WINCS Harmoni: Closed-loop dynamic neurochemical control of therapeutic interventions

Kendall H. Lee; J. Luis Lujan; James K. Trevathan; Erika K. Ross; John J. Bartoletta; Hyung Ook Park; Seungleal Brian Paek; Evan N. Nicolai; Jannifer H. Lee; Hoon-Ki Min; Christopher J. Kimble; Charles D. Blaha; Kevin E. Bennet

doi:10.1038/srep46675

journal article Open Access Apr 28, 2017

WINCS Harmoni: Closed-loop dynamic neurochemical control of therapeutic interventions

Kendall H. Lee J. Luis Lujan James K. Trevathan Erika K. Ross John J. Bartoletta Hyung Ook Park Seungleal Brian Paek Evan N. Nicolai Jannifer H. Lee Hoon-Ki Min

Christopher J. Kimble Charles D. Blaha Kevin E. Bennet

Scientific Reports Vol. 7 No. 1 · Springer Science and Business Media LLC

View at Publisher Save 10.1038/srep46675

Abstract

AbstractThere has been significant progress in understanding the role of neurotransmitters in normal and pathologic brain function. However, preclinical trials aimed at improving therapeutic interventions do not take advantage of real-time in vivo neurochemical changes in dynamic brain processes such as disease progression and response to pharmacologic, cognitive, behavioral, and neuromodulation therapies. This is due in part to a lack of flexible research tools that allow in vivo measurement of the dynamic changes in brain chemistry. Here, we present a research platform, WINCS Harmoni, which can measure in vivo neurochemical activity simultaneously across multiple anatomical targets to study normal and pathologic brain function. In addition, WINCS Harmoni can provide real-time neurochemical feedback for closed-loop control of neurochemical levels via its synchronized stimulation and neurochemical sensing capabilities. We demonstrate these and other key features of this platform in non-human primate, swine, and rodent models of deep brain stimulation (DBS). Ultimately, systems like the one described here will improve our understanding of the dynamics of brain physiology in the context of neurologic disease and therapeutic interventions, which may lead to the development of precision medicine and personalized therapies for optimal therapeutic efficacy.

Topics

No keywords indexed for this article. Browse by subject →

References

84

[1]

Jeanneteau, F. et al. A functional variant of the dopamine D3 receptor is associated with risk and age-at-onset of essential tremor. Proc. Natl. Acad. Sci. USA 103, 10753–10758 (2006). 10.1073/pnas.0508189103

[2]

Horak, F. B., Frank, J. & Nutt, J. Effects of dopamine on postural control in parkinsonian subjects: scaling, set, and tone. J. Neurophysiol. 75, 2380–2396 (1996). 10.1152/jn.1996.75.6.2380

[3]

Foley, T. E. & Fleshner, M. Neuroplasticity of dopamine circuits after exercise: implications for central fatigue. Neuromolecular Med. 10, 67–80 (2008). 10.1007/s12017-008-8032-3

[4]

Lewis, S. J. G., Dove, A., Robbins, T. W., Barker, R. A. & Owen, A. M. Cognitive Impairments in Early Parkinson’s Disease Are Accompanied by Reductions in Activity in Frontostriatal Neural Circuitry. J. Neurosci. 23, 6351–6356 (2003). 10.1523/jneurosci.23-15-06351.2003

[5]

Parsey, R. V. et al. Dopamine D2 receptor availability and amphetamine-induced dopamine release in unipolar depression. Biol. Psychiatry 50, 313–322 (2001). 10.1016/s0006-3223(01)01089-7

[6]

Schneier, F. R. et al. Dopamine transporters, D2 receptors, and dopamine release in generalized social anxiety disorder. Depress. Anxiety 26, 411–418 (2009). 10.1002/da.20543

[7]

Cummings, J. L. Depression and Parkinson’s disease: a review. Am. J. Psychiatry 149, 443–454 (1992). 10.1176/ajp.149.4.443

[8]

Naughton, M., Mulrooney, J. B. & Leonard, B. E. A review of the role of serotonin receptors in psychiatric disorders. Hum. Psychopharmacol. Clin. Exp. 15, 397–415 (2000). 10.1002/1099-1077(200008)15:6<397::aid-hup212>3.0.co;2-l

[9]

Organization, W. H. Neurological disorders: public health challenges. (World Health Organization, 2006).

