Advances in neurochemical measurements: A review of biomarkers and devices for the development of closed-loop deep brain stimulation systems

Abstract

Neurochemical recording techniques have expanded our understanding of the pathophysiology of neurological disorders, as well as the mechanisms of action of treatment modalities like deep brain stimulation (DBS). DBS is used to treat diseases such as Parkinson's disease, Tourette syndrome, and obsessive-compulsive disorder, among others. Although DBS is effective at alleviating symptoms related to these diseases and improving the quality of life of these patients, the mechanism of action of DBS is currently not fully understood. A leading hypothesis is that DBS modulates the electrical field potential by modifying neuronal firing frequencies to non-pathological rates thus providing therapeutic relief. To address this gap in knowledge, recent advances in electrochemical sensing techniques have given insight into the importance of neurotransmitters, such as dopamine, serotonin, glutamate, and adenosine, in disease pathophysiology. These studies have also highlighted their potential use in tandem with electrophysiology to serve as biomarkers in disease diagnosis and progression monitoring, as well as characterize response to treatment. Here, we provide an overview of disease-relevant neurotransmitters and their roles and implications as biomarkers, as well as innovations to the biosensors used to record these biomarkers. Furthermore, we discuss currently available neurochemical and electrophysiological recording devices, and discuss their viability to be implemented into the development of a closed-loop DBS system.

Keywords: closed-loop; deep brain stimulation; electrochemistry; electrophysiology; neuromodulation; voltammetry.

Figure 1:

Depiction of a closed-loop DBS system utilizing the OODA loop framework. Abbreviations: PCA – principle component analysis; ICA – independent component analysis; FFT – fast Fourier transform; PID – proportional-integral-derivative.

Figure 2:

A schematic showcasing disease-relevant biomarkers and applicable neurochemical sensing devices. Abbreviations: MDD – major depressive disorder; HDCV – high-definition cyclic voltammetry; FSCV – fast-scan cyclic voltammetry.