Closed-Loop tACS Delivered during Slow-Wave Sleep Reduces Retroactive Interference on a Paired-Associates Learning Task.

Previous studies have found a benefit of closed-loop transcranial alternating current stimulation (CL-tACS) matched to ongoing slow-wave oscillations (SWO) during sleep on memory consolidation for words in a paired associates task (PAT). Here, we examined the effects of CL-tACS in a retroactive interference PAT (ri-PAT) paradigm, where additional stimuli were presented to increase interference and reduce memory performance. Thirty-one participants were tested on a PAT before sleep, and CL-tACS was applied over the right and left DLPFC (F3 and F4) vs. mastoids for five cycles after detection of the onset of each discrete event of SWO during sleep. Participants were awoken the following morning, learned a new PAT list, and then were tested on the original list. There was a significant effect of stimulation condition (p = 0.04297; Cohen's d = 0.768), where verum stimulation resulted in reduced retroactive interference compared with sham and a significant interaction of encoding strength and stimulation condition (p = 0.03591). Planned simple effects testing within levels of encoding revealed a significant effect of stimulation only for low-encoders (p = 0.0066; Cohen's d = 1.075) but not high-encoders. We demonstrate here for the first time that CL-tACS during sleep can enhance the protective benefits on retroactive interference in participants who have lower encoding aptitude.

Transcranial direct current stimulation modulates working memory and prefrontal-insula connectivity after mild-moderate traumatic brain injury.

Background: Persistent posttraumatic symptoms (PPS) may manifest after a mild-moderate traumatic brain injury (mmTBI) even when standard brain imaging appears normal. Transcranial direct current stimulation (tDCS) represents a promising treatment that may ameliorate pathophysiological processes contributing to PPS. Objective/Hypothesis: We hypothesized that in a mmTBI population, active tDCS combined with training would result in greater improvement in executive functions and post-TBI cognitive symptoms and increased resting state connectivity of the stimulated region, i.e., left dorsolateral prefrontal cortex (DLPFC) compared to control tDCS. Methods: Thirty-four subjects with mmTBI underwent baseline assessments of demographics, symptoms, and cognitive function as well as resting state functional magnetic resonance imaging (rsfMRI) in a subset of patients (n = 24). Primary outcome measures included NIH EXAMINER composite scores, and the Neurobehavioral Symptom Inventory (NSI). All participants received 10 daily sessions of 30 min of executive function training coupled with active or control tDCS (2 mA, anode F3, cathode right deltoid). Imaging and assessments were re-obtained after the final training session, and assessments were repeated after 1 month. Mixed-models linear regression and repeated measures analyses of variance were calculated for main effects and interactions. Results: Both active and control groups demonstrated improvements in executive function (EXAMINER composite: p < 0.001) and posttraumatic symptoms (NSI cognitive: p = 0.01) from baseline to 1 month. Active anodal tDCS was associated with greater improvements in working memory reaction time compared to control (p = 0.007). Reaction time improvement correlated significantly with the degree of connectivity change between the right DLPFC and the left anterior insula (p = 0.02). Conclusion: Anodal tDCS improved reaction time on an online working memory task in a mmTBI population, and decreased connectivity between executive network and salience network nodes. These findings generate important hypotheses for the mechanism of recovery from PPS after mild-moderate TBI.

Digitalized transcranial electrical stimulation: A consensus statement.

OBJECTIVE: Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. The study aims are to discuss the implementation of tES digital trials by performing a systematic scoping review and strategic process mapping, evaluate methodological aspects of tES digital trial designs, and provide Delphi-based recommendations for implementing digital trials using tES. METHODS: We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided. RESULTS: The main strengths/opportunities of tES were: (i) non-pharmacological nature (92% of agreement), safety of these techniques (80%), affordability (88%), and potential scalability (78%). As for weaknesses/threats, we listed insufficient supervision (76%) and unclear regulatory status (69%). Many issues related to methodological biases did not reach consensus. Device appraisal showed moderate digitalization readiness, with high safety and potential for trial implementation, but low connectivity. CONCLUSIONS: Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; with no consensus about aspects regarding methodological biases. SIGNIFICANCE: We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials.