[10]

Parpura, V. et al. Neuromodulation: selected approaches and challenges. J. Neurochem. 124, 436–453 (2013). 10.1111/jnc.12105

[11]

Benabid, A. L., Pollak, P., Louveau, A., Henry, S. & de Rougemont, J. Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. Appl. Neurophysiol. 50, 344–346 (1987).

[12]

Benabid, A. L. et al. Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. The Lancet 337, 403–406 (1991). 10.1016/0140-6736(91)91175-t

[13]

Blomstedt, P. & Hariz, M. I. Deep brain stimulation for movement disorders before DBS for movement disorders. Parkinsonism Relat. Disord. 16, 429–433 (2010). 10.1016/j.parkreldis.2010.04.005

[14]

Youngerman, B. E., Chan, A. K., Mikell, C. B., McKhann, G. M. & Sheth, S. A. A decade of emerging indications: deep brain stimulation in the United States. J. Neurosurg. 125, 461–471 (2016). 10.3171/2015.7.jns142599

[15]

O’Reardon, J. P., Cristancho, P. & Peshek, A. D. Vagus Nerve Stimulation (VNS) and Treatment of Depression: To the Brainstem and Beyond. Psychiatry Edgmont Pa Townsh. 3, 54–63 (2006).

[16]

McIntyre, C. C., Savasta, M., Kerkerian-Le Goff, L. & Vitek, J. L. Uncovering the mechanism(s) of action of deep brain stimulation: activation, inhibition, or both. Clin. Neurophysiol. 115, 1239–1248 (2004). 10.1016/j.clinph.2003.12.024

[17]

Shah, R. S. et al. Deep Brain Stimulation: Technology at the Cutting Edge. J. Clin. Neurol. 6, 167 (2010). 10.3988/jcn.2010.6.4.167

[18]

Lee, K. H. et al. Dopamine efflux in the rat striatum evoked by electrical stimulation of the subthalamic nucleus: potential mechanism of action in Parkinson’s disease. Eur. J. Neurosci. 23, 1005–1014 (2006). 10.1111/j.1460-9568.2006.04638.x

[19]

Tremblay, S. et al. Relationship between transcranial magnetic stimulation measures of intracortical inhibition and spectroscopy measures of GABA and glutamate+ glutamine. J. Neurophysiol. 109, 1343–1349 (2013). 10.1152/jn.00704.2012

[20]

Cantello, R. et al. Parkinson’s disease rigidity: magnetic motor evoked potentials in a small hand muscle. Neurology 41, 1449–1456 (1991). 10.1212/wnl.41.9.1449

[21]

The natural history of central motor abnormalities in amyotrophic lateral sclerosis

K. R. Mills

Brain 2003 10.1093/brain/awg260

[22]

Ziemann, U., Paulus, W. & Rothenberger, A. Decreased motor inhibition in Tourette’s disorder: evidence from transcranial magnetic stimulation. Am. J. Psychiatry 154, 1277–1284 (1997). 10.1176/ajp.154.9.1277

[23]

Di Lazzaro, V. et al. Reduced cerebral cortex inhibition in dystonia: direct evidence in humans. Clin. Neurophysiol. Off. J. Int. Fed. Clin. Neurophysiol. 120, 834–839 (2009). 10.1016/j.clinph.2009.02.001

[24]

Dorr, A. E. & Debonnel, G. Effect of Vagus Nerve Stimulation on Serotonergic and Noradrenergic Transmission. J. Pharmacol. Exp. Ther. 318, 890–898 (2006). 10.1124/jpet.106.104166

[25]

