David A. Huddleston

Effects of 30 Hz Theta Burst Transcranial Magnetic Stimulation on the primary motor cortex

Theta Burst Stimulation (TBS) is a relatively new form of repetitive Transcranial Magnetic Stimulation (TMS) used to probe neuroplasticity in the human cortex. Thirty-Hz TBS, a variation of the originally described 50Hz TBS, has been shown to induce cortical changes in several nonmotor regions. However, its effects over the primary motor cortex have not been examined. Due to TMS device mechanical properties, 30Hz TBS is advantageous over 50Hz TBS in that it can be delivered at higher stimulation intensities. The goal of this pilot study is to examine the neurophysiologic effects of 30Hz TBS on the primary motor cortex (M1) of healthy adults. Eighteen right-handed adults (33±9.0 years; M:F=8:10) completed intermittent TBS (iTBS) or continuous TBS (cTBS) over left M1. TBS was performed with Magstim® SuperRapid2 with stimulation bursts (3 pulses at 30Hz) repeating every 200ms. For iTBS, each 2-s stimulation train was separated by 8s but there was no pause between trains for cTBS. Each TBS consisted of a total of 600 pulses delivered at an intensity of 90%*Resting Motor Threshold. Motor-Evoked Potentials (MEP) in the right first dorsal interosseous muscle were measured before, and one and ten minutes after TBS. Pre/post-TBS MEP amplitudes were compared using repeated-measures ANOVA. MEP amplitudes increased after 30Hz iTBS and decreased after 30Hz cTBS (TBS-Type*Time effect p=0.009). In conclusion, 30Hz TBS induced similar neurophysiologic effects over M1 as conventional 50Hz TBS.

Safety and tolerability of theta-burst transcranial magnetic stimulation in children.

Aim  Theta‐burst stimulation (TBS) is a lower intensity, high‐frequency repetitive transcranial magnetic stimulation technique developed recently for quantifying and modulating cerebral cortical function. Nearly all published studies have involved adults. The aim of this study was to obtain safety data as a basis for evaluating potential risks versus benefits of TBS research in children.

Functional MRI-navigated Repetitive Transcranial Magnetic Stimulation Over Supplementary Motor Area in Chronic Tic Disorders

BACKGROUND Open label studies have shown repetitive transcranial magnetic stimulation to be effective in reducing tics. OBJECTIVES 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 individuals 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. RESULT 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. CONCLUSION 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.

Safety and tolerability of theta burst stimulation vs. single and paired pulse transcranial magnetic stimulation: a comparative study of 165 pediatric subjects.

Background: Although single- and paired-pulse (sp/pp) transcranial magnetic stimulation (TMS) studies are considered minimal risk in adults and children, the safety profile for theta-burst TMS (TBS) is unknown. Objective: In this comparative analysis, we explored the rate, severity, and specific symptoms of TMS-related adverse effects (AEs) between sp/ppTMS and TBS in subjects between ages 6 and 18 years. Method: Data from 165 participants from 2009 to 2014 were analyzed. Assessment of AEs was performed based on baseline and post-TMS administration of a symptom-based questionnaire that rated AEs on a 5-level ordinal scale (minimal, mild, moderate, marked, severe). AE rates and severity were compared using Chi Square or Fisher’s Exact Test depending on data characteristics. Result: Overall, no seizures or severe-rated AEs were reported by 165 pediatric participants. The rate of AE in all TBS sessions was 10.5% (n = 76, 95% CI: 4.7–19.7%), whereas the rate of AE in all sp/ppTMS sessions was 12.4% (n = 89, 95% CI: 6.3–21.0%). There was no statistical difference in AE rates between TBS and sp/ppTMS (p = 0.71). In all sp/ppTMS and TBS sessions, 20 subjects reported a total of 35 AEs, among these 31 (~88.6%) were rated as “minimal” or “mild”. There was no difference in the severity of AE between TBS and sp/ppTMS (p = 1.0). Only one of 76 TBS participants reported an AE rated as more than minimal/mild. Conclusion: Our comparative analysis showed that TBS appears to be as safe as sp/ppTMS in terms of AE rate and severity. This report supports further investigation of TBS in children.

Reduced short interval cortical inhibition correlates with atomoxetine response in children with attention-deficit hyperactivity disorder (ADHD).

Clinical trials in children with attention-deficit hyperactivity disorder (ADHD) show variability in behavioral responses to the selective norepinephrine reuptake inhibitor atomoxetine. The objective of this study was to determine whether transcranial magnetic stimulation–evoked short interval cortical inhibition might be a biomarker predicting, or correlating with, clinical atomoxetine response. At baseline and after 4 weeks of atomoxetine treatment in 7- to 12-year-old children with ADHD, transcranial magnetic stimulation short interval cortical inhibition was measured, blinded to clinical improvement. Primary analysis was by multivariate analysis of covariance. Baseline short interval cortical inhibition did not predict clinical responses. However, paradoxically, after 4 weeks of atomoxetine, mean short interval cortical inhibition was reduced 31.9% in responders and increased 6.1% in nonresponders (analysis of covariance t 41 = 2.88; P = .0063). Percentage reductions in short interval cortical inhibition correlated with reductions in the ADHD Rating Scale (r = 0.50; P = .0005). In children ages 7 to 12 years with ADHD treated with atomoxetine, improvements in clinical symptoms are correlated with reductions in motor cortex short interval cortical inhibition.