Alpha power increase after transcranial alternating current stimulation at alpha frequency (α-tacs) reflects plastic changes rather than entrainment

Background: Periodic stimulation of occipital areas using transcranial alternating current stimulation (tACS) at alpha (α) frequency (8–12 Hz) enhances electroencephalographic (EEG) α-oscillation long after tACS-offset. Two mechanisms have been suggested to underlie these changes in oscillatory EEG activity: tACS-induced entrainment of brain oscillations and/or tACS-induced changes in oscillatory circuits by spike-timing dependent plasticity.<p></p> Objective: We tested to what extent plasticity can account for tACS-aftereffects when controlling for entrainment “echoes.” To this end, we used a novel, intermittent tACS protocol and investigated the strength of the aftereffect as a function of phase continuity between successive tACS episodes, as well as the match between stimulation frequency and endogenous α-frequency.<p></p> Methods: 12 healthy participants were stimulated at around individual α-frequency for 15–20 min in four sessions using intermittent tACS or sham. Successive tACS events were either phase-continuous or phase-discontinuous, and either 3 or 8 s long. EEG α-phase and power changes were compared after and between episodes of α-tACS across conditions and against sham.<p></p> Results: α-aftereffects were successfully replicated after intermittent stimulation using 8-s but not 3-s trains. These aftereffects did not reveal any of the characteristics of entrainment echoes in that they were independent of tACS phase-continuity and showed neither prolonged phase alignment nor frequency synchronization to the exact stimulation frequency.<p></p> Conclusion: Our results indicate that plasticity mechanisms are sufficient to explain α-aftereffects in response to α-tACS, and inform models of tACS-induced plasticity in oscillatory circuits. Modifying brain oscillations with tACS holds promise for clinical applications in disorders involving abnormal neural synchrony

Emotion perception improvement following high frequency transcranial random noise stimulation of the inferior frontal cortex.

Facial emotion perception plays a key role in interpersonal communication and is a precursor for a variety of socio-cognitive abilities. One brain region thought to support emotion perception is the inferior frontal cortex (IFC). The current study aimed to examine whether modulating neural activity in the IFC using high frequency transcranial random noise stimulation (tRNS) could enhance emotion perception abilities. In Experiment 1, participants received either tRNS to IFC or sham stimulation prior to completing facial emotion and identity perception tasks. Those receiving tRNS significantly outperformed those receiving sham stimulation on facial emotion, but not identity, perception tasks. In Experiment 2, we examined whether baseline performance interacted with the effects of stimulation. Participants completed a facial emotion and identity discrimination task prior to and following tRNS to either IFC or an active control region (area V5/MT). Baseline performance was a significant predictor of emotion discrimination performance change following tRNS to IFC. This effect was not observed for tRNS targeted at V5/MT or for identity discrimination. Overall, the findings implicate the IFC in emotion processing and demonstrate that tRNS may be a useful tool to modulate emotion perception when accounting for individual differences in factors such as baseline task performance

No interaction between tDCS current strength and baseline performance: a conceptual replication

Several recent studies have reported non-linear effects of transcranial direct current stimulation (tDCS), which has been attributed to an interaction between the stimulation parameters (e.g., current strength, duration) and the neural state of the cortex being stimulated (e.g., indexed by baseline performance ability, age) (see Fertonani and Miniussi, 2016). We have recently described one such non-linear interaction between current strength and baseline performance on a visuospatial attention (landmark) task (Benwell et al., 2015). In this previous study, we induced a small overall rightward shift of spatial attention across 38 participants using bi-hemispheric tDCS applied for 20 min (concurrent left posterior parietal (P5) anode and right posterior parietal (P6) cathode) relative to a sham protocol. Importantly, this shift in bias was driven by a state-dependent interaction between current intensity and the discrimination sensitivity of the participant at baseline (pre-stimulation) for the landmark task. Individuals with high discrimination sensitivity (HDS) shifted rightward in response to low- (1 mA) but not high-intensity (2 mA) tDCS, whereas individuals with low discrimination sensitivity (LDS) shifted rightward with high- but not low-intensity stimulation. However, in Benwell et al. (2015) current strength was applied as a between-groups factor, where half of the participants received 1 mA and half received 2 mA tDCS, thus we were unable to compare high and low-intensity tDCS directly within each individual. Here we aimed to replicate these findings using a within-group design. Thirty young adults received 15 min of 1 and 2 mA tDCS, and a sham protocol, each on different days, to test the concept of an interaction between baseline performance and current strength. We found no overall rightward shift of spatial attention with either current strength, and no interaction between performance and current strength. These results provide further evidence of low replicability of non-invasive brain stimulation protocols, and the need for further attempts to replicate the key experimental findings within this field

