Development of the Mayo Investigational Neuromodulation Control System: toward a closed-loop electrochemical feedback system for deep brain stimulation

Laboratory investigation

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  • 1 Departments of Neurologic Surgery and
  • 4 Physiology and Biomedical Engineering, and
  • 2 Division of Engineering, Mayo Clinic, Rochester, Minnesota; and
  • 3 Department of Psychology, University of Memphis, Tennessee
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Object

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.

Abbreviations used in this paper:ADC = analog-to-digital converter; CFM = carbon-fiber microelectrode; DAC = digital-to-analog converter; DBS = deep brain stimulation; FSCV = fast-scan cyclic voltammetry; MFB = medial forebrain bundle; MINCS = Mayo Investigational Neuromodulation Control System; WINCS = Wireless Instantaneous Neurochemical Concentration Sensing System.

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Contributor Notes

Dr. Chang and Mr. Kimble contributed equally to this work.

Address correspondence to: Kendall H. Lee, M.D., Ph.D., Departments of Neurologic Surgery and Physiology and Biomedical Engineering, Mayo Clinic, 200 First St. SW, Rochester, MN 55905. email: lee.kendall@mayo.edu.

Please include this information when citing this paper: published online October 11, 2013; DOI: 10.3171/2013.8.JNS122142.

  • 1

    Agarwal R, & Sarma SV: The effects of DBS patterns on basal ganglia activity and thalamic relay: a computational study. J Comput Neurosci 33:151167, 2012

    • Search Google Scholar
    • Export Citation
  • 2

    Agarwal R, & Sarma SV: Restoring the basal ganglia in Parkinson's disease to normal via multi-input phase-shifted deep brain stimulation. Conf Proc IEEE Eng Med Biol Soc 2010. 15391542, 2010

    • Search Google Scholar
    • Export Citation
  • 3

    Arfin SK, , Long MA, , Fee MS, & Sarpeshkar R: Wireless neural stimulation in freely behaving small animals. J Neurophysiol 102:598605, 2009

    • Search Google Scholar
    • Export Citation
  • 4

    Benabid AL: What the future holds for deep brain stimulation. Expert Rev Med Devices 4:895903, 2007

  • 5

    Benabid AL, , Chabardes S, , Mitrofanis J, & Pollak P: Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson's disease. Lancet Neurol 8:6781, 2009

    • Search Google Scholar
    • Export Citation
  • 6

    Benabid AL, & Torres N: New targets for DBS. Parkinsonism Relat Disord 18:Suppl 1 S21S23, 2012

  • 7

    Bledsoe JM, , Kimble CJ, , Covey DP, , Blaha CD, , Agnesi F, & Mohseni P, : Development of the Wireless Instantaneous Neurotransmitter Concentration System for intraoperative neurochemical monitoring using fast-scan cyclic voltammetry. Technical note. J Neurosurg 111:712723, 2009

    • Search Google Scholar
    • Export Citation
  • 8

    Carron R, , Chabardès S, & Hammond C: [Mechanisms of action of high-frequency deep brain stimulation. A review of the literature and current concepts.]. Neurochirurgie 58:209217, 2012. (Fr)

    • Search Google Scholar
    • Export Citation
  • 9

    Chang SY, , Jay T, , Muñoz J, , Kim I, & Lee KH: Wireless fast-scan cyclic voltammetry measurement of histamine using WINCS–a proof-of-principle study. Analyst 137:21582165, 2012

    • Search Google Scholar
    • Export Citation
  • 10

    Chang SY, , Kim I, , Marsh MP, , Jang DP, , Hwang SC, & Van Gompel JJ, : Wireless fast-scan cyclic voltammetry to monitor adenosine in patients with essential tremor during deep brain stimulation. Mayo Clin Proc 87:760765, 2012

    • Search Google Scholar
    • Export Citation
  • 11

    Cooper S, & Bowes M: Surgical considerations for tremor and dystonia. Cleve Clin J Med 79:Suppl 2 S40S43, 2012

