Behavioral effects of transcranial Direct Current Stimulation (tDCS) induced dorsolateral prefrontal cortex plasticity in alcohol dependence

Highlights

• Treatments have failed to successfully manage drug addiction.

• Transcranial Direct Current Stimulation (tDCS) has been shown to reduce craving in drug addicts.

• Repeated anodal tDCS over the left DLPFC seems to improve executive functions in alcoholics.

• Repeated anodal tDCS over the left DLPFC reduced depressive symptoms and craving in alcoholics.

• However, repeated anodal tDCS induced greater readiness for relapsing to the use of alcohol.

Abstract

Transcranial Direct Current Stimulation (tDCS) has been shown to reduce acute substance craving in drug addicts, and improve cognition in neuropsychiatric patients. Here we aimed to explore further tDCS induced behavioral and neurophysiological modulation including assessment of relapse rate over a prolonged time course in alcoholism. We examined the effects of repeated anodal tDCS (2 mA, 35 cm², 20 min) over the left dorsolateral prefrontal cortex (DLPFC) on relapse to the use of alcohol in alcoholics from outpatient services, who received additional routine clinical treatment. Furthermore, event related potentials (ERPs), cognitive and frontal executive processes, craving, depressive and anxiety symptoms were obtained before and after treatment. From thirteen alcoholic subjects, seven were randomized to sham-tDCS and six to real tDCS treatment (once a week for five consecutive weeks). Depressive symptoms and craving were reduced to a larger extent in the tDCS group compared to the sham group (p = 0.005 and p = 0.015, respectively). On the other hand, active tDCS was able to block the increase in neural activation triggered by alcohol related and neutral cues in prefrontal cortex (PFC) as indexed by ERP as seen in the sham-tDCS group. Finally, there was a trend for increased change in executive function in the tDCS group compared to the sham-tDCS group (p = 0.082), and, similarly, a trend for more relapses in the tDCS group compared to sham tDCS (four alcoholic subjects (66.7%) vs. one (14.3%), p = 0.053).These results confirm the previous findings of tDCS effects on craving in alcoholism and also extend these findings as we showed also tDCS-related mood improvement. However, potential increase in relapse is possible; thus the clinical value of an increase in craving and improvement in depression and executive function needs to be carefully assessed in further studies; including investigation of optimal parameters of stimulation.

Introduction

Transcranial Direct Current Stimulation (tDCS) is a method of noninvasive brain stimulation that modulates neuronal resting membrane potentials, leading to changes of cortical excitability, and activity, which can outlast the stimulation for hours. Cathodal current decreases cortical excitability, and anodal current increases it (Nitsche et al., 2002, Nitsche and Paulus, 2000, Nitsche and Paulus, 2001, Wassermann and Grafman, 2005). Beyond its physiological effects, tDCS has been shown to have an impact on cognition and behavior (Nitsche et al., 2003a, Nitsche et al., 2003b, Nitsche et al., 2008). For patients suffering from neuropsychiatric diseases, the potential benefit of neuromodulation induced by tDCS has been increasingly investigated in depression (Bikson et al., 2008, Boggio et al., 2008a, Fregni et al., 2006a, Fregni et al., 2006b, Nitsche, 2002), substance abuse and craving including alcohol (Boggio et al., 2008b, Nakamura-Palacios et al., 2012), tobacco (Fregni et al., 2008a), marijuana (Boggio et al., 2010) and also foods disorders (Fregni et al., 2008b). In these studies, tDCS of the prefrontal cortex was demonstrated to reduce acute craving in substance abuse.

Although pharmacologic treatments with naltrexone, topiramate and acamprosate for alcohol dependence in primary care and specialty medical setting alone and in combination with brief or more extensive psychosocial therapies are available, these have often only modest or even controversial effects (Assanangkornchai and Srisurapanont, 2007, Miller et al., 2011). Thus, better or adjuvant approaches that may enhance or facilitate the treatment of alcohol dependence remain highly required.

Drug dependence is known to be associated with structural and functional damage of the prefrontal cortex (PFC) culminating in a general reduction of frontal activity (Fein et al., 2002, Franklin et al., 2002, Goldstein and Volkow, 2002). Moreover, the PFC is critically involved in craving for smoking (McBride et al., 2006, Wilson et al., 2004) and drugs such as alcohol (Tapert et al., 2003); opiates (Sell et al., 2000) and cocaine (Garavan et al., 2000, Grant et al., 1996). Specifically, craving is associated with enhanced activity of this cortical area during drug cue presentation. Since the PFC is related to executive functions and to the brain’s reward circuitry (Desposito et al., 1995, Fuster, 2000, Hyman et al., 2006), this imbalance of general and drug cue-related prefrontal activation indicates that the cognitive ability to regulate drug-seeking behavior is decreased in substance addicts. Reducing craving and improving cognitive functions constitute great challenges in the treatment of drug addiction and, unfortunately, pharmacological and non-pharmacological approaches have not fully addressed these issues so far.

The potential use of tDCS in the clinical treatment of drug addiction has not been studied yet systematically. Since excitability-enhancing anodal tDCS has been shown to improve numerous cognitive processes (Boggio et al., 2006, Dockery et al., 2009, Fertonani et al., 2010, Fiori et al., 2011, Fregni et al., 2005, Jeon and Han, 2012, Jo et al., 2009, Kuo and Nitsche, 2012, Marshall et al., 2004), and diminished cognitive control in drug addicts might be related to prefrontal hypo-activity, we hypothesized that anodal tDCS over the dorsolateral prefrontal cortex (DLPFC) would enhance executive function, providing improved cognitive control, and thus reduce the probability of relapse to drug use.

We investigated the effects of anodal tDCS applied repeatedly to the left dorsolateral prefrontal cortex (DLPFC) on relapse probability to the use of alcohol in addicted subjects from outpatient services in a randomized clinical trial. Event related potentials (ERPs), cognitive and frontal executive functions, and depressive and anxiety symptoms before and after the treatment were also examined.