A Randomized Trial of Combined tDCS Over Right Inferior Frontal Cortex and Cognitive Bias Modification: Null Effects on Drinking and Alcohol Approach Bias.
ABSTRACT: 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.
Project description: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.
Project description:Both anodal transcranial direct current stimulation (tDCS) of the left IFG and cathodal stimulation of the right IFG were shown to improve rehabilitation of stroke patients with Broca's aphasia. The study aimed at assessing the impact of a bihemispheric IFG stimulation compared to sham on postacute non-fluent aphasia. Twelve patients with non-fluent aphasia were included at least 4 weeks following cerebral stroke. Ten daily sessions of 2 mA bihemispheric verum or sham tDCS (anode on left IFG and cathode on right IFG) were performed concomitantly with individual language therapy in a double-blinded randomized controlled study with parallel group design. Language functions [i.e., communication (ANELT), picture naming and the Aachen aphasia test (AAT)] were assessed up to 1 month following tDCS. The picture naming task significantly improved (increased number of nouns) at the end of the tDCS procedure in the verum but not sham group. Improvements in the picture naming task and the communication task of the AAT at 4 weeks after tDCS procedure were only seen in the verum group. In patients with postacute cerebral stroke, repeated sessions of tDCS applied on both IFG concomitantly with language therapy were able to induce immediate effects on picture naming presumably due to an early left shift of language-associated function that maintained for 4 weeks. Effects on clinically relevant communicative abilities are likely.
Project description:Adults with alcohol use disorders (AUDs) show marked immediate reward selection (or "Now") bias in intertemporal choice tasks. This Now bias persists long into abstinence, suggesting an irreversible consequence of chronic alcohol abuse or a pre-existing AUD intermediate phenotype. However, some data show substantial Now bias among emerging adults (18-25), regardless of drinking behavior, suggesting age-dependent effects on Now bias. The objectives of the present study were to determine (1) whether Now bias is greater among emerging adults relative to adults, (2) whether any such age effect on Now bias is diminished in sub-clinical heavy alcohol users, and (3) whether having a problem drinking first degree relative is independently associated with elevated Now bias. To achieve these objectives, we used an intertemporal choice task to quantify Now bias in n = 237 healthy participants (ages 18-40; 50% female), and a wide range of non-zero alcohol use, based on the Alcohol Use Disorders Identification Test (AUDIT). We found that among non-heavy drinkers, Now bias inversely correlated with age; this relationship was not present among heavy drinkers. We found no significant relationship between AUDIT score and Now bias among emerging adults, but AUDIT scores and Now bias were positively correlated among 26-40 year olds. Additionally, non-heavy drinking adults who reported a problem drinking first degree relative showed greater Now bias compared to those not reporting familial problem drinking. While not definitive, these findings lend support for elevated Now bias in adulthood as an intermediate phenotype for AUDs. Moreover, non-additive effects of age and heavy drinking on Now bias suggest perturbations in largely common neural circuits in both groups.
Project description:BACKGROUND:Brief interventions have empirical support for acutely reducing alcohol use among non-treatment-seeking heavy drinkers. Neuroimaging techniques allow for the examination of the neurobiological effect of behavioral interventions, probing brain systems putatively involved in clinical response to treatment. Few studies have prospectively evaluated whether psychosocial interventions attenuate neural cue reactivity that in turn reduces drinking in the same population. This study aimed to examine the effect of a brief intervention on drinking outcomes, neural alcohol cue reactivity, and the ability of neural alcohol cue reactivity to prospectively predict drinking outcomes. METHODS:Non-treatment-seeking heavy drinking participants were randomized to receive a brief interview intervention (n = 22) or an attention-matched control (n = 24). Immediately following the intervention or control, participants underwent a functional magnetic resonance imaging scan comprised of the alcohol taste cues paradigm. Four weeks after the intervention (or control), participants completed a follow-up visit to report on their past-month drinking. Baseline and follow-up percent heavy drinking days (PHDD) were calculated for each participant. RESULTS:There was no significant effect of the brief intervention on PHDD at follow-up or on modulating neural activation to alcohol relative to water taste cues. There was a significant association between neural response to alcohol taste cues and PHDD across groups (Z > 2.3, p < 0.05), such that individuals who had greater neural reactivity to alcohol taste cues in the precuneus and prefrontal cortex (PFC) had fewer PHDD at follow-up. CONCLUSIONS:This study did not find an effect of the brief intervention on alcohol use in this sample, and the intervention was not associated with differential neural alcohol cue reactivity. Nevertheless, greater activation of the precuneus and PFC during alcohol cue exposure predicted less alcohol use prospectively suggesting that these neural substrates subserve the effects of alcohol cues on drinking behavior.
