Increasing propensity to mind-wander by transcranial direct current stimulation? A registered report.

Transcranial direct current stimulation (tDCS) has been proposed to be able to modulate different cognitive functions. However, recent meta-analyses conclude that its efficacy is still in question. Recently, an increase in subjects' propensity to mind-wander has been reported as a consequence of anodal stimulation of the left dorsolateral prefrontal cortex (Axelrod et al., Proceedings of the National Academy of Sciences of the United States of America, 112, 2015). In addition, an independent group found a decrease in mind wandering after cathodal stimulation of the same region. These findings seem to indicate that high-level cognitive processes such as mind wandering can reliably be influenced by non-invasive brain stimulation. However, these previous studies used low sample sizes and are as such subject to concerns regarding the replicability of their findings. In this registered report, we implement a high-powered replication of Axelrod et al. (2015) finding that mind-wandering propensity can be increased by anodal tDCS. We used Bayesian statistics and a preregistered sequential-sampling design resulting in a total sample size of N = 192 participants collected across three different laboratories. Our findings show support against a stimulation effect on self-reported mind-wandering scores. The effect was small, in the opposite direction as predicted and not reliably different from zero. Using a Bayes Factor specifically designed to test for replication success, we found strong evidence against a successful replication of the original study. Finally, even when combining data from both the original and replication studies, we could not find evidence for an effect of anodal stimulation. Our results underline the importance of designing studies with sufficient power to detect evidence for or against behavioural effects of non-invasive brain stimulation techniques, preferentially using robust Bayesian statistics in preregistered reports.

Transcranial Magnetic and Direct Current Stimulation in the Treatment of Depression: Basic Mechanisms and Challenges of Two Commonly Used Brain Stimulation Methods in Interventional Psychiatry.

Noninvasive neuromodulation, including repetitive trans-cranial magnetic stimulation (rTMS) and direct current stimulation (tDCS), provides researchers and health care professionals with the ability to gain unique insights into brain functions and treat several neurological and psychiatric conditions. Undeniably, the number of published research and clinical papers on this topic is increasing exponentially. In parallel, several methodological and scientific caveats have emerged in the transcranial stimulation field; these include less robust and reliable effects as well as contradictory clinical findings. These inconsistencies are maybe due to the fact that research exploring the relationship between the methodological aspects and clinical efficacy of rTMS and tDCS is far from conclusive. Hence, additional work is needed to understand the mechanisms underlying the effects of magnetic stimulation and low-intensity transcranial electrical stimulation (TES) in order to optimize dosing, methodological designs, and safety aspects.

Medial prefrontal cortex involvement in aesthetic appreciation of paintings: a tDCS study.

Among the brain regions involved in the aesthetic evaluation of paintings, the prefrontal cortex seems to play a pivotal role. In particular, consistent neuroimaging evidence indicates that activity in the dorsolateral prefrontal cortex (mainly in the left hemisphere) and in medial and orbital sectors of the prefrontal cortex is linked to viewing aesthetically pleasing images. In this study, we focused on the contribution of the medial prefrontal cortex (mPFC) in mediating aesthetic decisions about paintings. We found that enhancing excitability in this region via anodal tDCS led participants to judge paintings as more beautiful. Although significant, the effects were moderate, possibly due to the neutral affective value of the artworks we used, suggesting that activity in mPFC may be critically dependent on the affective impact of the paintings.

Blinding is compromised for transcranial direct current stimulation at 1 mA for 20 min in young healthy adults.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method that is frequently used to study cortical excitability changes and their impact on cognitive functions in humans. While most stimulators are capable of operating in double-blind mode, the amount of discomfort experienced during tDCS may break blinding. Therefore, specifically designed sham stimulation protocols are being used. The "fade-in, short-stimulation, fade-out" (FSF) protocol has been used in hundreds of studies and is commonly believed to be indistinguishable from real stimulation applied at 1 mA for 20 min. We analysed subjective reports of 192 volunteers, who either received real tDCS (n = 96) or FSF tDCS (n = 96). Participants reported more discomfort for real tDCS and correctly guessed the condition above chance-level. These findings indicate that FSF does not ensure complete blinding and that better active sham protocols are needed.

