Efficiency and Safety of Microstimulation Via Different Electrode Materials - Summary
Our laboratory's long-term goal is to understand and characterize the effects of microelectrode implantation,
recording, and stimulation on brain tissue from a physiological perspective in both neuronal and non-neuronal
cells, as well as to improve the biological compatibility, device stability, and performance of neural implants
through the use of advanced materials and tissue engineering approaches. The goal of the parent BRAIN
initiative R01 project is to understand the charge transfer, electrochemical, and biocompatibility properties of
electrodes on the efficacy and safety of microstimulation. Researchers have used microstimulation to infer
functional connections between brain structures or causal links between structure and behavior. Currently,
microstimulation therapy is gaining interest for the restoration of visual, auditory, and somatosensory functions
in addition to applications in bioelectronic medicine. Current neural stimulation parameters and safety limits were
primarily established based on macroelectrodes using postmortem histology. They should be revised for
microelectrodes using technologies that capture dynamic changes to neural tissue health and function. Another
challenge with microstimulation is its susceptibility to host tissue responses. Implantation of electrodes causes
electrode fouling, progressive neuronal loss, and inflammatory gliosis, leading to decreased stimulation efficacy
and increased impedance over long-term implantation. To address these challenges, the specific objectives of
this project are to assess the acute efficiency and safety limits of neural stimulation via different electrode
materials in vivo (Aim 1), examine the effects of stimulation on electrode materials and cultured cells in vitro (Aim
2), and characterize the chronic safety and stability of microstimulation in vivo from different electrode materials
(Aim 3). Diversity Supplement funding is requested to support the research and training of Ms. Anna Kelly who
graduated from the Bioengineering Department at the University of Pittsburgh in 2022. Following her graduation,
Ms. Kelly received one year of support through the Diversity Supplement which allowed her to contribute towards
both acute and chronic mouse studies detailed in the parent award's first and third specific aims. In the acute
studies, microelectrodes were cortically implanted in transgenic mice expressing calcium indicators and
fluorescently labeled microglia. Experiments using 2-photon microscopy to assess stimulation thresholds and
tissue response are ongoing. Ms. Kelly’s independent project explores the response of the blood-brain barrier
(BBB) and vasculature to microstimulation. Specifically, vascular leakage of cells, plasma, and protein, and the
ensuing tissue response. She is also studying the peripheral leukocyte response to electrode implantation and
microstimulation. Ms. Kelly has made excellent progress in this work and with an additional year of support
through the Diversity Supplement, Ms. Kelly will continue to conduct these projects to an endpoint with significant
animal numbers and concrete findings. Additional research experience with a strong likelihood of multiple
publication credits will help to secure her chosen path of entering a top-tier research focused MD program.
