An approach for long-term, multi-probe Neuropixels recordings in unrestrained rats.
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ABSTRACT:
SUBMITTER: Luo TZ
PROVIDER: S-EPMC7721443 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Measuring the dynamics of neural processing across time scales requires following the spiking of thousands of individual neurons over milliseconds and months. To address this need, we introduce the Neuropixels 2.0 probe together with newly designed analysis algorithms. The probe has more than 5000 sites and is miniaturized to facilitate chronic implants in small mammals and recording during unrestrained behavior. High-quality recordings over long time scales were reliably obtained in mice and rats in six laboratories. Improved site density and arrangement combined with newly created data processing methods enable automatic post hoc correction for brain movements, allowing recording from the same neurons for more than 2 months. These probes and algorithms enable stable recordings from thousands of sites during free behavior, even in small animals such as mice.
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Project description:Extracellular recordings of electrical activity in freely moving rats are fundamental to understand brain function in health and disease. Such recordings require a small-size, lightweight device that includes movable electrodes (microdrive) to record either a new set of neurons every day or the same set of neurons over time. Ideally, microdrives should be easy to implant, allowing precise and smooth displacement of electrodes. The main caveat of most commercially available microdrives is their relatively short half-life span, in average ranging from weeks to a month. For most experiments, recording days-weeks is sufficient, but when the experiment depends on training animals for several months, it is crucial to develop new approaches. Here, we present a low-cost, reusable, and reimplantable device design as a solution to extend chronic recordings to long-term. This device is composed of a baseplate that is permanently fixed to the rodent's skull, as well as a reusable and replaceable microdrive that can be attached and detached from the baseplate, allowing its implantation and reimplantation. Reimplanting this microdrive is particularly convenient when no clear neuronal signal is present, or when the signal gradually decays across days. Our microdrive incorporates a mechanism for moving a 16 tungsten-wire bundle within a small (?15 mm3) lightweight device (?4 g). We present details of the design, manufacturing, and assembly processes. As a proof of concept, we show that recordings of the nucleus accumbens core (NAcc) in a freely behaving rat are stable over a month. Additionally, during a lever-press task, we found, as expected, that NAc single-unit activity was associated with rewarded lever presses. Furthermore, we also show that NAc shell (NAcSh) responses evoked by freely licking for sucrose, consistent with our previously published results, were conserved from a first implant to a second microdrive reimplant in the same rat, notably showing reimplantation is possible without overtly affecting the functional responses of the area of interest. In sum, here we present a novel microdrive design (low-cost, small size, and light weight) that can be used for long-term chronic recordings and reimplanted in freely behaving rats.
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Project description:Electromyography is a non-invasive method widely used to map muscle activation. For decades, it was commonly accepted that dry metallic electrodes establish poor electrode-skin contact, making them impractical for skin electromyography applications. Gelled electrodes are therefore the standard in electromyography with their use confined, almost entirely, to laboratory settings. Here we present novel dry electrodes, exhibiting outstanding electromyography recording along with excellent user comfort. The electrodes were realized using screen-printing of carbon ink on a soft support. The conformity of the electrodes helps establish direct contact with the skin, making the use of a gel superfluous. Plasma polymerized 3,4-ethylenedioxythiophene was used to enhance the impedance of the electrodes. Cyclic voltammetry measurements revealed an increase in electrode capacitance by a factor of up to 100 in wet conditions. Impedance measurements show a reduction factor of 10 in electrode impedance on human skin. The suitability of the electrodes for long-term electromyography recordings from the hand and from the face is demonstrated. The presented electrodes are ideally-suited for many applications, such as brain-machine interfacing, muscle diagnostics, post-injury rehabilitation, and gaming.
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Project description:Understanding the neural basis of human movement in naturalistic scenarios is critical for expanding neuroscience research beyond constrained laboratory paradigms. Here, we describe our Annotated Joints in Long-term Electrocorticography for 12 human participants (AJILE12) dataset, the largest human neurobehavioral dataset that is publicly available; the dataset was recorded opportunistically during passive clinical epilepsy monitoring. AJILE12 includes synchronized intracranial neural recordings and upper body pose trajectories across 55 semi-continuous days of naturalistic movements, along with relevant metadata, including thousands of wrist movement events and annotated behavioral states. Neural recordings are available at 500 Hz from at least 64 electrodes per participant, for a total of 1280 hours. Pose trajectories at 9 upper-body keypoints were estimated from 118 million video frames. To facilitate data exploration and reuse, we have shared AJILE12 on The DANDI Archive in the Neurodata Without Borders (NWB) data standard and developed a browser-based dashboard.
