Electrophysiological Response of the Non-Anesthetized Primate Brain to Minimally Invasive Local Infrared Neural Stimulation in Chronic Experiments.

Infrared neural stimulation (INS) represents an invasive technique for modulating brain activity in animals, particularly primates, which serve as effective models for human brain research. Noninvasive approaches, such as transcranial laser stimulation, are safer but have lower spatial and temporal resolution, primarily altering metabolic processes rather than directly stimulating specific neurons. Invasive techniques provide better resolution by targeting neurons with focused laser beams but require intricate surgeries that damage the meninges, limiting studies to short-term experiments conducted mostly on anesthetized animals. We present a minimally invasive approach for long-term, high-resolution laser INS that does not disrupt brain tissue integrity and minimizes the risk of inflammation. Laser radiation is delivered through contact between a flexible optical fiber and the outer surface of the dura mater, allowing for chronic experiments on non-anesthetized primates who maintain their cognitive functions and physical activities. This method has enabled us to conduct a multi-day INS experiment and collect statistically reliable data on neurophysiological responses in a cognitively intact primate subjected to targeted high-resolution INS. We analyzed electrocorticogram and evoked potentials in various cortical areas while applying infrared laser stimulation directed at a selected point on the primary visual cortex of a rhesus macaque. Results indicated that even low-intensity laser stimulation (below conscious perception thresholds) caused synchronous biopotential changes not only at the stimulation site but also in certain distant cortical regions, suggesting a more complex brain response mechanism to INS than merely the activation of stimulated neurons. We believe the presented method will significantly facilitate chronic INS studies, further contributing to fundamental and clinical outcomes.