Double-blind, randomized pilot clinical trial targeting alpha oscillations with transcranial alternating current stimulation (tACS) for the treatment of major depressive disorder (MDD).
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ABSTRACT:
SUBMITTER: Alexander ML
PROVIDER: S-EPMC6401041 | biostudies-literature | 2019 Mar
REPOSITORIES: biostudies-literature
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Project description:Brain oscillations, e.g. measured by electro- or magnetoencephalography (EEG/MEG), are causally linked to brain functions that are fundamental for perception, cognition and learning. Recent advances in neurotechnology provide means to non-invasively target these oscillations using frequency-tuned amplitude-modulated transcranial alternating current stimulation (AM-tACS). However, online adaptation of stimulation parameters to ongoing brain oscillations remains an unsolved problem due to stimulation artifacts that impede such adaptation, particularly at the target frequency. Here, we introduce a real-time compatible artifact rejection algorithm (Stimulation Artifact Source Separation, SASS) that overcomes this limitation. SASS is a spatial filter (linear projection) removing EEG signal components that are maximally different in the presence versus absence of stimulation. This enables the reliable removal of stimulation-specific signal components, while leaving physiological signal components unaffected. For validation of SASS, we evoked brain activity with known phase and amplitude using 10 Hz visual flickers across 7 healthy human volunteers. 64-channel EEG was recorded during and in absence of 10 Hz AM-tACS targeting the visual cortex. Phase differences between AM-tACS and the visual stimuli were randomized, so that steady-state visually evoked potentials (SSVEPs) were phase-locked to the visual stimuli but not to the AM-tACS signal. For validation, distributions of single-trial amplitude and phase of EEG signals recorded during and in absence of AM-tACS were compared for each participant. When no artifact rejection method was applied, AM-tACS stimulation artifacts impeded assessment of single-trial SSVEP amplitude and phase. Using SASS, amplitude and phase of single trials recorded during and in absence of AM-tACS were comparable. These results indicate that SASS can be used to establish adaptive (closed-loop) AM-tACS, a potentially powerful tool to target various brain functions, and to investigate how AM-tACS interacts with electric brain oscillations.
| S-EPMC7903161 | biostudies-literature
Project description:The P300 component of the event-related potential (ERP) is a well investigated phenomenon in the human electroencephalogram (EEG) and has been related to stimulus processing and attentional mechanisms. Event-related oscillations (ERO) represent a potential mechanism responsible for generating the ERP. In particular, oscillatory activity in the delta and theta frequency range has been associated with the generation of the P300 component. Transcranial Alternating Current Stimulation (tACS) is capable of modulating oscillatory brain activity in a frequency-specific manner. In this study, we aimed to modulate P300 amplitude using tACS by stimulating the individual ERO involved in the generation of the P300 component. TACS was applied precisely in time to the target P300 occurring in a visual oddball task. In order to achieve an appropriate current distribution, we designed an electrode configuration consisting of two clusters of stimulation electrodes on central-parietal locations. We could not demonstrate a group difference in P300 amplitude after applying tACS in the stimulation condition (N = 17) vs. the sham condition (N = 11). TACS condition and sham condition did not differ regarding their reaction times in response to target stimuli or their event-related spectral perturbation (ERSP) at stimulation frequency. Although a significant influence of stimulation could not yet be revealed on a statistical level, we suggest that the proposed method of using tACS for modulating EROs merits further investigation. Modulation of the P300 component in the ERP could help to gain further insights in the role of EROs generating ERPs and the functional relevance of the P300 component. In this study, we propose a novel approach of applying tACS and provide advice on using tACS for the modulation of EROs.
