Elsevier

Brain and Cognition

Volume 138, February 2020, 105512
Brain and Cognition

Bifrontal tDCS applied to the dorsolateral prefrontal cortex in heavy drinkers: Influence on reward-triggered approach bias and alcohol consumption

https://doi.org/10.1016/j.bandc.2019.105512Get rights and content

Highlights

  • An association between reward-triggered approach and alcohol consumption in the sham condition.

  • Bifrontal tDCS applied to the DLPFC resulted in reduced reward-triggered approach.

  • Bifrontal tDCS applied to the DLPFC resulted in reduced alcohol consumption.

  • Bifrontal tDCS applied to the DLPFC did not influence self-reported craving.

  • No association between reward-triggered approach and alcohol consumption following tDCS.

Abstract

Even though the ventromedial neural network (reward pathway) has been well documented to be a mediator for increased craving, the prefrontal cortex is receiving ever more attention for craving monitoring. In the current study, we examined whether causal modulation of the prefrontal cortex, and its associated neural network, diminishes reward-triggered approach bias (due to increased cognitive control), alcohol craving and consumption. Using a double-blind within-subjects design in a subclinical group of forty-five heavy drinkers, a single sham controlled session of bilateral transcranial direct current stimulation (tDCS) was applied to the dorsolateral prefrontal cortex (DLPFC). Following real and sham tDCS placing the anode over the right and cathode over the left DLPFC, a rewarded Go/NoGo paradigm was administrated to provoke behavioral biases (irrespective of the task goal) After the cognitive paradigm, alcohol consumption was examined using a beer taste test. Bifrontal tDCS resulted in a reduced reward-triggered approach bias and reduced alcohol consumption, but not self-reported craving. Interestingly, reward-triggered approach bias and alcohol consumption were reliably associated in the sham condition, but not in the tDCS condition. Reward-trigged approach biases might be a cognitive mechanism associated with alcohol prone behavior, and the role of the prefrontal network may be significant.

Introduction

Alcohol is one of the most widely used, socially accepted, and relatively easily available drug worldwide. Nonetheless, 5.1% of the global burden of disease and injury is attributable to alcohol, which is especially the case in young adults (World Health Organization, factsheet 2018). Hence, there is an urgent need to develop more effective treatments that target vulnerability mechanisms in patients with alcohol use disorders (AUD) (Coles, Kozak, & George, 2018).

In recent years, our neurobiological knowledge of addiction has expanded. The ventromedial neural network, also referred to as the reward pathway, has been well documented to be a mediator for increased desire or urge to use a substance (i.e., craving) (Dunlop, Hanlon, & Downar, 2017). The core brain areas involved in this pathway are the nucleus accumbens (NAcc) in the ventral striatum, medial orbitofrontal cortex (mOFC), and ventromedial prefrontal cortex (vmPFC), with strong connections to the mesolimbic dopaminergic structures, i.e., the ventral tegmental area (VTA) and substantia nigra, as well as other nuclei in the ventral striatum (for a seminal review, see Goldstein & Volkow, 2011). As such, craving is associated with phasic dopamine (DA) neuronal firing in the VTA, resulting in large, and short-lasting DA increases in the NAcc. This dopamine release is believed to reflect the expectation of receiving a reward. Research in AUD has demonstrated that drug induced repetitive dopamine overstimulation of the projections from VTA to the prefrontal cortex, as well as from VTA to the ventral striatum (including the NAcc), results in increased salience (or value) associated with that drug (Chaarani et al., 2017). This mechanism of increased salience often also results in a loss of self-regulation or control. More specifically, due to the repetitive dopamine overstimulation within the reward pathway, patients with AUD do not only have increased levels of craving and goal-directed behavior for alcohol, but also generate less inhibitory signals to control over their drug seeking behavior (Goldstein and Volkow, 2011, Naish et al., 2018). The latter is – amongst other factors - based on reduced prefrontal activation, a neural region being part of the salience network that is considered the anti-network of the reward network (Dunlop, Hanlon, & Downar, 2017). Overall, addictive behavior is considered to be a consequence of an imbalance between (excessive) automatic/implicit pursuit of pleasure and (diminished) controlled monitoring through the inhibition of inappropriate responses (Lapenta, Marques, Rego, Comfort, & Boggio, 2018).

