title: Functional MRI-navigated repetitive transcranial magnetic stimulation over supplementary motor area in chronic tic disorders.
abstract: BACKGROUND
  Open label studies have shown repetitive transcranial magnetic stimulation to be effective in reducing tics.
  
  
  OBJECTIVE
  To determine whether 8 sessions of continuous theta burst stimulation (cTBS) over supplementary motor area (SMA) given over 2 days may reduce tics and motor cortical network activity in Tourette syndrome/chronic tic disorders.
  
  
  METHODS
  This was a randomized (1:1), double-blind, sham-controlled trial of functional MRI (fMRI)-navigated, 30 Hz cTBS at 90% of resting motor threshold (RMT) over SMA in 12 patients ages 10-22 years. Comorbid ADHD (n = 8), OCD (n = 8), and stable concurrent medications (n = 9) were permitted. Neuro-navigation utilized each individual's event-related fMRI signal. Primary clinical and cortical outcomes were: 1) Yale Global Tic Severity Scale (YGTSS) at one week; 2) fMRI event-related signal in SMA and primary motor cortex (M1) during a finger-tapping motor task.
  
  
  RESULTS
  Baseline characteristics were not statistically different between groups (age, current tic/OCD/ADHD severities, tic-years, number of prior medication trials, RMT). Mean YGTSS scores decreased in both active (27.5 ± 7.4 to 23.2 ± 9.8) and sham (26.8 ± 4.8 to 21.7 ± 7.7) groups. However, no significant difference in video-based tic severity rating was detected between the two groups. Two-day post-treatment fMRI activation during finger tapping decreased significantly in active vs. sham groups for SMA (P = 0.02), left M1 (P = 0.0004), and right M1 (P < 0.0001). No serious adverse events occurred.
  
  
  CONCLUSIONS
  Active, fMRI-navigated cTBS administered in 8 sessions over 2 days to the SMA induced significant inhibition in the motor network (SMA, bilateral M1). However, both groups on average experienced tic reduction at 7 days. Larger sample size and protocol modifications may be needed to produce clinically significant tic reduction beyond placebo effect.
authors.affiliation: Cincinnati Children's Hospital Medical Center, Division of Neurology, 3333 Burnet Ave., MLC 2015, Cincinnati, OH 45229, USA. Electronic address: steve.wu@cchmc.org.
authors.forename: Steve W
authors.initials: SW
authors.lastname: Wu
authors.affiliation: Cincinnati Children's Hospital Medical Center, Division of Radiology, 3333 Burnet Ave., MLC 5033, Cincinnati, OH 45229, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Maloney
authors.affiliation: Cincinnati Children's Hospital Medical Center, Division of Neurology, 3333 Burnet Ave., MLC 2015, Cincinnati, OH 45229, USA.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Gilbert
authors.affiliation: Cincinnati Children's Hospital Medical Center, Division of Neurology, 3333 Burnet Ave., MLC 2015, Cincinnati, OH 45229, USA.
authors.forename: Stephan G
authors.initials: SG
authors.lastname: Dixon
authors.affiliation: Cincinnati Children's Hospital Medical Center, Division of Neurology, 3333 Burnet Ave., MLC 2015, Cincinnati, OH 45229, USA.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Horn
authors.affiliation: Cincinnati Children's Hospital Medical Center, Division of Neurology, 3333 Burnet Ave., MLC 2015, Cincinnati, OH 45229, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Huddleston
authors.affiliation: Cincinnati Children's Hospital Medical Center, Division of Radiology, 3333 Burnet Ave., MLC 5033, Cincinnati, OH 45229, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Eaton
authors.affiliation: Cincinnati Children's Hospital Medical Center, Division of Neurology, 3333 Burnet Ave., MLC 2015, Cincinnati, OH 45229, USA; Cincinnati Children's Hospital Medical Center, Division of Radiology, 3333 Burnet Ave., MLC 5033, Cincinnati, OH 45229, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Vannest
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000503:physiopathology; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009044:Motor Cortex / Q000503:physiopathology*; D013981:Tic Disorders / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
keywords: Plasticity; Repetitive transcranial magnetic stimulation; Supplementary motor area; Theta burst stimulation; Tourette syndrome