| S-EPMC6411790 | biostudies-literature
Project description:Amplitude modulated transcranial alternating current stimulation (AM-tACS) is a novel method of electrostimulation which enables the recording of electrophysiological signals during stimulation, thanks to an easier removable stimulation artefact compared to classical electrostimulation methods. To gauge the neuromodulatory potential of AM-tACS, we tested its capacity to induce phosphenes as an indicator of stimulation efficacy. AM-tACS was applied via a two-electrode setup, attached on FpZ and below the right eye. AM-tACS waveforms comprised of different carrier (50 Hz, 200 Hz, 1000 Hz) and modulation frequencies (8 Hz, 16 Hz, 28 Hz) were administered with at maximum 2 mA peak-to-peak stimulation strength. TACS conditions in the same frequencies were used as a benchmark for phosphene induction. AM-tACS conditions using a 50 Hz carrier frequency were able to induce phosphenes, but with no difference in phosphene thresholds between modulation frequencies. AM-tACS using a 200 Hz or 1000 Hz carrier frequency did not induce phosphenes. TACS conditions induced phosphenes in line with previous studies. Stimulation effects of AM-tACS conditions were independent of amplitude modulation and instead relied solely on the carrier frequency. A possible explanation may be that AM-tACS needs higher stimulation intensities for its amplitude modulation to have a neuromodulatory effect.
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Project description:The past decades have witnessed a huge interest in uncovering the neural bases of intelligence (e.g., Stelmack, & Houlihan, 1995; Stelmack, Knott, & Beauchamp, 2003). This study investigated the influence of transcranial alternating current stimulation (tACS) on fluid intelligence performance and corresponding brain activation. Previous findings showed that left parietal theta tACS leads to a transient increase in fluid reasoning performance. In an attempt to extend and replicate these findings, we combined theta tACS with fMRI. In a double-blind sham-controlled experiment, N = 20 participants worked on two intelligence tasks (matrices and paper folding) after theta tACS was applied to the left parietal cortex. Stimulation-induced brain activation changes were recorded during task processing using fMRI. Results showed that theta tACS significantly increased fluid intelligence performance when working on difficult items in the matrices test; no effect was observed for the visuo-spatial paper folding test. Whole-brain analyses showed that left parietal brain stimulation was accompanied by lower activation in task-irrelevant brain areas. Complemental ROI analyses revealed a tendency towards lower activation in the left inferior parietal cortex. These findings corroborate the functional role of left parietal theta activity in fluid reasoning and are in line with the neural efficiency hypothesis.
| S-EPMC5700801 | biostudies-literature
Project description:Numerous clinical reports have suggested that psychopathy like schizophrenia, anxiety and depression is accompanied by early attentional abnormalities in emotional processing. Recently, the efficacy of transcranial alternating current stimulation (tACS) in changing emotional functioning has been repeatedly observed and demonstrated a causal relationship between endogenous oscillations and emotional processing. Up to now, tACS effects on emotional attention have not yet been tested. To assess such ability, we delivered active-tACS at individual alpha frequency (IAF), 10 Hz or sham-tACS for 7 consecutive days in the bilaterally dorsolateral prefrontal cortex (dlPFC) to totally 79 healthy participants. IAF-tACS group showed significant alpha entrainment at-rest, especially in open state around stimulation area and showed an obvious advantage compared to 10 Hz-tACS. Event-related potential revealed a significant larger P200 amplitude after active-tACS and IAF group showed wider range of emotions than 10 Hz-tACS, indicating the attentional improvement in facial emotion processing. A notable positive correlation between alpha power and P200 amplitude provided an electrophysiological interpretation regarding the role of tACS in emotional attention modulation instead of somatosensory effects. These results support a seminal outcome for the effect of IAF-tACS on emotional attention modulation, demonstrating a feasible and individual-specific therapy for neuropsychiatric disorders related to emotion processing, especially regarding oscillatory disturbances.