A review of functional brain differences predicting relapse in substance use disorder: Actionable targets for new methods of noninvasive brain stimulation.

Neuroimaging studies have identified a variety of brain regions whose activity predicts substance use (i.e., relapse) in patients with substance use disorder (SUD), suggesting that malfunctioning brain networks may exacerbate relapse. However, this knowledge has not yet led to a marked improvement in treatment outcomes. Noninvasive brain stimulation (NIBS) has shown some potential for treating SUDs, and a new generation of NIBS technologies offers the possibility of selectively altering activity in both superficial and deep brain structures implicated in SUDs. The goal of the current review was to identify deeper brain structures involved in relapse to SUD and give an account of innovative methods of NIBS that might be used to target them. Included studies measured fMRI in currently abstinent SUD patients and tracked treatment outcomes, and fMRI results were organized with the framework of the Addictions Neuroclinical Assessment (ANA). Four brain structures were consistently implicated: the anterior and posterior cingulate cortices, ventral striatum and insula. These four deeper brain structures may be appropriate future targets for the treatment of SUD using these innovative NIBS technologies.

Transcranial Direct Current Stimulation Provides no Additional Benefit to Improvements in Self-Reported Craving Following Mindfulness-Based Relapse Prevention.

Objectives: Mindfulness-Based Relapse Prevention (MBRP) and transcranial direct current stimulation (tDCS) have each demonstrated efficacy in improving outcomes in those with alcohol use disorder (AUD), however a recent study that combined MBRP with tDCS found tDCS provided no additional benefit to MBRP for AUD. Differences in treatment adherence between active versus sham tDCS groups may have contributed to this result. The current study examined whether treatment adherence interacted with tDCS condition in predicting post-treatment mindfulness and craving. Methods: This study was a secondary data analysis from a randomized sham-controlled trial comparing MBRP paired with tDCS. Linear regression analyses were conducted examining the interaction between tDCS condition and two measures of treatment adherence (i.e., number of groups attended, number of tDCS administrations) on post-treatment mindfulness and craving. Results: There was no effect of treatment adherence by tDCS condition in predicting mindfulness, however the interaction between treatment adherence and tDCS condition significantly predicted post-treatment craving. There was a significant negative association between treatment adherence and post-treatment craving in the sham group, but there was no association in the active tDCS group. Conclusions: MBRP coupled with sham stimulation led to significant reductions in self-reported craving when patients attended more sessions and received a greater number of sham tDCS administrations, while no relationship was observed between treatment adherence and craving among those who received active tDCS. This result provides tentative evidence that, rather than improve the effects of MBRP on craving, this active tDCS protocol provides no additional benefit to MBRP in reducing craving. Pre-registration: This study was registered with clinicaltrials.gov (NCT02861807).

Revisiting Hemispheric Asymmetry in Mood Regulation: Implications for rTMS for Major Depressive Disorder.

Hemispheric differences in emotional processing have been observed for over half a century, leading to multiple theories classifying differing roles for the right and left hemisphere in emotional processing. Conventional acceptance of these theories has had lasting clinical implications for the treatment of mood disorders. The theory that the left hemisphere is broadly associated with positively valenced emotions, while the right hemisphere is broadly associated with negatively valenced emotions, drove the initial application of repetitive transcranial magnetic stimulation (rTMS) for the treatment of major depressive disorder (MDD). Subsequent rTMS research has led to improved response rates while adhering to the same initial paradigm of administering excitatory rTMS to the left prefrontal cortex (PFC) and inhibitory rTMS to the right PFC. However, accumulating evidence points to greater similarities in emotional regulation between the hemispheres than previously theorized, with potential implications for how rTMS for MDD may be delivered and optimized in the near future. This review will catalog the range of measurement modalities that have been used to explore and describe hemispheric differences, and highlight evidence that updates and advances knowledge of TMS targeting and parameter selection. Future directions for research are proposed that may advance precision medicine and improve efficacy of TMS for MDD.

Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years.

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.

Greater male than female variability in regional brain structure across the lifespan.

For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.

Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years.

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.