Modulation of Conflict Processing by Theta-Range tACS over the Dorsolateral Prefrontal Cortex.

Behavioral response conflict arises in the color-word Stroop task and triggers the cognitive control network. Midfrontal theta-band oscillations correlate with adaptive control mechanisms during and after conflict resolution. In order to prove causality, in two experiments, we applied transcranial alternating current stimulation (tACS) at 6 Hz to the dorsolateral prefrontal cortex (DLPFC) during Stroop task performance. Sham stimulation served as a control in both experiments; 9.7 Hz tACS served as a nonharmonic alpha band control in the second experiment. We employed generalized linear mixed models for analysis of behavioral data. Accuracy remained unchanged by any type of active stimulation. Over both experiments, the Stroop effect (response time difference between congruent and incongruent trials) was reduced by 6 Hz stimulation as compared to sham, mainly in trials without prior conflict adaptation. Alpha tACS did not modify the Stroop effect. Theta tACS can both reduce the Stroop effect and modulate adaptive mechanisms of the cognitive control network, suggesting midfrontal theta oscillations as causally involved in cognitive control.

Physiology of Transcranial Direct Current Stimulation.

Direct current stimulation is a neuromodulatory noninvasive brain stimulation tool, which was first introduced in animal and human experiments in the 1950s, and added to the standard arsenal of methods to alter brain physiology as well as psychological, motor, and behavioral processes and clinical symptoms in neurological and psychiatric diseases about 20 years ago. In contrast to other noninvasive brain stimulation tools, such as transcranial magnetic stimulation, it does not directly induce cerebral activity, but rather alters spontaneous brain activity and excitability by subthreshold modulation of neuronal membranes. Beyond acute effects on brain functions, specific protocols are suited to induce long-lasting alterations of cortical excitability and activity, which share features with long-term potentiation and depression. These neuroplastic processes are important foundations for various cognitive functions such as learning and memory formation and are pathologically altered in numerous neurological and psychiatric diseases. This explains the increasing interest to investigate transcranial direct current stimulation (tDCS) as a therapeutic tool. However, for tDCS to be used effectively, it is crucial to be informed about physiological mechanisms of action. These have been increasingly elucidated during the last years. This review gives an overview of the current knowledge available regarding physiological mechanisms of tDCS, spanning from acute regional effects, over neuroplastic effects to its impact on cerebral networks. Although knowledge about the physiological effects of tDCS is still not complete, this might help to guide applications on a scientifically sound foundation.

Transcranial electrical stimulation of the occipital cortex during visual perception modifies the magnitude of BOLD activity: A combined tES-fMRI approach.

The aim of this study was to investigate if the blood oxygenation level-dependent (BOLD) changes in the visual cortex can be used as biomarkers reflecting the online and offline effects of transcranial electrical stimulation (tES). Anodal transcranial direct current stimulation (tDCS) and 10Hz transcranial alternating current stimulation (tACS) were applied for 10min duration over the occipital cortex of healthy adults during the presentation of different visual stimuli, using a crossover, double-blinded design. Control experiments were also performed, in which sham stimulation as well as another electrode montage were used. Anodal tDCS over the visual cortex induced a small but significant further increase in BOLD response evoked by a visual stimulus; however, no aftereffect was observed. Ten hertz of tACS did not result in an online effect, but in a widespread offline BOLD decrease over the occipital, temporal, and frontal areas. These findings demonstrate that tES during visual perception affects the neuronal metabolism, which can be detected with functional magnetic resonance imaging (fMRI).

Transcranial Alternating Current and Random Noise Stimulation: Possible Mechanisms.

