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Background and aims: Alcohol use disorder (AUD) is a chronic disorder with high relapse rates. There are currently few clinical trials of high frequency repetitive transcranial magnetic stimulation (HF‐rTMS) to reduce alcohol use among AUD patients, and results are mixed. The current study tested the effect of 10 add‐on sessions of HF‐rTMS over the right dorsolateral pre‐frontal cortex (DLPFC) on alcohol use and craving. Design: Single‐center, single blind sham‐controlled parallel‐group RCT (n = 80), with 3 and 6 months follow‐up. Setting: Clinical treatment center in Amsterdam, the Netherlands. Participants: Eighty detoxified and abstinent AUD inpatients in clinical treatment (20 females, average age = 44.35 years). Intervention: Ten sessions of active or sham HF‐rTMS (60 10 Hz trains of 5 sec at 110% motor threshold) over the right DLPFC on 10 consecutive work‐days. Measurements The primary outcome measure is the number of abstinent days over 6‐month follow‐up (FU). Secondary outcome measures are craving over 6‐month FU (alcohol urge questionnaire and obsessive‐compulsive drinking scale), time to first relapse over 6‐month FU and grams of alcohol consumed over 6‐month FU. Additional outcome measures: full abstinence over 6‐month FU and treatment success over 12‐month FU. Findings HF‐rTMS did not affect the number of abstinent days over 6 months FU [sham = 124 ± 65.9 days, active = 115 ± 69.8 days, difference: 9 days, 95% confidence interval (CI) = Poisson model: 0.578–3.547]. Moreover, HF‐rTMS did not affect craving (AUQ/OCDS) (sham = 15.38/5.28, active = 17.48/4.75, differences = 2.1/−0.53, 95% CI mixed‐effects model = −9.14 to 2.07/−1.44 to 2.40). Conclusions: There was no clear evidence that high‐frequency repetitive transcranial magnetic stimulation over the right dorsolateral pre‐frontal cortex treatment has a long‐term positive effect on alcohol use or craving as add‐on treatment for alcohol use disorder. High treatment response at 6‐month follow‐up could have limited the possibility to find an effect. [ABSTRACT FROM AUTHOR]

Introduction: Alcohol use disorder (AUD) is characterized by increased impulsivity, which is multifactorial and can be assessed by tests like the delay discounting, Go-Nogo, and stop signal task (SST). Impulsivity has been related to poor treatment outcomes in substance use disorders, including AUD. In order to decrease impulsivity or improve inhibitory control, high frequency transcranial magnetic stimulation (HF-rTMS) has gained interest. Studies applying HF-rTMS over the DLPFC of individuals suffering from AUD assessing its effects on impulsivity measures are scarce, and results are inconclusive. Methods: The current study (registered in Netherlands Trial Register with trial number 5291: https://www.trialregister.nl/trial/5151) applied 10 sessions of HF-rTMS [sixty 10 Hz trains of 5 s at 110% motor threshold (MT)] over the right DLPFC of 80 alcohol dependent patients in clinical treatment on 10 consecutive workdays. At baseline, halfway and after the HF-rTMS treatment, the delay discounting, Go-NoGo, and SST were assessed. Results: Ten sessions of HF-rTMS over the right DLPFC versus sham HF-rTMS did not affect performance on the delay discounting, Go-NoGo, and SSTs. A significant effect of age was found for the Go-NoGo task, with higher age associated with better performance. Furthermore, no significant correlations were found between difference scores of task performance and baseline impulsivity or severity of AUD. Discussion: Results of this study, in combination with other studies using HF-rTMS studies in alcohol and substance use disorder, indicate mixed and inconclusive findings of HF-rTMS on impulsivity. Future studies within patient groups hospitalized at the same department are recommended to consider using a sham coil that mimics the sensations on the scalp of active HF-rTMS and to measure motivation across test sessions. [ABSTRACT FROM AUTHOR]

Background: In order to improve the current treatment of addictive disorders non-invasive neuromodulation over the dorsolateral prefrontal cortex (DLPFC) has gained attention. The DLPFC is crucially involved in executive functioning, functions which are related to the course of addictive disorders. Non-invasive stimulation of the DLPFC may lead to changes in executive functioning. Currently an overview of effects of neuromodulation on these functions is lacking. Therefore, this systematic review addresses the effects of non-invasive neuromodulation on executive functioning in addictive disorders. Methods: The current review is conducted and reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015) guidelines and has been registered in PROSPERO International Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/prospero/, registration number: CRD42018084157). Original articles were searched using the Ovid MEDLINE, Embase and PsycINFO database. Results: The systematic search resulted in 1,228 unique studies, of which sixteen were included in the current review. Some of these studies do not address the classic definition of executive functions, but another cognitive function. However, they were included in this review since the field is small and still under development and we aim to give an inclusive overview in its broadest sense. The following executive and other cognitive functioning domains were assessed: attention, cognitive flexibility, response inhibition, memory and learning, problem solving, social cognition, risk taking, cognitive bias modification and overall executive functioning. The executive function domain most positively affected was social cognition followed by memory & learning, response inhibition, cognitive flexibility and attention. Conclusions: The studies addressed in the current review used a large variability of stimulation protocols and study designs which complicates comparability of the results. Nevertheless, the results of these studies are promising in light of improvement of current treatment. Therefore, we recommend future studies that compare the effect of different types of stimulation, stimulation sides and number of stimulation sessions in larger clinical trials. This will significantly increase the comparability of the studies and thereby accelerate and clarify the conclusion on whether non-invasive neuromodulation is an effective add-on treatment for substance dependence. [ABSTRACT FROM AUTHOR]

Appetitive conditioning refers to the process of learning cue-reward associations and is mediated by the mesocorticolimbic system. Appetitive conditioned responses are difficult to extinguish, especially for highly salient reward such as food and drugs. We investigate whether aversive counterconditioning can alter reward reinstatement in the ventral striatum in healthy volunteers using functional magnetic resonance imaging (fMRI). In the initial conditioning phase, two different stimuli were reinforced with a monetary reward. In the subsequent counterconditioning phase, one of these stimuli was paired with an aversive shock to the wrist. In the following extinction phase, none of the stimuli were reinforced. In the final reinstatement phase, reward was reinstated by informing the participants that the monetary gain could be doubled. Our fMRI data revealed that reward signaling in the ventral striatum and ventral tegmental area following reinstatement was smaller for the stimulus that was counterconditioned with an electrical shock, compared to the non-counterconditioned stimulus. A functional connectivity analysis showed that aversive counterconditioning strengthened striatal connectivity with the hippocampus and insula. These results suggest that reward signaling in the ventral striatum can be attenuated through aversive counterconditioning, possibly by concurrent retrieval of the aversive association through enhanced connectivity with hippocampus and insula. [ABSTRACT FROM AUTHOR]