Large-scale neural recordings with single neuron resolution using Neuropixels probes in human cortex

Paulk, Angelique C.; Kfir, Yoav; Khanna, Arjun; Mustroph, Martina L.; Trautmann, Eric M.; Soper, Dan J.; Stavisky, Sergey D.; Welkenhuysen, Marleen; Dutta, B.; Shenoy, Krishna V.; Hochberg, Leigh R.; Richardson, R. Mark; Williams, Ziv; Cash, Sydney S.

doi:10.1038/s41593-021-00997-0

Cited by 127 publications

(132 citation statements)

References 79 publications

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“…While most of the methods for drift correction were mainly developed for and applied to data from rodents, a recent study featuring Neuropixels recordings in human subjects [60] showed that, at this spatial scale, the drift problem is more prominent and it is strongly modulated by cardiac and breathing cycles. The relatively fast dynamics of these oscillations might make the methods described above, which rely on spike detection and binning to correct for drift, to fall short, mainly because there would not be enough spikes to robustly estimate drift in such short periods (e.g.…”

Section: Drift Correctionmentioning

confidence: 99%

Spike sorting: new trends and challenges of the era of high-density probes

2022

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Recording from a large neuronal population of neurons is a crucial challenge to unravel how information is processed by the brain. In this review, we highlight the recent advances made in the ﬁeld of “spike sorting”, which is arguably a very essential processing step to extract neuronal activity from extracellular recordings. We more speciﬁcally target the challenges faced by newly manufactured high-density multielectrode array devices (HD-MEA), e.g. Neuropixels probes. Among them, we cover in depth the prominent problem of drifts (movements of the neurons with respect to the recording devices) and the current solutions to circumscribe it. In addition, we also review recent contributions making use of deep learning approaches for spike sorting, highlighting their advantages and disadvantages. Next, we highlight eﬀorts and advances in unifying, validating, and benchmarking spike sorting tools. Finally, we discuss the spike sorting ﬁeld in terms of its open and unsolved challenges, speciﬁcally regarding scalability and reproducibility. We conclude by providing our personal view on how the future of spike sorting, calling for a community-based development and validation of spike sorting algorithms and fully automated, cloud-based spike sorting solutions for the neuroscience community.

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Section: Drift Correctionmentioning

confidence: 99%

Spike sorting: new trends and challenges of the era of high-density probes

2022

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“…The ability to use silicon probes with known spacing between electrodes to differentiate real-time responses of current sources and sinks to systemically administered drugs is a unique strength of this methodology ( Buzsáki et al, 2015 ). Neuropixel silicon probes which enable recording neural activity data from over 200 well-isolated neurons in the human brain provide an unprecedented opportunity for comparing human data to observations in preclinical models ( Paulk et al, 2022 ). This approach has the potential to fundamentally transform the field of neurotoxicology and to advance our understanding of neurotoxic chemical effects beyond that attainable with electroencephalograpy ( Freeborn et al, 2015 ).…”

Section: Highlights and Conclusionmentioning

confidence: 99%

Probing the Neural Circuitry Targets of Neurotoxicants In Vivo Through High Density Silicon Probe Brain Implants

Ratner

Farb

2022

Front. Toxicol.