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Project description:OBJECTIVE:To determine the incidence of clinically relevant arrhythmias in refractory focal epilepsy and to assess the potential of postictal arrhythmias as risk markers for sudden unexpected death in epilepsy (SUDEP). METHODS:We recruited people with refractory focal epilepsy without signs of ictal asystole and who had at least one focal seizure per month and implanted a loop recorder with 2-year follow-up. The devices automatically record arrhythmias. Subjects and caregivers were instructed to make additional peri-ictal recordings. Clinically relevant arrhythmias were defined as asystole ? 6 seconds; atrial fibrillation < 55 beats per minute (bpm), or > 200 bpm and duration > 30 seconds; persistent sinus bradycardia < 40 bpm while awake; and second- or third-degree atrioventricular block and ventricular tachycardia/fibrillation. We performed 12-lead electrocardiography (ECG) and tilt table testing to identify non-seizure-related causes of asystole. RESULTS:We included 49 people and accumulated 1060 months of monitoring. A total of 16 474 seizures were reported, of which 4679 were captured on ECG. No clinically relevant arrhythmias were identified. Three people had a total of 18 short-lasting (<6 seconds) periods of asystole, resulting in an incidence of 2.91 events per 1000 patient-months. None of these coincided with a reported seizure; one was explained by micturition syncope. Other non-clinically relevant arrhythmias included paroxysmal atrial fibrillation (n = 2), supraventricular tachycardia (n = 1), and sinus tachycardia with a right bundle branch block configuration (n = 1). SIGNIFICANCE:We found no clinically relevant arrhythmias in people with refractory focal epilepsy during long-term follow-up. The absence of postictal arrhythmias does not support the use of loop recorders in people at high SUDEP risk.
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Project description:ObjectiveWe report on temporally clustered seizures detected from continuous long-term ambulatory human electroencephalographic data. The objective was to investigate short-term seizure clustering, which we have termed bursting, and consider implications for patient care, seizure prediction, and evaluating therapies.MethodsChronic ambulatory intracranial electroencephalography (EEG) data collected for the purpose of seizure prediction were annotated to identify seizure events. A detection algorithm was used to identify bursts of events. Burst events were compared to nonburst events to evaluate event dispersion, duration and dynamics.ResultsBursts of seizures were present in 6 of 15 subjects, and detections were consistent over long-term monitoring (>2 years). Subjects with bursts of seizures had highly overdispersed seizure rates, compared to other subjects. There was a complicated relationship between bursts and clinical seizures, although bursts were associated with multimodal distributions of seizure duration, and poorer predictive outcomes. For three subjects, bursts demonstrated distinctive preictal dynamics compared to clinical seizures.SignificanceWe have previously hypothesized that there are distinct physiologic pathways underlying short- and long-duration seizures. Herein we show that burst seizures fall almost exclusively within the short population of seizure durations; however, a short duration event was not sufficient to induce or imply bursting. We can therefore conclude that in addition to distinct mechanisms underlying seizure duration, there are separate factors regulating bursts of seizures. We show that bursts were a robust phenomenon in our patient cohort, which were consistent with overdispersed seizure rates, suggesting long-memory dynamics.
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Project description:Rodent models of cognitive behavior have greatly contributed to our understanding of human neuropsychiatric disorders. However, to elucidate the neurobiological underpinnings of such disorders or impairments, animal models are more useful when paired with methods for measuring brain function in awake, behaving animals. Standard tools used for systems-neuroscience level investigations are not optimized for large-scale and high-throughput behavioral battery testing due to various factors including cost, time, poor longevity, and selective targeting limited to measuring only a few brain regions at a time. Here we describe two different "user-friendly" methods for building extracellular electrophysiological probes that can be used to measure either single units or local field potentials in rats performing cognitive tasks. Both probe designs leverage several readily available, yet affordable, commercial products to facilitate ease of production and offer maximum flexibility in terms of brain-target locations that can be scalable (32-64 channels) based on experimental needs. Our approach allows neural activity to be recorded simultaneously with behavior and compared between micro (single unit) and more macro (local field potentials) levels of brain activity in order to gain a better understanding of how local brain regions and their connected networks support cognitive functions in rats. We believe our novel probe designs make collecting electrophysiology data easier and will begin to fill the gap in knowledge between basic and clinical research.