Background. Transcranial alternating current stimulation (tACS) is a relatively recent method suited to noninvasively modulate brain oscillations. Technically the method is similar but not identical to transcranial direct current stimulation (tDCS). While decades of research in animals and humans has revealed the main physiological mechanisms of tDCS, less is known about the physiological mechanisms of tACS. Method. Here, we review recent interdisciplinary research that has furthered our understanding of how tACS affects brain oscillations and by what means transcranial random noise stimulation (tRNS) that is a special form of tACS can modulate cortical functions. Results. Animal experiments have demonstrated in what way neurons react to invasively and transcranially applied alternating currents. Such findings are further supported by neural network simulations and knowledge from physics on entraining physical oscillators in the human brain. As a result, fine-grained models of the human skull and brain allow the prediction of the exact pattern of current flow during tDCS and tACS. Finally, recent studies on human physiology and behavior complete the picture of noninvasive modulation of brain oscillations. Conclusion. In future, the methods may be applicable in therapy of neurological and psychiatric disorders that are due to malfunctioning brain oscillations.

Imaging artifacts induced by electrical stimulation during conventional fMRI of the brain.

Functional magnetic resonance imaging (fMRI) of brain activation during transcranial electrical stimulation is used to provide insight into the mechanisms of neuromodulation and targeting of particular brain structures. However, the passage of current through the body may interfere with the concurrent detection of blood oxygen level-dependent (BOLD) signal, which is sensitive to local magnetic fields. To test whether these currents can affect concurrent fMRI recordings we performed conventional gradient echo-planar imaging (EPI) during transcranial direct current (tDCS) and alternating current stimulation (tACS) on two post-mortem subjects. tDCS induced signals in both superficial and deep structures. The signal was specific to the electrode montage, with the strongest signal near cerebrospinal fluid (CSF) and scalp. The direction of change relative to non-stimulation reversed with tDCS stimulation polarity. For tACS there was no net effect of the MRI signal. High-resolution individualized modeling of current flow and induced static magnetic fields suggested a strong coincidence of the change EPI signal with regions of large current density and magnetic fields. These initial results indicate that (1) fMRI studies of tDCS must consider this potentially confounding interference from current flow and (2) conventional MRI imaging protocols can be potentially used to measure current flow during transcranial electrical stimulation. The optimization of current measurement and artifact correction techniques, including consideration of the underlying physics, remains to be addressed.

Transcranial electrical stimulation modifies the neuronal response to psychosocial stress exposure.

Stress is a constant characteristic of everyday life in our society, playing a role in triggering several chronic disorders. Therefore, there is an ongoing need to develop new methods in order to manage stress reactions. The regulatory function of right medial-prefrontal cortex (mPFC) is frequently reported by imaging studies during psychosocial stress situations. Here, we examined the effects of inhibitory and excitatory preconditioning stimulation via cathodal and anodal transcranial direct current stimulation (tDCS) on psychosocial stress related behavioral indicators and physiological factors, including the cortisol level in the saliva and changes in brain perfusion. Twenty minutes real or sham tDCS was applied over the right mPFC of healthy subjects before the performance of the Trier Social Stress Test (TSST). Regional cerebral blood flow (rCBF) was measured during stimulation and after TSST, using pseudo-continuous arterial spin labeling (pCASL). Comparing the effect of the different stimulation conditions, during anodal stimulation we found higher rCBF in the right mPFC, compared to the sham and in the right amygdala, superior PFC compared to the cathodal condition. Salivary cortisol levels showed a decrease in the anodal and increase in cathodal groups after completion of the TSST. The behavioral stress indicators indicated the increase of stress level, however, did not show any significant differences among groups. In this study we provide the first insights into the neuronal mechanisms mediating psychosocial stress responses by prefrontal tDCS.

Comparing the efficacy of excitatory transcranial stimulation methods measuring motor evoked potentials.

