Radiomodulation—The Final Frontier of Radiosurgery?

Stereotactic radiosurgery (SRS) delivers high doses of focused ionizing radiation (IR) to a defined target while sparing surrounding tissues. The delivery of focused doses of IR has proven to be an effective modality for the treatment of brain tumors, cerebrovascular lesions, and primary neuropathic pain conditions. More recently, the emerging concept of "radiomodulation" to rewire neural circuitry through the delivery of focused IR to specific neural relay centers has emerged as an alternative way to treat neurological conditions, such as essential tremor, trigeminal neuralgia, and psychiatric illnesses. In this article, we performed a scoping review of the existing data supporting the ability of focused doses of ionizing radiation to achieve modulation of neural circuits for the treatment of neurological conditions. We review the current understanding of the neurophysiological mechanisms of radiomodulation, the gaps in knowledge limiting its widespread use for in-human applications and stress the unmet need for ongoing research to rigorously prove that radiomodulation may be the "final frontier" as a non-invasive, non-pharmacological, versatile, and tunable modality for the treatment of a multitude of neurological conditions.