.07; p=0.19) with PERTs. CONCLUSIONS: The PERT group showed an increased use of advanced therapies and a decreased utilisation of IVC filters. This was not associated with increased bleeding. Despite comprising more severe PE patients, there was a trend towards lower mortality in the PERT group.

Inhaled pulmonary vasodilators are not associated with improved gas exchange in mechanically ventilated patients with COVID-19: A retrospective cohort study.

PURPOSE: Measure the effect of inhaled pulmonary vasodilators on gas exchange in mechanically ventilated patients with COVID-19. METHODS: A retrospective observational cohort study at three New York University Hospitals was performed including eighty-four mechanically ventilated SARS Cov-2 nasopharyngeal PCR positive patients, sixty nine treated with inhaled nitric oxide (iNO) and fifteen with inhaled epoprostenol (iEPO). The primary outcomes were change in PAO2:FIO2 ratio, oxygenation Index (OI), and ventilatory ratio (VR) after initiation of inhaled pulmonary vasodilators. RESULTS: There was no significant change in PAO2:FIO2ratio after initiation of iNO (mean - 4.1, 95% CI -17.3-9.0, P = 0.54) or iEPO (mean - 3.4, 95% CI -19.7-12.9, P = 0.66), in OI after initiation of iNO (mean 2.1, 95% CI-0.04-4.2, P = 0.054) or iEPO (mean - 3.4, 95% CI -19.7-12.9, P = 0.75), or in VR after initiation of iNO (mean 0.17, 95% CI -0.03-0.36, P = 0.25) or iEPO (mean 0.33, 95% CI -0.0847-0.74, P = 0.11). PAO2:FIO2, OI and VR did not significantly change over a five day period starting the day prior to drug initiation in patients who received either iNO or iEPO assessed with a fixed effects model. CONCLUSION: Inhaled pulmonary vasodilators were not associated with significant improvement in gas exchange in mechanically ventilated patients with COVID-19.

CA2 beyond social memory: Evidence for a fundamental role in hippocampal information processing.

Hippocampal region CA2 has received increased attention due to its importance in social recognition memory. While its specific function remains to be identified, there are indications that CA2 plays a major role in a variety of situations, widely extending beyond social memory. In this targeted review, we highlight lines of research which have begun to converge on a more fundamental role for CA2 in hippocampus-dependent memory processing. We discuss recent proposals that speak to the computations CA2 may perform within the hippocampal circuit.

A local circadian clock for memory?

The master clock, suprachiasmatic nucleus, is believed to control peripheral circadian oscillators throughout the brain and body. However, recent data suggest there is a circadian clock involved in learning and memory, potentially housed in the hippocampus, which is capable of acting independently of the master clock. Curiously, the hippocampal clock appears to be influenced by the master clock and by hippocampal dependent learning, while under certain conditions it may also revert to its endogenous circadian rhythm. Here we propose a mechanism by which the hippocampal clock could locally determine the nature of its entrainment. We introduce a novel theoretical framework, inspired by but extending beyond the hippocampal memory clock, which provides a new perspective on how circadian clocks throughout the brain coordinate their rhythms. Importantly, a local clock for memory would suggest that hippocampal-dependent learning at the same time every day should improve memory, opening up a range of possibilities for non-invasive therapies to alleviate the detrimental effects of circadian rhythm disruption on human health.

Successful use of an automated proning system to achieve prone positioning in a patient with severe ARDS requiring veno-venous ECMO.

A morbidly obese middle aged woman in her 40's presented to another hospital with methicillin resistant staphylococcus aureus pneumonia and subsequently developed severe acute respiratory distress syndrome. Her oxygenation demonstrated no improvement with low tidal volume ventilation, paralysis, or prostagladin therapy. She was unable to be manually proned secondary to her habitus. She was subsequently transferred to our facility, where she was initiated on VV-ECMO. Maximal flow through the ECMO circuit was inadequate for oxygenation given significant systemic shunt through her native lungs. In order to optimize lung protective ventilation and treat ARDS, we used an automated kinetic system (Rotoprone Therapy System) to prone the patient. To our knowledge, this is the first description in the literature of using an automated proning system with an ECMO circuit in place. This report describes the technique we used to safely perform axial rotations for two days with fewer providers required than manual proning.

Robust Trajectory Generation for Robotic Control on the Neuromorphic Research Chip Loihi.

Neuromorphic hardware has several promising advantages compared to von Neumann architectures and is highly interesting for robot control. However, despite the high speed and energy efficiency of neuromorphic computing, algorithms utilizing this hardware in control scenarios are still rare. One problem is the transition from fast spiking activity on the hardware, which acts on a timescale of a few milliseconds, to a control-relevant timescale on the order of hundreds of milliseconds. Another problem is the execution of complex trajectories, which requires spiking activity to contain sufficient variability, while at the same time, for reliable performance, network dynamics must be adequately robust against noise. In this study we exploit a recently developed biologically-inspired spiking neural network model, the so-called anisotropic network. We identified and transferred the core principles of the anisotropic network to neuromorphic hardware using Intel's neuromorphic research chip Loihi and validated the system on trajectories from a motor-control task performed by a robot arm. We developed a network architecture including the anisotropic network and a pooling layer which allows fast spike read-out from the chip and performs an inherent regularization. With this, we show that the anisotropic network on Loihi reliably encodes sequential patterns of neural activity, each representing a robotic action, and that the patterns allow the generation of multidimensional trajectories on control-relevant timescales. Taken together, our study presents a new algorithm that allows the generation of complex robotic movements as a building block for robotic control using state of the art neuromorphic hardware.

