Neurophotonics: a comprehensive review, current challenges and future trends.

The human brain, with its vast network of billions of neurons and trillions of synapses (connections) between diverse cell types, remains one of the greatest mysteries in science and medicine. Despite extensive research, an understanding of the underlying mechanisms that drive normal behaviors and response to disease states is still limited. Advancement in the Neuroscience field and development of therapeutics for related pathologies requires innovative technologies that can provide a dynamic and systematic understanding of the interactions between neurons and neural circuits. In this work, we provide an up-to-date overview of the evolution of neurophotonic approaches in the last 10 years through a multi-source, literature analysis. From an initial corpus of 243 papers retrieved from Scopus, PubMed and WoS databases, we have followed the PRISMA approach to select 56 papers in the area. Following a full-text evaluation of these 56 scientific articles, six main areas of applied research were identified and discussed: (1) Advanced optogenetics, (2) Multimodal neural interfaces, (3) Innovative therapeutics, (4) Imaging devices and probes, (5) Remote operations, and (6) Microfluidic platforms. For each area, the main technologies selected are discussed according to the photonic principles applied, the neuroscience application evaluated and the more indicative results of efficiency and scientific potential. This detailed analysis is followed by an outlook of the main challenges tackled over the last 10 years in the Neurophotonics field, as well as the main technological advances regarding specificity, light delivery, multimodality, imaging, materials and system designs. We conclude with a discussion of considerable challenges for future innovation and translation in Neurophotonics, from light delivery within the brain to physical constraints and data management strategies.