Impact of theta transcranial alternating current stimulation on language production in adult classic galactosemia patients.

Patients with classic galactosemia (CG), an inborn error of galactose metabolism, suffer from impairments in cognition, including language processing. Potential causes are atypical brain oscillations. Recent electroencephalogram (EEG) showed differences in the P300 event-related-potential (ERP) and alterations in the alpha/theta-range during speech planning. This study investigated whether transcranial alternating current stimulation (tACS) at theta-frequency compared to sham can cause a normalization of the ERP post stimulation and improves language performance. Eleven CG patients and fourteen healthy controls participated in two tACS-sessions (theta 6.5 Hz/sham). They were engaged in an active language task, describing animated scenes at three moments, that is, pre/during/post stimulation. Pre and post stimulation, behavior (naming accuracy, voice-onset-times; VOT) and mean-amplitudes of ERP were compared, by means of a P300 time-window analysis and cluster-based-permutation testing during speech planning. The results showed that theta stimulation, not sham, significantly reduced naming error-percentage in patients, not in controls. Theta did not systematically speed up naming beyond a general learning effect, which was larger for the patients. The EEG analysis revealed a significant pre-post stimulation effect (P300/late positivity), in patients and during theta stimulation only. In conclusion, theta-tACS improved accuracy in language performance in CG patients compared to controls and altered the P300 and late positive ERP-amplitude, suggesting a lasting effect on neural oscillation and behavior.

Individualized, connectome-based, non-invasive stimulation of OCD deep-brain targets: A proof-of-concept.

Treatment-resistant obsessive-compulsive disorder (OCD) generally improves with deep-brain stimulation (DBS), thought to modulate neural activity at both the implantation site and in connected brain regions. However, its invasive nature, side-effects, and lack of customization, make non-invasive treatments preferable. Harnessing the established remote effects of cortical transcranial magnetic stimulation (TMS), connectivity-based approaches have emerged for depression that aim at influencing distant regions connected to the stimulation site. We here investigated whether effective OCD DBS targets (here subthalamic nucleus [STN] and nucleus accumbens [NAc]) could be modulated non-invasively with TMS. In a proof-of-concept study with nine healthy individuals, we used 7T magnetic resonance imaging (MRI) and probabilistic tractography to reconstruct the fiber tracts traversing manually segmented STN/NAc. Two TMS targets were individually selected based on the strength of their structural connectivity to either the STN, or both the STN and NAc. In a sham-controlled, within-subject cross-over design, TMS was administered over the personalized targets, located around the precentral and middle frontal gyrus. Resting-state functional 3T MRI was acquired before, and at 5 and 25 min after stimulation to investigate TMS-induced changes in the functional connectivity of the STN and NAc with other regions of the brain. Static and dynamic seed-to-voxel correlation analyses were conducted. TMS over both targets was able to modulate the functional connectivity of the STN and NAc, engaging both overlapping and distinct regions, and unfolding following different temporal dynamics. Given the relevance of the engaged connected regions to OCD pathology, we argue that a personalized, connectivity-based procedure is worth investigating as potential treatment for refractory OCD.

Target Engagement and Brain State Dependence of Transcranial Magnetic Stimulation: Implications for Clinical Practice.

Transcranial magnetic stimulation (TMS) is capable of noninvasively inducing lasting neuroplastic changes when applied repetitively across multiple treatment sessions. In recent years, repetitive TMS has developed into an established evidence-based treatment for various neuropsychiatric disorders such as depression. Despite significant advancements in our understanding of the mechanisms of action of TMS, there is still much to learn about how these mechanisms relate to the clinical effects observed in patients. If there is one thing about TMS that we know for sure, it is that TMS effects are state dependent. In this review, we describe how the effects of TMS on brain networks depend on various factors, including cognitive brain state, oscillatory brain state, and recent brain state history. These states play a crucial role in determining the effects of TMS at the moment of stimulation and are therefore directly linked to what is referred to as target engagement in TMS therapy. There is no control over target engagement without considering the different brain state dependencies of our TMS intervention. Clinical TMS protocols are largely ignoring this fundamental principle, which may explain the large variability and often still limited efficacy of TMS treatments. We propose that after almost 30 years of research on state dependency of TMS, it is time to change standard clinical practice by taking advantage of this fundamental principle. Rather than ignoring TMS state dependency, we can use it to our clinical advantage to improve the effectiveness of TMS treatments.

