Motor dominance and movement-outcome congruency influence the electrophysiological correlates of sensory attenuation for self-induced visual stimuli.

This study explores the impact of movement-outcome congruency and motor dominance on the action-associated modulations of early visual event-related potentials (ERPs). Employing the contingent paradigm, participants with varying degrees of motor dominance were exposed to stimuli depicting left or right human hands in the corresponding visual hemifields. Stimuli were either passively observed or evoked by voluntary button-presses with the dominant or non-dominant hand, in a manner that was either congruent or incongruent with stimulus laterality and hemifield. Early occipital responses (C1 and P1 components) revealed modulations consistent with sensory attenuation (SA) for self-evoked stimuli. Our findings suggest that sensory attenuation during the initial stages of visual processing (C1 component) is a general phenomenon across all degrees of handedness and stimulus/movement combinations. However, the magnitude of C1 suppression was modulated by handedness and movement-stimulus congruency, reflecting stronger SA in right-handed participants for stimuli depicting the right hand, when elicited by actions of the corresponding hand, and measured above the contralateral occipital lobe. P1 modulation suggested concurrent but opposing influences of attention and sensory prediction, with more pronounced suppression following stimulus-congruent button-presses over the hemisphere contralateral to movement, especially in left-handed individuals. We suggest that effects of motor dominance on the degree of SA may stem from functional/anatomical asymmetries in the processing of body parts (C1) and attention networks (P1). Overall, our results demonstrate the modulating effect of hand dominance and movement-outcome congruency on SA, underscoring the need for deeper exploration of their interplay. Additional empirical evidence in this direction could substantiate a premotor account for action-associated modulation of early sensory processing in the visual domain.

The antidepressant effect of intermittent theta burst stimulation (iTBS): study protocol for a randomized double-blind sham-controlled trial.

BACKGROUND: Intermittent theta burst stimulation (iTBS) when applied over the left dorsolateral prefrontal cortex (DLPFC) has been shown to be equally effective and safe to treat depression compared to traditional repetitive transcranial magnetic stimulation (rTMS) paradigms. This protocol describes a funded single-centre, double-blind, randomized placebo-controlled, clinical trial to investigate the antidepressive effects of iTBS and factors associated with an antidepressive response. METHODS: In this trial, outpatients (N = 96, aged 22-65 years) meeting the diagnostic criteria for at least moderate depression (Montgomery and Aasberg Depression Rating Scale score ≥ 20) will be enrolled prospectively and receive ten, once-a-day sessions of either active iTBS or sham iTBS to the left DLPFC, localized via a neuronavigation system. Participants may have any degree of treatment resistance. Prior to stimulation, participants will undergo a thorough safety screening and a brief diagnostic assessment, genetic analysis of brain-derived neurotropic factor, 5-HTTLPR and 5-HT1A, and cerebral MRI assessments. A selection of neuropsychological tests and questionnaires will be administered prior to stimulation and after ten stimulations. An additional follow-up will be conducted 4 weeks after the last stimulation. The first participant was enrolled on June 4, 2022. Study completion will be in December 2027. The project is approved by the Regional Ethical Committee of Medicine and Health Sciences, Northern Norway, project number 228765. The trial will be conducted according to Good Clinical Practice and published safety guidelines on rTMS treatment. DISCUSSION: The aims of the present trial are to investigate the antidepressive effect of a 10-session iTBS protocol on moderately depressed outpatients and to explore the factors that can explain the reduction in depressive symptoms after iTBS but also a poorer response to the treatment. In separate, but related work packages, the trial will assess how clinical, cognitive, brain imaging and genetic measures at baseline relate to the variability in the antidepressive effects of iTBS. TRIAL REGISTRATION: ClinicalTrials.gov NCT05516095. Retrospectively registered on August 25, 2022.

Transcranial direct-current stimulation enhances Pavlovian tendencies during intermittent loss of control.

