Abstract
Non-invasive brain stimulation (NIBS) is emerging as a robust treatment alternative for major depressive disorder, with a potential for achieving higher remission rates by providing targeted stimulation to underlying brain networks, such as the salience network (SN). Growing evidence suggests that these therapeutic effects are dependent on the frequency and phase synchrony between SN oscillations and stimulation as well as the task-specific state of the SN during stimulation. However, the development of phase-synchronized non-invasive stimulation has proved challenging until recently. Here, we use a phase-locked pulsed brain stimulation approach to study the effects of two NIBS methods: transcranial alternating current stimulation (tACS) versus phase-locked transcranial pulsed current stimulation (tPCS), on the SN during an SN activating task. 20 healthy volunteers participated in the study. Each volunteer partook in four sessions, receiving one stimulation type at random (theta-tACS, peak tPCS, trough tPCS or sham) while undergoing a learning game, followed by an unstimulated test based on learned material. Each session lasted approximately 1.5 h, with an interval of at least 2 days to allow for washout and to avoid cross-over effects. Our results showed no statistically significant effect of stimulation on the event related potential (ERP) recordings, resting electroencephalogram (EEG), and the performance of the volunteers. While stimulation effects were not apparent in this study, the nominal performance of the phase-locking algorithm offers a technical foundation for further research in determining effective stimulation paradigms and conditions. Specifically, future work should investigate stronger stimulation and true task-specific stimulation of SN nodes responsible for the task as well as their recording. If refined, NIBS could offer an effective, homebased treatment option.
Highlights
Non-invasive brain stimulation (NIBS) is an emerging alternative when conventional treatment approaches for Major Depressive Disorder (MDD) fail (Fregni and Pascual-Leone, 2007; Daskalakis et al, 2008; Ferrucci et al, 2009; Dayan et al, 2013)
In this work we attempted to engage the salience network (SN) by using transcranial alternating current stimulation (tACS) at theta frequency or phase-locked transcranial pulsed current stimulation (tPCS) synchronized to the frontal theta when the volunteers were engaged in a SN activating task
In this work we have attempted to modulate SN activity differentially, by applying theta tACS or phase-locked tPCS synchronized to the frontal theta when the volunteers were engaged in a SN activating task
Summary
Non-invasive brain stimulation (NIBS) is an emerging alternative when conventional treatment approaches for Major Depressive Disorder (MDD) fail (Fregni and Pascual-Leone, 2007; Daskalakis et al, 2008; Ferrucci et al, 2009; Dayan et al, 2013). NIBS technologies such as Food and Drug Administration (FDA)-approved repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have shown efficacy in helping with TRD in a large number of clinical trials, achieving 15–32% (O’Reardon et al, 2007; Berlim et al, 2014; Gaynes et al, 2014) and 7–43% (Berlim et al, 2013; Shiozawa et al, 2014) remission rates, respectively. In contrast to tDCS, transcranial alternating current stimulation (tACS) and transcranial pulsed current stimulation (tPCS) use oscillatory waveforms with sinusoidal and square pulses that better match the underlying natural physiological brain activity. It has been shown that tACS can have an effect in spike timing of single neurons elucidating the mechanism of action for these types of NIBS and opening the opportunity for future research into the effects of timing of the stimulation waveform with respect to the underlying brain activity (Krause et al, 2019)
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