Most interestingly, this latter imbalance can be prompted during an inhibitory control paradigm containing reward. Inhibitory control, also known as response inhibition, refers to an individual’s ability to inhibit a habitual or dominant behavioral response in favor of a goal-appropriate response. Inhibitory control is usually measured with a Go/NoGo or Stop-Signal paradigm that requires participants to respond rapidly to specific frequently appearing stimuli, but to inhibit responses to other stimuli that are presented less often. This results in an inappropriate or disadvantageous response tendency (i.e., press on a NoGo trial), which can even be amplified to stimuli that are associated with a monetary reward. In other words, it has been shown that stimuli for which a monetary incentive can be obtained, induce behavioral tendencies in the form of action or approach biases (i.e., tendency to press), even when this response is not in line with the current task goal (i.e. in the case of NoGo trials) (e.g., Freeman, Razhas, & Aron, 2014; see also Guitart-Masip, Beierholm, Dolan et al., 2011). These reward triggered response biases have been observed in individuals that are susceptible to the use of addictive substances (e.g., Luijten, O’Connor, Rossiter, Franken, Hester, 2013). Moreover, alcohol has been associated with an overall bias to press during a Stop-Signal task, and authors have linked this to impaired inhibitory control (Fillmore & Vogel-Sprott, 2000). Impaired inhibitory control is commonly reported in individuals with addictive behaviors (Naish et al., 2018), and has been associated with impaired self-control to inhibit a salient response (Poulton, Mackenzie, Harrington, Borg, & Hester, 2016). Reward-related response inhibition, as measured with the Go/NoGo task, has been found to be associated with neural activity within the ventromedial network (VMN), but also to prefrontal neural activity that supports cognitive control (e.g., Dunlop et al., 2017). It has been suggested that the VMN (mediating craving and urge) and the salience network (SN; mediating response selection and inhibition) play opposing roles in the behavioral regulation of patients with AUD. Yet, the causal implication of the prefrontal cortex and its associated neural network underlying this reward triggered approach bias, especially in individuals vulnerable for AUD, has still to be determined.

The prefrontal cortex and its associated neural network can be modulated using non-invasive brain stimulation (NIBS), such as repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS). For example, bifrontal tDCS has been found to induce changes in ventromedial prefrontal cortex activation, via efferent projections to the NA and VTA, in patients with substance use disorders (e.g., Nakamura-Palacios, Lopes, & Souza, 2016). Moreover, bilateral tDCS or rTMS is generally been found to reduce craving or consumption of substance, even though this observation is not consistent across studies (Luigjes, Segrave, de Joode, Figee, & Denys, 2018). In the reduction of craving, meta-analysis data indicated a moderate effect of 0.476 (Hedge's g) for active versus sham neuromodulation of the dorsolateral prefrontal cortex (DLPFC) (Coles et al., 2018, Jansen et al., 2013). It should be noted that there is a lot of disparity in stimulation methods and addiction/craving outcome measures that warrant further research. Likewise, prior research revealed that excitatory stimulation of the DLPFC enhances working memory (Brunoni & Vanderhasselt, 2014), even though the effects on inhibitory control are mixed (Naish et al., 2018). In a study of recently detoxified alcohol-dependent individuals, Herremans, Vanderhasselt, De Raedt, and Baeken (2013) assessed the effects of active excitatory rTMS applied to the right DLPFC compared to sham stimulation on performance on a Go/NoGo task, and observed better performance following real stimulation (Herremans, Vanderhasselt, De Raedt, and Baeken, 2013). However to the authors’ best knowledge, it has never been investigated whether tDCS applied to the DLPFC can modulate reward triggered automatic response actions during an inhibitory control task, and whether the latter is associated with alcohol prone behavior, such as craving and alcohol consumption. These insights would shed light on the role of the prefrontal cortex on the imbalance between ‘automatic’ pursuit of pleasure and ‘controlled’ behavior through the inhibition of inappropriate responses in patients with AUD.

