Brain-age prediction: Systematic evaluation of site effects, and sample age range and size.

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model. Here we expand this work to develop, empirically validate, and disseminate a pre-trained brain-age model to cover most of the human lifespan. To achieve this, we selected the best-performing model after systematically examining the impact of seven site harmonization strategies, age range, and sample size on brain-age prediction in a discovery sample of brain morphometric measures from 35,683 healthy individuals (age range: 5-90 years; 53.59% female). The pre-trained models were tested for cross-dataset generalizability in an independent sample comprising 2101 healthy individuals (age range: 8-80 years; 55.35% female) and for longitudinal consistency in a further sample comprising 377 healthy individuals (age range: 9-25 years; 49.87% female). This empirical examination yielded the following findings: (1) the accuracy of age prediction from morphometry data was higher when no site harmonization was applied; (2) dividing the discovery sample into two age-bins (5-40 and 40-90 years) provided a better balance between model accuracy and explained age variance than other alternatives; (3) model accuracy for brain-age prediction plateaued at a sample size exceeding 1600 participants. These findings have been incorporated into CentileBrain (https://centilebrain.org/#/brainAGE2), an open-science, web-based platform for individualized neuroimaging metrics.

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.

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.

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.

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.

Closed-Loop Slow-Wave tACS Improves Sleep-Dependent Long-Term Memory Generalization by Modulating Endogenous Oscillations.

Benefits in long-term memory retention and generalization have been shown to be related to sleep-dependent processes, which correlate with neural oscillations as measured by changes in electric potential. The specificity and causal role of these oscillations, however, are still poorly understood. Here, we investigated the potential for augmenting endogenous slow-wave (SW) oscillations in humans with closed-loop transcranial alternating current stimulation (tACS) with an aim toward enhancing the consolidation of recent experiences into long-term memory. Sixteen (three female) participants were trained presleep on a target detection task identifying targets hidden in complex visual scenes. During post-training sleep, closed-loop SW detection and stimulation were used to deliver tACS matching the phase and frequency of the dominant oscillation in the range of 0.5-1.2 Hz. Changes in performance were assessed the following day using test images that were identical to the training ("repeated"), and images generated from training scenes but with novel viewpoints ("generalized"). Results showed that active SW tACS during sleep enhanced the postsleep versus presleep target detection accuracy for the generalized images compared with sham nights, while no significant change was found for repeated images. Using a frequency-agnostic clustering approach sensitive to stimulation-induced spectral power changes in scalp EEG, this behavioral enhancement significantly correlated with both a poststimulation increase and a subsequent decrease in measured spectral power within the SW band, which in turn showed increased coupling with spindle amplitude. These results suggest that augmenting endogenous SW oscillations can enhance consolidation by specifically improving generalization over recognition or cued recall.SIGNIFICANCE STATEMENT This human study demonstrates the use of a closed-loop noninvasive brain stimulation method to enhance endogenous neural oscillations during sleep with the effect of improving consolidation of recent experiences into long-term memory. Here we show that transient slow oscillatory transcranial alternating current stimulation (tACS) triggered by endogenous slow oscillations and matching their frequency and phase can increase slow-wave power and coupling with spindles. Further, this increase correlates with overnight improvements in generalization of recent training to facilitate performance in a target detection task. We also provide novel evidence for a tACS-induced refractory period following the tACS-induced increase. Here slow-wave power is temporarily reduced relative to sham stimulation, which nonetheless maintains a positive relationship with behavioral improvements.

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.

Neuroenhancement: enhancing brain and mind in health and in disease.

Humans have long used cognitive enhancement methods to expand the proficiency and range of the various mental activities that they engage in, including writing to store and retrieve information, and computers that allow them to perform myriad activities that are now commonplace in the internet age. Neuroenhancement describes the use of neuroscience-based techniques for enhancing cognitive function by acting directly on the human brain and nervous system, altering its properties to increase performance. Cognitive neuroscience has now reached the point where it may begin to put theory derived from years of experimentation into practice. This special issue includes 16 articles that employ or examine a variety of neuroenhancement methods currently being developed to increase cognition in healthy people and in patients with neurological or psychiatric illness. This includes transcranial electromagnetic stimulation methods, such as transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS), along with deep brain stimulation, neurofeedback, behavioral training techniques, and these and other techniques in conjunction with neuroimaging. These methods can be used to improve attention, perception, memory and other forms of cognition in healthy individuals, leading to better performance in many aspects of everyday life. They may also reduce the cost, duration and overall impact of brain and mental illness in patients with neurological and psychiatric illness. Potential disadvantages of these techniques are also discussed. Given that the benefits of neuroenhancement outweigh the potential costs, these methods could potentially reduce suffering and improve quality of life for everyone, while further increasing our knowledge about the mechanisms of human cognition.