Brain connectivity alterations during sleep by closed-loop transcranial neurostimulation predict metamemory sensitivity.

Metamemory involves the ability to correctly judge the accuracy of our memories. The retrieval of memories can be improved using transcranial electrical stimulation (tES) during sleep, but evidence for improvements to metamemory sensitivity is limited. Applying tES can enhance sleep-dependent memory consolidation, which along with metamemory requires the coordination of activity across distributed neural systems, suggesting that examining functional connectivity is important for understanding these processes. Nevertheless, little research has examined how functional connectivity modulations relate to overnight changes in metamemory sensitivity. Here, we developed a closed-loop short-duration tES method, time-locked to up-states of ongoing slow-wave oscillations, to cue specific memory replays in humans. We measured electroencephalographic (EEG) coherence changes following stimulation pulses, and characterized network alterations with graph theoretic metrics. Using machine learning techniques, we show that pulsed tES elicited network changes in multiple frequency bands, including increased connectivity in the theta band and increased efficiency in the spindle band. Additionally, stimulation-induced changes in beta-band path length were predictive of overnight changes in metamemory sensitivity. These findings add new insights into the growing literature investigating increases in memory performance through brain stimulation during sleep, and highlight the importance of examining functional connectivity to explain its effects.

Baseline Differences in Anxiety Affect Attention and tDCS-Mediated Learning.

Variable responses to transcranial direct current stimulation (tDCS) protocols across individuals are widely reported, but the reasons behind this variation are unclear. This includes tDCS protocols meant to improve attention. Attentional control is impacted by top-down and bottom-up processes, and this relationship is affected by state characteristics such as anxiety. According to Attentional Control Theory, anxiety biases attention towards bottom-up and stimulus-driven processing. The goal of this study was to explore the extent to which differences in state anxiety and related measures affect visual attention and category learning, both with and without the influence of tDCS. Using discovery learning, participants were trained to classify pictures of European streets into two categories while receiving 30 min of 2.0 mA anodal, cathodal, or sham tDCS over the rVLPFC. The pictures were classifiable according to two separate rules, one stimulus and one hypothesis-driven. The Remote Associates Test (RAT), Profile of Mood States, and Attention Networks Task (ANT) were used to understand the effects of individual differences at baseline on subsequent tDCS-mediated learning. Multinomial logistic regression was fit to predict rule learning based on the baseline measures, with subjects classified according to whether they used the stimulus-driven or hypothesis-driven rule to classify the pictures. The overall model showed a classification accuracy of 74.1%. The type of tDCS stimulation applied, attentional orienting score, and self-reported mood were significant predictors of different categories of rule learning. These results indicate that anxiety can influence the quality of subjects' attention at the onset of the task and that these attentional differences can influence tDCS-mediated category learning during the rapid assessment of visual scenes. These findings have implications for understanding the complex interactions that give rise to the variability in response to tDCS.

Cerebral Perfusion Effects of Cognitive Training and Transcranial Direct Current Stimulation in Mild-Moderate TBI.

Background: Persistent post-traumatic symptoms (PPS) after traumatic brain injury (TBI) can lead to significant chronic functional impairment. Pseudocontinuous arterial spin labeling (pCASL) has been used in multiple studies to explore changes in cerebral blood flow (CBF) that may result in acute and chronic TBI, and is a promising neuroimaging modality for assessing response to therapies. Methods: Twenty-four subjects with chronic mild-moderate TBI (mmTBI) were enrolled in a pilot study of 10 days of computerized executive function training combined with active or sham anodal transcranial direct current stimulation (tDCS) for treatment of cognitive PPS. Behavioral surveys, neuropsychological testing, and magnetic resonance imaging (MRI) with pCASL sequences to assess global and regional CBF were obtained before and after the training protocol. Results: Robust improvements in depression, anxiety, complex attention, and executive function were seen in both active and sham groups between the baseline and post-treatment visits. Global CBF decreased over time, with differences in regional CBF noted in the right inferior frontal gyrus (IFG). Active stimulation was associated with static or increased CBF in the right IFG, whereas sham was associated with reduced CBF. Neuropsychological performance and behavioral symptoms were not associated with changes in CBF. Discussion: The current study suggests a complex picture between mmTBI, cerebral perfusion, and recovery. Changes in CBF may result from physiologic effect of the intervention, compensatory neural mechanisms, or confounding factors. Limitations include a small sample size and heterogenous injury sample, but these findings suggest promising directions for future studies of cognitive training paradigms in mmTBI.

