Multimodal optical imaging and modulation through Smart Dura in non-human primates

A multimodal neural interface integrating electrical and optical functionalities is a promising tool for recording and manipulating neuronal activity, providing multiscale information with enhanced spatiotemporal resolution. However, most technologies for multimodal implementation are limited in their applications to small animal models and lack the ability to translate to larger brains, such as non-human primates (NHPs). Recently, we have developed a large-scale neural interface for NHPs, Smart Dura, which enables electrophysiological recordings and high optical accessibility. In this paper, we demonstrate the multimodal applications of Smart Dura in NHPs by combining 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 transparent Smart Dura, we could obtain fluorescence images down to 200 μm and 550 μm depth using two-photon and three-photon microscopy, respectively. Integrated with simultaneous electrophysiology using the Smart Dura, we could also assess vascular and neural dynamics with OCTA and ISOI, induce ischemic stroke, and apply optogenetic neuromodulation over a wide coverage area of 20 mm diameter. This multimodal interface enables comprehensive investigations of brain dynamics in NHPs, advancing translational neurotechnology for human applications.