Battery powered thought: enhancement of attention, learning, and memory in healthy adults using transcranial direct current stimulation.

This article reviews studies demonstrating enhancement with transcranial direct current stimulation (tDCS) of attention, learning, and memory processes in healthy adults. Given that these are fundamental cognitive functions, they may also mediate stimulation effects on other higher-order processes such as decision-making and problem solving. Although tDCS research is still young, there have been a variety of methods used and cognitive processes tested. While these different methods have resulted in seemingly contradictory results among studies, many consistent and noteworthy effects of tDCS on attention, learning, and memory have been reported. The literature suggests that although tDCS as typically applied may not be as useful for localization of function in the brain as some other methods of brain stimulation, tDCS may be particularly well-suited for practical applications involving the enhancement of attention, learning, and memory, in both healthy subjects and in clinical populations.

High-order interactions observed in multi-task intrinsic networks are dominant indicators of aberrant brain function in schizophrenia.

Identifying the complex activity relationships present in rich, modern neuroimaging data sets remains a key challenge for neuroscience. The problem is hard because (a) the underlying spatial and temporal networks may be nonlinear and multivariate and (b) the observed data may be driven by numerous latent factors. Further, modern experiments often produce data sets containing multiple stimulus contexts or tasks processed by the same subjects. Fusing such multi-session data sets may reveal additional structure, but raises further statistical challenges. We present a novel analysis method for extracting complex activity networks from such multifaceted imaging data sets. Compared to previous methods, we choose a new point in the trade-off space, sacrificing detailed generative probability models and explicit latent variable inference in order to achieve robust estimation of multivariate, nonlinear group factors ("network clusters"). We apply our method to identify relationships of task-specific intrinsic networks in schizophrenia patients and control subjects from a large fMRI study. After identifying network-clusters characterized by within- and between-task interactions, we find significant differences between patient and control groups in interaction strength among networks. Our results are consistent with known findings of brain regions exhibiting deviations in schizophrenic patients. However, we also find high-order, nonlinear interactions that discriminate groups but that are not detected by linear, pairwise methods. We additionally identify high-order relationships that provide new insights into schizophrenia but that have not been found by traditional univariate or second-order methods. Overall, our approach can identify key relationships that are missed by existing analysis methods, without losing the ability to find relationships that are known to be important.

Reduced fMRI activity predicts relapse in patients recovering from stimulant dependence.

Relapse presents a significant problem for patients recovering from stimulant dependence. Here we examined the hypothesis that patterns of brain function obtained at an early stage of abstinence differentiates patients who later relapse versus those who remain abstinent. Forty-five recently abstinent stimulant-dependent patients were tested using a randomized event-related functional MRI (ER-fMRI) design that was developed in order to replicate a previous ERP study of relapse using a selective attention task, and were then monitored until 6 months of verified abstinence or stimulant use occurred. SPM revealed smaller absolute blood oxygen level-dependent (BOLD) response amplitude in bilateral ventral posterior cingulate and right insular cortex in 23 patients positive for relapse to stimulant use compared with 22 who remained abstinent. ER-fMRI, psychiatric, neuropsychological, demographic, personal and family history of drug use were compared in order to form predictive models. ER-fMRI was found to predict abstinence with higher accuracy than any other single measure obtained in this study. Logistic regression using fMRI amplitude in right posterior cingulate and insular cortex predicted abstinence with 77.8% accuracy, which increased to 89.9% accuracy when history of mania was included. Using 10-fold cross-validation, Bayesian logistic regression and multilayer perceptron algorithms provided the highest accuracy of 84.4%. These results, combined with previous studies, suggest that the functional organization of paralimbic brain regions including ventral anterior and posterior cingulate and right insula are related to patients' ability to maintain abstinence. Novel therapies designed to target these paralimbic regions identified using ER-fMRI may improve treatment outcome.

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.

A history of randomized task designs in fMRI.

