(Invited) Using Fast Scan Cyclic Voltammetry to elucidate the mechanism of action of Deep Brain Stimulation

Object The authors previously reported the development of the Wireless Instantaneous Neurotransmitter Concentration System (WINCS) for measuring dopamine and suggested that this technology may be useful for evaluating deep brain stimulation–related neuromodulatory effects on neurotransmitter systems. The WINCS supports fast-scan cyclic voltammetry (FSCV) at a carbon-fiber microelectrode (CFM) for real-time, spatially resolved neurotransmitter measurements. The FSCV parameters used to establish WINCS dopamine measurements are not suitable for serotonin, a neurotransmitter implicated in depression, because they lead to CFM fouling and a loss of sensitivity. Here, the authors incorporate into WINCS a previously described N-shaped waveform applied at a high scan rate to establish wireless serotonin monitoring. Methods Optimized for the detection of serotonin, FSCV consisted of an N-shaped waveform scanned linearly from a resting potential of +0.2 to +1.0 V, then to −0.1 V and back to +0.2 V, at a rate of 1000 V/second. Proof-of-principle tests included flow injection analysis and electrically evoked serotonin release in the dorsal raphe nucleus of rat brain slices. Results Flow cell injection analysis demonstrated that the N waveform, applied at a scan rate of 1000 V/second, significantly reduced serotonin fouling of the CFM, relative to that observed with FSCV parameters for dopamine. In brain slices, WINCS reliably detected subsecond serotonin release in the dorsal raphe nucleus evoked by local high-frequency stimulation. Conclusions The authors found that WINCS supported high-fidelity wireless serotonin monitoring by FSCV at a CFM. In the future such measurements of serotonin in large animal models and in humans may help to establish the mechanism of deep brain stimulation for psychiatric disease.

Download Full-text

Emerging techniques for elucidating mechanism of action of deep brain stimulation

2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society ◽

10.1109/iembs.2011.6090152 ◽

2011 ◽

Cited By ~ 3

Author(s):

Kendall H. Lee ◽

Su-Youne Chang ◽

Dong-Pyo Jang ◽

Inyong Kim ◽

Stephan Goerss ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Mechanism Of Action ◽

Brain Stimulation ◽

Deep Brain

Download Full-text

Analysis of the Mechanism of Action of Deep Brain Stimulation Using the Concepts of Dither Injection and the Equivalent Nonlinearity

IEEE Transactions on Biomedical Engineering ◽

10.1109/tbme.2009.2019962 ◽

2009 ◽

Vol 56 (11) ◽

pp. 2717-2720 ◽

Cited By ~ 24

Author(s):

Annraoi M. de Paor ◽

Madeleine M. Lowery

Keyword(s):

Deep Brain Stimulation ◽

Mechanism Of Action ◽

Brain Stimulation ◽

Deep Brain

Download Full-text

Coherence: a unifying mechanism of deep brain stimulation

Journal of Neurophysiology ◽

10.1152/jn.00563.2018 ◽

2019 ◽

Vol 121 (1) ◽

pp. 1-3 ◽

Cited By ~ 2

Author(s):

Bassam Al-Fatly

Keyword(s):

Deep Brain Stimulation ◽

Mechanism Of Action ◽

Brain Stimulation ◽

Neurological Diseases ◽

New Evidence ◽

Deep Brain

Deep brain stimulation is a powerful neurostimulation technique that proved its efficacy in treating a group of neurological diseases. Several scientific works tried to understand the mechanism of action of deep brain stimulation. Wang et al. ( J Neurosci 38: 4556–4568, 2018) demonstrated new evidence on the role of interregional neuro-oscillatory coherence as a promising model to explain mechanism the of deep brain stimulation.

