Multimodal Optical Imaging and Modulation with Simultaneous Electrophysiology Through Smart Dura in Non‐Human Primates

Abstract Multimodal neural interfaces that integrate electrical and optical functionalities are promising tools for neuroscientific and clinical applications that involve recording and manipulating neuronal activity. However, most technologies for multimodal implementation are largely restricted to small animal models and lack the ability to translate to the larger brains of non‐human primates (NHPs). Smart Dura, a recently developed large‐scale neural interface for NHPs, enables high‐density electrophysiological recordings and broad optical accessibility, providing multiscale information with enhanced spatiotemporal resolution. In this paper, the multimodal capabilities of Smart Dura are demonstrated through integration with multiphoton imaging, optical coherence tomography angiography (OCTA), and intrinsic signal optical imaging (ISOI), as well as optical manipulations such as photothrombotic lesioning and optogenetics. Through the Smart Dura, in vivo fluorescence vascular imaging is achieved down to depths of 200 and 550 µm using two‐photon and three‐photon microscopy, respectively. When combined with simultaneous electrophysiology, Smart Dura also enables the assessment of vascular and neural dynamics via OCTA and ISOI, the induction of ischemic stroke, and the application of optogenetic neuromodulation across a wide cortical area of 20 mm in diameter. These capabilities support comprehensive investigations of brain dynamics in NHPs, advancing translational neurotechnology for human applications.