Brief report
Lack of impact of repetitive High Frequency Transcranial Magnetic Stimulation on mood in healthy female subjects

https://doi.org/10.1016/j.jad.2005.09.013Get rights and content

Abstract

Background

High Frequency repetitive Transcranial Magnetic Stimulation (HF-rTMS) is currently used as an experimental tool to induce mood changes in normal volunteers and as a treatment option for depression. However, HF-rTMS, mostly performed on the left dorsolateral prefrontal cortex (DLPFC), has yielded divergent results and effects on mood which seem to be oppositely lateralized between these two groups. The inconsistent results that have been reported might be explained by methodological heterogeneity and drawbacks.

Methods

In this sham-controlled, single blind, crossover study, we tried to reproduce previous HF-rTMS findings of a negative mood induction in 28 healthy female subjects. To exclude individual anatomical differences, the left DLPFC was localised under magnetic resonance guidance (MRI). Mood assessment was performed before and just after HF-rTMS with Visual Analogue Scales and the Profile of Mood States. To detect possible delayed mood changes, ratings were also performed 30 min post HF-rTMS.

Results

We were unable to demonstrate significant mood changes from baseline after one single active HF-rTMS session on the left DLPFC.

Conclusions

Although this study controlled for several methodological problems, the hypothesis that one single session of HF-rTMS on the left DLPFC has negative mood effects in healthy female volunteers was not supported.

Introduction

Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive technique that is not only used to investigate neural conductions and connections in the human brain but is also of considerable interest for the understanding of the basic neurophysiology of mood generation and modulation in healthy subjects (Paus et al., 2001, Pascual-Leone et al., 2002).

Some evidence suggests that in healthy subjects positive mood effects of HF-rTMS of the left DLPFC are oppositely lateralized compared to those seen in patients with major depression (George et al., 1999, Burt et al., 2002), but other studies failed to demonstrate any mood effects in healthy volunteers (Mosimann et al., 2000). Moreover, results of rTMS studies involving normal subjects and low frequency stimulation to induce mood effects seem also inconclusive (Jenkins et al., 2002). Anyhow, rTMS frequency is thought to determine brain response: high frequencies (> 1 Hz) would enhance and low frequencies (≤ 1 Hz) would inhibit brain excitability (Post and Keck, 2001). This way, rTMS can either activate or suppress motor, sensory, or cognitive functions, depending on the brain location and parameters of its delivery (George and Belmaker, 2000). However, the high–low frequency activation or inhibition hypothesis has not only been confirmed in motor cortex studies, but also with contradictory results (Rounis et al., 2005).

In this study we tried to control for shortcomings in previous studies (George et al., 1996, Pascual-Leone et al., 1996, Dearing et al., 1997, Barrett et al., 2004) by using a sham-controlled condition, a time interval between stimulation sessions, a larger uniform sample, stimulation of one single region per session in order to exclude interaction effects with the previous stimulation, brain imaging to determine the exact target of stimulation, and a large number of pulses at high stimulation intensity. Moreover, we assessed mood changes with a well validated mood scale.

Consequently, the main purpose of the current study was to verify whether one single session of HF-rTMS of the left prefrontal cortex affects mood in a large sample of non-depressed young female subjects, extending previous research in several ways. Compared with previous research, the two major methodological modifications were 1. adding a sham-controlled condition with one week interval in a single blind crossover design, and 2. determining the correct anatomical localisation of the left DLPFC under MRI guidance, taking into account anatomical brain differences between subjects as proposed by Herwig et al. (2001). We expect a negative mood induction only after real HF-rTMS of the left DLPFC.

Section snippets

Participants

Twenty-eight healthy, drug-free, right-handed female volunteers were recruited to participate in this study (M = 24.68 years, S.D. =5.85). They all gave written informed consent. The study was approved by the local medical ethics committee. All subjects underwent a physical, neurological (EEG) and psychiatric examinations. Psychiatric disorders were excluded using the Mini-International Neuropsychiatric Interview (MINI; Sheehan et al., 1998) and the Beck Depression Inventory (BDI; Beck et al., 1961

Mood effects

Ratings were analysed separately for each VAS and POMS scale using ANOVA's (p level < .05). Within-subject factors were stimulation (sham or real) and time (T0, T1 and T30). Table 1 summarizes the mean and standard deviations for these ratings.

The ANOVA for the POMS-depression scale showed no significant main or interaction effects. The ANOVA for the VAS-depression scale showed a marginal significant overall effect of time (F(2, 48) = 2.95, p = .062). Post hoc tests revealed near significant

Discussion

Controlling for shortcomings in previous studies, we were unable to demonstrate any mood effects of HF-rTMS at the left DLPFC in healthy female volunteers. Our results are in line with other sham-controlled crossover studies that used larger numbers of subjects and did not find any mood effects either (Nedjat et al., 1998, Cohrs et al., 1998, Mosimann et al., 2000). To our knowledge this is the second study in normal volunteers that corrected for individual structural brain differences. In

Acknowledgement

This research was supported by a grant from the Scientific Fund W. Gepts AZ-VUB.

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