Biology subjects

Chung, J. E.

Publications and source records attributed to Chung, J. E..

9 recordsLinked to original sources

bioRxiv2024

Human precentral gyrus neurons link speech sequences from listening to speaking

Speech perception and production are interconnected processes, but the underlying neural mechanisms remain unclear. We investigated this relationship by recording large-scale single-neuron activity in the human brain during a delayed sentence repetition task. Contrary to the traditional view that the precentral gyrus is solely responsible for motor execution, we found that neurons there encoded activity across all task phases of listening, delay, initiation, and speaking. Notably, we discovered "mirror" neurons that activated transiently after hearing and before producing specific speech sounds, and "bridge" neurons that maintained activity between the same speech elements during listening and speaking. Population analysis revealed distinct latent components for each task phase and persistent dynamics for specific sentences. Overall, this study provides novel insights into the neuronal basis of speech processing, emphasizing the intricate interplay between perception, production, and verbal working memory.

neuroscience↗

bioRxiv2023

DREDge: robust motion correction for high-density extracellular recordings across species

High-density microelectrode arrays (MEAs) have opened new possibilities for systems neuroscience in human and non-human animals, but brain tissue motion relative to the array poses a challenge for downstream analyses, particularly in human recordings. We introduce DREDge (Decentralized Registration of Electrophysiology Data), a robust algorithm which is well suited for the registration of noisy, nonstationary extracellular electrophysiology recordings. In addition to estimating motion from spikes in the action potential (AP) frequency band, DREDge enables automated tracking of motion at high temporal resolution in the local field potential (LFP) frequency band. In human intraoperative recordings, which often feature fast (period <1s) motion, DREDge correction in the LFP band enabled reliable recovery of evoked potentials, and significantly reduced single-unit spike shape variability and spike sorting error. Applying DREDge to recordings made during deep probe insertions in nonhuman primates demonstrated the possibility of tracking probe motion of centimeters across several brain regions while simultaneously mapping single unit electrophysiological features. DREDge reliably delivered improved motion correction in acute mouse recordings, especially in those made with an recent ultra-high density probe. We also implemented a procedure for applying DREDge to recordings made across tens of days in chronic implantations in mice, reliably yielding stable motion tracking despite changes in neural activity across experimental sessions. Together, these advances enable automated, scalable registration of electrophysiological data across multiple species, probe types, and drift cases, providing a stable foundation for downstream scientific analyses of these rich datasets.

neuroscience↗

bioRxiv2021

High density single-unit human cortical recordings using the Neuropixels probe

A fundamental unit of neural computation is the action potential. While significant advances have been made in the ability to sample action potentials of large numbers of individual neurons in animal models, translation of these methodologies to humans has been lacking due to clinical time constraints, electrical noise in the operating room, and reliability of the methodology. Here we present a reliable method for intraoperative recording of dozens of neurons in humans using the Neuropixels probe, yielding up to [~]100 simultaneously-recorded single-units (n=596 across 11 recordings in 8 participants). Most single-units were active within 1 minute of reaching target depth, compatible with clinical time constraints. Cell pairs active close in time were spatially closer in most recordings, demonstrating the power to resolve complex cortical dynamics. Altogether, this approach provides access to population single-unit activity across the depth of human neocortex at scales previously only accessible in animal models. HighlightsO_LISingle units in 8 patients, yielding 596 putative single units across 11 recordings C_LIO_LIThe majority of putative neurons fire at least 1 spike within one minute after reaching target depth C_LIO_LIPutative neurons take longer to fire at least one spike in anesthetized compared to awake participants C_LIO_LICell-pairs that fire action potentials close in time are spatially closer together than those fire further apart in time C_LI

neuroscience↗

bioRxiv2020

Total recall: episodic memory retrieval,choice, and memory confidence in the rat

Episodic memory enables recollection of past experiences to guide future behavior. Humans know which memories to trust (high confidence) and which to doubt (low confidence). How memory retrieval, memory confidence, and memory-guided decisions are related, however, is not understood. Additionally, whether animals can assess confidence in episodic memories to guide behavior is unknown. We developed a spatial episodic memory task in which rats were incentivized to gamble their time: betting more following a correct choice yielded greater reward. Rat behavior reflected memory confidence, with higher temporal bets following correct choices. We applied modern machine learning to identify a memory decision variable, and built a generative model of memories evolving over time that accurately predicted both choices and confidence reports. Our results reveal in rats an ability thought to exist exclusively in primates, and introduce a unified model of memory dynamics, retrieval, choice, and confidence.

neuroscience↗

bioRxiv2020

Hippocampal replay of experience at real-world speeds

Representations related to past experiences play a critical role in memory and decision-making processes. The rat hippocampus expresses these types of representations during sharp-wave ripple (SWR) events, and previous work identified a minority of SWRs that contain "replay" of spatial trajectories at ~20x the movement speed of the animal. Efforts to understand replay typically make multiple assumptions about which events to examine and what sorts of representations constitute replay. We therefore lack a clear understanding of both the prevalence and the range of representational dynamics associated with replay. Here we develop a state space model that uses a combination of movement dynamics of different speeds to capture the spatial content and time evolution of replay during SWRs. Using this model, we find that the large majority of replay events contain spatially coherent, interpretable content. Furthermore, many events progress at real-world, rather than accelerated, movement speeds, consistent with actual experiences.

