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Cell Reports May 2023There are vast gaps in our understanding of the organization and operation of the human nervous system at the level of individual neurons and their networks. Here, we...
There are vast gaps in our understanding of the organization and operation of the human nervous system at the level of individual neurons and their networks. Here, we report reliable and robust acute multichannel recordings using planar microelectrode arrays (MEAs) implanted intracortically in awake brain surgery with open craniotomies that grant access to large parts of the cortical hemisphere. We obtained high-quality extracellular neuronal activity at the microcircuit, local field potential level and at the cellular, single-unit level. Recording from the parietal association cortex, a region rarely explored in human single-unit studies, we demonstrate applications on these complementary spatial scales and describe traveling waves of oscillatory activity as well as single-neuron and neuronal population responses during numerical cognition, including operations with uniquely human number symbols. Intraoperative MEA recordings are practicable and can be scaled up to explore cellular and microcircuit mechanisms of a wide range of human brain functions.
Topics: Humans; Microelectrodes; Neurons; Cerebral Cortex; Cognition; Hemispherectomy
PubMed: 37141095
DOI: 10.1016/j.celrep.2023.112467 -
IEEE Transactions on Bio-medical... Jul 2021Individuals with neurological disease or injury such as amyotrophic lateral sclerosis, spinal cord injury or stroke may become tetraplegic, unable to speak or even...
OBJECTIVE
Individuals with neurological disease or injury such as amyotrophic lateral sclerosis, spinal cord injury or stroke may become tetraplegic, unable to speak or even locked-in. For people with these conditions, current assistive technologies are often ineffective. Brain-computer interfaces are being developed to enhance independence and restore communication in the absence of physical movement. Over the past decade, individuals with tetraplegia have achieved rapid on-screen typing and point-and-click control of tablet apps using intracortical brain-computer interfaces (iBCIs) that decode intended arm and hand movements from neural signals recorded by implanted microelectrode arrays. However, cables used to convey neural signals from the brain tether participants to amplifiers and decoding computers and require expert oversight, severely limiting when and where iBCIs could be available for use. Here, we demonstrate the first human use of a wireless broadband iBCI.
METHODS
Based on a prototype system previously used in pre-clinical research, we replaced the external cables of a 192-electrode iBCI with wireless transmitters and achieved high-resolution recording and decoding of broadband field potentials and spiking activity from people with paralysis. Two participants in an ongoing pilot clinical trial completed on-screen item selection tasks to assess iBCI-enabled cursor control.
RESULTS
Communication bitrates were equivalent between cabled and wireless configurations. Participants also used the wireless iBCI to control a standard commercial tablet computer to browse the web and use several mobile applications. Within-day comparison of cabled and wireless interfaces evaluated bit error rate, packet loss, and the recovery of spike rates and spike waveforms from the recorded neural signals. In a representative use case, the wireless system recorded intracortical signals from two arrays in one participant continuously through a 24-hour period at home.
SIGNIFICANCE
Wireless multi-electrode recording of broadband neural signals over extended periods introduces a valuable tool for human neuroscience research and is an important step toward practical deployment of iBCI technology for independent use by individuals with paralysis. On-demand access to high-performance iBCI technology in the home promises to enhance independence and restore communication and mobility for individuals with severe motor impairment.
Topics: Brain; Brain-Computer Interfaces; Hand; Humans; Microelectrodes; Quadriplegia
PubMed: 33784612
DOI: 10.1109/TBME.2021.3069119 -
Biomaterials Oct 2022Brain computer interfaces (BCIs), including penetrating microelectrode arrays, enable both recording and stimulation of neural cells. However, device implantation...