Home-administered transcranial direct current stimulation with asynchronous remote supervision in the treatment of depression: feasibility, tolerability, and clinical effectiveness.

Introduction Background: Depression is an often chronic condition, characterized by wide-ranging physical, cognitive and psychosocial symptoms that can lead to disability, premature mortality or suicide. It affects 350 million people globally, yet up to 30% do not respond to traditional treatment, creating an urgent need for novel non-pharmacological treatments. This open-label naturalistic study assesses the practical feasibility, tolerability, and clinical effectiveness of home-administered transcranial direct current stimulation (tDCS) with asynchronous remote supervision, in the treatment of depression. Method: Over the course of 3 weeks, 40 patients with depression received psychotherapy and half of this group also received daily bi-frontal tDCS stimulation of the dorsolateral prefrontal cortex. These patients received tDCS for 30 min per session with the anode placed over F3 and the cathode over F4, at an intensity of 2 mA for 21 consecutive days. We measured patients' level of depression symptoms at four time points using the Beck Depression Inventory, before treatment and at 1-week intervals throughout the treatment period. We monitored practical feasibility such as daily protocol compliance and tolerability including side effects, with the PlatoScience cloud-based remote supervision platform. Results: Of the 20 patients in the tDCS group, 90% were able to comply with the protocol by not missing more than three of their assigned sessions, and none dropped out of the study. No serious adverse events were reported, with only 14 instances of mild to moderate side effects and two instances of scalp pain rated as severe, out of a total of 420 stimulation sessions. Patients in the tDCS group showed a significantly greater reduction in depression symptoms after 3 weeks of treatment, compared to the treatment as usual (TAU) group [t(57.2) = 2.268, p = 0.027]. The tDCS group also showed greater treatment response (50%) and depression remission rates (75%) compared to the TAU group (5 and 30%, respectively). Discussion Conclusion: These findings provide a possible indication of the clinical effectiveness of home-administered tDCS for the treatment of depression, and its feasibility and tolerability in combination with asynchronous supervision.

Modulating risk-taking behavior with theta-band tACS.

Although risk is prevalent in decision-making, the specific neural processes underlying risk-taking behavior remain unclear. Previous studies have suggested that frontal theta-band activity plays a crucial role in modulating risk-taking behavior. The functional relevance of theta in risk-taking behavior is yet to be clearly established and studies using noninvasive brain stimulation have yielded inconsistent findings. We aimed to investigate this relevance using transcranial alternating current stimulation (tACS) over right or left dorsolateral prefrontal cortex (DLPFC). We also studied the influence of stimulation intensity on risk-taking behavior and electrophysiological effects. We applied theta-band (6.5 Hz) tACS over the left (F3) and right (F4) DLPFC with lower (1.5 mA) and higher (3 mA) tACS intensities. We employed a single-blinded, sham-controlled, within-subject design and combined tACS with electroencephalography (EEG) measurements and the Maastricht Gambling Task (MGT) to elicit and evaluate risk-taking behavior. Our results show an increase in risk-taking behavior after left DLPFC stimulation at both intensities and a reduction of risk-taking behavior after 3 mA (and not 1.5 mA) right DLPFC stimulation compared to sham. Further analyses showed a negative correlation between resting-state frontal theta-power and risk-taking behavior. Overall, frontal theta-power was increased after left, but not right, theta-band tACS independent of stimulation intensity. Our findings confirm the functional relevance of frontal theta-band activity in decision-making under risk and the differential role of left and right DLPFC. We also were able to show that stimulation intensity did have an effect on behavioral responses, namely risk-taking behavior. Significant right hemisphere stimulation effects were observed only after high-intensity stimulation. Nevertheless, electrophysiological effects were only significant after left DLPFC stimulation, regardless of tACS intensity. Furthermore, the results indicate the role of the baseline frontal theta-power in the direction of behavioral effects after theta-band tACS.

Hemispheric Asymmetry in TMS-Induced Effects on Spatial Attention: A Meta-Analysis.