Project description:Background: Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, has been studied as an adjunctive therapeutic agent for alcohol dependence. In a previous study, we showed that five consecutive sessions of tDCS applied bilaterally over the dorsolateral prefrontal cortex (dlPFC) reduced relapse to the use of alcohol in alcohol use disorder (AUD) outpatients. However, no changes on craving scores were observed. In the present study, we investigated if an extended number of sessions of the same intervention would reduce craving and relapses for alcohol use in AUD inpatients. Methods: Thus, a randomized, double-blind, sham-controlled, clinical trial with parallel arms was conducted (https://clinicaltrials.gov/ct2/show/NCT02091284). AUD patients from two private and one public clinics for treatment of drug dependence were randomly allocated to two groups: real tDCS (5 × 7 cm2, 2 mA, for 20 min, cathodal over the left dlPFC, and anodal over the right dlPFC) and sham-tDCS. Real or sham-tDCS was applied once a day, every other day, in a total of 10 sessions. Craving was monitored by a 5-item obsessive compulsive drinking scale once a week (one time before, three times during and once after brain stimulation) over about 5 weeks. Results: Craving scores progressively decreased over five measurements in both groups but were significantly reduced only in the real tDCS group after treatment. Corrected Hedges' within-group (initial and final) effect sizes of craving scores were of 0.3 for the sham-tDCS and of 1.1 for the real tDCS group. Effect size was 3-fold larger in the real tDCS group. In addition, the between-group analysis on craving score difference was nearly significant, and the effect size was 0.58, in favor for a larger effect in the real tDCS group when compared to sham-tDCS. Furthermore, in a 3-months follow-up after intervention, 72.2% of sham-tDCS group relapsed to the alcohol use whereas 72.7% of tDCS group were abstinent. Conclusions: Multiple sessions of bilateral prefrontal tDCS were well tolerated with no significant adverse events. Thus, extended repetitive bilateral tDCS over the dlPFC is a promising adjunctive clinical tool that could be used to reduce alcohol craving and relapses and facilitate alcoholism cessation.
Project description:Transcranial Direct Current Stimulation (tDCS) over the Dorsolateral Prefrontal Cortex (DLPFC) has already been shown to decrease craving for food. However, it remains unclear whether a single session of tDCS combined with a cognitive bias modification (CBM) task may affect explicit and implicit measures of craving for chocolate. Fifty-one healthy volunteers (38 females; mean age: 22.12 ± 3.38) were randomly allocated to CBM training based on the Approach Avoidance task and either Sham, Right anodal-Left cathodal (RALC), or Left anodal-Right cathodal (LARC) tDCS. Results show that there was an increase in the explicit craving for chocolate, as assessed by the Visual Analog Scale [F(2, 46) = 3.239, p = 0.048], from the baseline to post-intervention. Participants which received LARC tDCS were explicitly self-reporting more craving for chocolate than those that received RALC tDCS (p = 0.023). Moreover, this effect was also observed on the implicit measure [F(2, 46) = 4.168, p = 0.022]. LARC tDCS significantly increased the implicit preference for chocolate when comparing to both RALC (p = 0.009) and Sham tDCS (p = 0.034). Previous studies have shown that RALC tDCS over the PFC is able to effectively decrease craving for food. Interestingly, the present data not only does not reproduce such result, but instead it suggests that LARC tDCS can actually increase the preference for chocolate. This result is compatible with recent models of brain laterality, in which cue craving seems to be more dependent on the left hemisphere. Thus, shifting the activity to the left hemisphere (while simultaneously reducing the activity over the homotopic region) may have led to this increased implicit as well as explicit preference for chocolate.
Project description:We use intensive longitudinal data methods to illuminate processes affecting patients' drinking in relation to the discontinuation of medications within an alcohol treatment study. Although previous work has focused on broad measures of medication adherence, we focus on dynamic changes in drinking both before and after patients discontinue.We conducted secondary data analyses using the COMBINE (Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence) study, focused on participants who discontinued medications prior to the planned end of treatment. Using an interrupted time-series analysis, we analysed drinking in the weeks before and after discontinuation and also studied outcomes at the end of the COMBINE follow-up.Unites States of America.We describe the subsample of COMBINE participants who discontinued medications (n = 450), and compare them with those who were medication-adherent (n = 559) and with those who discontinued but had substantial missing data (n = 217).The primary outcomes were percentage of days abstinent (PDA) and percentage of heavy drinking days (PHDD). Medication adherence data were used to approximate the date of discontinuation.For many patients, an increase in drinking began weeks before discontinuation (PDA: F(1,4803) = 19.07, P < 0.001; PHDD: F(1,4804) = 8.58, P = 0.003) then escalated at discontinuation (PDA: F(1,446) = 5.05, P = 0.025; PHDD: F(1,446) = 4.52, P = 0.034). Among other effects, the amount of change was moderated by the reason for discontinuation (e.g. adverse event; PDA: F(2,4803) = 3.85, P = 0.021; PHDD: F(2,4804) = 5.36, P = 0.005) and also whether it occurred in the first or second half of treatment (PDA: F(1,4803) = 5.23, P = 0.022; PHDD: F(1,4804) = 8.79, P = 0.003).A patient's decision to stop taking medications during alcohol treatment appears to take place during a weeks-long process of disengagement from treatment. Patients who discontinue medications early in treatment or without medical consultation appear to drink more frequently and more heavily.
