Repeatable, low-drift recordings in behaving non-human primates using flexible microelectrodes

Abstract

Neurophysiological recordings from non-human primates (NHPs) have traditionally relied on rigid microelectrode arrays made from stainless steel or silicon. While these devices enable high-quality recordings, a fundamental mechanical mismatch between rigid materials and soft brain tissue leads to inflammation, gliosis, and signal instability. In particular, brain micromotion causes continuous drifting of neurons relative to fixed electrodes, compromising single-unit tracking during both chronic and acute recordings. Flexible, penetrating electrodes offer a promising solution, but their adoption in NHPs has been hindered by the technical challenges of delivering ultra-thin polymers through thick dura mater. Here, we demonstrate a comprehensive approach for acute, repeated recordings in awake, behaving NHPs using flexible arrays. We fabricated a microelectrode array that spans cortical layers with 32 cellular-scale recording sites embedded in 7 m-thick Parylene-C. We developed a novel "telescopic" insertion method that combines concentric guide tubes with a retractable microwire shuttle. Our technique is compatible with standard chronic recording chambers and allowed for repeated penetration of free-floating arrays through intact dura over weeks without the need for a new craniotomy. Across two awake rhesus macaques, we optimized the electrode geometry and insertion procedure to achieve an 80% single-unit recording success rate. As animals performed an oculomotor delayed response task, we recorded task-responsive neurons from prefrontal and posterior parietal cortex with stable single-unit activity throughout 1-2-hour behavioral sessions. Critically, by comparing our flexible arrays to rigid probes in the same animals and recording chambers, we provide quantitative evidence that flexible electrodes reduce total single-unit drift from hundreds to tens of microns. Our work establishes flexible microelectrode arrays as a practical, dependable technology for NHP neuroscience and paves the way toward long-term, ultra-stable neurophysiology in large animal models.