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Project description:Neural interfaces which allow long-term recordings in deep brain structures in awake freely moving animals have the potential of becoming highly valuable tools in neuroscience. However, the recording quality usually deteriorates over time, probably at least partly due to tissue reactions caused by injuries during implantation, and subsequently micro-forces due to a lack of mechanical compliance between the tissue and neural interface. To address this challenge, we developed a gelatin embedded neural interface comprising highly flexible electrodes and evaluated its long term recording properties. Bundles of ultrathin parylene C coated platinum electrodes (N = 29) were embedded in a hard gelatin based matrix shaped like a needle, and coated with Kollicoat™ to retard dissolution of gelatin during the implantation. The implantation parameters were established in an in vitro model of the brain (0.5% agarose). Following a craniotomy in the anesthetized rat, the gelatin embedded electrodes were stereotactically inserted to a pre-target position, and after gelatin dissolution the electrodes were further advanced and spread out in the area of the subthalamic nucleus (STN). The performance of the implanted electrodes was evaluated under anesthesia, during 8 weeks. Apart from an increase in the median-noise level during the first 4 weeks, the electrode impedance and signal-to-noise ratio of single-units remained stable throughout the experiment. Histological postmortem analysis confirmed implantation in the area of STN in most animals. In conclusion, by combining novel biocompatible implantation techniques and ultra-flexible electrodes, long-term neuronal recordings from deep brain structures with no significant deterioration of electrode function were achieved.
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Project description:Skeletal (voluntary) muscle is the most abundant tissue in the body, thus making it an important biomedical research subject. Studies of neuromuscular transmission, including disorders of ion channels or receptors in autoimmune or genetic neuromuscular disorders, require high-spatial-resolution measurement techniques and an ability to acquire repeated recordings over time in order to track pharmacological interventions. Preclinical techniques for studying diseases of neuromuscular transmission can be enhanced by physiologic ex vivo models of tissue-tissue and cell-cell interactions. Here, we present a method, which allows tracking the development of primary skeletal muscle cells from myoblasts into mature contracting myotubes over more than 2 months. In contrast to most previous studies, the myotubes did not detach from the surface but instead formed functional networks between the myotubes, whose electrical signals were observed over the entire culturing period. Primary cultures of mouse myoblasts differentiated into contracting myotubes on a chip that contained an array of 26,400 platinum electrodes at a density of 3,265 electrodes per mm2. Our ability to track extracellular action potentials at subcellular resolution enabled study of skeletal muscle development and kinetics, modes of spiking and spatio-temporal relationships between muscles. The developed system in turn enables creation of a novel electrophysiological platform for establishing ex vivo disease models.
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Project description:BackgroundRemarkable work has been recently introduced to enhance the usage of Electromyography (EMG) signals in operating prosthetic arms. Despite the rapid advancements in this field, providing a reliable, naturalistic myoelectric prosthesis remains a significant challenge. Other challenges include the limited number of allowed movements, lack of simultaneous, continuous control and the high computational power that could be needed for accurate decoding. In this study, we propose an EMG-based multi-Kalman filter approach to decode arm kinematics; specifically, the elbow angle (θ), wrist joint horizontal (X) and vertical (Y) positions in a continuous and simultaneous manner.ResultsTen subjects were examined from which we recorded arm kinematics and EMG signals of the biceps, triceps, lateral and anterior deltoid muscles corresponding to a randomized set of movements. The performance of the proposed decoder is assessed using the correlation coefficient (CC) and the normalized root-mean-square error (NRMSE) computed between the actual and the decoded kinematic. Results demonstrate that when training and testing the decoder using same-subject data, an average CC of 0.68 ± 0.1, 0.67 ± 0.12 and 0.64 ± 0.11, and average NRMSE of 0.21 ± 0.06, 0.18 ± 0.03 and 0.24 ± 0.07 were achieved for θ, X, and Y, respectively. When training the decoder using the data of one subject and decoding the data of other subjects, an average CC of 0.61 ± 0.19, 0.61 ± 0.16 and 0.48 ± 0.17, and an average NRMSE of 0.23 ± 0.07, 0.2 ± 0.05 and 0.38 ± 0.15 were achieved for θ, X, and Y, respectively.ConclusionsThese results suggest the efficacy of the proposed approach and indicates the possibility of obtaining a subject-independent decoder.
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