Introduction: Pavlovian bias is an innate motivational tendency to approach rewards and remain passive in the face of punishment. The relative reliance on Pavlovian valuation has been found to increase when the perceived control over environmental reinforcers is compromised, leading to behavior resembling learned helplessness (LH). Methods: Sixty healthy young adults underwent a Go-NoGo reinforcement learning task and received anodal high-definition transcranial direct current stimulation (HD-tDCS) over the medial prefrontal/dorsal anterior cingulate cortex in our randomized, double-blind, sham- controlled study. Furthermore, we evaluated changes in cue-locked mid-frontal theta power derived from simultaneous electroencephalography (EEG). We hypothesized that active stimulation would reduce Pavlovian bias during manipulation of outcome controllability, and the effect would be accompanied by stronger mid-frontal theta activity, representing arbitration between choice strategies in favor of instrumental relative to Pavlovian valuation. Results: We found a progressive decrease in Pavlovian bias during and after loss of control over feedback. Active HD-tDCS counteracted this effect while not affecting the mid-frontal theta signal. Discussion: The results were at odds with our hypotheses but also with previous findings reporting LH-like patterns during and after loss of control without brain stimulation. The discrepancy may be related to different protocols for the controllability manipulation. We argue that the subjective evaluation of task controllability is crucial in mediating the balance between Pavlovian and instrumental valuation during reinforcement learning and that the medial prefrontal/dorsal anterior cingulate cortex is a key region in this respect. These findings have implications for understanding the behavioral and neural underpinnings of LH in humans.

Modulation of mind wandering using transcranial direct current stimulation: A meta-analysis based on electric field modeling.

Mind wandering (MW) is a heterogeneous construct involving task-unrelated thoughts. Recently, the interest in modulating MW propensity via non-invasive brain stimulation techniques has increased. Single-session transcranial direct current stimulation (tDCS) in healthy controls has led to mixed results in modulating MW propensity, possibly due to methodological heterogeneity. Therefore, our aim was to conduct a systematic meta-analysis to examine the influence of left dorsolateral prefrontal cortex (lDLPFC) and right inferior parietal lobule (rIPL) targeted tDCS on MW propensity. Importantly, by computational modeling of tDCS-induced electric fields, we accounted for differences in tDCS-dose across studies that varied strongly in their applied methodology. Fifteen single-session, sham-controlled tDCS studies published until October 2021 were included. All studies involved healthy adult participants and used cognitive tasks combined with MW thought-probes. Heterogeneity in tDCS electrode placement, stimulation polarity and intensity were controlled for by means of electric field simulations, while overall methodological quality was assessed via an extended risk of bias (RoB) assessment. We found that RoB was the strongest predictor of study outcomes. Moreover, the rIPL was the most promising cortical area for influencing MW, with stronger anodal electric fields in this region being negatively associated with MW propensity. Electric field strength in the lDLPFC was not related to MW propensity. We identified several severe methodological problems that could have contributed to overestimated effect sizes in this literature, an issue that needs urgent attention in future research in this area. Overall, there is no reliable evidence for tDCS influencing MW in the healthy. However, the analysis also revealed that increasing neural excitability in the rIPL via tDCS might be associated with reduced MW propensity. In an exploratory approach, we also found some indication that targeting prefrontal regions outside the lDLPFC with tDCS could lead to increased MW propensity.

Two-year changes in sleep duration are associated with changes in psychological distress in adolescent girls and boys: the fit futures study.

Objective: Studies indicate an inverse association between sleep duration and psychological distress. We aimed to explore associations between changes in sleep duration and changes in psychological distress in girls and boys. Methods: The Fit Futures Study is a broad adolescent study providing data from 373 girls and 294 boys aged 15-18 years collected in 2010/2011 (FF1) and 2012/2013 (FF2). Psychological distress was measured by the Hopkins Symptom Checklist (HSCL-10) and sleep duration was self-reported. Change score variables were calculated as the change between baseline and follow-up for sleep duration and HSCL-10, respectively. Associations between changes in sleep duration and changes in HSCL-10 were explored by linear regressions, in gender-stratified analyses. Results: At FF1, girls and boys slept on average 6.93 (SD = 1.08) and 7.05 (SD = 1.20) hours per night respectively, and correspondingly, 6.83 (SD = 1.19) and 6.85 (SD = 1.21) at FF2. At FF1, 22.8% of the girls and 25.8% of the boys slept ≤ 6 h per night, and correspondingly 28.0% and 28.2% at FF2. In girls and boys, one unit increase (30 min) in sleep duration was associated with a decrease in HSCL-10 score of B [95% CI] = -0.090 [-0.131, -0.048], p < 0.001, and -0.054 [-0.091, -0.017], p < 0.001, respectively. The associations remained significant after adjusting for confounders. Conclusion: Our findings show that increased sleep duration was associated with decreased psychological distress during adolescence. Future studies should examine the causality between sleep duration and psychological distress.