The common aim of transcranial stimulation methods is the induction or alterations of cortical excitability in a controlled way. Significant effects of each individual stimulation method have been published; however, conclusive direct comparisons of many of these methods are rare. The aim of the present study was to compare the efficacy of three widely applied stimulation methods inducing excitability enhancement in the motor cortex: 1 mA anodal transcranial direct current stimulation (atDCS), intermittent theta burst stimulation (iTBS), and 1 mA transcranial random noise stimulation (tRNS) within one subject group. The effect of each stimulation condition was quantified by evaluating motor-evoked-potential amplitudes (MEPs) in a fixed time sequence after stimulation. The analyses confirmed a significant enhancement of the M1 excitability caused by all three types of active stimulations compared to sham stimulation. There was no significant difference between the types of active stimulations, although the time course of the excitatory effects slightly differed. Among the stimulation methods, tRNS resulted in the strongest and atDCS significantly longest MEP increase compared to sham. Different time courses of the applied stimulation methods suggest different underlying mechanisms of action. Better understanding may be useful for better targeting of different transcranial stimulation techniques.

Uncorking the limitation-improving dual tasking using transcranial electrical stimulation and task training in the elderly: a systematic review.

Introduction: With aging, dual task (DT) ability declines and is more cognitively demanding than single tasks. Rapidly declining DT performance is regarded as a predictor of neurodegenerative disease. Task training and non-invasive transcranial electrical stimulation (tES) are methods applied to optimize the DT ability of the elderly. Methods: A systematic search was carried out in the PUBMED, TDCS (transcranial direct current stimulation) databases, as well as Web of Science, and a qualitative analysis was conducted in 56 included studies. Aiming to summarize the results of studies that implemented tES, task training, or the combination for improving DT ability and related performance changes in healthy elderly and geriatric patients. For different approaches, the training procedures, parameters, as well as outcomes were discussed. Results: Task training, particularly cognitive-motor DT training, has more notable effects on improving DT performance in the elderly when compared to the neuromodulation method. Discussion: Anodal transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (L-DLPFC), or its combination with task training could be promising tools. However, additional evidence is required from aged healthy people and patients, as well as further exploration of electrode montage.

Beyond social engagement: cognitive training leads to greater cognitive improvement in older adults.

Aging is often accompanied by a decline in cognitive functions, with memory being particularly affected. Recent studies suggest that cognitive training sessions that teach memory strategies relevant to daily life may benefit seniors who live in the community. However, it is possible that the cognitive improvement observed in these programs results from the social encounters embedded in them. In this study, we aimed to investigate the effect of a social cognitive training group, which met regularly for an extended period, on enhancing cognitive indices compared to a control group that only received social engagement meetings without training. Sixty-six participants with a mean age of 78 took part in 12 sessions of a social engagement group, with or without strategy training. Cognitive performance was assessed before and after training using four memory tasks, two similar to the trained tasks (near-transfer tasks) and two novel (far-transfer tasks). Both groups showed a slight improvement in most of the evaluation tasks, but the cognitive training combined with social engagement group showed a significant improvement in the Word Recall and Verbal Fluency tests compared to the social engagement group without training. Our findings suggest that cognitive training sessions may be a useful tool in promoting cognitive improvement among older adults living in the community, even beyond the improvement obtained from the social engagement that occurs during the training sessions.Trial registration number:NCT05016336. Date of registration: 20 August 2021. Retrospectively registered.

Boosting working memory in the elderly: driving prefrontal theta-gamma coupling via repeated neuromodulation.

The escalating global burden of age-related neurodegenerative diseases and associated healthcare costs necessitates innovative interventions to stabilize or enhance cognitive functions. Deficits in working memory (WM) are linked to alterations in prefrontal theta-gamma cross-frequency coupling. Low-intensity transcranial alternating current stimulation (tACS) has emerged as a non-invasive, low-cost approach capable of modulating ongoing oscillations in targeted brain areas through entrainment. This study investigates the impact of multi-session peak-coupled theta-gamma cross-frequency tACS administered to the dorsolateral prefrontal cortex (DLPFC) on WM performance in older adults. In a randomized, sham-controlled, triple-blinded design, 77 participants underwent 16 stimulation sessions over six weeks while performing n-back tasks. Signal detection measures revealed increased 2-back sensitivity and robust modulations of response bias, indicating improved WM and decision-making adaptations, respectively. No effects were observed in the 1-back condition, emphasizing dependencies on cognitive load. Repeated tACS reinforces behavioral changes, indicated by increasing effect sizes. This study supports prior research correlating prefrontal theta-gamma coupling with WM processes and provides unique insights into the neurocognitive benefits of repeated tACS intervention. The well-tolerated and highly effective multi-session tACS intervention among the elderly underscores its therapeutic potential in vulnerable populations.

