Background: The number of cases from the coronavirus disease 2019 (COVID-19) global pandemic has overwhelmed existing medical facilities and forced clinicians, patients, and families to make pivotal decisions with limited time and information. Main body: While machine learning (ML) methods have been previously used to augment clinical decisions, there is now a demand for "Emergency ML." Throughout the patient care pathway, there are opportunities for MLsupported decisions based on collected vitals, laboratory results, medication orders, and comorbidities. With rapidly growing datasets, there also remain important considerations when developing and validating ML models. Conclusion: This perspective highlights the utility of evidence-based prediction tools in a number of clinical settings, and how similar models can be deployed during the COVID-19 pandemic to guide hospital frontlines and healthcare administrators to make informed decisions about patient care and managing hospital volume.
Background The common marmoset (Callithrix jacchus) has been proposed as a suitable bridge between rodents and larger primates. They have been used in several types of research including auditory, vocal, visual, pharmacological and genetics studies. However, marmosets have not been used as much for behavioral studies. New Method Here we present data from training 12 adult marmosets for behavioral neuroscience studies. We discuss the husbandry, food preferences, handling, acclimation to laboratory environments and neurosurgical techniques. In this paper, we also present a custom built “scoop” and a monkey chair suitable for training of these animals. Results The animals were trained for three tasks: 4 target center-out reaching task, reaching tasks that involved following robot actions, and touch screen task. All animals learned the center-out reaching task within 1–2 weeks whereas learning reaching tasks following robot actions task took several months of behavioral training where the monkeys learned to associate robot actions with food rewards. Comparison to Existing Method We propose the marmoset as a novel model for behavioral neuroscience research as an alternate for larger primate models. This is due to the ease of handling, quick reproduction, available neuroanatomy, sensorimotor system similar to larger primates and humans, and a lissencephalic brain that can enable implantation of microelectrode arrays relatively easier at various cortical locations compared to larger primates. Conclusion All animals were able to learn behavioral tasks well and we present the marmosets as an alternate model for simple behavioral neuroscience tasks.
The ventral spinal roots contain the axons of spinal motoneurons and provide the only location in the peripheral nervous system where recorded neural activity can be assured to be motor rather than sensory. This study demonstrates recordings of single unit activity from these ventral root axons using floating microelectrode arrays (FMAs). Ventral root recordings were characterized by examining single unit yield and signal-to-noise ratios (SNR) with 32-channel FMAs implanted chronically in the L6 and L7 spinal roots of nine cats. Single unit recordings were performed for implant periods of up to 12 weeks. Motor units were identified based on active discharge during locomotion and inactivity under anesthesia. Motor unit yield and SNR were calculated for each electrode, and results were grouped by electrode site size, which were varied systematically between 25 and 160 μm to determine effects on signal quality. The unit yields and SNR did not differ significantly across this wide range of electrode sizes. Both SNR and yield decayed over time, but electrodes were able to record spikes with SNR >2 up to 12 weeks post-implant. These results demonstrate that it is feasible to record single unit activity from multiple isolated motor units with penetrating microelectrode arrays implanted chronically in the ventral spinal roots. This approach could be useful for creating a spinal nerve interface for advanced neural prostheses, and results of this study will be used to improve design of microelectrodes for chronic neural recording in the ventral spinal roots.
Current neuroprosthetics rely on stable, high quality recordings from chronically implanted microelectrode arrays (MEAs) in neural tissue. While chronic electrophysiological recordings and electrode failure modes have been reported from rodent and larger non-human primate (NHP) models, chronic recordings from the marmoset model have not been previously described. The common marmoset is a New World primate that is easier to breed and handle compared to larger NHPs and has a similarly organized brain, making it a potentially useful smaller NHP model for neuroscience studies. This study reports recording stability and signal quality of MEAs chronically implanted in behaving marmosets. Six adult male marmosets, trained for reaching tasks, were implanted with either a 16-channel tungsten microwire array (five animals) or a Pt-Ir floating MEA (one animal) in the hand-arm region of the primary motor cortex (M1) and another MEA in the striatum targeting the nucleus accumbens (NAcc). Signal stability and quality was quantified as a function of array yield (active electrodes that recorded action potentials), neuronal yield (isolated single units during a recording session), and signal-to-noise ratio (SNR). Out of 11 implanted MEAs, nine provided functional recordings for at least three months, with two arrays functional for 10 months. In general, implants had high yield, which remained stable for up to several months. However, mechanical failure attributed to MEA connector was the most common failure mode. In the longest implants, signal degradation occurred, which was characterized by gradual decline in array yield, reduced number of isolated single units, and changes in waveform shape of action potentials. This work demonstrates the feasibility of longterm recordings from MEAs implanted in cortical and deep brain structures in the marmoset model. The ability to chronically record cortical signals for neural prosthetics applications in the common marmoset extends the potential of this model in neural interface research.