Electrical stimulation of cranial nerves in cognition and disease.

The cranial nerves are the pathways through which environmental information (sensation) is directly communicated to the brain, leading to perception, and giving rise to higher cognition. Because cranial nerves determine and modulate brain function, invasive and non-invasive cranial nerve electrical stimulation methods have applications in the clinical, behavioral, and cognitive domains. Among other neuromodulation approaches such as peripheral, transcranial and deep brain stimulation, cranial nerve stimulation is unique in allowing axon pathway-specific engagement of brain circuits, including thalamo-cortical networks. In this review we amalgamate relevant knowledge of 1) cranial nerve anatomy and biophysics; 2) evidence of the modulatory effects of cranial nerves on cognition; 3) clinical and behavioral outcomes of cranial nerve stimulation; and 4) biomarkers of nerve target engagement including physiology, electroencephalography, neuroimaging, and behavioral metrics. Existing non-invasive stimulation methods cannot feasibly activate the axons of only individual cranial nerves. Even with invasive stimulation methods, selective targeting of one nerve fiber type requires nuance since each nerve is composed of functionally distinct axon-types that differentially branch and can anastomose onto other nerves. None-the-less, precisely controlling stimulation parameters can aid in affecting distinct sets of axons, thus supporting specific actions on cognition and behavior. To this end, a rubric for reproducible dose-response stimulation parameters is defined here. Given that afferent cranial nerve axons project directly to the brain, targeting structures (e.g. thalamus, cortex) that are critical nodes in higher order brain networks, potent effects on cognition are plausible. We propose an intervention design framework based on driving cranial nerve pathways in targeted brain circuits, which are in turn linked to specific higher cognitive processes. State-of-the-art current flow models that are used to explain and design cranial-nerve-activating stimulation technology require multi-scale detail that includes: gross anatomy; skull foramina and superficial tissue layers; and precise nerve morphology. Detailed simulations also predict that some non-invasive electrical or magnetic stimulation approaches that do not intend to modulate cranial nerves per se, such as transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS), may also modulate activity of specific cranial nerves. Much prior cranial nerve stimulation work was conceptually limited to the production of sensory perception, with individual titration of intensity based on the level of perception and tolerability. However, disregarding sensory emulation allows consideration of temporal stimulation patterns (axon recruitment) that modulate the tone of cortical networks independent of sensory cortices, without necessarily titrating perception. For example, leveraging the role of the thalamus as a gatekeeper for information to the cerebral cortex, preventing or enhancing the passage of specific information depending on the behavioral state. We show that properly parameterized computational models at multiple scales are needed to rationally optimize neuromodulation that target sets of cranial nerves, determining which and how specific brain circuitries are modulated, which can in turn influence cognition in a designed manner.

Transcranial direct current stimulation facilitates category learning.

BACKGROUND: After two decades of transcranial direct current stimulation (tDCS) research, it is still unclear which applications benefit most from which tDCS protocols. One prospect is the acceleration of learning, where previous work has demonstrated that anodal tDCS applied to the right ventrolateral prefrontal cortex (rVLPFC) is capable of doubling the rate of learning in a visual camouflaged threat detection and category learning task. GOALS: Questions remain as to the specific cognitive mechanisms underlying this learning enhancement, and whether it generalizes to other tasks. The goal of the current project was to expand previous findings by employing a novel category learning task. METHODS: Participants learned to classify pictures of European streets within a discovery learning paradigm. In a double-blind design, 54 participants were randomly assigned to 30 min of tDCS using either 2.0 mA anodal (n = 18), cathodal (n = 18), or 0.1 mA sham (n = 18) tDCS over the rVLPFC. RESULTS: A linear mixed-model revealed a significant effect of tDCS condition on classification accuracy across training (p = 0.001). Compared to a 4.2% increase in sham participants, anodal tDCS over F10 increased performance by 20.6% (d = 1.71) and cathodal tDCS by 14.4% (d = 1.16). CONCLUSIONS: These results provide further evidence for the capacity of tDCS applied to rVLPFC to enhance learning, showing a greater than quadrupling of test performance after training (491% of sham) in a difficult category learning task. Combined with our previous studies, these results suggest a generalized performance enhancement. Other tasks requiring sustained attention, insight and/or category learning may also benefit from this protocol.