Prefrontal theta-gamma transcranial alternating current stimulation improves non-declarative visuomotor learning in older adults.

The rise in the global population of older adults underscores the significance to investigate age-related cognitive disorders and develop early treatment modalities. Previous research suggests that non-invasive transcranial Alternating Current Stimulation (tACS) can moderately improve cognitive decline in older adults. However, non-declarative cognition has received relatively less attention. This study investigates whether repeated (16-day) bilateral theta-gamma cross-frequency tACS targeting the Dorsolateral Prefrontal Cortex (DLPFC) enhances non-declarative memory. Computerized cognitive training was applied alongside stimulation to control for the state-of-the-brain. The Alternating Serial Reaction Time (ASRT) task was employed to assess non-declarative functions such as visuomotor skill and probabilistic sequence learning. Results from 35 participants aged 55-82 indicated that active tACS led to more substantial improvements in visuomotor skills immediately after treatment, which persisted 3 months later, compared to sham tACS. Treatment benefit was more pronounced in older adults of younger age and those with pre-existing cognitive decline. However, neither intervention group exhibited modulation of probabilistic sequence learning. These results suggest that repeated theta-gamma tACS can selectively improve distinct non-declarative cognitive aspects when targeting the DLPFC. Our findings highlight the therapeutic potential of tACS in addressing deficits in learning and retaining general skills, which could have a positive impact on the quality of life for cognitively impaired older individuals by preserving independence in daily activities.

No add-on therapeutic benefit of at-home anodal tDCS of the primary motor cortex to mindfulness meditation in patients with fibromyalgia.

OBJECTIVE: This study investigated the efficacy of combining at-home anodal transcranial direct current stimulation (tDCS) of the left primary motor cortex (M1) with mindfulness meditation (MM) in fibromyalgia patients trained in mindfulness. METHODS: Thirty-seven patients were allocated to receive ten daily sessions of MM paired with either anodal or sham tDCS over the primary motor cortex. Primary outcomes were pain intensity and quality of life. Secondary outcomes were psychological impairment, sleep quality, mood, affective pain, mindfulness level, and transcranial magnetic stimulation (TMS) measures of cortical excitability. Outcomes were analyzed pre- and post-treatment, with a one-month follow-up. RESULTS: We found post-tDCS improvement in all clinical outcomes, including mindfulness level, except for positive affect and stress, in both groups without significant difference between active and sham conditions. No significant group*time interaction was found for all clinical and TMS outcomes. CONCLUSIONS: Our findings demonstrate no synergistic or add-on efffect of anodal tDCS of the left M1 compared to the proper effect of MM in patients with fibromyalgia. SIGNIFICANCE: Our findings challenge the potential of combining anodal tDCS of the left M1 and MM in fibromyalgia.

The consequences of the new European reclassification of non-invasive brain stimulation devices and the medical device regulations pose an existential threat to research and treatment: An invited opinion paper.

A significant amount of European basic and clinical neuroscience research includes the use of transcranial magnetic stimulation (TMS) and low intensity transcranial electrical stimulation (tES), mainly transcranial direct current stimulation (tDCS). Two recent changes in the EU regulations, the introduction of the Medical Device Regulation (MDR) (2017/745) and the Annex XVI have caused significant problems and confusions in the brain stimulation field. The negative consequences of the MDR for non-invasive brain stimulation (NIBS) have been largely overlooked and until today, have not been consequently addressed by National Competent Authorities, local ethical committees, politicians and by the scientific communities. In addition, a rushed bureaucratic decision led to seemingly wrong classification of NIBS products without an intended medical purpose into the same risk group III as invasive stimulators. Overregulation is detrimental for any research and for future developments, therefore researchers, clinicians, industry, patient representatives and an ethicist were invited to contribute to this document with the aim of starting a constructive dialogue and enacting positive changes in the regulatory environment.