Adaptability and reproducibility of a memory disruption rTMS protocol in the PharmaCog IMI European project

Transcranial magnetic stimulation (TMS) can interfere with cognitive processes, such as transiently impairing memory. As part of a multi-center European project, we investigated the adaptability and reproducibility of a previously published TMS memory interfering protocol in two centers using EEG or fMRI scenarios. Participants were invited to attend three experimental sessions on different days, with sham repetitive TMS (rTMS) applied on day 1 and real rTMS on days 2 and 3. Sixty-eight healthy young men were included. On each experimental day, volunteers were instructed to remember visual pictures while receiving neuronavigated rTMS trains (20 Hz, 900 ms) during picture encoding at the left dorsolateral prefrontal cortex (L-DLPFC) and the vertex. Mixed ANOVA model analyses were performed. rTMS to the L-DLPFC significantly disrupted recognition memory on experimental day 2. No differences were found between centers or between fMRI and EEG recordings. Subjects with lower baseline memory performances were more susceptible to TMS disruption. No stability of TMS-induced memory interference could be demonstrated on day 3. Our data suggests that adapted cognitive rTMS protocols can be implemented in multi-center studies incorporating standardized experimental procedures. However, our center and modality effects analyses lacked sufficient statistical power, hence highlighting the need to conduct further studies with larger samples. In addition, inter and intra-subject variability in response to TMS might limit its application in crossover or longitudinal studies

Enhancing anger perception in older adults by stimulating inferior frontal cortex with high frequency transcranial random noise stimulation

Extensive behavioural evidence has shown that older people have declined ability in facial emotion perception. Recent work has begun to examine the neural mechanism that contribute to this, and potential tools to support emotion perception during aging. The aim of this study was to investigate whether high frequency tRNS applied to the inferior frontal cortex would enhance facial expression perception in older adults. Healthy aged adults (60+ years) were randomly assigned to receive active high-frequency or sham tRNS targeted at bilateral inferior frontal cortices. Each group completed tests of facial identity perception, facial happiness perception and facial anger perception. These tasks were completed before and after stimulation. The results showed that, compared to the sham group, the active tRNS group showed greater gains in performance after stimulation in anger perception (relative to performance before stimulation). The same tRNS stimulation did not significantly change performance on the two other face perception tasks assessing facial identity and facial happiness perception. Examination of how inter-individual variability related to changes in anger perception following tRNS indicated that the degree of performance change in anger perception following active tRNS to inferior frontal cortex was predicted by baseline ability and gender of older adult participants. The findings suggest that high frequency tRNS may be a potential tool to aid anger perception in typical aging, but flag that performance variability and gender may interact with stimulation leading to different outcomes

Modulation of Working Memory Using Transcranial Electrical Stimulation: A Direct Comparison Between TACS and TDCS