Background The autonomic nervous system (ANS) maintains physiological homeostasis in various organ systems via parasympathetic and sympathetic branches. ANS function is altered in common diffuse and focal conditions and heralds the beginning of environmental and disease stresses. Reliable, sensitive, and quantitative biomarkers, first defined in healthy participants, could discriminate among clinically useful changes in ANS function. This framework combines controlled autonomic testing with feature extraction during physiological responses. Methods Twenty-one individuals were assessed in two morning and two afternoon sessions over two weeks. Each session included five standard clinical tests probing autonomic function: squat test, cold pressor test, diving reflex test, deep breathing, and Valsalva maneuver. Noninvasive sensors captured continuous electrocardiography, blood pressure, breathing, electrodermal activity, and pupil diameter. Heart rate, heart rate variability, mean arterial pressure, electrodermal activity, and pupil diameter responses to the perturbations were extracted, and averages across participants were computed. A template matching algorithm calculated scaling and stretching features that optimally fit the average to an individual response. These features were grouped based on test and modality to derive sympathetic and parasympathetic indices for this healthy population. Results A significant positive correlation (p = 0.000377) was found between sympathetic amplitude response and body mass index. Additionally, longer duration and larger amplitude sympathetic and longer duration parasympathetic responses occurred in afternoon testing sessions; larger amplitude parasympathetic responses occurred in morning sessions. Conclusions These results demonstrate the robustness and sensitivity of an algorithmic approach to extract multimodal responses from standard tests. This novel method of quantifying ANS function can be used for early diagnosis, measurement of disease progression, or treatment evaluation. Trial registration This study registered with Clinicaltrials.gov, identifier NCT04100486. Registered September 24, 2019, https://www.clinicaltrials.gov/ct2/show/NCT04100486.
Objective: Spinal cord injury (SCI) remains an ailment with no comprehensive cure, and affected patients suffer from a greatly diminished quality of life. This large population could significantly benefit from prosthetic technologies to replace missing limbs, reanimate nonfunctional limbs, and enable new modes of technologies to restore muscle control and function. While cortically driven brain machine interfaces (BMIs) have achieved great success in interfacing with an external device to restore lost functions, interfacing with the spinal cord can provide an additional site to record motor control signals, which can have its own advantages, albeit challenges from using a smaller non-human primate (NHP) model. The goal of this study is to develop such a spinal cord neural interface to record motor signals from the high cervical levels of the spinal cord in a common marmoset (Callithrix jacchus) model. Approach and MainResults: Detailed methods are discussed for this smaller NHP model that includes behavioral training, surgical methods for electrode placement, connector placement and wire handling, electrode specifications and modifications for accessing high cervical level interneurons and motorneurons. The study also discusses the methods and challenges involved in behavioral multi-channel extracellular recording from the marmoset spinal cord, including the major recording failure mechanisms encountered during the study.Significance: Marmosets provide a good step between rodent and larger NHP models due to their small size, ease of handling, cognitive abilities, and similarities to other primate motor systems. The study shows the feasibility of recording spinal cord signals and using marmosets as a smaller NHP model in behavioral neuroscience studies. Interfacing with the spinal cord in chronically implanted animals can provide useful information about how motor control signals within the spinal cord are transformed to cause limb movements.
The autonomic nervous system (ANS), which maintains physiological homeostasis in various organ systems via parasympathetic and sympathetic branches, is altered in common diffuse and focal conditions. Sensitive, quantitative biomarkers could detect changes in ANS function, first here in healthy participants and eventually in patients displaying dysautonomia. This framework combines controlled autonomic testing with feature extraction from physiological responses. Twenty-one individuals were assessed in two morning and two afternoon sessions over two weeks. Each session included five standard clinical tests probing autonomic function: squat test, cold pressor test, diving reflex test, deep breathing, and Valsalva maneuver. Noninvasive sensors captured continuous electrocardiography, blood pressure, breathing, electrodermal activity, and pupil diameter. Heart rate, heart rate variability, mean arterial pressure, electrodermal activity, and pupil diameter responses to the perturbations were extracted, and averages across participants were computed. A template matching algorithm calculated scaling and stretching features that optimally fit the average to an individual response. These features were grouped based on test and modality to derive sympathetic and parasympathetic indices for this healthy population. A significant positive correlation (p = 0.000377) was found between sympathetic amplitude response and body mass index. Additionally, longer duration and larger amplitude sympathetic and longer duration parasympathetic responses occurred in afternoon testing sessions; larger amplitude parasympathetic responses occurred in morning sessions. These results demonstrate the robustness and sensitivity of an algorithmic approach to extract multimodal responses from standard tests. This novel method of quantifying ANS function can be used for early diagnosis, measurement of disease progression, or treatment evaluation.
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