Decreases in the Late Positive Potential to Alcohol Images Among Alcohol Treatment Seekers Following Mindfulness-Based Relapse Prevention.

AIM: Heightened craving among individuals with alcohol use disorder (AUD) has been attributed to a hypersensitivity to alcohol cues in attentional brain networks. Active mindfulness training has been shown to help improve attentional control. Here, we examined alcohol cue-related hypersensitivity among individuals with AUD who received rolling group mindfulness-based relapse prevention (MBRP) in combination with transcranial direct current stimulation (tDCS), over right inferior frontal gyrus. METHODS: Participants (n = 68) viewed a series of emotionally negative, emotionally neutral and alcohol-related images. Following image presentation, participants were asked to rate their level of craving for the alcohol cues, and their level of negative affect evoked by neutral and negative cues. During the task, electroencephalogram (EEG) was recorded to capture an event-related component shown to relate to emotionally salient stimuli: the late positive potential (LPP). Participants who completed a follow-up EEG (n = 37) performed the task a second time after up to eight sessions of MBRP coupled with active or sham tDCS. RESULTS: We found that both craving ratings and the LPP significantly decreased in response to alcohol cues from pre- to post-treatment, but not for other image cues. The magnitude of alcohol image craving reductions was associated with the number of MBRP group sessions attended. Active tDCS was not associated with craving ratings, but it was associated with greater LPP amplitudes across image types. CONCLUSIONS: Taken together, these results suggest that disruption of alcohol-cue hypersensitivity in people with AUD may be a target mechanism of MBRP.

Transcranial electrical and magnetic stimulation (tES and TMS) for addiction medicine: A consensus paper on the present state of the science and the road ahead.

There is growing interest in non-invasive brain stimulation (NIBS) as a novel treatment option for substance-use disorders (SUDs). Recent momentum stems from a foundation of preclinical neuroscience demonstrating links between neural circuits and drug consuming behavior, as well as recent FDA-approval of NIBS treatments for mental health disorders that share overlapping pathology with SUDs. As with any emerging field, enthusiasm must be tempered by reason; lessons learned from the past should be prudently applied to future therapies. Here, an international ensemble of experts provides an overview of the state of transcranial-electrical (tES) and transcranial-magnetic (TMS) stimulation applied in SUDs. This consensus paper provides a systematic literature review on published data - emphasizing the heterogeneity of methods and outcome measures while suggesting strategies to help bridge knowledge gaps. The goal of this effort is to provide the community with guidelines for best practices in tES/TMS SUD research. We hope this will accelerate the speed at which the community translates basic neuroscience into advanced neuromodulation tools for clinical practice in addiction medicine.

A Randomized Trial of Combined tDCS Over Right Inferior Frontal Cortex and Cognitive Bias Modification: Null Effects on Drinking and Alcohol Approach Bias.