Hemispheric asymmetry is a fundamental principle in the functional architecture of the brain. It plays an important role in attention research where right hemisphere dominance is core to many attention theories. Lesion studies seem to confirm such hemispheric dominance with patients being more likely to develop left hemineglect after right hemispheric stroke than vice versa. However, the underlying concept of hemispheric dominance is still not entirely clear. Brain stimulation studies using transcranial magnetic stimulation (TMS) might be able to illuminate this concept. To examine the putative hemispheric asymmetry in spatial attention, we conducted a meta-analysis of studies applying inhibitory TMS protocols to the left or right posterior parietal cortices (PPC), assessing effects on attention biases with the landmark and line bisection task. A total of 18 studies including 222 participants from 1994 to February 2022 were identified. The analysis revealed a significant shift of the perceived midpoint towards the ipsilateral hemifield after right PPC suppression (Cohen's d = 0.52), but no significant effect after left PPC suppression (Cohen's d = 0.26), suggesting a hemispheric asymmetry even though the subgroup difference does not reach significance (p = .06). A complementary Bayesian meta-analysis revealed a high probability of at least a medium effect size after right PPC disruption versus a low probability after left PPC disruption. This is the first quantitative meta-analysis supporting right hemisphere-specific TMS-induced spatial attention deficits, mimicking hemineglect in healthy participants. We discuss the result in the light of prominent attention theories, ultimately concluding how difficult it remains to differentiate between these theories based on attentional bias scores alone.

Investigating the role of task relevance during rhythmic sampling of spatial locations.

Recently it has been discovered that visuospatial attention operates rhythmically, rather than being stably employed over time. A low-frequency 7-8 Hz rhythmic mechanism coordinates periodic windows to sample relevant locations and to shift towards other, less relevant locations in a visual scene. Rhythmic sampling theories would predict that when two locations are relevant 8 Hz sampling mechanisms split into two, effectively resulting in a 4 Hz sampling frequency at each location. Therefore, it is expected that rhythmic sampling is influenced by the relative importance of locations for the task at hand. To test this, we employed an orienting task with an arrow cue, where participants were asked to respond to a target presented in one visual field. The cue-to-target interval was systematically varied, allowing us to assess whether performance follows a rhythmic pattern across cue-to-target delays. We manipulated a location's task relevance by altering the validity of the cue, thereby predicting the correct location in 60%, 80% or 100% of trials. Results revealed significant 4 Hz performance fluctuations at cued right visual field targets with low cue validity (60%), suggesting regular sampling of both locations. With high cue validity (80%), we observed a peak at 8 Hz towards non-cued targets, although not significant. These results were in line with our hypothesis suggesting a goal-directed balancing of attentional sampling (cued location) and shifting (non-cued location) depending on the relevance of locations in a visual scene. However, considering the hemifield specificity of the effect together with the absence of expected effects for cued trials in the high valid conditions we further discuss the interpretation of the data.

Accelerated intermittent theta burst stimulation in smoking cessation: No differences between active and placebo stimulation when using advanced placebo coil technology. A double-blind follow-up study

Objective: This study aims to investigate the longer-term effects of accelerated intermittent theta burst stimulation (aiTBS) in smoking cessation and to examine whether there is a difference in outcome between active and placebo stimulation. The present study constitutes an ancillary study from a main Randomized Controlled Trial (RCT) evaluating the acute effects of aiTBS in smoking reduction. Method: A double-blind randomized control trial was conducted where 89 participants were randomly allocated to three groups (transcranial magnetic stimulation (TMS)&N group: active aiTBS stimulation combined with neutral videos; TMS&S group: active aiTBS stimulation combined with smoking-related videos; Placebo group: placebo stimulation combined with smoking-related videos). Nicotine dependence, tobacco craving, perceived stress and motivation to quit smoking were measured after completion of 20 aiTBS sessions and during various follow ups (post one week, post one month and post six months). Results: Our results show that the positive effect on nicotine dependence and tobacco craving that occurred at the end of treatment lasts at least one month post treatment. This effect seems to dissipate six months post treatment. No significant differences were found between the three groups. Conclusion: Both active and placebo stimulation were equally effective in reducing nicotine dependence and tobacco craving up to one month after the end of treatment. (AU)

The functional relevance of right DLPFC and VMPFC in risk-taking behavior.