Hence, young heavy drinkers that did not fulfill the criteria for AUD were selected for the current study. It has been shown that heavy drinkers report increased craving (Heinz, Beck, & Grusser, 2009) and automatic approach when confronted with alcoholic drinks (Schoenmakers, Wiers, & Field, 2008), possibly associated with an overactive ventromedial reward system (Stuke et al., 2016). In the current study, the effects of sham-controlled bilateral tDCS (with anode placed over the right and cathode placed over the left DLPFC, Nakamura-Palacios et al., 2016) on reward-triggered biases and alcohol-related approach behavior were investigated. During tDCS, alcohol-cue exposure with visual and other sensory stimuli (olfactory, auditory, and taste) was performed. Following tDCS, participants completed a rewarded Go/NoGo task, and each session ended with a beer-tasting test with the aim to assess the level of alcohol consumption (Houben, Nederkoorn, Wiers, & Jansen, 2011). Firstly, based on the above-mentioned literature describing that the prefrontal cortex (as part of the salience network, implicated in control monitoring) is inversely associated to the ventromedial network (responsible for reward-triggered and alcohol-related approach behavior) (e.g., Dunlop et al., 2017), we expected active (as compared to sham) bilateral tDCS would 1) reduce reward-triggered approach tendencies and 2) reduce self-reported craving and alcohol consumption after being exposed to alcohol stimuli to induce craving. In addition, based on prior literature showing that modulation of individuals’ cognitive abilities in the context of alcohol- and food-related cues is associated with subsequent consumption in taste-and-rate tasks (e.g., Houben et al., 2011, Jones et al., 2011), we expected that more reward-triggered approach biases would be associated with more alcohol craving and consumption, and that bifrontal tDCS would modulate this association.

Section snippets

Participants

Participants were recruited via online platforms, and were recruited if they 1) had a score of 16 or higher on the Alcohol Use Disorders Identification Test, AUDIT, indicating severe alcohol related problematic behavior (Saunder et al. 2013, with at least a score ≥ 1 on questions two and three); 2) were Dutch speaking, right handed and between 18 and 30 years old; 3) had no present or history of psychopathology based on the Mini-international neuropsychiatric interview, MINI (Sheehan et al., 1998

Results

tDCS blinding seemed unsuccessful as the proportion of correct gauging of the stimulation session order (0.71) was higher than chance level (0.50), p = .01. However, there was no association between the correct gauging of the stimulation order and the dependent variables (see below), as logistic regressions with tDCS order gauging as dependent variable, showed no effect of the difference (active tDCS - sham) in beer consumption, B = -0.12, SE = 1.06, Wald = 0.01, p = .91, or the difference (active

Discussion

The aim of the present study was to evaluate the effects of bilateral tDCS applied to the DLPFC (anode right DLPFC and cathode left DLPFC) on reward-triggered behavioral tendencies, as well as alcohol-related craving and behavior in heavy drinkers. As hypothesized, results of the rewarded Go/NoGo task (over both neuromodulation conditions) demonstrated a reward-triggered approach bias, meaning that participants were more prone to press during trials during which a monetary reward could be

Author contribution

MAV, JA, and SH were responsible for the study concept and design. JA contributed to the acquisition of data. JA performed the analysis. MAV, CB, RDR, RMK assisted with data analysis and interpretation of findings. MAV drafted the manuscript. CB, RDR, RMK provided critical revision of the manuscript for important intellectual content. All authors critically reviewed content and approved final version for publication. The authors thank Philippe Ciers and Lien Ruysschaert for their help in

Funding

This study was supported by Grant BOFSTA2017002501 for research at Ghent University (awarded to MAV), Grant BOF16/GOA/017 for a Concerted Research Action of Ghent University (awarded to RDR and CB) and by a starting grant of the European Research Council (ERC) under the Horizon 2020 framework (grant No. 636116 awarded to RMK).

CRediT authorship contribution statement

Marie-Anne Vanderhasselt: Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Writing - original draft. Jens Allaert: Data curation, Formal analysis, Investigation, Methodology, Software, Visualization, Writing - review & editing. Rudi De Raedt: Conceptualization, Funding acquisition, Writing - review & editing. Chris Baeken: Resources, Software, Supervision, Writing - review & editing. Ruth M. Krebs:

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

References (32)

  • N.D. Volkow et al.

    The Brain on Drugs: From Reward to Addiction

    Cell

    (2015)
  • B.S. Chaarani et al.

    The neural basis of response inhibition and substance abuse

  • A.S. Coles et al.

    A review of brain stimulation methods to treat substance use disorders

    American Journal on Addictions

    (2018)
  • K. Dunlop et al.

    Noninvasive brain stimulation treatments for addiction and major depression

    Annals of the New York Academy of Sciences

    (2017)
  • R.Z. Goldstein et al.

    Dysfunction of the prefrontal cortex in addiction: Neuroimaging findings and clinical implications

    Nature Reviews Neuroscience

    (2011)
  • M. Guitart-Masip et al.

    Vigor in the face of fluctuating rates of reward: An experimental examination

    Journal of Cognitive Neuroscience

    (2011)
  • Cited by (0)

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