Corrigendum: C-Reactive Protein and TGF-α Predict Psychological Distress at Two Years of Follow-Up in Healthy Adolescent Boys: The Fit Futures Study.

[This corrects the article DOI: 10.3389/fpsyg.2022.823420.].

C-Reactive Protein and TGF-α Predict Psychological Distress at Two Years of Follow-Up in Healthy Adolescent Boys: The Fit Futures Study.

Objective: The scarcity of research on associations between inflammatory markers and symptoms of depression and anxiety during adolescence has yielded inconsistent results. Further, not all studies have controlled for potential confounders. We explored the associations between baseline inflammatory markers and psychological distress including moderators at follow-up in a Norwegian adolescent population sample. Methods: Data was derived from 373 girls and 294 boys aged 15-18 years at baseline, in the Fit Futures Study, a large-scale 2-year follow-up study on adolescent health. Baseline data was gathered from 2010 to 2011 and follow-up data from 2012 to 2013. Psychological distress was measured with Hopkins Symptom Checklist (HSCL-10). Serum levels of the following inflammatory markers were measured: C-reactive protein (CRP), Interleukin 6 (IL-6), Transforming growth factor alpha (TGF-α), Tumor necrosis factor alpha variant 1 (TRANCE), and variant 2 (TWEAK). Independent associations between baseline inflammatory markers and HSCL-10 at follow-up were explored by linear regressions, in sex-stratified analyses. Results: In girls, analyses showed positive associations between all inflammatory markers and HSCL-10, except for TRANCE. However, all associations were non-significant in crude as well as in adjusted analyses. In boys, CRP (p = 0.03) and TGF-α (p < 0.01) showed significant associations with HSCL-10, that remained significant after adjustment. Additionally, moderators were found. In boys, CRP was associated with HSCL-10 in those with high body fat and those being physical inactive, and the association between TWEAK and HSCL-10 was dependent upon sleep duration. Conclusion: There were significant prospective associations between CRP, TFG-α, and HSCL-10 in boys aged 15-18 years at baseline.

Are pro-inflammatory markers associated with psychological distress in a cross-sectional study of healthy adolescents 15-17 years of age? The Fit Futures study.

BACKGROUND: Inflammatory markers have been associated with depression and anxiety disorder in adolescents. Less is known about the association between inflammation and subclinical symptoms in the form of psychological distress. We investigated prevalence of psychological distress and examined the associations between common pro-inflammatory markers and psychological distress in an adolescent population sample. METHODS: The study was based on data from 458 girls and 473 boys aged 15-17 years from the Fit Futures Study, a large-scale study on adolescent health, conducted in Northern Norway. Psychological distress was measured with the Hopkins Symptom Checklist (HSCL-10). Serum-levels of the following low-grade inflammatory markers were measured: C-reactive protein (CRP), interleukin 6 (IL-6), transforming growth factor-alpha (TGF-α), tumor necrosis factor alpha variant 1 (TRANCE) and tumor necrosis factor alpha variant 2 (TWEAK). Associations between quartiles of inflammatory markers and HSCL-10 were examined by logistic regression and adjusted for potential confounders in sex-stratified analyses. RESULTS: The proportion of psychological distress above cutoff were 26.9% and 10.8% among girls and boys, respectively. In both girls and boys, crude analysis showed positive associations between all inflammatory markers and HSCL-10, except for TWEAK and TRANCE in boys. However, none of these associations were statistically significant. Further, there were no significant findings in the adjusted analyses. CONCLUSION: There was a higher prevalence of psychological distress in girls compared to boys. Pro-inflammatory markers were not significantly associated with psychological distress in data from healthy adolescents aged 15-17 years.

Catching wandering minds with tapping fingers: neural and behavioral insights into task-unrelated cognition.