Transcranial electrical stimulation (TES) has been considered a promising tool for improving working memory (WM) performance. Recent studies have demonstrated modulation of networks underpinning WM processing through application of transcranial alternating current (TACS) as well as direct current (TDCS) stimulation. Differences between study designs have limited direct comparison of the efficacy of these approaches, however. Here we directly compared the effects of theta TACS (6 Hz) and anodal TDCS on WM, applying TACS to the frontal-parietal loop and TDCS to the dorsolateral prefrontal cortex (DLPFC). WM was evaluated using a visual 2-back WM task. A within-subject, crossover design was applied (N = 30) in three separate sessions. TACS, TDCS, and sham stimulation were administered in a counterbalanced order, and the WM task was performed before, during, and after stimulation. Neither reaction times for hits (RT-hit) nor accuracy differed according to stimulation type with this study design. A marked practice effect was noted, however, with improvement in RT-hit irrespective of stimulation type, which peaked at the end of the second session. Pre-stimulation RT-hits in session three returned to the level observed pre-stimulation in session two, irrespective of stimulation type. The participants who received sham stimulation in session one and had therefore improved their performance due to practice alone, had thus reached a plateau by session two, enabling us to pool RT-hits from sessions two and three for these participants. The pooling allowed implementation of a within-subject crossover study design, with a direct comparison of the effects of TACS and TDCS in a subgroup of participants (N = 10), each of whom received both stimulation types, in a counterbalanced order, with pre-stimulation performance the same for both sessions. TACS resulted in a greater improvement in RT-hits than TDCS (F(2,18) = 4.31 p = 0.03). Our findings suggest that future work optimizing the application of TACS has the potential to facilitate WM performance

Lasting EEG/MEG aftereffects on human brain oscillations after rhythmic transcranial brain stimulation: Level of control over oscillatory network activity

A number of rhythmic protocols have emerged for non-invasive brain stimulation (NIBS) in humans, including transcranial alternating current stimulation (tACS), oscillatory transcranial direct current stimulation (otDCS) and repetitive (also called rhythmic) transcranial magnetic stimulation (rTMS). With these techniques, it is possible to match the frequency of the externally applied electromagnetic fields to the intrinsic frequency of oscillatory neural population activity ("frequency-tuning"). Mounting evidence suggests that by this means tACS, otDCS, and rTMS can entrain brain oscillations and promote associated functions in a frequency-specific manner, in particular during (i.e. online to) stimulation. Here, we focus instead on the changes in oscillatory brain activity that persist after the end of stimulation. Understanding such aftereffects in healthy participants is an important step for developing these techniques into potentially useful clinical tools for the treatment of specific patient groups. Reviewing the electrophysiological evidence in healthy participants, we find aftereffects on brain oscillations to be a common outcome following tACS/otDCS and rTMS. However, we did not find a consistent, predictable pattern of aftereffects across studies, which is in contrast to the relative homogeneity of reported online effects. This indicates that aftereffects are partially dissociated from online, frequency-specific (entrainment) effects during tACS/otDCS and rTMS. We outline possible accounts and future directions for a better understanding of the link between online entrainment and offline aftereffects, which will be key for developing more targeted interventions into oscillatory brain activity