| S-EPMC10640550 | biostudies-literature
Project description:BackgroundLeft frontal alpha oscillations are associated with decreased approach motivation and have been proposed as a target for noninvasive brain stimulation for the treatment of depression and anhedonia. Indeed, transcranial alternating current stimulation (tACS) at the alpha frequency reduced left frontal alpha power and was associated with a higher response rate than placebo stimulation in patients with major depressive disorder (MDD) in a recent double-blind, placebo-controlled clinical trial.MethodsIn this current study, we aimed to replicate successful target engagement by delineating the effects of a single session of bifrontal tACS at the individualized alpha frequency (IAF-tACS) on alpha oscillations in patients with MDD. Eighty-four participants were randomized to receive verum or sham IAF-tACS. Electrical brain activity was recorded during rest and while viewing emotionally salient images before and after stimulation to investigate whether the modulation of alpha oscillation by tACS exhibited specificity with regard to valence.ResultsIn agreement with the previous study of tACS in MDD, we found that a single session of bifrontal IAF-tACS reduced left frontal alpha power during the resting state when compared with placebo. Furthermore, the reduction of left frontal alpha oscillation by tACS was specific for stimuli with positive valence. In contrast, these effects on left frontal alpha power were not found in healthy control participants.ConclusionsTogether, these results support an important role of tACS in reducing left frontal alpha oscillations as a future treatment for MDD.
| S-EPMC8758795 | biostudies-literature
Project description:BackgroundOver 55 million people worldwide are currently diagnosed with Alzheimer's disease (AD) and live with debilitating episodic memory deficits. Current pharmacological treatments have limited efficacy. Recently, transcranial alternating current stimulation (tACS) has shown memory improvement in AD by normalizing high-frequency neuronal activity. Here we investigate the feasibility, safety, and preliminary effects on episodic memory of an innovative protocol where tACS is administered within the homes of older adults with AD with the help of a study companion (HB-tACS).MethodsEight participants diagnosed with AD underwent multiple consecutive sessions of high-definition HB-tACS (40 Hz, 20-min) targeting the left angular gyrus (AG), a key node of the memory network. The Acute Phase comprised 14-weeks of HB-tACS with at least five sessions per week. Three participants underwent resting state electroencephalography (EEG) before and after the 14-week Acute Phase. Subsequently, participants completed a 2-3-month Hiatus Phase not receiving HB-tACS. Finally, in the Taper phase, participants received 2-3 sessions per week over 3-months. Primary outcomes were safety, as determined by the reporting of side effects and adverse events, and feasibility, as determined by adherence and compliance with the study protocol. Primary clinical outcomes were memory and global cognition, measured with the Memory Index Score (MIS) and Montreal Cognitive Assessment (MoCA), respectively. Secondary outcome was EEG theta/gamma ratio. Results reported as mean ± SD.ResultsAll participants completed the study, with an average of 97 HB-tACS sessions completed by each participant; reporting mild side effects during 25% of sessions, moderate during 5%, and severe during 1%. Acute Phase adherence was 98 ± 6.8% and Taper phase was 125 ± 22.3% (rates over 100% indicates participants completed more than the minimum of 2/week). After the Acute Phase, all participants showed memory improvement, MIS of 7.25 ± 3.77, sustained during Hiatus 7.00 ± 4.90 and Taper 4.63 ± 2.39 Phases compared to baseline. For the three participants that underwent EEG, a decreased theta/gamma ratio in AG was observed. Conversely, participants did not show improvement in the MoCA, 1.13 ± 3.80 after the Acute Phase, and there was a modest decrease during the Hiatus -0.64 ± 3.28 and Taper -2.56 ± 5.03 Phases.ConclusionThis pilot study shows that the home-based, remotely-supervised, study companion administered, multi-channel tACS protocol for older adults with AD was feasible and safe. Further, targeting the left AG, memory in this sample was improved. These are preliminary results that warrant larger more definite trials to further elucidate tolerability and efficacy of the HB-tACS intervention. NCT04783350.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT04783350?term=NCT04783350&draw=2&rank=1, identifier NCT04783350.
| S-EPMC10272342 | biostudies-literature
Project description:Multitasking is associated with the generation of stimulus-locked theta (4-7 Hz) oscillations arising from prefrontal cortex (PFC). Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation technique that influences endogenous brain oscillations. Here, we investigate whether applying alternating current stimulation within the theta frequency band would affect multitasking performance, and explore tACS effects on neurophysiological measures. Brief runs of bilateral PFC theta-tACS were applied while participants were engaged in a multitasking paradigm accompanied by electroencephalography (EEG) data collection. Unlike an active control group, a tACS stimulation group showed enhancement of multitasking performance after a 90-minute session (F1,35 = 6.63, p = 0.01, ?p2 = 0.16; effect size = 0.96), coupled with significant modulation of posterior beta (13-30 Hz) activities (F1,32 = 7.66, p = 0.009, ?p2 = 0.19; effect size = 0.96). Across participant regression analyses indicated that those participants with greater increases in frontal theta, alpha and beta oscillations exhibited greater multitasking performance improvements. These results indicate frontal theta-tACS generates benefits on multitasking performance accompanied by widespread neuronal oscillatory changes, and suggests that future tACS studies with extended treatments are worth exploring as promising tools for cognitive enhancement.