Download Full-text

S.21.04 The mechanism of action of deep brain stimulation: preclinical and clinical evidence

European Neuropsychopharmacology ◽

10.1016/s0924-977x(12)70182-7 ◽

2012 ◽

Vol 22 ◽

pp. S139

Author(s):

D. Denys

Keyword(s):

Deep Brain Stimulation ◽

Mechanism Of Action ◽

Brain Stimulation ◽

Clinical Evidence ◽

Deep Brain

Download Full-text

Deep Brain Stimulation for Alzheimer's Disease: Stimulation Parameters and Potential Mechanisms of Action

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.619543 ◽

2021 ◽

Vol 13 ◽

Author(s):

Yinpei Luo ◽

Yuwei Sun ◽

Xuelong Tian ◽

Xiaolin Zheng ◽

Xing Wang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Deep Brain Stimulation ◽

Mechanism Of Action ◽

Brain Stimulation ◽

Animal Studies ◽

Potential Mechanism ◽

Stimulation Parameters ◽

Positive Effect ◽

Deep Brain

Deep brain stimulation (DBS) is a neurosurgical technique that regulates neuron activity by using internal pulse generators to electrodes in specific target areas of the brain. As a blind treatment, DBS is widely used in the field of mental and neurological diseases, although its mechanism of action is still unclear. In the past 10 years, DBS has shown a certain positive effect in animal models and patients with Alzheimer's disease (AD), but there are also different results that may be related to the stimulation parameters of DBS. Based on this, determining the optimal stimulation parameters for DBS in AD and understanding its mechanism of action are essential to promote the clinical application of DBS in AD. This review aims to explore the therapeutic effect of DBS in AD, and to analyze its stimulation parameters and potential mechanism of action. The keywords “Deep brain stimulation” and “Alzheimer's Disease” were used for systematic searches in the literature databases of Web of Science and PubMed (from 1900 to September 29, 2020). All human clinical studies and animal studies were reported in English, including individual case studies and long-term follow-up studies, were included. These studies described the therapeutic effects of DBS in AD. The results included 16 human clinical studies and 14 animal studies, of which 28 studies clearly demonstrated the positive effect of DBS in AD. We analyzed the current stimulation parameters of DBS in AD from stimulation target, stimulation frequency, stimulation start time, stimulation duration, unilateral/bilateral treatment and current intensity, etc., and we also discussed its potential mechanism of action from multiple aspects, including regulating related neural networks, promoting nerve oscillation, reducing β-amyloid and tau levels, reducing neuroinflammation, regulating the cholinergic system, inducing the synthesis of nerve growth factor.

Download Full-text

Development of intraoperative electrochemical detection: wireless instantaneous neurochemical concentration sensor for deep brain stimulation feedback

Neurosurgical FOCUS ◽

10.3171/2010.5.focus10110 ◽

2010 ◽

Vol 29 (2) ◽

pp. E6 ◽

Cited By ~ 28

Author(s):

Jamie J. Van Gompel ◽

Su-Youne Chang ◽

Stephan J. Goerss ◽

In Yong Kim ◽

Christopher Kimble ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Electrochemical Detection ◽

Brain Stimulation ◽

Fast Scan Cyclic Voltammetry ◽

Detection Techniques ◽

Detection Systems ◽

Electrochemical Application ◽

Neurochemical Changes ◽

Deep Brain

Deep brain stimulation (DBS) is effective when there appears to be a distortion in the complex neurochemical circuitry of the brain. Currently, the mechanism of DBS is incompletely understood; however, it has been hypothesized that DBS evokes release of neurochemicals. Well-established chemical detection systems such as microdialysis and mass spectrometry are impractical if one is assessing changes that are happening on a second-to-second time scale or for chronically used implanted recordings, as would be required for DBS feedback. Electrochemical detection techniques such as fast-scan cyclic voltammetry (FSCV) and amperometry have until recently remained in the realm of basic science; however, it is enticing to apply these powerful recording technologies to clinical and translational applications. The Wireless Instantaneous Neurochemical Concentration Sensor (WINCS) currently is a research device designed for human use capable of in vivo FSCV and amperometry, sampling at subsecond time resolution. In this paper, the authors review recent advances in this electrochemical application to DBS technologies. The WINCS can detect dopamine, adenosine, and serotonin by FSCV. For example, FSCV is capable of detecting dopamine in the caudate evoked by stimulation of the subthalamic nucleus/substantia nigra in pig and rat models of DBS. It is further capable of detecting dopamine by amperometry and, when used with enzyme linked sensors, both glutamate and adenosine. In conclusion, WINCS is a highly versatile instrument that allows near real-time (millisecond) detection of neurochemicals important to DBS research. In the future, the neurochemical changes detected using WINCS may be important as surrogate markers for proper DBS placement as well as the sensor component for a “smart” DBS system with electrochemical feedback that allows automatic modulation of stimulation parameters. Current work is under way to establish WINCS use in humans.

Download Full-text