Neurochemical changes that occur as a function of electrical stimulation are thought to play a role in various therapeutic applications of neural stimulation in the central and peripheral nervous system. Fast scan cyclic voltammetry (FSCV) is a technique that is capable of measuring these neurochemical changes in real-time with sub-second and sub-millimeter resolution. FSCV involves applying a specific holding potential and ramping to different potentials in a cyclic manner, driving electroactive molecules to oxidize and reduce, which results in a transfer of electrons between electrochemically active molecules and the electrode in real time. This technique has allowed measurement of the neurochemical correlates of deep brain stimulation and behavioral studies in small and large animal models. In order to better understand the underlying changes following neural stimulation, we have developed a unique system that leverages FSCV to measure neurochemical changes in vivo. Through years of experience, we found that stimulation-evoked neurochemical release can be very focally located, and thus difficult to find; therefore, we developed a method to identify the global changes that occur following stimulation by mapping blood oxygen level-dependent (BOLD) increases with functional magnetic resonance imaging (fMRI) to guide the precise placement of FSCV neurochemical sensing electrodes in the central nervous system. Despite these studies, FSCV has not been translated to other areas of the body outside the central nervous system.
There is a growing interest in stimulation of end organs and the autonomic nervous system as an emerging treatment of disorders such as hypertension and heart failure. An ideal biomarker for response to this stimulation is a real-time and clearly quantifiable measurement at a minimally invasive surface, making FSCV an interesting candidate. With peripheral nerve stimulation for disorders including hypertension and heart failure, a biomarker of action would be norepinephrine, as it is known that norepinephrine release in the kidney will increase blood pressure and heart rate. Norepinephrine has been measured in the blood using various techniques such as enzyme-linked immunosorbent assays (ELISA), mass-spectroscopy, and high performance liquid chromography (HPLC) with electrochemical detection; however, all of these techniques suffer the same weakness in that they require the blood to be drawn with variable post-draw lab time, which is too slow to capture a meaningful snapshot of effect. Measurement of FSCV in the blood gives a direct, sub-second biomarker of clinical stimulation for a variety of disorders that span the central and peripheral nervous system. This tutorial will cover the potential application of FSCV as a biomarker of effect for neural stimulation in the central and peripheral nervous system.
Erika K. Ross, Ph.D.
Erika is currently an Assistant Professor in Neurosurgery working in the Neural Engineering Laboratories at the Mayo Clinic. Prior to this, Erika completed her M.S. in Molecular Biology at the University of Denver and Ph.D. in Neuroscience at the Mayo Clinic. Her current research focus is investigating the circuit dynamics of neural stimulation and potential feedback mechanisms to improve central and peripheral nerve stimulation. Specifically, her work involves using fast scan cyclic voltammetery (FSCV) and imaging techniques to understand the local and global changes that occur with brain stimulation, with the goal of improving therapeutic application.