Distinguishing Photoacoustic and Photothermal Neuron Stimulation Through Quantitative Mapping Spatiotemporal Field Evolution

Abstract

Neuromodulation is a rapidly advancing strategy for modulating brain function and treating neurological disorders, yet the mechanisms of optical neural stimulation remain incompletely understood. A central challenge is that photoacoustic (PA) and photothermal (PT) effects are typically generated simultaneously and evolve on overlapping spatial and temporal scales, making their contributions to neuronal activation difficult to distinguish. Here, we overcome this limitation by integrating two carbon-based emitters with a spatial-offset pump-probe imaging platform to distinguish PA and PT neuromodulation through direct mapping of spatiotemporal field evolution. The two emitters produce nearly identical thermal fields while exhibiting a 26-fold difference in acoustic output, enabling decoupled comparison of thermal and acoustic contributions. To directly characterize the physical fields, we establish a spatial-offset pump-probe imaging system capable of visualizing both temperature and pressure evolution, confirming matched thermal profiles between the two emitters. Neuronal stimulation experiments further show that neurons are markedly more responsive to PA stimulation than to PT stimulation. Beyond resolving a longstanding mechanistic question, this work demonstrates the enhanced efficiency of PA stimulation and provides general guidance for designing high-performance optical neural interfaces.