  • 12

    Deuschl G, , Raethjen J, , Hellriegel H, & Elble R: Treatment of patients with essential tremor. Lancet Neurol 10:148161, 2011

  • 13

    Feng XJ, , Shea-Brown E, , Greenwald B, , Kosut R, & Rabitz H: Optimal deep brain stimulation of the subthalamic nucleus—a computational study. J Comput Neurosci 23:265282, 2007

    • Search Google Scholar
    • Export Citation
  • 14

    Foutz TJ, & McIntyre CC: Evaluation of novel stimulus waveforms for deep brain stimulation. J Neural Eng 7:066008, 2010

  • 15

    Garris PA, , Christensen JR, , Rebec GV, & Wightman RM: Real-time measurement of electrically evoked extracellular dopamine in the striatum of freely moving rats. J Neurochem 68:152161, 1997

    • Search Google Scholar
    • Export Citation
  • 16

    Greenberg BD, , Rauch SL, & Haber SN: Invasive circuitry-based neurotherapeutics: stereotactic ablation and deep brain stimulation for OCD. Neuropsychopharmacology 35:317336, 2010

    • Search Google Scholar
    • Export Citation
  • 17

    Griessenauer CJ, , Chang SY, , Tye SJ, , Kimble CJ, , Bennet KE, & Garris PA, : Wireless Instantaneous Neurotransmitter Concentration System: electrochemical monitoring of serotonin using fast-scan cyclic voltammetry—a proof-of-principle study. Laboratory investigation. J Neurosurg 113:656665, 2010

    • Search Google Scholar
    • Export Citation
  • 18

    Hammond C, , Ammari R, , Bioulac B, & Garcia L: Latest view on the mechanism of action of deep brain stimulation. Mov Disord 23:21112121, 2008

    • Search Google Scholar
    • Export Citation
  • 19

    Holtzheimer PE, & Mayberg HS: Deep brain stimulation for psychiatric disorders. Annu Rev Neurosci 34:289307, 2011

  • 20

    Johnson MD, , Miocinovic S, , McIntyre CC, & Vitek JL: Mechanisms and targets of deep brain stimulation in movement disorders. Neurotherapeutics 5:294308, 2008

    • Search Google Scholar
    • Export Citation
  • 21

    Kimble CJ, , Johnson DM, , Winter BA, , Whitlock SV, , Kressin KR, & Horne AE, : Wireless Instantaneous Neurotransmitter Concentration Sensing System (WINCS) for intraoperative neurochemical monitoring. Conf Proc IEEE Eng Med Biol Soc 2009:48564859, 2009

    • Search Google Scholar
    • Export Citation
  • 22

    Kuhr WG, , Bigelow JC, & Wightman RM: In vivo comparison of the regulation of releasable dopamine in the caudate nucleus and the nucleus accumbens of the rat brain. J Neurosci 6:974982, 1986

    • Search Google Scholar
    • Export Citation
  • 23

    Lee KH, , Blaha CD, & Bledsoe JM, Mechanisms of action of deep brain stimulation: a review. Krames ES, , Peckham PH, & Rezai AR: Neuromodulation Burlington, MA, Academic Press, 2009. 157169

    • Search Google Scholar
    • Export Citation
  • 24

    Lee KH, , Blaha CD, , Garris PA, , Mohseni P, , Horne AE, & Bennet KE, : Evolution of deep brain stimulation: human electrometer and smart devices supporting the next generation of therapy. Neuromodulation 12:85103, 2009

    • Search Google Scholar
    • Export Citation
  • 25

    Maciunas RJ, , Maddux BN, , Riley DE, , Whitney CM, , Schoenberg MR, & Ogrocki PJ, : Prospective randomized double-blind trial of bilateral thalamic deep brain stimulation in adults with Tourette syndrome. J Neurosurg 107:10041014, 2007

