Chained lightning: advances in neuromodulation.

The cornerstone of functional neurosurgery historically has been the modulation of known neural circuits and neuroanatomic pathways to achieve a predictable therapeutic effect. A lack of suitable alternatives once made lesioning the primary treatment for certain severe medically refractory movement, psychiatric, and chronic pain disorders. Vast improvements in lesioning techniques were accomplished with refinement of stereotactic radiosurgery. These have improved the safety, accuracy, and fidelity of such irreversible neuromodulatory interventions. However, lesioning remains hindered both by being a static intervention and by causing irreversible destruction of neural tissue. In contrast, stimulation-based neuromodulation holds the advantages of being reversible, nondestructive, and dynamic. Although stimulation-based animal research to achieve antinociception was attempted in the early 20th century, clinical application of reversible, nondestructive, and dynamic neuromodulatory stimulation was not pioneered until the 1960s and 1970s.30,34,51 In 1987, Benabid et al.6 first recognized the potential for a durable motor effect during a thalamotomy for essential tremor. When applied during mapping, high-frequency stimulation resulted in nearly immediate tremor suppression. This recognition spawned the use of high-frequency electrical stimulation as a reversible, nondestructive treatment for afflictions of both the peripheral and central nervous systems. Continuous high-frequency stimulation of the deep gray matter, deep brain stimulation (DBS), is currently indicated for essential tremor, some forms of dystonia, and Parkinson’s Disease. Respective targets include the ventral intermediate nucleus of the thalamus, internal segment of the globus pallidum, and subthalamic nucleus (STN). A human device exemption has also been granted for treatment of medically refractory obsessive-compulsive disorder. Vigorous clinical research, through physicianand industry-sponsored trials are currently pursuing alternative indications. These include but are not limited to cluster headache, minimally conscious state, obsessive-compulsive disorder, Tourette’s syndrome, depression, chronic pain, obesity, and anorexia. In parallel, engineering insights and advancements from basic, translational, and clinical research studies promise to vastly improve the current technologies used in DBS. These include improvement in hardware design, introduction of the concept of dynamic targeting and programming strategies, and an exploration of the neuromodulatory potential of biologics-based therapeutics.