BACKGROUND: The prefrontal cortex can be partialized in various anatomical and functional sub regions. Among those regions, both right dorsolateral prefrontal cortex (rDLPFC) and ventromedial prefrontal cortex (VMPFC) have been associated with risk-taking behavior based on neuroimaging studies. Noninvasive brain stimulation (NIBS) studies aiming at demonstrating the functional relevance of neural activity in these areas almost exclusively focused on the rDLPFC, where its experimental stimulation with a (generally) inhibitory protocol lead to a measurable increase in risk-taking behavior due to reduced cognitive control. The functional relevance of VMPFC in risk-taking behavior has not yet been addressed using NIBS, although multiple neuroimaging studies correlate this area's activity with valuation. OBJECTIVE/HYPOTHESIS: Here, we used NIBS to investigate the functional relevance of both, the rDLPFC and VMPFC in risk-taking behavior. We hypothesized that, compared to sham stimulation, VMPFC suppression leads to a reduction in risk-taking behavior by reducing the appeal to higher value options and consequently the attractiveness of riskier options, whereas rDLPFC suppression leads to an increase in risk taking, replicating previous findings. METHODS: We applied continuous theta burst stimulation (cTBS), a generally inhibitory protocol, to stimulate either VMPFC or DLPFC before the execution of the computerized Maastricht Gambling Task (MGT) in a within-subject design with 30 participants. The MGT allowed the analysis of potential brain region-specific effects of cTBS on risk-taking behavior such as participants' choices of average values, probabilities, and response time. RESULTS: cTBS applied to either rDLPFC or VMPFC both led to an increase in risk-taking behavior and in the average value chosen as compared to sham transcranial magnetic stimulation. No effect on the choice of probabilities was found. A significant increase in response time was observed exclusively after suppressing rDLPFC. We speculate that these similar behavioral consequences following cTBS over DLPFC and VMPFC are likely due to the strong anatomical and functional interconnection between both brain regions.

Accelerated intermittent theta burst stimulation in smoking cessation: No differences between active and placebo stimulation when using advanced placebo coil technology. A double-blind follow-up study.

Objective: This study aims to investigate the longer-term effects of accelerated intermittent theta burst stimulation (aiTBS) in smoking cessation and to examine whether there is a difference in outcome between active and placebo stimulation. The present study constitutes an ancillary study from a main Randomized Controlled Trial (RCT) evaluating the acute effects of aiTBS in smoking reduction. Method: A double-blind randomized control trial was conducted where 89 participants were randomly allocated to three groups (transcranial magnetic stimulation (TMS)&N group: active aiTBS stimulation combined with neutral videos; TMS&S group: active aiTBS stimulation combined with smoking-related videos; Placebo group: placebo stimulation combined with smoking-related videos). Nicotine dependence, tobacco craving, perceived stress and motivation to quit smoking were measured after completion of 20 aiTBS sessions and during various follow ups (post one week, post one month and post six months). Results: Our results show that the positive effect on nicotine dependence and tobacco craving that occurred at the end of treatment lasts at least one month post treatment. This effect seems to dissipate six months post treatment. No significant differences were found between the three groups. Conclusion: Both active and placebo stimulation were equally effective in reducing nicotine dependence and tobacco craving up to one month after the end of treatment.

Brain stimulation reveals distinct motives underlying reciprocal punishment and reward.

Reciprocal fairness, in the form of punishment and reward, is at the core of human societal order. Its underlying neural mechanisms are, however, not fully understood. We systemize suggestive evidence regarding the involvement of the right dorsolateral prefrontal cortex (rDLPFC) and medial prefrontal cortex (mPFC) in reciprocal fairness in three cognitive mechanisms (cognitive control, domain-general and self-reference). We test them and provide novel insights in a comprehensive behavioural experiment with non-invasive brain stimulation where participants can punish greedy actions and reward generous actions. Brain stimulation of either brain area decreases reward and punishment when reciprocation is costly but unexpectedly increases reward when it is non-costly. None of the hypothesized mechanisms fully accounts for the observed behaviour, and the asymmetric involvement of the investigated brain areas in punishment and reward suggests that different psychological mechanisms are underlying punishing selfishness and rewarding generosity. We propose that, for reciprocal punishment, the rDLPFC and the mPFC process self-relevant information, in terms of both personal cost and personal involvement; for reciprocal reward, these brain regions are involved in controlling selfish and pure reciprocity motives, while simultaneously promoting the enforcement of fairness norms. These insights bear importance for endeavours to build biologically plausible models of human behaviour.