Brain computer interfaces (BCIs), including penetrating microelectrode arrays, enable both recording and stimulation of neural cells. However, device implantation inevitably causes injury to brain tissue and induces a foreign body response, leading to reduced recording performance and stimulation efficacy. Astrocytes in the healthy brain play multiple roles including regulating energy metabolism, homeostatic balance, transmission of neural signals, and neurovascular coupling. Following an insult to the brain, they are activated and gather around the site of injury. These reactive astrocytes have been regarded as one of the main contributors to the formation of a glial scar which affects the performance of microelectrode arrays. This study investigates the dynamics of astrocytes within the first 2 weeks after implantation of an intracortical microelectrode into the mouse brain using two-photon microscopy. From our observation astrocytes are highly dynamic during this period, exhibiting patterns of process extension, soma migration, morphological activation, and device encapsulation that are spatiotemporally distinct from other glial cells, such as microglia or oligodendrocyte precursor cells. This detailed characterization of astrocyte reactivity will help to better understand the tissue response to intracortical devices and lead to the development of more effective intervention strategies to improve the functional performance of neural interfacing technology.
Topics: Animals; Astrocytes; Electrodes, Implanted; Gliosis; Mice; Microelectrodes; Microglia; Neuroglia
PubMed: 36103781
DOI: 10.1016/j.biomaterials.2022.121784 -
Nature Communications Jun 2023This report describes a 3D microelectrode array integrated on a thin-film flexible cable for neural recording in small animals. The fabrication process combines...
This report describes a 3D microelectrode array integrated on a thin-film flexible cable for neural recording in small animals. The fabrication process combines traditional silicon thin-film processing techniques and direct laser writing of 3D structures at micron resolution via two-photon lithography. Direct laser-writing of 3D-printed electrodes has been described before, but this report is the first to provide a method for producing high-aspect-ratio structures. One prototype, a 16-channel array with 300 µm pitch, demonstrates successful electrophysiological signal capture from bird and mouse brains. Additional devices include 90 µm pitch arrays, biomimetic mosquito needles that penetrate through the dura of birds, and porous electrodes with enhanced surface area. The rapid 3D printing and wafer-scale methods described here will enable efficient device fabrication and new studies examining the relationship between electrode geometry and electrode performance. Applications include small animal models, nerve interfaces, retinal implants, and other devices requiring compact, high-density 3D electrodes.
Topics: Mice; Animals; Electrodes; Microelectrodes; Nervous System; Writing; Electrodes, Implanted
PubMed: 37330565
DOI: 10.1038/s41467-023-39152-7 -
Angewandte Chemie (International Ed. in... Oct 2022Impact experiments enable single particle analysis for many applications. However, the effect of the trajectory of a particle to an electrode on impact signals still...
Impact experiments enable single particle analysis for many applications. However, the effect of the trajectory of a particle to an electrode on impact signals still requires further exploration. Here, we investigate the particle impact measurements versus motion using micromotors with controllable vertical motion. With biocatalytic cascade reactions, the micromotor system utilizes buoyancy as the driving force, thus enabling more regulated interactions with the electrode. With the aid of numerical simulations, the dynamic interactions between the electrode and micromotors are categorized into four representative patterns: approaching, departing, approaching-and-departing, and departing-and-reapproaching, which correspond well with the experimentally observed impact signals. This study offers a possibility of exploring the dynamic interactions between the electrode and particles, shedding light on the design of new electrochemical sensors.
Topics: Biocatalysis; Microelectrodes
PubMed: 35946544
DOI: 10.1002/anie.202209747 -
Journal of Neural Engineering Dec 2021To understand neural circuit dynamics, it is critical to manipulate and record many individual neurons. Traditional recording methods, such as glass microelectrodes, can...
