Multi-session electrical neuromodulation effects on craving, relapse and cognitive functions in cocaine use disorder: A randomized, sham-controlled tDCS study

Background: The use of transcranial Direct Current Stimulation (tDCS) has previously shown promising results for reducing craving in cocaine use disorder. In this study we further explored the potential of tDCS as add-on intervention in the treatment of cocaine use disorder. Methods: In a randomized, placebo-controlled, between subject study, we applied tDCS bilaterally with the anodal electrode targeting the right dorsolateral prefrontal cortex (DLPFC; https://clinicaltrials.gov/ct2/show/ NCT03025321). Patients with cocaine use disorder were allocated to ten sessions of either active tDCS (n = 29) or sham (n = 30) on five consecutive days. Inhibitory control and risky decision-making were measured via a Go-NoGo task and a two-choice gambling task, respectively, each at baseline, one day after all tDCS sessions and after three months. Relapse at follow-up and craving were also assessed. Results: There was no significant effect of active tDCS on the number of cocaine use days and craving. Relapse was frequent among patients who had received either active or sham tDCS (48.0 % and 69.2 %, respectively), despite an overall decrease in craving during the first two weeks of treatment. No effects were found on cognitive functions. An exploratory analysis for crack cocaine use only revealed that relapse rates were significantly reduced after active tDCS (n = 17) as compared to sham (n = 19). Conclusions: No beneficial effects of tDCS on number of cocaine use days, craving and cognitive functions were found in the present study, but somewhat promising results were obtained regarding relapse rates among crackcocaine users specifically. Further research is required to determine the efficacy of tDCS as a complementary treatment in cocaine use disorde

Multi-session electrical neuromodulation effects on craving, relapse and cognitive functions in cocaine use disorder: A randomized, sham-controlled tDCS study

Background: The use of transcranial Direct Current Stimulation (tDCS) has previously shown promising results for reducing craving in cocaine use disorder. In this study we further explored the potential of tDCS as add-on intervention in the treatment of cocaine use disorder. Methods: In a randomized, placebo-controlled, between subject study, we applied tDCS bilaterally with the anodal electrode targeting the right dorsolateral prefrontal cortex (DLPFC; https://clinicaltrials.gov/ct2/show/NCT03025321). Patients with cocaine use disorder were allocated to ten sessions of either active tDCS (n = 29) or sham (n = 30) on five consecutive days. Inhibitory control and risky decision-making were measured via a Go-NoGo task and a two-choice gambling task, respectively, each at baseline, one day after all tDCS sessions and after three months. Relapse at follow-up and craving were also assessed. Results: There was no significant effect of active tDCS on the number of cocaine use days and craving. Relapse was frequent among patients who had received either active or sham tDCS (48.0 % and 69.2 %, respectively), despite an overall decrease in craving during the first two weeks of treatment. No effects were found on cognitive functions. An exploratory analysis for crack cocaine use only revealed that relapse rates were significantly reduced after active tDCS (n = 17) as compared to sham (n = 19). Conclusions: No beneficial effects of tDCS on number of cocaine use days, craving and cognitive functions were found in the present study, but somewhat promising results were obtained regarding relapse rates among crack-cocaine users specifically. Further research is required to determine the efficacy of tDCS as a complementary treatment in cocaine use disorder

Investigating the neural mechanisms of transcranial direct current stimulation effects on human cognition: current issues and potential solutions

Transcranial direct current stimulation (tDCS) has been studied extensively for its potential to enhance human cognitive functions in healthy individuals and to treat cognitive impairment in various clinical populations. However, little is known about how tDCS modulates the neural networks supporting cognition and the complex interplay with mediating factors that may explain the frequently observed variability of stimulation effects within and between studies. Moreover, research in this field has been characterized by substantial methodological variability, frequent lack of rigorous experimental control and small sample sizes, thereby limiting the generalizability of findings and translational potential of tDCS. The present manuscript aims to delineate how these important issues can be addressed within a neuroimaging context, to reveal the neural underpinnings, predictors and mediators of tDCS-induced behavioral modulation. We will focus on functional magnetic resonance imaging (fMRI), because it allows the investigation of tDCS effects with excellent spatial precision and sufficient temporal resolution across the entire brain. Moreover, high resolution structural imaging data can be acquired for precise localization of stimulation effects, verification of electrode positions on the scalp and realistic current modeling based on individual head and brain anatomy. However, the general principles outlined in this review will also be applicable to other imaging modalities. Following an introduction to the overall state-of-the-art in this field, we will discuss in more detail the underlying causes of variability in previous tDCS studies. Moreover, we will elaborate on design considerations for tDCS-fMRI studies, optimization of tDCS and imaging protocols and how to assure high-level experimental control. Two additional sections address the pressing need for more systematic investigation of tDCS effects across the healthy human lifespan and implications for tDCS studies in age-associated disease, and potential benefits of establishing large-scale, multidisciplinary consortia for more coordinated tDCS research in the future. We hope that this review will contribute to more coordinated, methodologically sound, transparent and reproducible research in this field. Ultimately, our aim is to facilitate a better understanding of the underlying mechanisms by which tDCS modulates human cognitive functions and more effective and individually tailored translational and clinical applications of this technique in the future