Study protocol of transcranial electrical stimulation at alpha frequency applied during rehabilitation: A randomized controlled trial in chronic stroke patients with visuospatial neglect.

BACKGROUND: A frequent post stroke disorder in lateralized attention is visuospatial neglect (VSN). As VSN has a strong negative impact on recovery in general and independence during daily life, optimal treatment is deemed urgent. Next to traditional stroke treatment, non-invasive brain stimulation offers the potential to facilitate stroke recovery as a complementary approach. In the present study, visual scanning training (VST; the current conventional treatment) will be combined with transcranial alternating current stimulation (tACS) to evaluate the additive effects of repeated sessions of tACS in combination with six-weeks VST rehabilitation. METHODS: In this double-blind randomized placebo-controlled intervention study (RCT), we will compare the effects of active tACS plus VST to sham (placebo) tACS plus VST, both encompassing 18 VST training sessions, 40 minutes each, during 6 weeks. Chronic stroke patients with VSN (> 6 months post-stroke onset) are considered eligible for study participation. In total 22 patients are needed for the study. The primary outcome is change in performance on a cancellation task. Secondary outcomes are changes in performance on a visual detection task, two line bisection tasks, and three measures to assess changes in activities of daily living. Assessment is at baseline, directly after the first and ninth training session, after the last training session (post training), and 1 week and 3 months after termination of the training (follow-up). DISCUSSION: If effective, a tACS-VST rehabilitation program could be implemented as a treatment option for VSN. TRIAL REGISTRATION: ClinicalTrials.gov ; registration number: NCT05466487; registration date: July 18, 2022 retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT05466487.

A Different rTMS Protocol for a Different Type of Depression: 20.000 rTMS Pulses for the Treatment of Bipolar Depression Type II.

In this open-label naturalistic study, we assess the feasibility, tolerability, and effectiveness of a repetitive transcranial magnetic stimulation protocol with a reduced total pulse number for treating patients suffering from bipolar disorder type II. All patients received one rTMS treatment session of 1000 pulses for 20 consecutive working days, accumulating to 20.000 rTMS pulses applied over 4 weeks. We measured the patients' symptoms before the start, halfway through, directly after, and one month after treatment. We quantified the depression symptoms using both the Beck depression inventory scale and the symptom checklist-90 depression subscale. Patients showed a significant reduction in depression symptoms directly after treatment and an even further reduction one month after treatment. The remission rates were at 26% halfway through treatment (after the 10th session), 61% directly after treatment (after the 20th session), and increased to 78% at the 1-month follow-up. Importantly, the protocol proved to be feasible and highly tolerable in this patient population, with no adverse effects being reported. Considering these positive results, further research should focus on replicating these findings in larger clinical samples with control groups and longer follow-up periods, while potentially adding maintenance sessions to optimize the treatment effect and stability for bipolar disorder type II patients.

Transcranial magnetic stimulation over posterior parietal cortex modulates alerting and executive control processes in attention.

Attention includes three different functional components: generating and maintaining an alert state (alerting), orienting to sensory events (orienting), and resolving conflicts between alternative actions (executive control). Neuroimaging and patient studies suggest that the posterior parietal cortex (PPC) is involved in all three attention components. Transcranial magnetic stimulation (TMS) has repeatedly been applied over the PPC to study its functional role for shifts and maintenance of visuospatial attention. Most TMS-PPC studies used only detection tasks or orienting paradigms to investigate TMS-PPC effects on attention processes, neglecting the alerting and executive control components of attention. The objective of the present study was to investigate the role of PPC in all three functional components of attention: alerting, orienting, and executive control. To this end, we disrupted PPC with TMS (continuous theta-burst stimulation), to modulate subsequent performance on the Lateralized-Attention Network Test, used to assess the three attention components separately. Our results revealed hemifield-specific effects on alerting and executive control functions, but we did not find stimulation effects on orienting performance. While this field of research and associated clinical development have been predominantly focused on orienting performance, our results suggest that parietal cortex and its modulation may affect other aspects of attention as well.

