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Greene, R.

Publications and source records attributed to Greene, R..

4 recordsLinked to original sources

Isoflurane anesthesia CNS recovery state: ultra-slow oscillations and cellular-stress-responsive gene expression

General anesthesia and NREM sleep share slow-wave EEG features, yet whether anesthesia substitutes for physiological sleep remains unclear. We compared recovery from 4h of isoflurane anesthesia (IA) with time-matched sleep and sleep deprivation (SD) in male C57BL/6J mice using continuous EEG/EMG recordings and frontal cortex RNA sequencing. IA recovery produced transient, rebound arousal, reduced early NREM and REM sleep, and, fragmented subsequent NREM bouts, and persistant, ultra-slow EEG-oscillations that normalized within two weeks. Whereas, SD induced consolidated rebound sleep and slow wave activity. Transcriptomic profiling at ZT6 showed that IA and SD induced largely distinct cortical gene-expression programs. IA preferentially enriched integrated stress response and unfolded protein response genes, whereas SD showed a comparatively orthogonal, growth-permissive, mTOR-associated profile. Although IA-induced gene-expression suggests cellular stress, corticosterone measurements argued against systemic stress as the primary driver. These findings indicate that isoflurane recovery is neurophysiologically and molecularly distinct from restorative sleep.

neuroscience↗

Toward A Whole-Brain Interface Enabled by High-Resolution Surface Electrophysiology

The goal of building a whole-brain interface - capable of generating a real-time digital representation of the state of the entire central nervous system - has long been framed as a hardware challenge of recording simultaneously from ever-larger numbers of microelectrodes. Advances in high-resolution neural interfaces now enable electrophysiologic interaction with the human nervous system at spatial and temporal resolutions previously unattainable without disrupting tissue architecture or physiology. These capabilities create new opportunities for mechanistic neuroscience, neuroprosthetics, and precision-guided neurosurgery. With the advent of modern microelectrode array technology, however, the whole-brain interface has also become a data challenge. Rather than pursuing large-scale human brain recording purely through a single device placed in a single patient, we demonstrate here that systematic multi-subject aggregation, across brain regions and behavioral paradigms, in a common anatomical framework, can achieve something functionally similar to a whole-brain interface. Here we present an approach to a functional atlas of the human central nervous system derived from high-resolution surface electrophysiology recordings obtained in the first 70 patients implanted with an anatomically conformal, thin-film neural interface positioned in more than 100 locations. The atlas comprises >100,000 electrode deployments and catalogs placement across a broad range of neuroanatomic targets spanning the motor, sensory, language, auditory, and associative domains, as well as brainstem and spinal cord structures that have historically been difficult to access at high electrophysiologic resolution. Across participants, aggregated recordings reveal somatotopic organization, including digit representations that follow a lateral-to-medial ordering consistent with classical homuncular maps, with transitions between adjacent representations occurring over spatial scales of approximately 0.8 - 2.0 mm; canonical frequency-band signatures, such as movement-related beta-band suppression and focal high-gamma (70 - 200 Hz) increases during motor and speech behaviors; and task-modulated population dynamics in both evoked and spontaneous activity across cortical, brainstem, and spinal cord regions. These findings yield insight into patterns of mesoscale electrophysiological dynamics conserved across the entire human central nervous system, suggesting that fine-scale functional organization is preserved across individuals when aligned to common anatomical landmarks. We further demonstrate several applications of these high-resolution recordings, including real-time neural decoding from upper extremity motor cortex to enable real-time neuroprosthetic control, and from ventrolateral cortex to decode cortical correlates of spoken language, facial movements, and complex facial expressions of emotion, supporting initial feasibility of combined verbal and nonverbal communication interfaces. Together, these results establish a paradigm for approaching large-scale interfaces with the human brain, as well as a starting point for a scalable, extensible atlas of human electrophysiologic function designed to accelerate discovery across basic neuroscience, translational research, and clinical neurotechnology.

neuroscience↗

UnitRefine: A Community Toolbox for Automated Spike Sorting Curation

High-density electrophysiology simultaneously captures the activity from hundreds of neurons, but isolating single-unit activity still relies on slow and subjective manual curation. As datasets keep increasing, this poses a major bottleneck in the field. We therefore developed UnitRefine, a classification toolbox that automates curation by training various machine-learning models directly on human expert annotations. Fully integrated in the SpikeInterface ecosystem, UnitRefine combines established and novel quality metrics, cascading classification and comprehensive hyperparameter search to provide optimized models for different applications. UnitRefine achieves human-level performance across diverse datasets, spanning species, probe types, and laboratories, including recordings from mice, rats, mole rats, primates, and human patients. Applied to a large brain-wide dataset, UnitRefine doubled single unit yield and improved behavioral decoding performance. A streamlined graphical interface allows models to be fine-tuned to new datasets and shared via the Hugging Face Hub, enabling broad adoption and community-driven improvement of automated curation workflows.

neuroscience↗

A novel in vitro 3D cancer model based on modular tissue engineering approach

An emerging tool to better recapitulate the complexity of tumor biology in vitro is 3D culture models. Here, we describe a free-floating collagen-based hydrogel system with embedded cancer cells, called microtissues. The microtissues are based on the well-established modular tissue engineering method. They mimic the natural development of the tumor microenvironment, with features such as hypoxia and treatment resistance. To demonstrate the utility of microtissues as a 3D tumor model system, triple negative breast cancer cells were cultured using this method and were shown to maintain cell viability and proliferation with minimal cell death, along with mimicking natural emergence of tumor properties such as, a hypoxic core. Furthermore, by screening the model with commonly used anti-breast cancer chemotherapeutics, we observed drug resistance to concentrations which are largely in accordance with the used doses in the clinics. Therefore, our model offers the opportunity to naturally reproduce fundamental features of a tumor in vitro, leading to emergence of a similar cell reprogramming which is responsible for clinical drug resistance.

cancer biology↗