neuroscience↗

bioRxiv2019

A microfabricated, 3D-sharpened silicon shuttle for insertion of flexible electrode arrays through dura mater into brain

Electrode arrays for chronic implantation in the brain are a critical technology in both neuroscience and medicine. Recently, flexible, thin-film polymer electrode arrays have shown promise in facilitating stable, single-unit recordings spanning months in rats. While array flexibility enhances integration with neural tissue, it also requires removal of the dura mater, the tough membrane surrounding the brain, and temporary bracing to penetrate the brain parenchyma. Durotomy increases brain swelling, vascular damage, and surgical time. Insertion using a bracing shuttle results in additional vascular damage and brain compression, which increase with device diameter; while a higher-diameter shuttle will have a higher critical load and more likely penetrate dura, it will damage more brain parenchyma and vasculature. One way to penetrate the intact dura and limit tissue compression without increasing shuttle diameter is to reduce the force required for insertion by sharpening the shuttle tip. We describe a novel design and fabrication process to create silicon insertion shuttles that are sharp in three dimensions and can penetrate rat dura, for faster, easier, and less damaging implantation of polymer arrays. Sharpened profiles are obtained by reflowing patterned photoresist, then transferring its sloped profile to silicon with dry etches. We demonstrate that sharpened shuttles can reliably implant polymer probes through dura to yield high quality single unit and local field potential recordings for at least 95 days. On insertion directly through dura, tissue compression is minimal. This is the first demonstration of a rat dural-penetrating array for chronic recording. This device obviates the need for a durotomy, reducing surgical time and risk of damage to the blood-brain barrier. This is an improvement to state-of-the-art flexible polymer electrode arrays that facilitates their implantation, particularly in multi-site recording experiments. This sharpening process can also be integrated into silicon electrode array fabrication.

neuroscience↗

bioRxiv2019

Regular cycling between representations of alternatives in the hippocampus

Cognitive faculties such as imagination, planning, and decision-making require the ability to represent alternative scenarios. In animals, split-second decision-making implies that the brain can represent alternatives at a commensurate speed. Yet despite this insight, it has remained unknown whether there exists neural activity that can consistently represent alternatives in <1 s. Here we report that neural activity in the hippocampus, a brain structure vital to cognition, can regularly cycle between representations of alternative locations (bifurcating paths in a maze) at 8 Hz. This cycling dynamic was paced by the internally generated 8 Hz theta rhythm, often occurred in the absence of overt deliberative behavior, and unexpectedly also governed an additional hippocampal representation defined by alternatives (heading direction). These findings implicate a fast, regular, and generalized neural mechanism underlying the representation of competing possibilities.

neuroscience↗

bioRxiv2018

CRISPR-Cas9 interrogation of a putative fetal globin repressor in human erythroid cells.

Sickle Cell Disease and {beta}-thalassemia, which are caused by defective or deficient adult {beta}-globin (HBB) respectively, are the most common serious genetic blood diseases in the world. Expression of the fetal {beta}-like globin, also known as {gamma}-globin, can ameliorate both disorders by serving in place of the adult {beta}-globin. Here we use CRISPR-Cas9 gene editing to explore a putative {gamma}-globin silencer region identified by comparison of naturally-occurring deletion mutations associated with up-regulated {gamma}-globin. We find that deletion of a 1.7 kb consensus element or select 350 bp sub-regions from bulk populations of cells increases levels of fetal hemoglobin (HbF) or {gamma}-globin. Screening of individual sgRNAs in one sub-region revealed three single guides that caused mild increases in {gamma}-globin expression. However, clonal cell lines with the 1.7 kb region deleted did not up-regulate {gamma}-globin and neither did lines with either of two of sub-regions identified in the screen deleted. These data suggest that the region is not an autonomous {gamma}-globin silencer, and thus by itself is not a suitable therapeutic target in the {beta}-hemoglobinopathies.

genetics↗

bioRxiv2018

A polymer probe-based system for high density, long-lasting electrophysiological recordings across distributed neuronal circuits

The brain is a massive neuronal network, organized into anatomically distributed sub-circuits, with functionally relevant activity occurring at timescales ranging from milliseconds to months. Current methods to monitor neural activity, however, lack the necessary conjunction of anatomical spatial coverage, temporal resolution, and long-term stability to measure this distributed activity. Here we introduce a large-scale, multi-site recording platform that integrates polymer electrodes with a modular stacking headstage design supporting up to 1024 recording channels in freely behaving rats. This system can support months-long recordings from hundreds of well-isolated units across multiple brain regions. Moreover, these recordings are stable enough to track 25% of single units for over a week. This platform enables large-scale electrophysiological interrogation of the fast dynamics and long-timescale evolution of anatomically distributed circuits, and thereby provides a new tool for understanding brain activity.

neuroscience↗