Examining the feasibility and tolerability of a clinically informed multisite, repetitive transcranial magnetic stimulation protocol

Highlights

• We evaluate the safety and tolerability of multi-site brain stimulation.

• Low and high frequency rTMS is applied sequentially to three cortical regions.

• The multi-site protocol is safe and tolerable.

• Participants receiving active stimulation reported more side effects.

• No significant changes to neurocognitive functioning were identified.

Abstract

Background

Multi-site repetitive transcranial magnetic stimulation (rTMS) has been applied experimentally in the treatment of obsessive compulsive disorder (OCD).

New method

This study was conducted to systematically evaluate the safety, tolerability and neurocognitive effects of rTMS applied to three cortical regions over a period of three months.

New method

Twenty healthy participants aged 22–33 years were randomly allocated to receive one session of active or sham stimulation of low and high frequency rTMS applied sequentially to the pre-supplementary motor area, right-dorsolateral prefrontal cortex and left-orbitofrontal cortex totalling 9 min. Tolerability and safety was evaluated using a standardised safety questionnaire. Neurocognitive functioning was examined using the Cambridge Neuropsychological Test Automated Battery and measures of verbal fluency from the Delis-Kaplan Executive Functioning Test™ at five time points over three months.

Results

The protocol was safe and tolerable. Frequencies of minor adverse effects were higher in active (17 endorsements) than sham (1 endorsement) conditions. No between group differences in neurocognitive functioning were identified over three months.

Comparison with existing method: This study is the first to evaluate the feasibility of low and high frequency parameters applied sequentially in a single session to the three selected cortical regions whilst providing neurocognitive data.

Conclusions

rTMS applied sequentially over three cortical regions was found to be safe and tolerable in healthy individuals with no major neurocognitive effects over three months. Such findings can be used to inform the development of rTMS protocols involving multi-site stimulation for OCD.

Introduction

Repetitive transcranial magnetic stimulation (rTMS) is a neuromodulation technique which has been trialled experimentally in the treatment of obsessive compulsive disorder (OCD) (Jaafari et al., 2012). Low frequency stimulation (pulses delivered at ≤1 Hz) applied to the left-orbitofrontal cortex (OFC) and pre-supplementary motor cortex (SMA) has shown promise in reducing OCD symptoms (Jaafari et al., 2012). Additionally, high frequency stimulation (pulses delivered at>1 Hz) applied to the right-dorsolateral prefrontal cortex (DLPFC) in OCD patients may confer antidepressant effects (Jaafari et al., 2012). One clinical trial by Kang et al. (2009) employed a novel rTMS protocol involving the sequential application of low frequency stimulation to the SMA then high frequency stimulation to the right-DLPFC. Although they did not find any clinically improvement in their sample of OCD patients, other multisite rTMS protocols may have therapeutic potential.

Due to its demonstrated and well-established safety profile, rTMS is also used routinely in healthy populations (Rossi et al., 2009). An early study by Wasserman et al. (1996) examined the side effect profile of rTMS applied to multiple regions. They delivered either high or low frequency stimulation on separate days to six cortical regions (the DLPFC, the primary motor cortex and parietal cortex, bilaterally) and found their multisite protocol to be safe and tolerable. They also administered a neurocognitive battery consisting of a finger tapping task, the immediate and delayed story recall tests from the Wechsler Memory Scale Revised and a verbal fluency test and found no impairments in neurocognitive functioning (Wassermann et al., 1996). In the current investigation, a broad range of neurocognitive tests were also selected to examine potential changes in neurocognition. Following from the recommendations of Wassermann (2002), the test battery comprised of tasks that measured reaction time, word generation, task inhibition, working memory and executive functioning.

The current study was thus conducted with the primary aim of systematically evaluating the tolerability, safety profile and feasibility of a clinically informed, multisite rTMS protocol in a healthy sample. rTMS was administered to three cortical regions in a single-blind randomised control trial. A secondary aim was to evaluate potential acute or long term changes to neurocognitive functioning over three months.