When the human mind wanders, it engages in episodes during which attention is focused on self-generated thoughts rather than on external task demands. Although the sustained attention to response task is commonly used to examine relationships between mind wandering and executive functions, limited executive resources are required for optimal task performance. In the current study, we aimed to investigate the relationship between mind wandering and executive functions more closely by employing a recently developed finger-tapping task to monitor fluctuations in attention and executive control through task performance and periodical experience sampling during concurrent functional magnetic resonance imaging (fMRI) and pupillometry. Our results show that mind wandering was preceded by increases in finger-tapping variability, which was correlated with activity in dorsal and ventral attention networks. The entropy of random finger-tapping sequences was related to activity in frontoparietal regions associated with executive control, demonstrating the suitability of this paradigm for studying executive functioning. The neural correlates of behavioral performance, pupillary dynamics, and self-reported attentional state diverged, thus indicating a dissociation between direct and indirect markers of mind wandering. Together, the investigation of these relationships at both the behavioral and neural level provided novel insights into the identification of underlying mechanisms of mind wandering.

Transcranial Direct Current Stimulation above the Medial Prefrontal Cortex Facilitates Decision-Making following Periods of Low Outcome Controllability.

Recent studies suggest that choice behavior in reinforcement learning tasks is shaped by the level of outcome controllability. In particular, Pavlovian bias (PB) seems to be enhanced under low levels of control, manifesting in approach tendencies toward rewards and response inhibition when facing potential losses. The medial prefrontal cortex (mPFC) has been implicated both in evaluating outcome controllability and in the recruitment of cognitive control (CC) to suppress maladaptive PB during reinforcement learning. The current study tested whether high-definition transcranial direct current stimulation (HD-tDCS) above the mPFC of healthy humans can influence PB, and counteract the previously documented, deleterious behavioral effects of low outcome controllability on decision-making. In a preregistered, between-group, double-blind study (N = 103 adults, both sexes), we tested the interaction between controllability and HD-tDCS on parameters of choice behavior in a Go/NoGo task. Relative to sham stimulation, HD-tDCS resulted in more robust performance improvement following reduced control, an effect that was more pronounced in appetitive trials. In addition, we found evidence for weaker PB when HD-tDCS was administered during low controllability over outcomes. Computational modeling revealed that parameter estimates of learning rate and choice randomness were modulated by controllability, HD-tDCS and their interaction. Overall, these results highlight the potential of our HD-tDCS protocol for interfering with choice arbitration under low levels of control, resulting in more adaptive behavior.

High-Definition Transcranial Direct Current Stimulation Improves Delayed Memory in Alzheimer's Disease Patients: A Pilot Study Using Computational Modeling to Optimize Electrode Position.

BACKGROUND: The optimal stimulation parameters when using transcranial direct current stimulation (tDCS) to improve memory performance in patients with Alzheimer's disease (AD) are lacking. In healthy individuals, inter-individual differences in brain anatomy significantly influence current distribution during tDCS, an effect that might be aggravated by variations in cortical atrophy in AD patients. OBJECTIVE: To measure the effect of individualized HD-tDCS in AD patients. METHODS: Nineteen AD patients were randomly assigned to receive active or sham high-definition tDCS (HD-tDCS). Computational modeling of the HD-tDCS-induced electric field in each patient's brain was analyzed based on magnetic resonance imaging (MRI) scans. The chosen montage provided the highest net anodal electric field in the left dorsolateral prefrontal cortex (DLPFC). An accelerated HD-tDCS design was conducted (2 mA for 3×20 min) on two separate days. Pre- and post-intervention cognitive tests and T1 and T2-weighted MRI and diffusion tensor imaging data at baseline were analyzed. RESULTS: Different montages were optimal for individual patients. The active HD-tDCS group improved significantly in delayed memory and MMSE performance compared to the sham group. Five participants in the active group had higher scores on delayed memory post HD-tDCS, four remained stable and one declined. The active HD-tDCS group had a significant positive correlation between fractional anisotropy in the anterior thalamic radiation and delayed memory score. CONCLUSION: HD-tDCS significantly improved delayed memory in AD. Our study can be regarded as a proof-of-concept attempt to increase tDCS efficacy. The present findings should be confirmed in larger samples.

Probing the neural signature of mind wandering with simultaneous fMRI-EEG and pupillometry.

