High-Density Multi-Depth Human Recordings Using 45 mm Long Neuropixels Probes

Neuropixels probes, initially developed for use in small animal models, have transformed basic neuroscience by enabling high-density, single-cell resolution recordings across multiple brain regions simultaneously. The recent development of Neuropixels 1.0 NHP Long-a longer probe designed for non-human primates-has expanded this capability, enabling unprecedented simultaneous access to multiple cortical layers and deep brain structures of large-brained animals. This probe features 4,416 recording sites along a 45 mm shank, with 384 channels selectable for simultaneous recording. Here, we report the first use of these probes in humans, aiming to establish safe intraoperative use and assess feasibility for clinical and research applications.

Nine patients undergoing neurosurgical procedures-including epilepsy or tumor resection and deep brain stimulation (DBS) implantation-were enrolled. The authors developed sterilizable, custom-designed 3D-printed tools and protocols to facilitate long Neuropixels probe insertion, optimize recordings, and maintain sterility. Strategies were implemented to mitigate potential failure modes, including motion artifacts and electrical interference.

Successful intraoperative recordings were obtained from surface and deep cortical structures without probe breakage or adverse events. Compared with conventional electrodes, the Neuropixels probe enabled dense sampling across multiple parenchymal depths with submillisecond temporal resolution. Recordings were obtained from deep targets including the hippocampus (n = 3) and cingulate cortex (n = 1), as well as from regions that are challenging to access with single-unit precision, such as the superior frontal sulcus (n = 1). Custom tools and refined workflows lowered technical barriers for operative use and improved recording stability. Neural activity was observed across all recordings.

Neuropixels 1.0-NHP Long probes can be deployed in the human operating room, enabling simultaneous recordings from multiple brain structures at single-neuron resolution. These methods expand opportunities for studying human brain function and pathology in vivo, and may ultimately support the development of more precise neurosurgical interventions.