    • Search Google Scholar
    • Export Citation
  • 26

    McIntyre CC, , Grill WM, , Sherman DL, & Thakor NV: Cellular effects of deep brain stimulation: model-based analysis of activation and inhibition. J Neurophysiol 91:14571469, 2004

    • Search Google Scholar
    • Export Citation
  • 27

    McIntyre CC, , Savasta M, , Walter BL, & Vitek JL: How does deep brain stimulation work? Present understanding and future questions. J Clin Neurophysiol 21:4050, 2004

    • Search Google Scholar
    • Export Citation
  • 28

    Michael DJ, , Joseph JD, , Kilpatrick MR, , Travis ER, & Wightman RM: Improving data acquisition for fast-scan cyclic voltammetry. Anal Chem 71:39413947, 1999

    • Search Google Scholar
    • Export Citation
  • 29

    Paxinos G, & Watson C: The Rat Brain in Stereotaxic Coordinates ed 4 New York, Academic Press, 1998

  • 30

    Robinson DL, , Venton BJ, , Heien ML, & Wightman RM: Detecting subsecond dopamine release with fast-scan cyclic voltammetry in vivo. Clin Chem 49:17631773, 2003

    • Search Google Scholar
    • Export Citation
  • 31

    Schiff ND: Moving toward a generalizable application of central thalamic deep brain stimulation for support of forebrain arousal regulation in the severely injured brain. Ann N Y Acad Sci 1265:5668, 2012

    • Search Google Scholar
    • Export Citation
  • 32

    Shon YM, , Chang SY, , Tye SJ, , Kimble CJ, , Bennet KE, & Blaha CD, : Comonitoring of adenosine and dopamine using the Wireless Instantaneous Neurotransmitter Concentration System: proof of principle. Laboratory investigation. J Neurosurg 112:539548, 2010

    • Search Google Scholar
    • Export Citation
  • 33

    Shon YM, , Lee KH, , Goerss SJ, , Kim IY, , Kimble C, & Van Gompel JJ, : High frequency stimulation of the subthalamic nucleus evokes striatal dopamine release in a large animal model of human DBS neurosurgery. Neurosci Lett 475:136140, 2010

    • Search Google Scholar
    • Export Citation
  • 34

    Siddiqui MS, , Haq IU, & Okun MS: Deep brain stimulation in movement disorders. Continuum (Minneap Minn) 16:1 Movement Disorders 110130, 2010

    • Search Google Scholar
    • Export Citation
  • 35

    Welter ML, , Grabli D, & Vidailhet M: Deep brain stimulation for hyperkinetics disorders: dystonia, tardive dyskinesia, and tics. Curr Opin Neurol 23:420425, 2010

    • Search Google Scholar
    • Export Citation
  • 36

    Wiedemann DJ, , Garris PA, , Near JA, & Wightman RM: Effect of chronic haloperidol treatment on stimulated synaptic overflow of dopamine in the rat striatum. J Pharmacol Exp Ther 261:574579, 1992

    • Search Google Scholar
    • Export Citation
  • 37

    Wiedemann DJ, , Kawagoe KT, , Kennedy RT, , Ciolkowski EL, & Wightman RM: Strategies for low detection limit measurements with cyclic voltammetry. Anal Chem 63:29652970, 1991

    • Search Google Scholar
    • Export Citation
  • 38

    Wightman RM: Detection technologies. Probing cellular chemistry in biological systems with microelectrodes. Science 311:15701574, 2006

    • Search Google Scholar
    • Export Citation
  • 39

    Zimmerman JB, , Kennedy RT, & Wightman RM: Evoked neuronal activity accompanied by transmitter release increases oxygen concentration in rat striatum in vivo but not in vitro. J Cereb Blood Flow Metab 12:629637, 1992

    • Search Google Scholar
    • Export Citation
  • 40

    Zimmerman JB, & Wightman RM: Simultaneous electrochemical measurements of oxygen and dopamine in vivo. Anal Chem 63:2428, 1991

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