The Active Electrode in the Living Brain: The Response of the Brain Parenchyma to Chronically Implanted Deep Brain Stimulation Electrodes

BACKGROUND: Deep brain stimulation is an established symptomatic surgical therapy for Parkinson disease, essential tremor, and a number of other movement and neuropsychiatric disorders. The well-established foreign body response around implanted electrodes is marked by gliosis, neuroinflammation, and neurodegeneration. However, how this response changes with the application of chronic stimulation is less well-understood. OBJECTIVE: To integrate the most recent evidence from basic science, patient, and postmortem studies on the effect of such an "active"electrode on the parenchyma of the living brain. METHODS: A thorough and in-part systematic literature review identified 49 papers. RESULTS: Increased electrode-tissue impedance is consistently observed in the weeks following electrode implantation, stabilizing at approximately 3 to 6 mo. Lower impedance values are observed around stimulated implanted electrodes when compared with unstimulated electrodes. A temporary reduction in impedance has also been observed in response to stimulation in nonhuman primates. Postmortem studies from patients confirm the presence of a fibrous sheath, astrocytosis, neuronal loss, and neuroinflammation in the immediate vicinity of the electrode. When comparing stimulated and unstimulated electrodes directly, there is some evidence across animal and patient studies of altered neurodegeneration and neuroinflammation around stimulated electrodes. CONCLUSION: Establishing how stimulation influences the electrical and histological properties of the surrounding tissue is critical in understanding how these factors contribute to DBS efficacy, and in controlling symptoms and side effects. Understanding these complex issues will aid in the development of future neuromodulation systems that are optimized for the tissue environment and required stimulation protocols.