Project description:BACKGROUND:Chronic alcohol use disorders (AUDs) and traumatic brain injury (TBI) are highly comorbid and share commonly affected neuronal substrates (i.e., prefrontal cortex, limbic system, and cerebellum). However, no studies have examined how combined physical trauma and heavy drinking affect neurocircuitry relative to heavy drinking alone. METHODS:The current study investigated whether comorbid AUDs and mild or moderate TBI (AUDs+TBI) would negatively affect maladaptive drinking behaviors (n = 90 AUDs+TBI; n = 62 AUDs) as well as brain structure (i.e., increased atrophy; n = 62 AUDs+TBI; n = 44 AUDs) and function (i.e., activation during gustatory cue reactivity; n = 55 AUDs+TBI; n = 37 AUDs) relative to AUDs alone. RESULTS:Participants reported a much higher incidence of trauma (59.2%) compared with the general population. There were no differences in demographic and clinical measures between groups, suggesting that they were well matched. Although maladaptive drinking behaviors tended to be worse for the AUDs+TBI group, effect sizes were small and not statistically significant. Increased alcohol-cue reactivity was observed in bilateral anterior insula and orbitofrontal cortex, anterior cingulate cortex, medial prefrontal cortex, posterior cingulate cortex, dorsal striatum, thalamus, brainstem, and cerebellum across both groups relative to a carefully matched appetitive control. However, there were no significant differences in structural integrity or functional activation between AUDs+TBI and AUDs participants, even when controlling for AUD severity. CONCLUSIONS:Current results indicate that a combined history of mild or moderate TBI was not sufficient to alter drinking behaviors and/or underlying neurocircuitry at detectable levels relative to heavy drinking alone. Future studies should examine the potential long-term effects of combined alcohol and trauma on brain functioning.
Project description:BACKGROUND:Modifying attentional processes with attentional bias modification (ABM) might be a relevant add-on to treatment in addiction. This study investigated whether influencing cortical plasticity with transcranial direct current stimulation (tDCS) could increase training effects. tDCS could also help alcohol-dependent patients to overcome craving and reduce relapse, independent of training. These approaches were combined to investigate effects in the treatment of alcoholism. METHODS:Ninety-eight patients (analytical sample = 83) were randomly assigned to 4 groups in a 2-by-2 factorial design. Patients received 4 sessions of ABM (control or real training) combined with 2 mA tDCS (active: 20 minutes or sham: 30 seconds) over the left dorsolateral prefrontal cortex. Alcohol bias and craving were assessed, and treatment outcome was measured as relapse after 1 year. RESULTS:Attentional bias scores indicated that during the training only the group with active tDCS and real ABM displayed an overall avoidance bias (p < 0.05). From pre- to postassessment, there were no main or interaction effects of tDCS and ABM on the bias scores, craving, or relapse (p > 0.2). However, effects on relapse after active tDCS were in the expected direction. CONCLUSIONS:There was no evidence of a beneficial effect of tDCS or ABM or the combination. Whether the absence of effect was due to issues with the outcome measurements (e.g., lack of craving, high dropout, and unreliable measurements) or aspects of the intervention should be further investigated.
Project description:Alcohol use disorders (AUDs) are a major public health issue and produce enormous societal and economic burdens. Current Food and Drug Administration (FDA)-approved pharmacotherapies for treating AUDs suffer from deleterious side effects and are only effective in a subset of individuals. It is therefore essential to find improved medications for the management of AUDs. Emerging evidence suggests that anticonvulsants are a promising class of drugs for treating individuals with AUDs. In these studies, we used integrative functional genomics to demonstrate that genes that encode Kv7 channels (i.e. Kcnq2/3) are related to alcohol (ethanol) consumption, preference and acceptance in rodents. We then tested the ability of the FDA-approved anticonvulsant retigabine, a Kv7 channel opener, to reduce voluntary ethanol consumption of Wistar rats in a two-bottle choice intermittent alcohol access paradigm. Systemic administration and microinjections of retigabine into the nucleus accumbens significantly reduced alcohol drinking, and retigabine was more effective at reducing intake in high- versus low-drinking populations of Wistar rats. Prolonged voluntary drinking increased the sensitivity to the proconvulsant effects of pharmacological blockade of Kv7 channels and altered surface trafficking and SUMOylation patterns of Kv7.2 channels in the nucleus accumbens. These data implicate Kcnq2/3 in the regulation of ethanol drinking and demonstrate that long-term drinking produces neuroadaptations in Kv7 channels. In addition, these results have identified retigabine as a potential pharmacotherapy for treating AUDs and Kv7 channels as a novel therapeutic target for reducing heavy drinking.