Shouliang Guan

Consciousness transitions, including awakening from anesthesia or falling asleep, involve complex neural dynamics across multiple brain regions. Understanding these transitions requires simultaneous and stable monitoring of large-scale neural activity in freely moving animals. Here, a flexible microelectrode array system (FlexiPixels probe) is demonstrated that integrates a multishank flexible microelectrode array with Neuropixels chips. This lightweight FlexiPixels probe enables stable and long-term neural signal recording across multiple brain regions in freely moving rats and tracking of neuronal activities during consciousness transitions from anesthesia to wakefulness and subsequent sleep states. Distinct state-dependent firing patterns emerge across different brain regions and neuronal types. CA1 neurons show similar activity during wakefulness and sleep, while DG neurons exhibit unique anesthesia sensitivity. These findings demonstrate FlexiPixels' capabilities for stable multiregion neural recording in freely moving animals and potential to unravel region-specific signatures in consciousness studies.

Practical application of brain-computer interfaces (BCIs) requires stable mapping between neuronal activity and behavior through various behavioral contexts and for different individuals. Due to neural activity instability, BCIs require frequent recalibration to maintain robust performance. Early approaches to addressing BCI stability issues mainly focused on tackling the challenge of neural activity changes over time. However, future BCI applications involve diversified scenarios and subjects, requiring solutions that address neural variability across time, subjects, and tasks. This study proposes a meta-learning-based algorithm to achieve BCI stability, named “Meta-AlignNN.” By capitalizing on the consistency of neural population dynamics, it provides a unified solution for maintaining BCI stability, robustness, and scalability across subjects, time, and tasks. Tested over two years on four tasks with three monkeys, as well as on public datasets, the approach has achieved significantly excellent performance in both offline decoding and real-time brain-control, outperforming existing methods. Our findings provides a foundation for meeting the clinical demands of longterm, efficient, and stable usability across patients and tasks, offering a compelling solution for practical BCI applications.

Optogenetics has emerged as a pivotal tool in neuroscience, enabling precise control of neural activity through light stimulation. However, the current microLED arrays lack sufficient density and scalability. This study proposes an innovative optogenetic device capable of integrating hundreds of microLEDs and electrocorticography (ECOG) electrodes. Individual or multiple microLEDs in the device can be selectively controlled with a custom controller. The light intensity of microLEDs decreases with increasing brain tissue penetration while maintaining a low temperature rise during pulse stimulations. In addition, interference from microLED pulses on ECOG electrode recordings could be alleviated with local mean subtraction data processing. The optogenetic device enables high-quality neural signal recording and triggers a significant enhancement in neural activity following light stimulation. Integration of microLED arrays and ECOG electrodes in the optogenetic device represents a promising advancement in neuroscientific research, providing improved spatial and temporal recording and control over neural activity.

Ultraflexible microelectrode arrays (MEAs) that can stably record from a large number of neurons after their chronic implantation offer opportunities for understanding neural circuit mechanisms and developing next-generation brain–computer interfaces. The implementation of ultraflexible MEAs requires their reliable implantation into deep brain tissues in a minimally invasive manner, as well as their precise integration with optogenetic tools to enable the simultaneous recording of neural activity and neuromodulation. Here, we describe the process for the preparation of elastocapillary self-assembled ultraflexible MEAs, their use in combination with adeno-associated virus vectors carrying opsin genes and promoters to form an optrode probe and their in vivo experimental use in the brains of rodents, enabling electrophysiological recordings and optical modulation of neuronal activity over long periods of time (on the order of weeks to months). The procedures, including device fabrication, probe assembly and implantation, can be completed within 3 weeks. The protocol is intended to facilitate the applications of ultraflexible MEAs for long-term neuronal activity recording and combined electrophysiology and optogenetics. The protocol requires users with expertise in clean room facilities for the fabrication of ultraflexible MEAs.

Implantable neural probes that are mechanically compliant with brain tissue offer important opportunities for stable neural interfaces in both basic neuroscience and clinical applications. Here, we developed a Neurotassel consisting of an array of flexible and high–aspect ratio microelectrode filaments. A Neurotassel can spontaneously assemble into a thin and implantable fiber through elastocapillary interactions when withdrawn from a molten, tissue-dissolvable polymer. Chronically implanted Neurotassels elicited minimal neuronal cell loss in the brain and enabled stable activity recordings of the same population of neurons in mice learning to perform a task. Moreover, Neurotassels can be readily scaled up to 1024 microelectrode filaments, each with a neurite-scale cross-sectional footprint of 3 × 1.5 μm², to form implantable fibers with a total diameter of ~100 μm. With their ultrasmall sizes, high flexibility, and scalability, Neurotassels offer a new approach for stable neural activity recording and neuroprosthetics.