Modulation exekutiver Funktionen durch transkranielle Gleichstromstimulation

Hintergrund: Versuchen wir zwei Reize gleichzeitig zu verarbeiten und auf sie zu reagieren, sind wir in der Regel langsamer in unseren Reaktionen und machen mehr Fehler. Im experimentellen Rahmen wird ein solcher Zusammenhang mit dem Doppelaufgabenparadigma untersucht. Bei der Bewältigung dieser Doppelaufgaben spielen exekutive Funktionen eine Rolle und sind in bildgebenden Studien mit einer Aktivierung im inferioren frontalen Kreuzungsareal (engl. inferior frontal junction, IFJ) im Bereich des lateralen präfrontalen Cortex assoziiert. Dabei zeigten sich unterschiedliche Aktivierungsmuster zwischen linker und rechter Hemisphäre. Durch ein nicht-invasives Hirnstimulationsverfahren, der sog. transkraniellen Gleichstromstimulation (engl. transcranial direct current stimulation, tDCS), lassen sich neuronale Aktivitäten stimulierter Areale modulieren und entsprechende Verhaltenseffekte messen. Hierüber lassen sich kausale Zusammenhänge zwischen Hirnarealen und kognitiven Funktionen aufstellen. Vorangegangene Arbeiten zeigten, dass die Applikation von tDCS über der linken IFJ Leistungen in Doppelaufgaben verbessert. Erstmalig untersuchten wir in der vorliegenden Studie die Rolle der rechten IFJ in der Bewältigung von Doppelaufgaben. Methoden: In einer placebokontrollierten Studie an 30 jungen, gesunden Probanden untersuchten wir den Effekt von tDCS über der rechten IFJ in gemixten Doppelaufgaben. Die Doppelaufgaben waren kombinierte Wahlreaktionsaufgaben mit je einem visuellen und einem auditorischen Reiz, welche in ihrer Reihenfolge und ihrem Zeitabstand (200ms/400ms) variierten. Während der Aufgabendurchführung applizierten wir in zwei getrennten Sitzungen jeweils anodale tDCS (1mA, 20min) bzw. Placebostimulation (1mA, 30s) über der rechten IFJ. Reaktionszeiten und Fehlerraten wurden mittels mehrfaktorieller Varianzanalysen mit Messwiederholungen evaluiert. Ergebnisse: Unter dem Einfluss anodaler tDCS zeigten sich im Vergleich zur Placebostimulation signifikant niedrigere Fehlerraten in gemixten Doppelaufgaben (p<.05). Die Effekte traten jedoch nur unter Bedingungen gleichbleibender Reizreihenfolge und kurzen zeitlichen Reizabständen auf. Ein Stimulationseffekt auf die Reaktionszeiten war nicht festzustellen. Der leistungssteigernde Effekt auf die Fehlerraten war umso größer, je schlechter die Ausgangsperformanz vor Stimulationsbeginn war (p<.01). Schlussfolgerung: Die signifikant niedrigere Fehlerrate unter dem Einfluss anodaler tDCS über der rechten IFJ deutet auf einen kausalen Zusammenhang dieses Hirnareals und exekutiven Funktionen in Doppelaufgaben hin. Dass die Probanden mit der schlechtesten Ausgangsperformanz am meisten von der Stimulation profitierten, ist vereinbar mit der in vielen Studien bestätigten Annahme, dass tDCS Effekte positiv mit dem Schwierigkeitslevel der Aufgabe korrelieren. Die Leistungsverbesserung könnte durch gesteigerte Koordinations- oder Arbeitsgedächtnisprozesse bedingt sein. Welche kognitiven Prozesse moduliert wurden, um die beobachteten Verhaltenseffekte hervorzurufen, lässt sich aus dieser Untersuchung nicht schließen. Zukünftige Studien sollten spezifischere Doppelaufgabenparadigmen anwenden, um einzelne kognitive Funktionen gezielter zu untersuchen.Background: Processing and reacting to two stimuli simultaneously makes our reactions slower and more prone to errors. In an experimental design this phenomenon is investigated in dual-task paradigms. Executive functions are essential when processing dual tasks. Functional imaging studies show a related activation in the lateral prefrontal cortex, especially of the inferior frontal junction (IFJ), revealing different activation patterns between the left and right hemisphere. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, modulates neuronal activities of stimulated brain areas. The evaluation of tDCS-induced behavioral effects facilitates conclusions about causal relations between stimulated brain areas and cognitive functions. Previous studies have reported that tDCS over the left IFJ improves performance in dual-task situations. In the present study, we investigated the functional role of the right IFJ in dual-task processing for the first time. Methods: In a placebo-controlled trial with 30 young, healthy patients we evaluated the effects of tDCS over the right IFJ in dual tasks with a random task order. The dual tasks were combined choice reaction tasks consisting of a visual and an auditory stimulus, which varied in their task order and time interval (200ms/400ms). In two separate sessions subjects received anodal tDCS (1mA, 20min) in contrast to placebo stimulation (1mA, 30s) during task execution. Reaction times and error rates were evaluated in multifactorial analyses of variance with repeated measurements. Results: Anodal tDCS reduced error rates significantly in random order dual tasks in comparison to placebo stimulation (p<.05). However, the effects occurred exclusively in trials with repeated task order and a short time interval (200ms) between stimuli. No effect on reaction times could be observed. The baseline performance correlated with tDCS-induced performance improvement in error rates (p<.01). Conclusions: Anodal tDCS over the right IFJ reduced error rates significantly implicating its causal relation to executive functioning in dual-task processing. The fact that the subjects with the worst initial performance benefited most from the stimulation is consistent with the findings of precedent studies that the level of task difficulty correlates with tDCS-induced effects positively. The performance improvement could be due to coordination or working memory processes. It is not possible to determine exactly which cognitive processes lead to the observed behavioral effects. Future studies should apply more specific dual-task paradigms to investigate separate cognitive functions in a more targeted manner