| S-EPMC5451121 | biostudies-literature
Project description:BACKGROUND:Transcranial alternating current stimulation (tACS) offers a new approach for adult patients with major depressive disorder (MDD). The study is to evaluate the efficacy and safety of tACS treating MDD. METHODS:This is an 8-week, double-blind, randomized, placebo-controlled study. Ninety-two drug-naive patients with MDD aged 18 to 65 years will receive 20 daily 40-min, 77.5-Hz, 15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas on weekdays for 4 consecutive weeks (week 4), following a 4-week observation period (week 8). The primary outcome is the remission rate defined as the 17-item Hamilton depression rating scale (HDRS-17) score ≤7 at week 8. Secondary outcomes are the rates of response at weeks 4 and 8 and rate of remission at week 4 based on HDRS-17, the proportion of participants having improvement in the clinical global impression-improvement, the change in HDRS-17 score (range, 0-52, with higher scores indicating more depression) over the study, and variations of brain imaging and neurocognition from baseline to week 4. Safety will be assessed by vital signs at weeks 4 and 8, and adverse events will be collected during the entire study. DISCUSSION:The tACS applied in this trial may have treatment effects on MDD with minimal side effects. TRIAL REGISTRATION:Chinese Clinical Trial Registry, ChiCTR1800016479; http://www.chictr.org.cn/showproj.aspx?proj=22048.
| S-EPMC7028208 | biostudies-literature
Project description:Objective: To determine whether remotely-monitored transcranial alternating current stimulation (tACS) may be a viable and safe treatment option for Mal de Débarquement Syndrome (MdDS). Background: Mal de Débarquement Syndrome is a neurotological disorder characterized by persistent oscillating vertigo that is triggered by entrainment to passive oscillatory motion such as occurs during water-based travel. Treatment options for MdDS are limited, variably effective, and can be undone by further travel. Design and Methods: This was a remotely-monitored open-label optional extension phase of a double-blind randomized onsite study of tACS for medically refractory MdDS. The primary goal was to determine safety, feasibility, and blinded participant feedback. The secondary goal was to determine efficacy. Thirteen participants (all women), aged 22-67 years, experiencing a duration of illness of 11-72 months, were a subset of 24 individuals who participated in an on-site study of tACS. They had either not responded to the on-site protocol or had relapsed after travel home. Treatment accessories and a tablet controlled tACS stimulator (Pulvinar XCSITE-100) were mailed to participants. Three teaching sessions were performed via webcam followed by on-going remote monitoring of treatment logs and participants' reports through a daily on-line diary and weekly questionnaires. Treatment continued until an effective protocol was administered for 4 weeks and then tapered over 4 weeks. Participants completed a blinded feedback survey and a debriefing interview at the completion of the entire study. Results: Treatment duration ranged from 4 to 31 weeks followed by a 4-week taper accounting for 578 verified sessions. Of the 13 total participants, seven agreed or agreed strongly in the blinded survey that tACS treatment was beneficial; 2) Twelve were comfortable utilizing tACS on their own; 3) Eleven preferred stimulation above their individual alpha frequency; 4) Side effects were generally mild and typical of tACS. In the debriefing interview completed 2-9 months after the last stimulation, five participants reported doing "great," with no to minimal symptoms, four reported doing "good," with moderate symptoms, and four reported no change compared to pre-study baseline. Conclusion: Remotely-monitored tACS may be a safe treatment option for MdDS with the potential for lasting outcomes, increased accessibility, and reduction in travel-related treatment reversal.
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