Effect Of Transcranial Direct Current Stimulation On Relapse Of Alcohol

OBJECTIVE: Neuromodulatory interventions like transcranial direct current stimulation (tDCS) is an emerging and potential therapeutic strategy to help in reducing craving and relapse prevention in patients of alcohol dependence syndrome (1–4). The potential target for alcohol dependence is the dorsolateral pre-frontal cortex (dlPFC) as frontal dysfunction is a hallmark of alcoholism, even in alcohol dependence subjects with no major clinical and global cognitive deficits (5). In this context, this study was designed to explore the effect of tDCS treatment on craving and relapse prevention and its correlation to dorsolateral prefrontal cortex (DLPFC) activation in alcohol dependent patients. METHODOLOGY: This study was a double blinded randomized sham control trial, conducted at National Institute of Mental Health and Neurosciences, Bangalore after approval by the Institute Ethics Committee. Twenty-four patients of alcohol dependence syndrome were recruited after informed consent. After detoxification patients underwent baseline fMRI scans. Followed by tDCS with intensity of 2mA and duration of 20 minutes per day was administered for 5 consecutive days with cathode over left dorsolateral prefrontal cortex (DLPFC) and anode over right DLPFC. On the 5th day post fMRI scans were repeated. Both investigator and subjects remained blind throughout the study period. During scans patients were exposed to visual alcohol cues using VICE (visual image- Induced craving for ethanol) paradigm. Pre- treatment and post-treatment scans were analysed using SPM-12 software. RESULTS: At the beginning of the study, 24 subjects were selected but 2 subjects dropped out before post fMRI scan. The baseline comparison of socio-demographic and clinical variables found to have no differences among both groups. fMRI results: At baseline, the true and sham tDCS groups had comparable BOLD activation patterns and there were no between-group differences in activation pattern noted for alcohol vs. neutral cues contrast. Following 5 sessions of tDCS, there is significantly increased activation observed in true tDCS group, from Pre- to Post- treatment scans. Brain activity at DLPFC (Post-Pre) was positively associated with time to first alcohol lapse (p=0.048, Spearman’s rho =0.426). This suggests that greater the increase in brain activity at DLPFC after treatment with bilateral repetitive tDCS longer was the time to first lapse. [Image: see text] CONCLUSION: This study has shown bilateral repetitive transcranial direct current stimulation in alcohol dependent subjects, activates dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) along with increase in the connectivity strength between medial frontal gyrus (MFG) and sub cortical reward centre (NAc), which facilitated abstinence from alcohol. So from this study we better understood the mechanism of tDCS in preventing relapse to alcohol by activation of dorsolateral prefrontal cortex and anterior cingulated cortex. Though the fMRI results were statistically significant for relapse and DLPFC activation, but it would be difficult to establish the clinical significance of the improvement in craving in the background of small sample size. Hence further studies with larger sample size are required in near future. Referrences: 1. Klauss J, Penido Pinheiro LC, Silva Merlo BL, Correia Santos GDA, Fregni F, Nitsche MA, et al. A randomized controlled trial of targeted prefrontal cortex modulation with tDCS in patients with alcohol dependence. Int J Neuropsychopharmacol. 2014;17(11):1793–803. 2. Boggio PS, Sultani N, Fecteau S, Merabet L, Mecca T, Pascual-Leone A, et al. Prefrontal cortex modulation using transcranial DC stimulation reduces alcohol craving: A double-blind, sham-controlled study. Drug Alcohol Depend. 2008;92(1–3):55–60. 3. Nakamura-Palacios EM, Lopes IBC, Souza RA, Klauss J, Batista EK, Conti CL, et al. Ventral medial prefrontal cortex (vmPFC) as a target of the dorsolateral prefrontal modulation by transcranial direct current stimulation (tDCS) in drug addiction. J Neural Transm. 2016;123(10):1179–94. 4. da Silva MC, Conti CL, Klauss J, Alves LG, do Nascimento Cavalcante HM, Fregni F, et al. Behavioral effects of transcranial Direct Current Stimulation (tDCS) induced dorsolateral prefrontal cortex plasticity in alcohol dependence. J Physiol. 2013;107(6):493–502. 5. Nakamura-Palacios EM, Souza RSM, Zago-Gomes MP, de Melo AMF, Braga FS, Kubo TTA, et al. Gray Matter Volume in Left Rostral Middle Frontal and Left Cerebellar Cortices Predicts Frontal Executive Performance in Alcoholic Subjects. Alcohol Clin Exp Res [Internet]. 2014 Apr 1 ;38(4):1126–33. Available from: http://doi.wiley.com/10.1111/ acer.12308