Polarity specific effects of cross-hemispheric tDCS coupled with approach-avoidance training on chocolate craving

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.This work was partially supported by Funded with National Funds through the Portuguese Foundation for Science and Technology (FCT) and co-funded through COMPETE 2020 - PO Competitividade e Internacionalizacao/Portugal 2020/Uniao Europeia, FEDER (Fundos Europeus Estruturais e de Investimento - FEEI) under the number: PTDC/PSI-ESP/30280/2017. SC was funded by the Portuguese Foundation for Science and Technology (FCT) with the Grant IF/00091/2015 and under FCT and COMPETE 2020 (PTDC/PSI-ESP/29701/2017). JL was funded also through FCT and COMPETE (P2020-PTDC/MHC-PCN/3950/2014) and from an internal grant from Portucalense University

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

Analysis of Resting-State fMRI Topological Graph Theory Properties in Methamphetamine Drug Users Applying Box-Counting Fractal Dimension

Introduction: Graph theoretical analysis of functional Magnetic Resonance Imaging (fMRI) data has provided new measures of mapping human brain in vivo. Of all methods to measure the functional connectivity between regions, Linear Correlation (LC) calculation of activity time series of the brain regions as a linear measure is considered the most ubiquitous one. The strength of the dependence obligatory for graph construction and analysis is consistently underestimated by LC, because not all the bivariate distributions, but only the marginals are Gaussian. In a number of studies, Mutual Information (MI) has been employed, as a similarity measure between each two time series of the brain regions, a pure nonlinear measure. Owing to the complex fractal organization of the brain indicating self-similarity, more information on the brain can be revealed by fMRI Fractal Dimension (FD) analysis. Methods: In the present paper, Box-Counting Fractal Dimension (BCFD) is introduced for graph theoretical analysis of fMRI data in 17 methamphetamine drug users and 18 normal controls. Then, BCFD performance was evaluated compared to those of LC and MI methods. Moreover, the global topological graph properties of the brain networks inclusive of global efficiency, clustering coefficient and characteristic path length in addict subjects were investigated too. Results: Compared to normal subjects by using statistical tests (P<0.05), topological graph properties were postulated to be disrupted significantly during the resting-state fMRI.&nbsp; Conclusion: Based on the results, analyzing the graph topological properties (representing the brain networks) based on BCFD is a more reliable method than LC and MI

Hepatitis C infection in hemodialysis patients in Iran: A systematic review

Hemodialysis (HD) patients are recognized as one of the high-risk groups for hepatitis C virus (HCV) infection. The prevalence of HCV infection varies widely between 5.5 and 24 among different Iranian populations. Preventive programs for reducing HCV infection prevalence in these patients require accurate information. In the present study, we estimated HCV infection prevalence in Iranian HD patients. In this systematic review, we collected all published and unpublished documents related to HCV infection prevalence in Iranian HD patients from April 2001 to March 2008. We selected descriptive/analytic cross-sectional studies/surveys that have sufficiently declared objectives, a proper sampling method with identical and valid measurement instruments for all study subjects, and proper analysis methods regarding sampling design and demographic adjustments. We used a meta-analysis method to calculate nationwide prevalence estimation. Eighteen studies from 12 provinces (consisting 49.02 of the Iranian total population) reported the prevalence of HCV infection in Iranian HD patients. The HCV infection prevalence in Iranian HD patients is 7.61 (95 confidence interval: 6.06-9.16) with the recombinant immunoblot assay method. Iran is among countries with low HCV infection prevalence in HD patients. © 2010 The Authors. Journal compilation © 2010 International Society for Hemodialysis

Noninvasive brain stimulation for addiction medicine: From monitoring to modulation

Addiction is a chronic relapsing brain disease with significant economical and medical burden on the societies but with limited effectiveness in the available treatment options. Better understanding of the chemical, neuronal, regional, and network alterations of the brain due to drug abuse can ultimately lead to tailoring individualized and more effective interventions. To this end, employing new assessment and intervention procedures seems crucial. Noninvasive brain stimulation (NIBS) techniques including transcranial electrical and magnetic stimulations (tES and TMS) have provided promising opportunities for the addiction medicine in two main domains: (1) providing new insights into neurochemical and neural circuit changes in the human brain cortex and (2) understanding the role of different brain regions by using NIBS and modulating cognitive functions, such as drug craving, risky decision making, inhibitory control and executive functions to obtain specific treatment outcomes. In spite of preliminary positive results, there are several open questions, which need to be addressed before routine clinical utilization of NIBS techniques in addiction to medicine, such as how to account for interindividual differences, define optimal cognitive and neural targets, optimize stimulation protocols, and integrate NIBS with other therapeutic methods. Therefore, in this chapter we revise the available literature on the use of NIBS (TMS and tES) in the diagnostic, prognostic, and therapeutic aspects of the addiction medicine.J.L. (SFRH/BPD/86027/2012) and S.C. (SFRH/BPD/86041/2012) are supported by grants from the Portuguese Foundation for Science and Technology (FCT) and European Union (FSE-POPH). H.E. is supported by grant from Iranian National Center for Addiction Studies (INCAS)