P300 event-related potential in abstinent methamphetamine-dependent patients

Highlights

• The first ERP follow-up study on the processing of MA-related cues

• P300 data were obtained during the MA-Addiction Stroop Task.

• A relationship was found between changes of P300 and craving during abstinence.

• ERP may be a potential objective indicator of changes in MA craving.

Abstract

Background

Substance use and abuse are characterized by biases in the attentional processing of substance-related stimuli. There are no event related potential (ERP)-based studies of attentional bias for substance-related cues among methamphetamine (MA) dependent patients. The study aimed to measure changes in P300 event-related potentials elicited by MA-related words in MA-dependent individuals at baseline and after 3 and 6 months of abstinence, examining the relationship of ERP changes to craving.

Method

26 MA-dependent patients (14 male) newly enrolled in two compulsory treatment centers in China and 29 healthy controls (15 male) were included in this study. At baseline (2–3 weeks in treatment) and after 3 and 6 months of abstinence from MA use, we obtained ERP data during a Stroop color-matching task using MA-related and neutral words. Self-reported craving was measured by a Visual Analog Scale (VAS).

Findings

Increased P300 amplitudes elicited by MA-related words were observed over left-anterior electrode sites. Abnormal P300 amplitudes declined to the normal levels of healthy controls at the end of 3 months of abstinence, and the decrease was maintained up to the end of 6 months of abstinence. The behavioral data did not show similar changes. The positive relationship between the changes of VAS scores for MA craving and the changes of P300 amplitudes over left anterior electrode sites elicited by MA-related words within the first 3 months was significant.

Conclusion

These findings highlight the potential use of ERP as an objective index to track changes in subjective MA craving among abstinent MA-dependent patients.

Introduction

Amphetamine-type stimulant (ATS) drugs are the second most widely used illicit substances after cannabis [36]. Notably, abuse of methamphetamine (MA), the most common ATS, appears to be increasing rapidly. For example, 798,000 of the 2.098 million drug addicts registered by the national public security system in China are addicted to ATS drugs and other synthetic stimulants, a 35.9% increase compared with the end of 2011 [29]. However, research on the biological basis for MA use disorder is limited.

Drug craving can be considered as the primary characteristic of drug use disorders and the main reason for relapsing to drugs, but the standard method for assessing craving is self-rating measurement. Because self-report assessment is susceptible to subjective factors, improved psycho-physiological and behavioral assessments of craving for MA are crucial targets for diagnosis and evaluation of treatment efficacy for MA-dependent patients. Cue-induced craving has been systematically studied in laboratory settings using the cue reactivity paradigm, and exposure to MA-related cues in the laboratory can give researchers a chance to model how craving would result in continued drug-seeking behaviors and relapse [32]. However, there are a limited number of laboratory-based research studies on MA cue reactivity in human subjects.

A meta-analysis showed that attentional bias for substance-related cues and craving have a mutual excitatory relationship such that increases in one lead to increases in the other. For example, correlations between subjective craving and measures of attentional bias have been found among tobacco smokers [27], alcohol abusers [11], and other illegal drug users [4], [9]. A better understanding of the brain mechanisms and patterns of attentional bias for substance-related cues could contribute to the development of more effective diagnosis and methods of evaluating craving.

The Addiction Stroop, a modification of the classic Stroop procedure, is an objective assessment of attentional bias to salient drug-related stimuli [33]. The basic principle of the classic Stroop paradigm is that the color of words can be named faster and more accurately when the color and the meaning of the words are congruent [35]. Incongruent color–word conditions result in more errors and longer reaction time [24]. If incongruent word meaning interferes with color naming, then other words for example substance-related words might show a similar interference effect. In the Addiction Stroop procedure, substance-related words and “neutral” or contrast words are used as stimuli instead of color names, but the task remains the same. A meta-analytic review [6] of over 30 studies using some version of an Addiction Stroop task concluded that Addiction Stroop interference effects, including longer reaction time and higher error rate, are indicative of attentional bias for substance-related cues. This measure has been shown to correlate with drug craving, as well as to successfully distinguish dependent from recreational stimulant users and to help to predict outcomes in treatment-seeking individuals [33].

Event-related potentials (ERPs), which have been elicited using the Addiction Stroop tasks, usually have been used to study the attentional bias for substance-related stimuli and the brain mechanisms associated with craving. One advantage of ERP is its excellent temporal resolution in comparison with imaging techniques [23]. Moreover, the ERP device is easy to conduct and is inexpensive for regular use.

ERP measurements showed characteristic components associated with substance-related cues across different substances. Several ERP components, including P/N100, P300, and Slow Positive Wave (SPW) were thought to be influenced by attentional processes with substance-related cues. Among those components, the late positive ERP component, named P3 or P300, is the most studied and has been found consistently associated with attentional processes. More studies disclosed higher P300 amplitudes elicited by substance-related cues as compared with controls when drug-related cues were used; see for example, studies of smokers [38], [39]; alcohol users [17], [28]; heroin users [13]; cocaine users [12], [37]; and cannabis users [30]. It is generally believed that P300 reflects the mental processes underlying the deployment of attentional resources to task-relevant stimuli. However, we found limited research about effects on attentional bias for substance-related cues among individuals with MA dependence. Furthermore, follow-up studies are needed to examine how attentional bias for substance-related stimuli changes with time.

Numerous studies have used ERP technology in conjunction with the Addiction Stroop task among users of alcohol, nicotine, and cannabis. Researchers have found that there was a relationship between the ERP component elicited by substance-related cues and self-reported craving scores [5], [21], [28]. Confirming such a relationship among MA-dependent patients would indicate a feasible laboratory evaluation of attentional bias for MA-related stimuli, which would be useful as a neurophysiological indicator for the diagnosis and treatment of MA dependence.

With the goal of advancing the understanding of drug-related P300 potentials, which are hypothesized as a correlate of subjective craving in MA-dependent patients, we developed a Chinese language version of an Addiction Stroop task focusing on MA issues (“MA Addiction Stroop Task”) and we used high-density ERP techniques to compare patterns of attentional bias to substance-related word cues among MA-dependent patients in comparison with healthy subjects who had never used MA. We hypothesized that: (i) patients would show higher P300 amplitudes elicited by MA-related word cues in the MA Addiction Stroop Task, similar to results from most studies on other drugs and (ii) the trends of P300 amplitudes elicited by MA-related word cues would be associated with the patterns of self-reported subjective craving scores within 6 months of abstinence after detoxification.