title: Wireless control of intraspinal microstimulation in a rodent model of paralysis.
abstract: OBJECTIVE
  Despite a promising outlook, existing intraspinal microstimulation (ISMS) techniques for restoring functional motor control after spinal cord injury are not yet suitable for use outside a controlled laboratory environment. Thus, successful application of ISMS therapy in humans will require the use of versatile chronic neurostimulation systems. The objective of this study was to establish proof of principle for wireless control of ISMS to evoke controlled motor function in a rodent model of complete spinal cord injury.
  
  
  METHODS
  The lumbar spinal cord in each of 17 fully anesthetized Sprague-Dawley rats was stimulated via ISMS electrodes to evoke hindlimb function. Nine subjects underwent complete surgical transection of the spinal cord at the T-4 level 7 days before stimulation. Targeting for both groups (spinalized and control) was performed under visual inspection via dorsal spinal cord landmarks such as the dorsal root entry zone and the dorsal median fissure. Teflon-insulated stimulating platinum-iridium microwire electrodes (50 μm in diameter, with a 30- to 60-μm exposed tip) were implanted within the ventral gray matter to an approximate depth of 1.8 mm. Electrode implantation was performed using a free-hand delivery technique (n = 12) or a Kopf spinal frame system (n = 5) to compare the efficacy of these 2 commonly used targeting techniques. Stimulation was controlled remotely using a wireless neurostimulation control system. Hindlimb movements evoked by stimulation were tracked via kinematic markers placed on the hips, knees, ankles, and paws. Postmortem fixation and staining of the spinal cord tissue were conducted to determine the final positions of the stimulating electrodes within the spinal cord tissue.
  
  
  RESULTS
  The results show that wireless ISMS was capable of evoking controlled and sustained activation of ankle, knee, and hip muscles in 90% of the spinalized rats (n = 9) and 100% of the healthy control rats (n = 8). No functional differences between movements evoked by either of the 2 targeting techniques were revealed. However, frame-based targeting required fewer electrode penetrations to evoke target movements.
  
  
  CONCLUSIONS
  Clinical restoration of functional movement via ISMS remains a distant goal. However, the technology presented herein represents the first step toward restoring functional independence for individuals with chronic spinal cord injury.
authors.affiliation: Mayo Graduate School, Mayo Clinic, Rochester, Minnesota.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Grahn
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota.|Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota.
authors.forename: Kendall H
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota.
authors.forename: Aimen
authors.initials: A
authors.lastname: Kasasbeh
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota.
authors.forename: Grant W
authors.initials: GW
authors.lastname: Mallory
authors.affiliation: Mayo Graduate School, Mayo Clinic, Rochester, Minnesota.|Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota.
authors.forename: Jan T
authors.initials: JT
authors.lastname: Hachmann
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota.
authors.forename: John R
authors.initials: JR
authors.lastname: Dube
authors.affiliation: Division of Engineering, Mayo Clinic, Rochester, Minnesota.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Kimble
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota.
authors.forename: Darlene A
authors.initials: DA
authors.lastname: Lobel
authors.affiliation: Mayo Graduate School, Mayo Clinic, Rochester, Minnesota.|Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota.|Department of Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Allan
authors.initials: A
authors.lastname: Bieber
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota.
authors.forename: Ju Ho
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota.|Division of Engineering, Mayo Clinic, Rochester, Minnesota.
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Bennet
authors.affiliation: Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota.|Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota.
authors.forename: J Luis
authors.initials: JL
authors.lastname: Lujan
mesh_terms: D000818:Animals; D004558:Electric Stimulation / Q000379:methods*; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D008839:Microelectrodes; D023421:Models, Animal; D009068:Movement / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation / Q000502:physiology; D010243:Paralysis / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000628:therapy*; D016896:Treatment Outcome; D059015:Wireless Technology
keywords: EMG = electromyographic; ISMS = intraspinal microstimulation; MINCS = Mayo investigational neuromodulation control system; SCI = spinal cord injury; diagnostic and operative techniques; functional electrical stimulation; intraspinal microstimulation; spinal cord injury