To understand neural circuit dynamics, it is critical to manipulate and record many individual neurons. Traditional recording methods, such as glass microelectrodes, can only control a small number of neurons. More recently, devices with high electrode density have been developed, but few of them can be used for intracellular recording or stimulation in intact nervous systems. Carbon fiber electrodes (CFEs) are 8m-diameter electrodes that can be assembled into dense arrays (pitches ⩾ 80m). They have good signal-to-noise ratios (SNRs) and provide stable extracellular recordings both acutely and chronically in neural tissue(e.g. rat motor cortex). The small fiber size suggests that arrays could be used for intracellular stimulation.We tested CFEs for intracellular stimulation using the large identified and electrically compact neurons of the marine mollusk. Neuron cell bodies inrange from 30m to over 250m. We compared the efficacy of CFEs to glass microelectrodes by impaling the same neuron's cell body with both electrodes and connecting them to a DC coupled amplifier.We observed that intracellular waveforms were essentially identical, but the amplitude and SNR in the CFE were lower than in the glass microelectrode. CFE arrays could record from 3 to 8 neurons simultaneously for many hours, and many of these recordings were intracellular, as shown by simultaneous glass microelectrode recordings. CFEs coated with platinum-iridium could stimulate and had stable impedances over many hours. CFEs not within neurons could record local extracellular activity. Despite the lower SNR, the CFEs could record synaptic potentials. CFEs were less sensitive to mechanical perturbations than glass microelectrodes.The ability to do stable multi-channel recording while stimulating and recording intracellularly make CFEs a powerful new technology for studying neural circuit dynamics.
Topics: Animals; Carbon Fiber; Electrodes, Implanted; Microelectrodes; Neurons; Rats; Signal-To-Noise Ratio
PubMed: 34826825
DOI: 10.1088/1741-2552/ac3dd7 -
Behavioural Neurology 2020Physiological behaviours such as the sleep-wake cycle and exploratory behaviours are important parameters in intact and sham-operated animals and are usually thought to...
Physiological behaviours such as the sleep-wake cycle and exploratory behaviours are important parameters in intact and sham-operated animals and are usually thought to be unaffected by experimental protocols in which neurosurgery is performed. However, there is insufficient evidence in the literature on the behavioural and cognitive effects observed after deep microelectrode implantation surgery in animal models of neurological diseases. Similarly, in studies that utilize animal models of neurological diseases, the impact of surgery on the pathological phenomena being studied is often minimized. Based on these considerations, we performed a temporal analysis of the effects of deep microelectrode implantation surgery in the hippocampus of rats on quiet wakefulness, sleep, and exploratory activity and the pathological behaviours such as convulsive seizures according to the Racine scale. Male Wistar rats (210-300 g) were used and grouped in sham and epileptic animals. Single doses of pilocarpine hydrochloride (2.4 mg/2 l; i.c.v.) were administered to the animals to generate spontaneous and recurrent seizures. Deep microelectrode implantation surgeries in both groups and analysis of Fast ripples were performed. Physiological and pathological behaviours were recorded through direct video monitoring of animals (24/7). Our principal findings showed that in epileptic animals, one of the main behaviours affected by surgery is sleep; as a consequence of this behavioural change, a decrease in exploratory activity was also found as well as the mean time spent daily in seizures of scale 4 and the number of seizure events of scales 4 and 5 was increased after surgery. No significant correlations between the occurrence of FR and seizure events of scale 4 (rho 0.63, value 0.25) or 5 (rho -0.7, value 0.18) were observed. In conclusion, microelectrode implantation surgeries modified some physiological and pathological behaviours; therefore, it is important to consider this fact when it is working with animal models.
Topics: Animals; Brain; Disease Models, Animal; Electrodes, Implanted; Electroencephalography; Epilepsy; Exploratory Behavior; Hippocampus; Male; Microelectrodes; Pilocarpine; Rats; Rats, Wistar; Seizures; Sleep; Wakefulness
PubMed: 32211080
DOI: 10.1155/2020/4385706 -
Journal of Neurochemistry Dec 2021This Editorial highlights a remarkable study in the current issue of the Journal of Neurochemistry in which Ganesana & Venton (2021) report new data showing that brain...
Does the inability of CA1 area to respond to ischemia with early rapid adenosine release contribute to hippocampal vulnerability?: An Editorial Highlight for "Spontaneous, transient adenosine release is not enhanced in the CA1 region of hippocampus during severe ischemia models".