Hashimoto, T., Elder, C. M., Okun, M. S., Patrick, S. K. & Vitek, J. L. Stimulation of the Subthalamic Nucleus Changes the Firing Pattern of Pallidal Neurons. J. Neurosci. 23, 1916–1923 (2003). 10.1523/jneurosci.23-05-01916.2003

[26]

Kita, H., Tachibana, Y., Nambu, A. & Chiken, S. Balance of Monosynaptic Excitatory and Disynaptic Inhibitory Responses of the Globus Pallidus Induced after Stimulation of the Subthalamic Nucleus in the Monkey. J. Neurosci. 25, 8611–8619 (2005). 10.1523/jneurosci.1719-05.2005

[27]

Miocinovic, S. et al. Computational Analysis of Subthalamic Nucleus and Lenticular Fasciculus Activation During Therapeutic Deep Brain Stimulation. J. Neurophysiol. 96, 1569–1580 (2006). 10.1152/jn.00305.2006

[28]

Benazzouz, A. et al. Effect of high-frequency stimulation of the subthalamic nucleus on the neuronal activities of the substantia nigra pars reticulata and ventrolateral nucleus of the thalamus in the rat. Neuroscience 99, 289–295 (2000). 10.1016/s0306-4522(00)00199-8

[29]

Maurice, N., Thierry, A.-M., Glowinski, J. & Deniau, J.-M. Spontaneous and Evoked Activity of Substantia Nigra Pars Reticulata Neurons during High-Frequency Stimulation of the Subthalamic Nucleus. J. Neurosci. 23, 9929–9936 (2003). 10.1523/jneurosci.23-30-09929.2003

[30]

Smith, I. D. & Grace, A. A. Role of the subthalamic nucleus in the regulation of nigral dopamine neuron activity. Synap. N. Y. N 12, 287–303 (1992). 10.1002/syn.890120406

[31]

Malone, D. A. et al. Deep brain stimulation of the ventral capsule/ventral striatum for treatment-resistant depression. Biol. Psychiatry 65, 267–275 (2009). 10.1016/j.biopsych.2008.08.029

[32]

Deep Brain Stimulation for Treatment-Resistant Depression

Helen S. Mayberg, Andres M. Lozano, Valerie Voon et al.

Neuron 2005 10.1016/j.neuron.2005.02.014

[33]

Haslinger, B. et al. Differential modulation of subcortical target and cortex during deep brain stimulation. NeuroImage 18, 517–524 (2003). 10.1016/s1053-8119(02)00043-5

[34]

Perlmutter, J. S. et al. Blood flow responses to deep brain stimulation of thalamus. Neurology 58, 1388–1394 (2002). 10.1212/wnl.58.9.1388

[35]

Deuschl, G. et al. The pathophysiology of parkinsonian tremor: a review. J. Neurol. 247 Suppl 5, V33–48 (2000). 10.1007/pl00007781

[36]

Schnitzler, A., Münks, C., Butz, M., Timmermann, L. & Gross, J. Synchronized brain network associated with essential tremor as revealed by magnetoencephalography. Mov. Disord. Off. J. Mov. Disord. Soc. 24, 1629–1635 (2009). 10.1002/mds.22633

[37]

Robbins, T. W. & Everitt, B. J. Functions of dopamine in the dorsal and ventral striatum. Semin. Neurosci. 4, 119–127 (1992). 10.1016/1044-5765(92)90010-y

[38]

Agnesi, F. et al. Wireless Instantaneous Neurotransmitter Concentration System–based amperometric detection of dopamine, adenosine, and glutamate for intraoperative neurochemical monitoring. J. Neurosurg. 111, 701 (2009). 10.3171/2009.3.jns0990

[39]

Bledsoe, J. M. et al. Development of the Wireless Instantaneous Neurotransmitter Concentration System for intraoperative neurochemical monitoring using fast-scan cyclic voltammetry: Technical note. J. Neurosurg. 111, 712 (2009). 10.3171/2009.3.jns081348

[40]

Robinson, D. L., Venton, B. J., Heien, M. L. A. V. & Wightman, R. M. Detecting subsecond dopamine release with fast-scan cyclic voltammetry in vivo . Clin. Chem. 49, 1763–1773 (2003). 10.1373/49.10.1763