Neuromodulation of chronic headaches: position statement from the European Headache Federation.

The medical treatment of patients with chronic primary headache syndromes (chronic migraine, chronic tension-type headache, chronic cluster headache, hemicrania continua) is challenging as serious side effects frequently complicate the course of medical treatment and some patients may be even medically intractable. When a definitive lack of responsiveness to conservative treatments is ascertained and medication overuse headache is excluded, neuromodulation options can be considered in selected cases. Here, the various invasive and non-invasive approaches, such as hypothalamic deep brain stimulation, occipital nerve stimulation, stimulation of sphenopalatine ganglion, cervical spinal cord stimulation, vagus nerve stimulation, transcranial direct current stimulation, repetitive transcranial magnetic stimulation, and transcutaneous electrical nerve stimulation are extensively published although proper RCT-based evidence is limited. The European Headache Federation herewith provides a consensus statement on the clinical use of neuromodulation in headache, based on theoretical background, clinical data, and side effect of each method. This international consensus further gives recommendations for future studies on these new approaches. In spite of a growing field of stimulation devices in headaches treatment, further controlled studies to validate, strengthen and disseminate the use of neurostimulation are clearly warranted. Consequently, until these data are available any neurostimulation device should only be used in patients with medically intractable syndromes from tertiary headache centers either as part of a valid study or have shown to be effective in such controlled studies with an acceptable side effect profile.

Stimulated brains and meditative minds: A systematic review on combining low intensity transcranial electrical stimulation and meditation in humans.

Background: Low intensity transcranial electrical stimulation (tES) and meditation are two promising, yet variable, non-pharmacological interventions. Growing research is investigating combined effects of both techniques on one's cognitive, emotional, and physical health. Objective: This article reviews the current research that combines tES and meditation interventions in healthy and diseased participants. The review considers the intervention parameters and their effects in a well-organized manner. Method: A systematic search for clinical and experimental published studies was conducted in the PubMed, Cochrane, and transcranial direct current stimulation (tDCS) databases using common keywords for tES and for meditation techniques well defined by previous studies. Unpublished ongoing studies were identified with the ClinicalTrials.gov and DRKS.de clinical trial websites. Results: 20 published studies and 13 ongoing studies were included for qualitative analysis. 13 published articles studied patients with chronic pain, psychological disorders, cognitive impairment, and movement disorders. Anodal tDCS was the only tES technique while mindfulness meditation was the most common meditation type. Eight studies had a main group effect, with outcome improvement in the active combined intervention. However, most published studies showed improvements after at least one combined intervention with variable effects. Conclusion: Pairing anodal tDCS with meditation shows promising improvements of the physical, mental, and emotional aspects of daily life. Further studies are required to confirm the relevance of this combination in the clinic.

Why Temporal Inference Stimulation May Fail in the Human Brain: A Pilot Research Study.

Temporal interference stimulation (TIS) aims at targeting deep brain areas during transcranial electrical alternating current stimulation (tACS) by generating interference fields at depth. Although its modulatory effects have been demonstrated in animal and human models and stimulation studies, direct experimental evidence is lacking for its utility in humans (in vivo). Herein, we directly test and compare three different structures: firstly, we perform peripheral nerve and muscle stimulation quantifying muscle twitches as readout, secondly, we stimulate peri-orbitally with phosphene perception as a surrogate marker, and thirdly, we attempt to modulate the mean power of alpha oscillations in the occipital area as measured with electroencephalography (EEG). We found strong evidence for stimulation efficacy on the modulated frequency in the PNS, but we found no evidence for its utility in the CNS. Possible reasons for failing to activate CNS targets could be comparatively higher activation thresholds here or inhibitory stimulation components to the carrier frequency interfering with the effects of the modulated signal.