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Adverse effects of drugs on the human nervous system are rarely possible to anticipate based on preclinical neurotoxicity data, thus propagating the centuries long single most important obstacle to drug discovery and development for disorders of the nervous system. An emerging body of evidence indicates that in vivo electrophysiology using chronically implanted high-density electrodes (ciHDE) in freely moving animals is a rigorous method with enhanced potential for use in translational research. In particular, the structure and function of the hippocampal trisynaptic circuit (HTC) is conserved from rodents to primates, including Homo sapiens, suggesting that the effects of therapeutic agents and other potential neurologically active agents, whether beneficial or adverse, are likely to translate across species when interrogated using a conserved neural circuitry platform. This review explores science advances in the rapidly moving field of in vivo ciHDE in animal models of learning and memory. For this reason we focus on the HTC, where substantial research has investigated neural circuitry level responses and specific behaviors that reflect memory permitting a test of the ground truth validity of the findings. Examples of changes in neural network activity induced by endogenous neurotoxicants associated with neurodegenerative diseases, as well as exogenous therapeutics, drugs, and neurotoxicants are presented. Several illustrative examples of relevant findings that involve longer range neural circuitry outside of the HTC are discussed. Lastly, the limitations of in vivo ciHDE as applied to preclinical neurotoxicology are discussed with a view toward leveraging circuitry level actions to enhance our ability to project the specificity of in vitro target engagement with the desired psychopharmacological or neurological outcome. At the same time, the goal of reducing or eliminating significant neurotoxic adverse events in human is the desired endpoint. We believe that this approach will lead to enhanced discovery of high value neuroactive therapeutics that target neural circuitry domains as their primary mechanism of action, thus enhancing their ultimate contribution toward discovery of precision therapeutics.

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“…The technology of neuronal data acquisition using high density multi-electrode arrays (HD-MEAs) in tissue and cell cultures has grown dramatically over the past decade (Maccione et al, 2013(Maccione et al, , 2014(Maccione et al, , 2015Ingebrandt, 2015;Müller et al, 2015;Dragas et al, 2017;Viswam et al, 2017;Steinmetz et al, 2019;Paulk et al, 2022). A brief history of MEA technology and advancement of these devices is discussed extensively by Didier et al (2020).…”

Section: Introductionmentioning

confidence: 99%

Xenon LFP Analysis Platform Is a Novel Graphical User Interface for Analysis of Local Field Potential From Large-Scale MEA Recordings

2022

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High-density multi-electrode array (HD-MEA) has enabled neuronal measurements at high spatial resolution to record local field potentials (LFP), extracellular action potentials, and network-wide extracellular recording on an extended spatial scale. While we have advanced recording systems with over 4,000 electrodes capable of recording data at over 20 kHz, it still presents computational challenges to handle, process, extract, and view information from these large recordings. We have created a computational method, and an open-source toolkit built in Python, rendered on a web browser using Plotly’s Dash for extracting and viewing the data and creating interactive visualization. In addition to extracting and viewing entire or small chunks of data sampled at lower or higher frequencies, respectively, it provides a framework to collect user inputs, analyze channel groups, generate raster plots, view quick summary measures for LFP activity, detect and isolate noise channels, and generate plots and visualization in both time and frequency domain. Incorporated into our Graphical User Interface (GUI), we also created a novel seizure detection method, which can be used to detect the onset of seizures in all or a selected group of channels and provide the following measures of seizures: distance, duration, and propagation across the region of interest. We demonstrate the utility of this toolkit, using datasets collected from an HD-MEA device comprising of 4,096 recording electrodes. For the current analysis, we demonstrate the toolkit and methods with a low sampling frequency dataset (300 Hz) and a group of approximately 400 channels. Using this toolkit, we present novel data demonstrating increased seizure propagation speed from brain slices of Scn1aHet mice compared to littermate controls. While there have been advances in HD-MEA recording systems with high spatial and temporal resolution, limited tools are available for researchers to view and process these big datasets. We now provide a user-friendly toolkit to analyze LFP activity obtained from large-scale MEA recordings with translatable applications to EEG recordings and demonstrate the utility of this new graphic user interface with novel biological findings.

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Large-scale neural recordings with single neuron resolution using Neuropixels probes in human cortex

Cited by 127 publications

References 79 publications

Spike sorting: new trends and challenges of the era of high-density probes

Spike sorting: new trends and challenges of the era of high-density probes

Probing the Neural Circuitry Targets of Neurotoxicants In Vivo Through High Density Silicon Probe Brain Implants

Xenon LFP Analysis Platform Is a Novel Graphical User Interface for Analysis of Local Field Potential From Large-Scale MEA Recordings

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