[41]

Swamy, B. E. K. & Venton, B. J. Carbon nanotube-modified microelectrodes for simultaneous detection of dopamine and serotonin in vivo . The Analyst 132, 876–884 (2007). 10.1039/b705552h

[42]

Griessenauer, C. J. et al. Wireless Instantaneous Neurotransmitter Concentration System: electrochemical monitoring of serotonin using fast-scan cyclic voltammetry–a proof-of-principle study. J. Neurosurg. 113, 656–665 (2010). 10.3171/2010.3.jns091627

[43]

Hashemi, P., Dankoski, E. C., Wood, K. M., Ambrose, R. E. & Wightman, R. M. In vivo electrochemical evidence for simultaneous 5-HT and histamine release in the rat substantia nigra pars reticulata following medial forebrain bundle stimulation. J. Neurochem. 118, 749–759 (2011). 10.1111/j.1471-4159.2011.07352.x

[44]

Trevathan, J. K. et al. Computational Modeling of Neurotransmitter Release Evoked by Electrical Stimulation: Nonlinear Approaches to Predicting Stimulation-Evoked Dopamine Release. ACS Chem. Neurosci. 8, 394–410 (2017). 10.1021/acschemneuro.6b00319

[45]

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

Su-Youne Chang, Christopher J. Kimble, Inyong Kim et al.

Journal of Neurosurgery 2013 10.3171/2013.8.jns122142

[46]

Venton, B. J., Troyer, K. P. & Wightman, R. M. Response Times of Carbon Fiber Microelectrodes to Dynamic Changes in Catecholamine Concentration. Anal. Chem. 74, 539–546 (2002). 10.1021/ac010819a

[47]

Bucher, E. S. & Wightman, R. M. Electrochemical Analysis of Neurotransmitters. Annu. Rev. Anal. Chem. 8, 239–261 (2015). 10.1146/annurev-anchem-071114-040426

[48]

Crowell, A. L., Garlow, S. J., Riva-Posse, P. & Mayberg, H. S. Characterizing the therapeutic response to deep brain stimulation for treatment-resistant depression: a single center long-term perspective. Front. Integr. Neurosci. 9, 41 (2015). 10.3389/fnint.2015.00041

[49]

Cury, R. G. et al. Effects of deep brain stimulation on pain and other nonmotor symptoms in Parkinson disease. Neurology 83, 1403–1409 (2014). 10.1212/wnl.0000000000000887

[50]

Miocinovic, S., de Hemptinne, C., Qasim, S., Ostrem, J. L. & Starr, P. A. Patterns of Cortical Synchronization in Isolated Dystonia Compared With Parkinson Disease. JAMA Neurol. 72, 1244–1251 (2015). 10.1001/jamaneurol.2015.2561

Showing 50 of 84 references

Cited By

56

Sensitive and Selective Measurement of Serotonin in Vivo Using Fast Cyclic Square-Wave Voltammetry

HoJin Shin, Yoonbae Oh · 2019

Analytical Chemistry

Approaches to closed-loop deep brain stimulation for movement disorders

Chao-Hung Kuo, Gabrielle A. White-Dzuro · 2018

Neurosurgical Focus

Metrics

56

Citations

84

References

Details

Published: Apr 28, 2017
Vol/Issue: 7(1)
License: View

Authors

K

Kendall H. Lee

Departments of Neurologic Surgery,; Biomedical Engineering,

Radiology, and

Christopher J. Kimble

C

Charles D. Blaha

Department of Psychology; University of Memphis; Memphis TN USA

K

Kevin E. Bennet

Cite This Article

Kendall H. Lee, J. Luis Lujan, James K. Trevathan, et al. (2017). WINCS Harmoni: Closed-loop dynamic neurochemical control of therapeutic interventions. Scientific Reports, 7(1). https://doi.org/10.1038/srep46675

WINCS Harmoni: Closed-loop dynamic neurochemical control of therapeutic interventions

You May Also Like