BACKGROUND: Deriving novel treatments for alcohol use disorders (AUDs) is of critical importance, as existing treatments are only modestly effective for reducing drinking. Two promising strategies for treating AUDs include cognitive bias modification (CBM) and transcranial direct current stimulation (tDCS). While each strategy has shown positive results in reducing drinking or alcohol-related constructs (e.g., craving), initial tests of the combination of CBM and tDCS have shown mixed results. The present study investigated the degree to which combining CBM and tDCS (2.0 mA anodal current over F10) could reduce alcohol approach biases and alcohol consumption. METHODS: Seventy-nine at-risk drinkers were randomized to 1 of 4 conditions in a 2 × 2 factorial design: verum CBM/verum tDCS, verum CBM/sham tDCS, sham CBM/verum tDCS, or sham CBM/sham tDCS. Participants completed a baseline assessment of alcohol approach bias and drinking quantity/frequency (i.e., drinks per drinking day [DDD] and percent heavy drinking days [PHDD]), 4 sessions of combined CBM and tDCS, and follow-up assessments of approach bias and alcohol consumption. RESULTS: Results indicated that while participants did demonstrate significant alcohol approach biases at baseline, neither CBM, tDCS, nor the interaction reduced the bias at the follow-up. In addition, there was evidence of a trend toward reducing DDD from baseline to the 1-week/1-month follow-ups, but there was no significant effect of the intervention on either DDD or PHDD. CONCLUSIONS: These results partially replicated null results presented in similar CBM/tDCS trials and suggest that this combination, at least with anodal stimulation over dorsolateral or inferior frontal sites, may have limited utility to reduce drinking.

Mindfulness-Based Relapse Prevention and Transcranial Direct Current Stimulation to Reduce Heavy Drinking: A Double-Blind Sham-Controlled Randomized Trial.

BACKGROUND: Mindfulness-based relapse prevention (MBRP) and transcranial direct current stimulation (tDCS) have independently shown benefits for treating alcohol use disorder (AUD). Recent work suggests tDCS may enhance mindfulness. The combination of MBRP and tDCS may provide synergistic benefits and may target both behavioral and neurobiological dysfunctions in AUD. The goal of this double-blind sham-controlled randomized trial was to examine the efficacy of a rolling group MBRP treatment combined with tDCS among individuals interested in reducing their drinking. METHODS: Individuals who were interested in reducing their alcohol use (n = 84; 40.5% female; mean age = 52.3; 98.9% with current AUD) were randomized to receive active (2.0 milliamps) or sham (0.0 milliamps) anodal tDCS (5 cm × 3 cm electrode) of the right inferior frontal gyrus with the 5 cm × 3 cm cathodal electrode applied to the left upper arm, combined with 8 weeks of outpatient MBRP rolling group treatment. Assessments were conducted at baseline, posttreatment, and 2 months following treatment. The primary outcome was drinks per drinking day, and secondary outcomes were percent heavy drinking days, self-reported craving, alcohol cue reactivity in an alcohol cue task, and response inhibition in a stop signal reaction time task. RESULTS: Results indicated significant reductions in drinks per drinking day over time, B(SE) = -0.535 (0.16), p = 0.001, and a significant dose effect for number of groups attended, B(SE) = -0.259 (0.11), p = 0.01. There were also significant effects of time and dose for number of groups attended on secondary outcomes of percent heavy drinking days and alcohol cue reactivity. There were no effects of active versus sham tDCS on primary or secondary outcomes. CONCLUSIONS: Findings from the current study provide initial support for the effectiveness of rolling group MBRP as an outpatient treatment for drinking reduction. The current study did not find additive effects of this tDCS protocol in enhancing MBRP among individuals with drinking reduction goals.

Transcranial Current Stimulation During Sleep Facilitates Insight into Temporal Rules, but does not Consolidate Memories of Individual Sequential Experiences.

Slow-wave sleep (SWS) is known to contribute to memory consolidation, likely through the reactivation of previously encoded waking experiences. Contemporary studies demonstrate that when auditory or olfactory stimulation is administered during memory encoding and then reapplied during SWS, memory consolidation can be enhanced, an effect that is believed to rely on targeted memory reactivation (TMR) induced by the sensory stimulation. Here, we show that transcranial current stimulations (tCS) during sleep can also be used to induce TMR, resulting in the facilitation of high-level cognitive processes. Participants were exposed to repeating sequences in a realistic 3D immersive environment while being stimulated with particular tCS patterns. A subset of these tCS patterns was then reapplied during sleep stages N2 and SWS coupled to slow oscillations in a closed-loop manner. We found that in contrast to our initial hypothesis, performance for the sequences corresponding to the reapplied tCS patterns was no better than for other sequences that received stimulations only during wake or not at all. In contrast, we found that the more stimulations participants received overnight, the more likely they were to detect temporal regularities governing the learned sequences the following morning, with tCS-induced beta power modulations during sleep mediating this effect.