Haggerty, J. | bioRxiv Science

bioRxiv2026

Scalable hardware and software for high-density, multi-regional electrophysiology in non-human primates

Understanding how distributed neural circuits generate complex behaviors requires long-duration recordings from populations of individual neurons across multiple brain regions. High-density Neuropixels probes have revolutionized rodent systems neuroscience. Extending these capabilities to non-human primates (NHPs) for chronic, multi-regional recordings requires compact, implantable microdrive hardware and reliable automated spike-sorting software. NHPs provide access to complex and flexible behaviors that are difficult to study in other model systems. Extending the Neuropixels revolution to NHPs therefore depends on integrating hardware and software for long-duration, multi-regional recordings. Here, we present a scalable hardware-software platform co-designed for high-density neural data acquisition and reliable single-unit identification in NHPs. The Multi-regional Implantable NeuroDrive (MIND) is a lightweight, implantable microdrive that provides stable recordings from multiple independently positioned Neuropixels probes and is designed to support chronic, ambulatory, head-free recordings. We paired MIND with UnitAssay, an automated post-sorting curation framework that identifies and curates characteristic spike-sorting errors with minimal computational cost. Together, MIND and UnitAssay provide an integrated platform for implanted, multi-regional recordings in NHPs performing complex and naturalistic behaviors. We tested MIND and UnitAssay across parietal, prefrontal, and motor cortices in rhesus macaques performing reaching and eye-movement tasks. MIND enabled stable multi-probe recordings across cortical regions and durations. UnitAssay enabled automated curation of large-scale spike-sorting output and improved reliable single-unit identification relative to Kilosort 4 labels and standard SpikeInterface quality control. Together, MIND and UnitAssay provide a scalable solution for high-density, multi-regional, long-duration electrophysiology in NHPs.

neuroscience↗

bioRxiv2026

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↗