Histological Assessment of Thermal Damage in the Brain Following Infrared Neural Stimulation

Abstract

Infrared neural stimulation (INS) is a novel technique for modulating neural function. Its advantages over electrical stimulation include high spatial specificity, lack of electrical artifact and contact-free stimulation. INS acts via a rapid, focal increase in temperature. However, in order to become a viable experimental and therapeutic tool, the safety of INS must be demonstrated. Our aim was to determine the upper limit for the radiant exposure of INS in the brain without causing damage, using an INS sequence previously shown to induce both behavioral and electrophysiological effects in rodents and non-human primates. We stimulated the brains of anesthetized rodents and two squirrel monkeys using an infrared laser, depositing radiant energies from 0.3 to 0.9 J/cm2 per pulse in 0.5 s-long 200 Hz trains. At the end of the experiment, the animals were euthanized, perfused and the brains processed using standard histological techniques. Radiant exposures greater than or equal to 0.4 J/cm2 resulted in identifiable lesions in brain sections. The lesions had a shape of a parabola and could further be subdivided into three concentric zones based on the type of damage observed. The thermal damage threshold following our INS paradigm was between 0.3 and 0.4 J/cm2 per pulse. This value is lower than the one found previously in peripheral nerve. The differences are likely due to the structure of the INS sequence itself, particularly the repetition rate. The results warrant further modeling and experimental work in order to delimit the INS parameter space that is both safe and effective.