This Editorial highlights a remarkable study in the current issue of the Journal of Neurochemistry in which Ganesana & Venton (2021) report new data showing that brain ischemia does not elicit transient adenosine release in the CA1 hippocampal area. Using fast-scan cyclic voltammetry at a carbon-fiber microelectrode implanted in the CA1 subfield of the hippocampus, it was shown that none of three different ischemia/reperfusion models could increase spontaneous, transient adenosine release, and more severe models even suppressed this presumably neuroprotective release. Since the authors have previously shown that in the caudate putamen, ischemia increased the frequency of spontaneous adenosine release (Ganesana & Venton, 2018), the new data may disclose a mechanism underlying important regional differences in rapid neuroprotective adenosine signaling. The phenomenon of selective susceptibility of the hippocampus to ischemia/hypoxia is well-documented, and the reported failure of its CA1 area to respond to ischemia by rapid adenosine release may be indicative of an insufficiency of this neuroprotective mechanism contributing to hippocampal vulnerability.
Topics: Adenosine; Brain Ischemia; Hippocampus; Humans; Ischemia; Microelectrodes
PubMed: 34480345
DOI: 10.1111/jnc.15498 -
Scientific Data Mar 2022We present a dataset of microelectrode array (MEA) recordings from human pluripotent stem cell (hPSC)-derived and rat embryonic cortical neurons during their in vitro...
We present a dataset of microelectrode array (MEA) recordings from human pluripotent stem cell (hPSC)-derived and rat embryonic cortical neurons during their in vitro maturation. The data were prepared to assess extracellularly recorded spontaneous activity and to compare the functional development of these neuronal networks. In addition to recordings of spontaneous activity, we provide pharmacological responses of hPSC-derived and rat cortical cultures at their mature stage. Together with the recorded electrode raw data, we share the analysis code to form a comprehensive dataset including spike times, spike waveforms, burst activity and network synchronization metrics calculated with two different connectivity estimators. Moreover, we provide the analysis code that produced the key scientific findings published previously with this dataset. This large dataset enables investigation of the functional aspects of maturing cortical neuronal networks and provides substantial parameters to assess the differences and similarities between hPSC-derived and rat cortical networks in vitro. This publicly available dataset will be beneficial, especially for experimental and computational neuroscientists.
Topics: Animals; Humans; Microelectrodes; Neurons; Pluripotent Stem Cells; Rats
PubMed: 35354837
DOI: 10.1038/s41597-022-01242-4 -
Science Advances Jul 2023Transparent microelectrode arrays (MEAs) that allow multimodal investigation of the spatiotemporal cardiac characteristics are important in studying and treating heart...
Transparent microelectrode arrays (MEAs) that allow multimodal investigation of the spatiotemporal cardiac characteristics are important in studying and treating heart disease. Existing implantable devices, however, are designed to support chronic operational lifetimes and require surgical extraction when they malfunction or are no longer needed. Meanwhile, bioresorbable systems that can self-eliminate after performing temporary functions are increasingly attractive because they avoid the costs/risks of surgical extraction. We report the design, fabrication, characterization, and validation of a soft, fully bioresorbable, and transparent MEA platform for bidirectional cardiac interfacing over a clinically relevant period. The MEA provides multiparametric electrical/optical mapping of cardiac dynamics and on-demand site-specific pacing to investigate and treat cardiac dysfunctions in rat and human heart models. The bioresorption dynamics and biocompatibility are investigated. The device designs serve as the basis for bioresorbable cardiac technologies for potential postsurgical monitoring and treating temporary patient pathological conditions in certain clinical scenarios, such as myocardial infarction, ischemia, and transcatheter aortic valve replacement.
Topics: Humans; Rats; Animals; Absorbable Implants; Microelectrodes; Heart; Heart Diseases
PubMed: 37406128
DOI: 10.1126/sciadv.adi0757