Mind wandering reflects the shift in attentional focus from task-related cognition driven by external stimuli toward self-generated and internally-oriented thought processes. Although such task-unrelated thoughts (TUTs) are pervasive and detrimental to task performance, their underlying neural mechanisms are only modestly understood. To investigate TUTs with high spatial and temporal precision, we simultaneously measured fMRI, EEG, and pupillometry in healthy adults while they performed a sustained attention task with experience sampling probes. Features of interest were extracted from each modality at the single-trial level and fed to a support vector machine that was trained on the probe responses. Compared to task-focused attention, the neural signature of TUTs was characterized by weaker activity in the default mode network but elevated activity in its anticorrelated network, stronger functional coupling between these networks, widespread increase in alpha, theta, delta, but not beta, frequency power, predominantly reduced amplitudes of late, but not early, event-related potentials, and larger baseline pupil size. Particularly, information contained in dynamic interactions between large-scale cortical networks was predictive of transient changes in attentional focus above other modalities. Together, our results provide insight into the spatiotemporal dynamics of TUTs and the neural markers that may facilitate their detection.

The interplay between executive control, behavioural variability and mind wandering: Insights from a high-definition transcranial direct-current stimulation study.

While the involvement of executive processes in mind wandering is largely undebated, their exact relationship is subject to an ongoing debate and rarely studied dynamically within-subject. Several brain-stimulation studies using transcranial direct current stimulation (tDCS) have attempted to modulate mind-wandering propensity by stimulating the left dorsolateral prefrontal cortex (DLPFC) which is an important hub in the prefrontal control network. In a series of three studies testing a total of N = 100 participants, we develop a novel task that allows to study the dynamic interplay of mind wandering, behavioural varibility and the flexible recruitment of executive resources as indexed by the randomness (entropy) of movement sequences generated by our participants. We consistently find that behavioural variability is increased and randomness is decreased during periods of mind wandering. Interestingly, we also find that behavioural variability interacts with the entropy-MW effect, opening up the possibility to detect distinct states of off-focus cognition. When applying a high-definition transcranial direct-current stimulation (HD-tDCS) montage to the left DLPFC, we find that propensity to mind wander is reduced relative to a group receiving sham stimulation.

Newborn Behavioral Observation, maternal stress, depressive symptoms and the mother-infant relationship: results from the Northern Babies Longitudinal Study (NorBaby).

BACKGROUND: Families can experience the postpartum period as overwhelming and many report a special need for support. The Newborn Behavioral Observation (NBO) aims to promote a positive parent-infant relationship by sensitising parents to the infant's signals. This article evaluates the NBO as a universal preventive intervention within the regular well-baby clinic service on measures of maternal depressive symptoms, parental stress, the mother-infant relationship and satisfaction/benefit of the postpartum follow-up. METHODS: This investigation is part of a larger longitudinal study comprising 220 women and 130 of their partners recruited between 2015 and 2017. The study had a non-randomised cluster-controlled design with 6 measurement points. This article is based on a sample of 196 women using data from T1 (gestational weeks 13-39), T4 (5-15 weeks postpartum) and T5 (3-9 months postpartum). Participants were allocated to a group receiving the NBO (n = 82) and a care as usual comparison group (n = 114). We measured maternal depressive symptoms and parental stress using the Edinburgh Postnatal Depression Scale (EPDS) and the Parenting Stress Index (PSI). The mother-infant relationship was assessed with the Parental Reflective Functioning Questionnaire (PRFQ), the Maternal Postnatal Attachment Scale (MPAS) and the Maternal Confidence Questionnaire (MCQ). Participants also answered questions about satisfaction/benefit of the postpartum follow-up. RESULTS: A Mann-Whitney U test indicated that participants in the NBO-group learned significantly more than the comparison group from the follow-up about the baby's signals in relation to sleep/sleep patterns, social interaction and crying/fuzziness. Multivariate analyses of covariance (MANCOVA) and repeated measures ANCOVA found no significant differences between the groups for the mother-infant relationship domain and few differences in depressive symptoms and parental stress. The repeated measures ANCOVA found that participants in the NBO-group scored slightly higher on parental stress, although the difference was small. CONCLUSIONS: The results indicate that the NBO-group learned more than the comparison group about reading their child's signals in important everyday situations. However, the benefits of the NBO were limited for depressive symptoms, parental stress and self-reported mother-infant relationship. The study sample was generally well-functioning, and the results indicate that the benefits of the NBO may be limited within a well-functioning sample. TRIAL REGISTRATION: ClinicalTrials, NCT02538497, Registered 2 September 2015.

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.

Intermittent Absence of Control during Reinforcement Learning Interferes with Pavlovian Bias in Action Selection.

