Furthermore, ERPs to addiction-related stimuli may be useful as a predictor of abstinence success in recently detoxified patients. Alcohol use is among the most relevant risk factors contributing to disease-related death and disability-adjusted life years worldwide [ 1 ], with relapse prediction being a major issue in the treatment of alcohol use disorder [ 2 , 3 ].
Investigations of brain responses to addiction-related cues have emerged as a door to the assessment of relapse behavior; and the incentive salience theory [ 4 ] has been established as a major contribution providing a theoretical framework for research into cue reactivity.
A major suggestion of this theory is that not only is the drug associated with increased and persistent incentive salience, but that drug-related cues and even drug-related context signals elicit biased attention, trigger dopamine-related reward systems and may lead to active drug approach behavior, thus initiating relapse [ 5 ]. Studies on cue reactivity have measured altered peripheral physiological signals [ 6 ], evoked response potential ERP data derived from EEGs [ 7 , 8 ] and neuroimaging brain activation changes [ 9 ] to drug- related cues.
Carter and Tiffany , for example, analyzed more than 40 studies measuring cue- related changes in physiological signals [ 6 ]. With regard to ERP research, Littel et al. Patients with substance abuse disorders showed heightened P and slow wave amplitudes in reaction to drug-related stimuli [ 10 — 12 ]. These results are of importance since exaggerated ERP amplitudes to drug cues have been associated with relapse behavior.
For example, Petit and colleagues [ 12 ] recently found that P oddball task parameters in response to alcohol stimuli are related to successful 3-month abstinence in detoxified alcohol dependent patients. Expanding upon this more traditional approach to ERP research in alcohol use disorders, Maurage and colleagues established the assessment of occipital evoked potential components which allows the evaluation of early visual processing in research on alcohol use disorders [ 13 — 15 ]. The occipital positive P component indexes early visual processing, and its amplitude is more closely confined to the perceptual properties of the stimulus as compared to the negative N component, which has been widely studied with regard to face processing [ 16 , 17 ].
In a recent meta-analysis on studies assessing the N in the context of face processing, the authors not only found that this component is sensitive to emotional expressions, but also that the N was modulated in amplitude when the attention of subjects was directed to non-face-related visual target features [ 18 ].
In line with the research focus on the N component in face processing experiments, Maurage [ 14 ] assessed emotional face processing and reported prolonged P and N latencies, and lower N amplitudes, in recently detoxified alcohol-dependent patients. Early visual processing abnormalities with respect to face stimuli were replicated in alcohol dependent patients and in binge drinkers [ 13 , 21 ]. Although these studies targeted aspects of visual face processing in general, and not addiction-specific cue reactivity, they demonstrated that it is worthwhile to study occipital processing in experiments on stimulus processing in addicted individuals.
This is further supported by a recent study by Petit et al. Taken together, these studies support the idea that, with respect to the occipital P and N components, alcohol-related stimuli may be processed differently from non-alcohol-related stimuli, when they act as targets.
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Due to their probable specific significance for addicted patients, and in accordance with the results of Hinojosa et al. In the present study, we aimed to investigate the P and N components of early occipital visual processing in response to alcohol and non-alcohol-related pictures in recently detoxified alcohol dependent patients.
We applied a conventional oddball paradigm using a frequently presented non-alcohol-related and non-target stimulus tea in combination with non-alcohol orange juice and alcohol-related target stimuli beer, Go-condition. In a second part of the experiment, the tea stimulus acted as a target, and the same two less frequently presented stimuli acted as to-be-ignored non-target stimuli NoGo condition. Based on existing evidence, and given the specific significance of alcohol-related stimuli to alcohol-dependent patients, we expected heightened occipital P and N amplitudes in patients, but not controls, in response to drug-related stimuli, specifically when such stimuli act as targets, and perhaps even when attention is focused on non-drug stimuli.
Successful 3-month abstinence may be associated with lowered ERP amplitudes when taking into consideration the results of Petit et al. We assessed 30 patients with alcohol dependence and 31 control subjects. All subjects gave written informed consent before participation in the study. The study was approved by the ethics committee of the faculty of medicine of the University of Duisburg-Essen. Participating patients had recently successfully completed an inpatient detoxification treatment program in a specialized hospital ward for addictive disorders.
Symptoms of alcohol withdrawal were alleviated by temporary administration of clonazepam or clomethiazole, respectively, according to the German treatment guidelines regarding the detoxification of alcohol addicts [ 22 ]. Medication dosage was based on the monitoring of withdrawal intensity by a symptom checklist.
Exclusion criteria were use of psychotropic medication and sedatives e.
Exclusion criteria were present or past substance dependency apart from nicotine , major psychiatric disorders e. Controls received 40 Euros in exchange for their participation in the study. In order to verify inclusion and exclusion criteria, patients and controls were assessed using the structured interview for DSM-IV criteria, the Mini-International Neuropsychiatric Interview [ 23 ]. In order to assess additional symptom dimensions, all subjects completed the self-rating scales set forth in the Beck Depression Inventory [ 28 ] and the Barratt Impulsivity Scale [ 11 , 29 ].