Transcranial alternating brain stimulation at alpha frequency reduces hemispatial neglect symptoms in stroke patients

Background/Objective: Non-invasive brain stimulation techniques such as transcranial alternating current stimulation (tACS) may help alleviate attention deficits in stroke patients with hemispatial neglect by modulating oscillatory brain activity. We applied high-definition (HD)-tACS at alpha frequency over the contralesional hemisphere to support unilateral oscillatory alpha activity and correct for the pathologically altered attention bias in neglect patients.Methods: We performed a within-subject, placebo-controlled study in which sixteen stroke patients with hemispatial neglect underwent 10 Hz (alpha) as well as sham (placebo) stimulation targeting the contralesional posterior parietal cortex. Attentional bias was measured with a computerized visual detection paradigm and two standard paper-and-pencil neglect tests.Results: We revealed a significant shift of attentional resources after alpha-HD-tACS, but not sham tACS, toward the ipsilateral and thus contralesional hemifield leading to a reduction in neglect symptoms, measured with a computerized visual detection paradigm and a widely used standard paper and pencil neglect tests.Conclusions: We showed a significant alpha-HD-tACS-induced shift of attentional resources toward the contralesional hemifield, thus leading to a reduction in neglect symptoms. Importantly, HD-tACS effects persisted after the stimulation itself had ended. This tACS protocol, based on intrinsic oscillatory processes, may be an effective and well-tolerated treatment option for neglect. (AU)

Transcranial alternating brain stimulation at alpha frequency reduces hemispatial neglect symptoms in stroke patients.

Background/Objective: Non-invasive brain stimulation techniques such as transcranial alternating current stimulation (tACS) may help alleviate attention deficits in stroke patients with hemispatial neglect by modulating oscillatory brain activity. We applied high-definition (HD)-tACS at alpha frequency over the contralesional hemisphere to support unilateral oscillatory alpha activity and correct for the pathologically altered attention bias in neglect patients. Methods: We performed a within-subject, placebo-controlled study in which sixteen stroke patients with hemispatial neglect underwent 10 Hz (alpha) as well as sham (placebo) stimulation targeting the contralesional posterior parietal cortex. Attentional bias was measured with a computerized visual detection paradigm and two standard paper-and-pencil neglect tests. Results: We revealed a significant shift of attentional resources after alpha-HD-tACS, but not sham tACS, toward the ipsilateral and thus contralesional hemifield leading to a reduction in neglect symptoms, measured with a computerized visual detection paradigm and a widely used standard paper and pencil neglect tests. Conclusions: We showed a significant alpha-HD-tACS-induced shift of attentional resources toward the contralesional hemifield, thus leading to a reduction in neglect symptoms. Importantly, HD-tACS effects persisted after the stimulation itself had ended. This tACS protocol, based on intrinsic oscillatory processes, may be an effective and well-tolerated treatment option for neglect.

The effects of probiotics on risk and time preferences.

Animal models, human neuroimaging and lesion studies revealed that the gut microbiota can influence the interaction between the central and the enteric nervous systems via the gut-brain axis (GBA) and can affect brain regions linked to basic emotional and cognitive processes. The role of the gut microbiota in decision-making in healthy humans thus far remains largely unknown. Our study establishes a functional relationship between the gut microbiota and healthy humans' decisions that involve risk and time. We conducted a between subjects' placebo-controlled double-blinded design, with two groups and two sessions separated by 28 days, during which participants received daily doses of probiotics or a placebo. We investigated whether the prolonged and controlled intake of probiotics affects risk-taking behavior and intertemporal choices using incentivized economic tasks. We found a significant decrease in risk-taking behavior and an increase in future-oriented choices in the probiotics group as compared to the placebo group. These findings provide the first direct experimental evidence suggesting a potential functional role on the part of the microbiota-gut-brain axis in decision-making, creating a path for potential clinical applications and allowing for a better understanding of the underlying neural mechanisms of risk-taking behavior and intertemporal choices.

