title: Development of the Mayo Investigational Neuromodulation Control System: toward a closed-loop electrochemical feedback system for deep brain stimulation.
abstract: OBJECTIVE
  Conventional deep brain stimulation (DBS) devices continue to rely on an open-loop system in which stimulation is independent of functional neural feedback. The authors previously proposed that as the foundation of a DBS "smart" device, a closed-loop system based on neurochemical feedback, may have the potential to improve therapeutic outcomes. Alterations in neurochemical release are thought to be linked to the clinical benefit of DBS, and fast-scan cyclic voltammetry (FSCV) has been shown to be effective for recording these evoked neurochemical changes. However, the combination of FSCV with conventional DBS devices interferes with the recording and identification of the evoked analytes. To integrate neurochemical recording with neurostimulation, the authors developed the Mayo Investigational Neuromodulation Control System (MINCS), a novel, wirelessly controlled stimulation device designed to interface with FSCV performed by their previously described Wireless Instantaneous Neurochemical Concentration Sensing System (WINCS).
  
  
  METHODS
  To test the functionality of these integrated devices, various frequencies of electrical stimulation were applied by MINCS to the medial forebrain bundle of the anesthetized rat, and striatal dopamine release was recorded by WINCS. The parameters for FSCV in the present study consisted of a pyramidal voltage waveform applied to the carbon-fiber microelectrode every 100 msec, ramping between -0.4 V and +1.5 V with respect to an Ag/AgCl reference electrode at a scan rate of either 400 V/sec or 1000 V/sec. The carbon-fiber microelectrode was held at the baseline potential of -0.4 V between scans.
  
  
  RESULTS
  By using MINCS in conjunction with WINCS coordinated through an optic fiber, the authors interleaved intervals of electrical stimulation with FSCV scans and thus obtained artifact-free wireless FSCV recordings. Electrical stimulation of the medial forebrain bundle in the anesthetized rat by MINCS elicited striatal dopamine release that was time-locked to stimulation and increased progressively with stimulation frequency.
  
  
  CONCLUSIONS
  Here, the authors report a series of proof-of-principle tests in the rat brain demonstrating MINCS to be a reliable and flexible stimulation device that, when used in conjunction with WINCS, performs wirelessly controlled stimulation concurrent with artifact-free neurochemical recording. These findings suggest that the integration of neurochemical recording with neurostimulation may be a useful first step toward the development of a closed-loop DBS system for human application.
authors.affiliation: Departments of Neurologic Surgery and.
authors.forename: Su-Youne
authors.initials: SY
authors.lastname: Chang
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Kimble
authors.forename: Inyong
authors.initials: I
authors.lastname: Kim
authors.forename: Seungleal B
authors.initials: SB
authors.lastname: Paek
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Kressin
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Boesche
authors.forename: Sidney V
authors.initials: SV
authors.lastname: Whitlock
authors.forename: Diane R
authors.initials: DR
authors.lastname: Eaker
authors.forename: Aimen
authors.initials: A
authors.lastname: Kasasbeh
authors.forename: April E
authors.initials: AE
authors.lastname: Horne
authors.forename: Charles D
authors.initials: CD
authors.lastname: Blaha
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Bennet
authors.forename: Kendall H
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000818:Animals; D015374:Biosensing Techniques / Q000592:standards; D003342:Corpus Striatum / Q000378:metabolism; D046690:Deep Brain Stimulation / Q000295:instrumentation* / Q000379:methods / Q000592:standards; D004298:Dopamine / Q000378:metabolism; D055664:Electrochemical Techniques / Q000592:standards; D004867:Equipment Design / Q000592:standards; D004864:Equipment and Supplies / Q000592:standards*; D025461:Feedback, Physiological / Q000502:physiology*; D008297:Male; D008474:Medial Forebrain Bundle / Q000502:physiology; D008839:Microelectrodes / Q000706:statistics & numerical data; D018377:Neurotransmitter Agents / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018377:Neurotransmitter Agents; D004298:Dopamine