In the early days of fMRI, data were acquired using methods adapted mainly from PET imaging. Sets of similar stimuli were presented in extended blocks, with stimulus conditions changing from block to block. While this method provided optimum statistical power, it also presented a variety of potential confounds, including changes in attention, alertness, expectancy, and practice effects within and between blocks. Event-related paradigms using unpredictable, randomized stimulus sequences had been used in EEG studies for over 50 years before the development of fMRI, and provided a means to overcome these issues. However, the temporal dispersion of BOLD fMRI activity resulted in responses to successive stimuli adding together, making it difficult to perform rapid event-related paradigms using fMRI. Here we describe the background and history of methods developed to overcome this limitation, allowing rapid, randomized stimulus sequences to be used with fMRI. The advantages and disadvantages of this technique and how these methods have been applied in a variety of experimental settings are discussed.

TDCS guided using fMRI significantly accelerates learning to identify concealed objects.

The accurate identification of obscured and concealed objects in complex environments was an important skill required for survival during human evolution, and is required today for many forms of expertise. Here we used transcranial direct current stimulation (tDCS) guided using neuroimaging to increase learning rate in a novel, minimally guided discovery-learning paradigm. Ninety-six subjects identified threat-related objects concealed in naturalistic virtual surroundings used in real-world training. A variety of brain networks were found using functional magnetic resonance imaging (fMRI) data collected at different stages of learning, with two of these networks focused in right inferior frontal and right parietal cortex. Anodal 2.0 mA tDCS performed for 30 min over these regions in a series of single-blind, randomized studies resulted in significant improvements in learning and performance compared with 0.1 mA tDCS. This difference in performance increased to a factor of two after a one-hour delay. A dose-response effect of current strength on learning was also found. Taken together, these brain imaging and stimulation studies suggest that right frontal and parietal cortex are involved in learning to identify concealed objects in naturalistic surroundings. Furthermore, they suggest that the application of anodal tDCS over these regions can greatly increase learning, resulting in one of the largest effects on learning yet reported. The methods developed here may be useful to decrease the time required to attain expertise in a variety of settings.

Enhancement of object detection with transcranial direct current stimulation is associated with increased attention.

BACKGROUND: We previously found that Transcranial Direct Current Stimulation (tDCS) improves learning and performance in a task where subjects learn to detect potential threats indicated by small target objects hidden in a complex virtual environment. In the present study, we examined the hypothesis that these effects on learning and performance are related to changes in attention. The effects of tDCS were tested for three forms of attention (alerting, orienting, and executive attention) using the Attention Network Task (ANT), which were compared with performance on the object-learning task. RESULTS: Participants received either 0.1 mA (N = 10) or 2.0 mA (N = 9) tDCS during training and were tested for performance in object-identification before training (baseline-test) and again immediately after training (immediate test). Participants next performed the Attention Networks Task (ANT), and were later tested for object-identification performance a final time (delayed test). Alerting, but not orienting or executive attention, was significantly higher for participants receiving 2.0 mA compared with 0.1 mA tDCS (p < 0.02). Furthermore, alerting scores were significantly correlated with the proportion of hits (p < 0.01) for participants receiving 2.0 mA. CONCLUSIONS: These results indicate that tDCS enhancement of performance in this task may be related in part to the enhancement of alerting attention, which may benefit the initial identification, learning and/or subsequent recognition of target objects indicating potential threats.

Cigarette smoking and white matter microstructure in schizophrenia.

The majority of patients with schizophrenia smoke cigarettes. Both nicotine use and schizophrenia have been associated with alterations in brain white matter microstructure as measured by diffusion tensor imaging (DTI). The purpose of this study was to examine fractional anisotropy (FA) in smoking and non-smoking patients with schizophrenia and in healthy volunteers. A total of 43 patients (28 smoking and 15 non-smoking) with schizophrenia and 40 healthy, non-smoking participants underwent DTI. Mean FA was calculated in four global regions of interest (ROIs) (whole brain, cerebellum, brainstem, and total cortical) as well as in four regional ROIs (frontal, temporal, parietal and occipital lobes). The non-smoking patient group had a significantly higher intellectual quotient (IQ) compared with the patients who smoked, and our results varied according to whether IQ was included as a covariate. Without IQ correction, significant between-group effects for FA were found in four ROIs: total brain, total cortical, frontal lobe and the occipital lobe. In all cases the FA was lower among the smoking patient group, and highest in the control group. Smoking patients differed significantly from non-smoking patients in the frontal lobe ROI. However, these differences were no longer significant after IQ correction. FA differences between non-smoking patients and controls were not significant. Among smoking and non-smoking patients with schizophrenia but not healthy controls, FA was correlated with IQ. In conclusion, group effects of smoking on FA in schizophrenia might be mediated by IQ. Further, low FA in specific brain areas may be a neural marker for complex pathophysiology and risk for diverse problems such as schizophrenia, low IQ, and nicotine addiction.

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.

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).