Using Remotely Supervised At-Home TES for Enhancing Mental Resilience.

We are in the midst of a mental health crisis with major depressive disorder being the most prevalent among mental health disorders and up to 30% of patients not responding to first-line treatments. Noninvasive Brain Stimulation (NIBS) techniques have proven to be effective in treating depression. However, there is a fundamental problem of scale. Currently, any type of NIBS treatment requires patients to repeatedly visit a clinic to receive brain stimulation by trained personnel. This is an often-insurmountable barrier to both patients and healthcare providers in terms of time and cost. In this perspective, we assess to what extent Transcranial Electrical Stimulation (TES) might be administered with remote supervision in order to address this scaling problem and enable neuroenhancement of mental resilience at home. Social, ethical, and technical challenges relating to hardware- and software-based solutions are discussed alongside the risks of stimulation under- or over-use. Solutions to provide users with a safe and transparent ongoing assessment of aptitude, tolerability, compliance, and/or misuse are proposed, including standardized training, eligibility screening, as well as compliance and side effects monitoring. Looking into the future, such neuroenhancement could be linked to prevention systems which combine home-use TES with digital sensor and mental monitoring technology to index decline in mental wellbeing and avoid relapse. Despite the described social, ethical legal, and technical challenges, the combination of remotely supervised, at-home TES setups with dedicated artificial intelligence systems could be a powerful weapon to combat the mental health crisis by bringing personalized medicine into people's homes.

Accelerated Intermittent Theta Burst Stimulation in Smoking Cessation: Placebo Effects Equal to Active Stimulation When Using Advanced Placebo Coil Technology.

Smoking is currently one of the main public health problems. Smoking cessation is known to be difficult for most smokers because of nicotine dependence. Repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) has been shown to be effective in the reduction of nicotine craving and cigarette consumption. Here, we evaluated the efficacy of accelerated intermittent theta burst stimulation (aiTBS; four sessions per day for 5 consecutive days) over the left DLPFC in smoking cessation, and we investigated whether the exposure to smoking-related cues compared to neutral cues during transcranial magnetic stimulation (TMS) impacts treatment outcome. A double-blind, randomized, controlled study was conducted in which 89 participants (60 males and 29 females; age 45.62 ± 13.42 years) were randomly divided into three groups: the first group received active aiTBS stimulation while watching neutral videos, the second group received active aiTBS stimulation while watching smoking-related videos and the last group received sham stimulation while watching smoking-related videos. Our results suggest that aiTBS is a tolerable treatment. All treatment groups equally reduced cigarette consumption, nicotine dependence, craving and perceived stress. The effect on nicotine dependence, general craving and perceived stress lasted for at least 1 week after the end of treatment. Active aiTBS over the left DLPFC, combined with smoking related cues, is as effective as active aiTBS combined with neutral cues as well as placebo aiTBS in smoking cessation. These findings extend the results of previous studies indicating that TMS therapy is associated with considerably large placebo effects and that these placebo effects may be further increased when using advanced placebo coil technology. Clinical Trial Registration: www.clinicaltrials.gov, identifier NCT05271175.

Concurrent frontal and parietal network TMS for modulating attention.

Transcranial magnetic stimulation (TMS) has been applied to frontal eye field (FEF) and intraparietal sulcus (IPS) in isolation, to study their role in attention. However, these nodes closely interact in a "dorsal attention network". Here, we compared effects of inhibitory TMS applied to individually fMRI-localized FEF or IPS (single-node TMS), to effects of simultaneously inhibiting both regions ("network TMS"), and sham. We assessed attention performance using the lateralized attention network test, which captures multiple facets of attention: spatial orienting, alerting, and executive control. TMS showed no effects on alerting and executive control. For spatial orienting, only network TMS showed a reduction of the orienting effect in the right hemifield compared to the left hemifield, irrespective of the order of TMS application (IPS→FEF or FEF→IPS). Network TMS might prevent compensatory mechanisms within a brain network, which is promising for both research and clinical applications to achieve superior neuromodulation effects.