A modular cranial window enabling maintainable widefield optical access in non-human primates

Longitudinal optical imaging of the primate cortex requires stable yet maintainable cortical access, but existing cranial window approaches remain limited by mechanical instability and tissue responses that progressively degrade optical clarity. These challenges are amplified in primates, where large craniotomies and physiological variability complicate chronic experiments. Moving beyond conventional fixed cranial windows, we present the PRIME cranial window (Primate Reconfigurable Interchangeable Modular Enclosure), a modular platform enabling maintainable, long-term, and widefield optical access in awake macaques. Built on a modular architecture, PRIME supports non-invasive adjustment, repeated cortical access, and on-demand maintenance, including tissue removal, without surgical re-entry, while a dual-ring sealing mechanism prevents cerebrospinal fluid leakage and contamination. Combined with optimized viral delivery, implantation, and maintenance strategies, PRIME preserves cortical integrity and optical clarity for long-term optical imaging. PRIME establishes a versatile, re-accessible experimental framework for chronic, large-area optical studies of the primate brain.