The ability to control the occurrence of rewarding and punishing events is crucial for our well-being. Two ways to optimize performance are to follow heuristics like Pavlovian biases to approach reward and avoid loss or to rely more on slowly accumulated stimulus-action associations. Although reduced control over outcomes has been linked to suboptimal decision-making in clinical conditions associated with learned helplessness, it is unclear how uncontrollability of the environment is related to the arbitration between different response strategies. This study directly tested whether a behavioral manipulation designed to induce learned helplessness in healthy adults (intermittent loss of control over feedback in a reinforcement learning task; "yoking") would modulate the magnitude of Pavlovian bias and the neurophysiological signature of cognitive control (frontal midline theta power) in healthy adults. Using statistical analysis and computational modeling of behavioral data and electroencephalographic signals, we found stronger Pavlovian influences and alterations in frontal theta activity in the yoked group. However, these effects were not accompanied by reduced performance in experimental blocks with regained control, indicating that our behavioral manipulation was not potent enough for inducing helplessness and impaired coping ability with task demands. We conclude that the level of contingency between instrumental choices and rewards/punishments modulates Pavlovian bias during value-based decision-making, probably via interfering with the implementation of cognitive control. These findings might have implications for understanding the mechanisms underlying helplessness in various psychiatric conditions.

A novel experimental paradigm with improved ecological validity reveals robust action-associated enhancement of the N1 visual event-related potential in healthy adults.

The association between an action and its sensory consequence has been linked to our sense of agency (SoA). While ecological validity is crucial in investigating such a complex phenomenon, previous paradigms focusing on the cortical analysis of movement-related images used simplified experimental protocols. Here, we examined the influence of action-associated predictive processes on visual event-related potentials (ERPs) in a paradigm that models everyday actions more precisely, using a commercial gesture control device, ecological stimuli depicting a human hand and a behavioural training to reinforce the sense of control over action outcomes. We assessed whether a more natural setup would result in robust ERP modifications following self-initiated movements relative to passive viewing of the same images. We found no compelling evidence for amplitude modulation for the early occipital C1 and P1 components. Crucially, we observed strong action-associated amplitude enhancement for the posterior N1, an effect that was not present in our previous study that relied on conventional button-presses. We propose that the N1 effect in our ecologically more valid paradigm can either reflect stronger attentional amplification of domain-specific visual processes following self-initiated actions, or indicate that sensory predictions in the visual N1 latency range manifest in larger (rather than reduced) ERPs. Overall, our novel approach utilizing a gesture-control device can be a potent tool for investigating the behavioural and neural manifestations of SoA in the visual modality.

Mild Effect of Nalmefene on Alcoholic Cue-Induced Response Invigoration in Alcohol Use Disorder Without Accompanying Changes in Electrophysiological Signatures of Early Visual Processing and Executive Control.

Nalmefene is approved for as-needed pharmacological treatment in alcohol use disorder (AUD) by the European Medicines Agency. While the cellular effects of nalmefene have been thoroughly investigated, data are very limited on how this agent influences neural signals associated with inhibitory control and the visual analysis of environmental cues. This double-blind crossover study assessed the behavioral and neural effects of acute nalmefene administration in patients diagnosed with AUD. In experiment 1, we validated our experimental paradigm (electroencephalography combined with a modified Go/NoGo task using images of alcoholic and nonalcoholic drinks as prime stimuli) in 20 healthy adults to ensure that our protocol is suitable for assessing the behavioral and neural aspects of executive control. In experiment 2, we recruited 19 patients with AUD, and in a double-blind crossover design, we investigated the effects of nalmefene versus placebo on task performance (response accuracy, the sensitivity index, and reaction times), visual responses to appetitive cues (occipital P1, N1, and P2 components), and electrophysiological markers of conflict detection and response inhibition (frontal N2 and P3 waveforms). Under placebo, patients produced faster reaction times to alcohol-primed Go stimuli, an effect that was weak despite being statistically significant. However, the effect of alcoholic cues on the speed of response initiation disappeared after receiving nalmefene. We found no placebo versus nalmefene difference regarding our patients' ability to accurately inhibit responses to NoGo stimuli or for occipital and frontal event-related potentials. Our results suggest that nalmefene might be potent in reducing the vigor to act upon alcoholic cues in AUD patients, but this effect is most probably mediated via subcortical (rather than cortical) neural circuits.

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.