title: A neurochemical closed-loop controller for deep brain stimulation: toward individualized smart neuromodulation therapies.
abstract: Current strategies for optimizing deep brain stimulation (DBS) therapy involve multiple postoperative visits. During each visit, stimulation parameters are adjusted until desired therapeutic effects are achieved and adverse effects are minimized. However, the efficacy of these therapeutic parameters may decline with time due at least in part to disease progression, interactions between the host environment and the electrode, and lead migration. As such, development of closed-loop control systems that can respond to changing neurochemical environments, tailoring DBS therapy to individual patients, is paramount for improving the therapeutic efficacy of DBS. Evidence obtained using electrophysiology and imaging techniques in both animals and humans suggests that DBS works by modulating neural network activity. Recently, animal studies have shown that stimulation-evoked changes in neurotransmitter release that mirror normal physiology are associated with the therapeutic benefits of DBS. Therefore, to fully understand the neurophysiology of DBS and optimize its efficacy, it may be necessary to look beyond conventional electrophysiological analyses and characterize the neurochemical effects of therapeutic and non-therapeutic stimulation. By combining electrochemical monitoring and mathematical modeling techniques, we can potentially replace the trial-and-error process used in clinical programming with deterministic approaches that help attain optimal and stable neurochemical profiles. In this manuscript, we summarize the current understanding of electrophysiological and electrochemical processing for control of neuromodulation therapies. Additionally, we describe a proof-of-principle closed-loop controller that characterizes DBS-evoked dopamine changes to adjust stimulation parameters in a rodent model of DBS. The work described herein represents the initial steps toward achieving a "smart" neuroprosthetic system for treatment of neurologic and psychiatric disorders.
authors.affiliation: Mayo Clinic College of Medicine, Mayo Clinic Rochester, MN, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Grahn
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic Rochester, MN, USA.
authors.forename: Grant W
authors.initials: GW
authors.lastname: Mallory
authors.affiliation: Mayo Clinic College of Medicine, Mayo Clinic Rochester, MN, USA.
authors.forename: Obaid U
authors.initials: OU
authors.lastname: Khurram
authors.affiliation: Mayo Clinic College of Medicine, Mayo Clinic Rochester, MN, USA.
authors.forename: B Michael
authors.initials: BM
authors.lastname: Berry
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic Rochester, MN, USA.
authors.forename: Jan T
authors.initials: JT
authors.lastname: Hachmann
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic Rochester, MN, USA ; Department of Neurology, Mayo Clinic Rochester, MN, USA.
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Bieber
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic Rochester, MN, USA ; Division of Engineering, Mayo Clinic Rochester, MN, USA.
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Bennet
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic Rochester, MN, USA ; Department of Physiology and Biomedical Engineering, Mayo Clinic Rochester, MN, USA.
authors.forename: Hoon-Ki
authors.initials: HK
authors.lastname: Min
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic Rochester, MN, USA.
authors.forename: Su-Youne
authors.initials: SY
authors.lastname: Chang
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic Rochester, MN, USA ; Department of Physiology and Biomedical Engineering, Mayo Clinic Rochester, MN, USA.
authors.forename: Kendall H
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic Rochester, MN, USA ; Department of Physiology and Biomedical Engineering, Mayo Clinic Rochester, MN, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Lujan
keywords: deep brain stimulation (DBS); fast scan cyclic voltammetry (FSCV); feedback control systems; individualized medicine; local field potentials (LFP); machine learning