Selective neuromodulation and mutual inhibition within the CA3-CA2 system can prioritize sequences for replay.

To make optimal use of previous experiences, important neural activity sequences must be prioritized during hippocampal replay. Integrating insights about the interplay between CA3 and CA2, we propose a conceptual framework that allows the two regions to control which sequences are reactivated. We suggest that neuromodulatory-gated plasticity and mutual inhibition enable discrete assembly sequences in both regions to support each other while suppressing competing sequences. This perspective provides a coherent interpretation for a variety of seemingly disconnected functional properties of CA2 and paves the way for a more general understanding of CA2.

Development and Evaluation of a Cognitive Aid Booklet for Use in Rapid Response Scenarios.

INTRODUCTION: Rapid response teams (RRTs) have become ubiquitous among hospitals in North America, despite lack of robust evidence supporting their effectiveness. Many RRTs do not yet use cognitive aids during these high-stakes, low-frequency scenarios, and there are no standardized cognitive aids that are widely available for RRTs on medicine patients. We sought to design an emergency manual to improve resident performance in common RRT calls. METHODS: Residents from the New York University School of Medicine Internal Medicine Residency Program were asked to volunteer for the study. The intervention group was provided with a 2-minute scripted informational session on cognitive aids as well as access to a cognitive aid booklet, which they were allowed to use during the simulation. RESULTS: Resident performance was recorded and scored by a physician who was blinded to the purpose of the study using a predefined scoring card. Residents in the intervention group performed significantly better in the simulated RRT, by overall score (mean score = 7.33/10 and 6.26/10, respectively, P = 0.02), and by performance on the two critical interventions, giving the correct dose of naloxone (89% and 39%, respectively, P < 0.001) and checking the patient's blood glucose level (93% and 52%, respectively, P = 0.001). CONCLUSIONS: In a simulated scenario of opiate overdose, internal medicine residents who used a cognitive aid performed better on critical tasks than those residents who did not have a cognitive aid. The use of an appropriately designed cognitive aid with sufficient education could improve performance in critical scenarios.

Rats in a levered T-maze task show evidence of time-place discriminations in two different measures.

It is difficult for rats to learn to go to an arm of a T-maze to receive food that is dependent on the time of day, unless the amount of food in each daily session is different. In the same task, rats show evidence of time-place discriminations if they are required to press levers in the arms of the T-maze, but learning is only evident when the first lever press is considered, and not the first arm visited. These data suggest that rats struggle to use time as a discriminative stimulus unless the rewards/events differ in some dimension, or unless the goal locations can be visited prior to making a response. If both of these conditions are met in the same task, it might be possible to compare time-place learning in two different measures that essentially indicate performance before and after entering the arms of the T-maze. In the present study, we investigated time-place learning in rats with a levered T-maze task in which the amounts of food varied depending on the time of day. The first arm choices and first lever presses both indicated that the rats had acquired time-place discriminations, and both of these measures became significantly different from chance during the same block. However, there were subtle differences between the two measures, which suggest that time-place discrimination is aided by visiting the goal locations.

In a daily time-place learning task, time is only used as a discriminative stimulus if each daily session is associated with a distinct spatial location.

It is difficult for rats to acquire daily time-place (TP) learning tasks. One theory suggests that rats do not use time of day as a stimulus signaling a specific response. In the present study, we tested rats' ability to use time of day as a discriminative stimulus. A fixed-interval procedure was used in which one lever provided reinforcement on a FI-5-s schedule in morning sessions, and the same lever provided reinforcement on a FI-30-s schedule in afternoon sessions. Because only one place was used in this paradigm, the rats could only use time of day to acquire the task. Mean responses during the first 5 s of the first trial in each session indicated that the rats did not discriminate between the two sessions. In Phase II, a different lever location was used for each of the two daily sessions, which meant that both spatial and temporal information could be used to acquire the task. The rats readily acquired the task in this phase, and probe trials indicated that the rats were using a combination of spatial and temporal information to discriminate between the two different trial types. When the spatial cue was removed in Phase III, rats no longer discriminated the two sessions, suggesting that time can only be used as a discriminative stimulus when each daily session is associated with a distinct spatial location.

Differential effects of reciprocity and attitude similarity across long- versus short-term mating contexts.

Participants were 24 male and 32 female undergraduate and graduate students whom the authors recruited for an examination of the effects of attitude similarity and reciprocity on the degree of attraction toward potential mates. The authors examined the effects of these 2 variables on degree of liking in long-term and short-term contexts. The authors administered a vignette about a bogus stranger to each participant, varying the stranger's attitude similarity with and liking of the participant. The authors enclosed the vignette in a folder that described the stranger as having either very similar or very different attitudes from the participant and that included a passage that notified the participant that the stranger either likes or does not like him or her. The dependent variables included 4 indexes of the extent to which participants reported liking the bogus stranger: a scale that measured short-term mating items, a scale that measured long-term mating items, a degree-of-liking scale, and a behavioral-intention item. Across these 4 attraction-relevant dependent variables, the authors found significant main effects of the reciprocity variable. Also, the authors found a significant main effect of attitude similarity on the likability measure. The authors found significant main effects of reciprocity in a long-term mating context and a short-term mating context.