Second-Derivative-Based Background Drift Removal for a Tonic Dopamine Measurement in Fast-Scan Cyclic Voltammetry

Abstract

The dysregulation of dopamine, a neuromodulator, is associated with a broad spectrum of brain disorders, including Parkinson's disease, addiction, and schizophrenia. Quantitative measurements of dopamine are essential for understanding dopamine functional dynamics. Fast-scan cyclic voltammetry (FSCV) is the most widely used electrochemical technique for measuring real-time in vivo dopamine level changes. Standard FSCV has only been used to analyze "phasic dopamine" (changes in seconds), because the gradual generation of background charging current is inevitable, and acts as the main noise source in the low-frequency band. Although "tonic dopamine" (changes in minutes to hours) is key for understanding the dopamine system, an electrochemical technique capable of simultaneously measuring phasic and tonic dopamine in an in vivo environment has not been established. Several modified voltammetric techniques have been developed for measuring tonic dopamine, but the sampling rates (0.1-0.05 Hz) are too low to be useful. Further investigation of the in vivo applicability of previously developed background drift removal methods for measuring tonic dopamine levels is required. We developed a second-derivative-based background removal (SDBR) method for simultaneously measuring phasic and tonic neurotransmitter levels in real-time. The performance of this technique was tested via in silico and in vitro tonic dopamine experiments. Furthermore, its applicability was tested in vivo. SDBR is a simple, robust, post-processing technique that can extract tonic neurotransmitter levels from all FSCV data. As SDBR is calculated in individual-scan voltammogram units, it can be applied to any real-time closed-loop system that uses a neurotransmitter as a biomarker.

Continuous long-range measurement of tonic dopamine with advanced FSCV for pharmacodynamic analysis of levodopa-induced dyskinesia in Parkinson’s disease

“…Thus, the tonic DA level remains unaffected by background drift accumulation over repeated scans (blue arrow) ( Figure 1F ). In the previous study, we confirmed sensitivity and selectivity of the advanced FSCV technique with SDBR in vitro ( Kang et al, 2022 ). Regarding the sensitivity of its method, we analyzed calibration plot against various dopamine concentrations (62.5–1,000 nM).…”

“…However, continuous FSCV amplifies noise signals, notably from chemical adsorption on the surface of the carbon probe, which poses challenges in signal detection. In the previous study, we developed an FSCV technique used in conjunction with the SDBR method and examined the DA selectivity and sensitivity of the technique in vitro and in vivo ( Kang et al, 2022 ). In the current study, while building upon our prior findings, we have extended the application of this technique for in vivo pharmacodynamic analysis of levodopa-induced dyskinesia (LID) in the PD model.…”

“…The recorded in vivo SDBR value was converted into an estimated DA concentration with linear regression performed using an in vitro test result. Detailed procedures and outcomes across all in vitro experiments, including sensitivity and selectivity tests, were described in the previous research ( Kang et al, 2022 ). In short, CFME and Ag/AgCl reference electrodes were placed in a beaker filled with 0.05 M, pH 7.4 phosphate-buffered saline (PBS).…”

“…Recently, we introduced the advanced FSCV technique with second-derivative-based background drift removal (SDBR), which identifies the continuous dynamics of tonic DA levels with the high temporal resolution offered by standard FSCV data recorded over long durations. This dopamine sensing platform has been validated on its sensitivity and selectivity by in vitro and in vivo experiments ( Kang et al, 2022 ).…”

Highly Deformable Double‐Sided Neural Probe with All‐in‐One Electrode System for Real‐Time In Vivo Detection of Dopamine for Parkinson's Disease

“…Real-time monitoring of DA levels in the brain is crucial, and various techniques have been developed to achieve this, ranging from microdialysis to fast-scan cyclic voltammetry (FSCV) techniques, using different types of neural probes. [10][11][12] While various types of probes have been proven to be useful tools for studying DA dynamics in the brain, they often suffer from drawbacks associated with the use of rigid materials. [13][14][15] One of the most significant drawbacks is the potential for undesirable tissue damage caused by the mechanical mismatch between the rigid probe and the soft tissues of the brain.…”