Two patients received zopiclone the night before the assessment. Three months after the EEG assessment, patients were re-contacted in a telephone survey inquiring as to whether or not they continued to be abstinent. Interviews were conducted by a physician CMR known to the patients from their time at the hospital, and the occurrence of a relapse was determined based on the information given by the patients during the interview.
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A relapse was diagnosed when patients reported a return to alcohol consumption rates at or near the level of their pre-detoxification use. The telephone survey did not include additional physical or psychological investigations. The EEG assessments were conducted with subjects seated in a reclining chair in an electrically shielded room. Subjects with nicotine dependency were asked if they craved nicotine, and allowed to smoke following the first two runs in order to minimize the effects of acute nicotine deprivation on the EEG signals.
Subjects were presented with three stimuli which depicted either three freshly drawn glasses of beer, an ensemble of a mug and a glass of orange juice or a cup of tea with the tea bag just being withdrawn. All three stimuli were licensed from a provider of professional food images stockfood. Stimuli were selected from among a variety of images via a pre-study in which 20 alcohol dependent patients rated the images based on popularity and craving potential.
Among alcohol-related stimuli it turned out that beer scored the highest in popularity, followed by vodka and wine. Beer pictures which patients associated with brands from southern Germany scored low in popularity, and were therefore not taken into consideration. In selecting the neutral tea and juice stimuli it proved to be of relevance not to choose stimuli which patients may associate with alcoholic drinks. The selected pctures may be looked up and viewed by their reference numbers at stockfood.
In the NoGo condition, subjects had to press a button with their right index finger upon appearance of the frequent tea stimulus, and had to ignore the rare beer and orange juice stimuli. All stimuli were presented using Presentation software Neurobehavioral Systems Inc.
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Please ignore the beer and the juice pictures. This had to be done for six control subjects and three patients. EEG data were amplified using a 32 channel Neuroscan Synamps amplifier in the frequency range of 0. EEG data analysis was performed using Neuroscan Edit v4. The EEG data were screened for sequences containing complex artifacts i. Blink artifacts were corrected using the method described by Semlitsch [ 32 ], as implemented in Scan V. Single subject averages were computed separately for stimulus categories and conditions. Here we report data from electrodes O1 and O2.
Single subject average curves were analyzed for event-related components P and N amplitudes. Behavioral data were analyzed with regard to error percent data for each stimulus under both task conditions using t-statistics. Patients and controls did not differ with regard to age, gender, education or handedness. Mean breath alcohol concentration at hospitalization was 1. The mean number of previous inpatient detoxification treatments among patients was 4.
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On questionnaires and in interviews, patients scored higher than controls in terms of smoking, alcohol use, compulsive drinking and depression symptoms, but not in in terms of impulsivity as measured by the Barratt Impulsivity Scale. Relapse assessment was successfully achieved in 23 out of 30 patients. Eleven patients remained abstinent from alcohol and 12 patients relapsed within the 3-month evaluation period. With regard to the Go and NoGo conditions, the amount of errors was slightly larger for patients under both conditions. Differences between patients and controls, however, failed to reach the level of statistical significance under both conditions and all three stimuli.
ERP grand average curves for patients and controls are given in Fig. Details on analysis of variance and covariance results may be found in the Additional file 1. Grand averages of event-related responses in patients and controls to tea, orange juice and beer stimuli a in the Go and b the NoGo condition at occipital electrodes O1 and O2. Mean and standard errors of the N component amplitudes of event-related responses to tea, orange juice and beer stimuli in the Go and NoGo condition at occipital electrodes O1 and O2 for patients and controls a and for patients with and without 3-months relapse b.
P amplitudes were larger in the NoGo as compared to the Go condition. The juice stimulus showed lower amplitudes as compared to the tea and beer stimuli, regardless of condition and group. O1 electrode amplitudes were larger than O2 amplitudes for tea and beer but not for the juice stimuli. For P amplitudes we found no results involving the group factor. N amplitudes were larger i. The beer stimulus resulted in more negative amplitudes as compared to the tea and juice stimuli. Significant effects related to group were further examined under separate analyses for each task condition with two within factor stimulus type tea, juice, beer x between factor group patient, control MANOVAs for the Go and the NoGo condition.
Upon closer examination of the three-way interaction involving the group factor with these two MANOVA analyses conducted separately for the Go and the NoGo condition, the stimulus type x group interaction in the Go condition for the N component was not significant F 1. Therefore, the effect of heightened N amplitudes in response to the beer stimulus in the patients as compared to controls was attributable to the NoGo condition, where subjects had to react to the tea and ignore the juice and beer stimuli.
Since depression symptoms may act as a confounding variable, we conducted additional analyses of variance, replicating previous analyses which included Beck Depression Inventory scores as covariate.
No other effects were statistically significant. While P latencies may vary with different stimuli at the two occipital electrodes with depression scores, this effect is unrelated to alcohol addiction in our study. The main effect for stimulus type, however, was no longer significant.