The effects of repetitive transcranial magnetic stimulation on cortical inhibition in healthy human subjects

Abstract

It has been suggested that the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) are mediated through changes in cortical inhibition (CI). However, in healthy human subjects the effects of rTMS on CI have been inconsistent. Therefore, this study sought to improve on the methodological limitations of previous studies by exploring several different rTMS-stimulus conditions on inhibition in the human motor cortex. In the first experiment, 12 healthy control subjects were randomly assigned to receive regular 1, 10 or 20 Hz rTMS in a counterbalanced order with sessions separated by at least 1 week. In the second experiment, 10 of these 12 subjects received priming rTMS (600 stimuli at 6 Hz followed by 600 stimuli at 1 Hz). Cortical inhibition was indexed using short-interval intracortical inhibition (SICI) and cortical silent period (CSP). Corticospinal excitability was indexed using motor threshold and MEP amplitude. We found no significant overall change in SICI, although there was a significant correlation between changes in SICI with baseline SICI. Subjects with greater SICI at baseline tended to have reduction in SICI post-rTMS, whereas subjects with less SICI tended to have increase in SICI post-rTMS. There was also a significant lengthening of the CSP with higher stimulation frequencies compared to lower stimulation frequencies. These findings suggest that rTMS increases CI, particularly in subjects with reduced baseline inhibition, a finding consistent with the concept of homeostatic plasticity. Baseline physiological characteristics may be further explored as a method to select patients who may benefit from rTMS treatment.

Potentiation of Gamma Oscillatory Activity through Repetitive Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex

“…In addition, during WM tasks, the activity of these GABAergic neurons contribute to the spatial tuning of the neuronal response, and are thus considered to be related to the WM task itself (Rao et al, 2000), whereas the injection of GABAergic antagonists in the DLPFC resulted in a disruption in WM performance (Sawaguchi et al, 1989). Taken together with the finding that 20 Hz rTMS potentiates GABAergic inhibitory neurotransmission indexed through CSP (Daskalakis et al, 2006), we contend that high-frequency rTMS exerts its effects on g-oscillatory activity through GABA receptor-mediated inhibitory neurotransmission to ultimately affect WM performance. Future studies combining paired-pulse TMS with EEG recording to index GABA receptor-mediated neurotransmission in the DLPFC (Daskalakis et al, 2008) will be needed, however, to determine whether g-oscillatory activity is indeed potentiated directly through enhanced GABA.…”

“…For example, high-frequency rTMS has been shown to improve language functions in healthy individuals (Sparing et al, 2001), as well as to improve different aspects of memory in major depressive disorder patients (Little et al, 2000;Martis et al, 2003;O'Connor et al, 2005). In addition, rTMS on the motor cortex has been shown to enhance GABA-mediated inhibitory neurotransmission in healthy individualsFthat is, Daskalakis et al (2006) reported a lengthening of the cortical silent period (CSP), a measure reflective of GABA Bmediated inhibitory neurotransmission (Ziemann et al, 1996) with increased stimulation frequency, which was maximal at 20 Hz (Daskalakis et al, 2006). High-frequency (ie, 20 Hz) rTMS thus represents a possible mechanism through which to potentiate g-oscillatory activity, which may, in turn, improve WM performance.…”

Time-course of “off-line” prefrontal rTMS effects — a PET study

“…This interpretation, however, implies that low frequency rTMS as used in the current study increases the activity of inhibitory interneurons. As several studies suggested, low-frequency rTMS of the primary motor cortex does not lead to increased intracortical inhibition as revealed by subsequent paired-pulse TMS (Brighina et al, 2005;Daskalakis et al, 2006;Fitzgerald et al, 2002;Romero et al, 2002). Based on this evidence it seems less likely that the observed increased rCBF results from an active inhibition process induced by low-frequency rTMS.…”

Repeated Transcranial Magnetic Stimulation (rTMS) to improve Electroconvulsive Therapy (ECT) in Treatment-Resistant Depression: A Report of Two Cases

“…However, a single session of ECT does not increase CSP 23 while several ECT increase CSP (24), a finding consistent with GABAergic activity of ECT. Transcranial magnetic stimulation also increases the CSP and depressed patients who responded to the high frequency rTMS (20Hz) of the left DLPFC have an increase of CSP and ICI [25][26][27]. Change of ICI was correlated with improved HAM-D score (Hamilton Rating Scale for Depression) [28].…”