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P.6.a.002 Cue-induced activation in alcohol-dependent patients pre and post treatment with and without cue-exposure based training
S520
P.6.a Addiction – Alcohol (clinical)
P.6.a.002 Cue-induced activation in alcohol-dependent patients pre and post treatment with and without cue-exposure based training S. Vollst¨adt-Klein1 , S. L¨ober1 , R. Stadelmann1 , C. von der Goltz1 , K. Mann1 , F. Kiefer1 ° . 1 Central Institute of Mental Health, Dept. of Addictive Behavior & Addiction Medicine, Mannheim, Germany Purpose of the study: Cue-exposure based extinction training of conditioned drug-related responses has been advocated as potentially effective treatment of addiction, based on the importance of classical and instrumental conditioning in the development and maintenance of addictive disorders, e.g. [1]. Using functional magnetic resonance imaging (fMRI) techniques exposure to alcohol related visual cues to alcohol dependent volunteers results in a cue-induced activation of regions tightly associated with mesolimbic dopaminergic pathways, e.g. [2]. Therefore fMRI cue-reactivity could be a potential measure of therapy outcome of cue-exposure based extinction training. In an own study we already found an association between fMRI cue-reactivity and therapy outcome during standard clinical treatment: the magnitude of the neural response in reward-related areas predicted the amount of alcohol intake during a three-month follow-up period [3]. Methods: In an ongoing study we used functional magnetic resonance imaging (fMRI) to measure the effects of cue-exposure based intervention on cue-reactivity and the processing of alcoholrelated cues in abstinent alcohol-dependent patients. Day clinic patients with alcohol-dependence were treated with cue exposure based extinction training (3 weeks, 3 sessions per week). fMRI cue reactivity was measured pre and post treatment. Control subjects who were also day clinic patients but did not take part in the extinction training also underwent these 2 fMRI measurements. Subjects’ first fMRI session took place during an early stage of abstinence during the first three weeks after detoxification. The fMRI paradigm consisted of 30 stimulation blocks alternating with a fixation condition. Alcohol-associated visual stimuli were drawn from an own picture series with alcoholic beverages, separated into blocks with beer, wine and spirits. Neutral pictures from the International Affective Picture System IAPS were selected as neutral control stimuli. Images were presented via MR compatible goggles. After each block presentation the volunteers assessed their subjective craving on a visual analogue scale (VAS) using MR compatible response pads. The total duration of the experiment was 18 minutes. Scanning was performed with a 3 T whole-body tomograph (MAGNETOM Trio with TIM technology; Siemens, Erlangen, Germany). T2* weighted echo-planar images were acquired covering the whole brain. In addition a T1-weighted 3D MPRAGE dataset was acquired. Data were analyzed with SPM5. Group analyses were done by including individual contrast images (alcohol vs. neutral cues) of all subjects in second-level random effects analyses. Results: In accordance with previous studies we found cueinduced fMRI activation of limbic, reward-related and attentionassociated areas in a preliminary alcohol-dependent patient group of our ongoing study. These activations were decreased post treatment but still prominent. Conclusions: During the phase of early alcohol abstinence cueinduced fMRI activation seems to decrease. Conclusions about the effect of cue-exposure based extinction training can be made with increasing sample size at the date of the poster presentation.
References [1] Drummond, D.C., Cooper, T., & Glautier, S.P., 1990 Conditioned learning in alcohol dependence: Implications for cue exposure treatment. British Journal of Addiction, 85, 725–743. [2] Myrick, H., Anton R.F., Li X., Henderson S., Drobes D., Voronin K., George MS, 2004 Differential brain activity in alcoholics and social drinkers to alcohol cues: relationship to craving. Neuropsychopharmacology, 29, 393–402. [3] Gr¨usser, S.M., Wrase, J., Klein, S., Hermann, D., Smolka, M.N., Ruf, M., Weber-Fahr, W., Flor, H., Mann, K., Braus, D.F., Heinz, A., 2004 Cue-induced activation of the striatum and medial prefrontal cortex is associated with subsequent relapse in abstinent alcoholics. Psychopharmacology (Berl), 175, 296–302.
P.6.a.003 Is attentional bias a good measure of incentive properties of alcohol-associated stimuli in alcohol-dependent patients? S. Loeber1 ° , S. Vollstaedt-Klein1 , C. von der Goltz1 , K. Mann1 , F. Kiefer1 . 1 Central Institute of Mental Health, Department of Addictive Behavior and Addiction Medicine, Mannheim, Germany Purpose of the study: Within the treatment of alcohol dependence the combination of psychotherapeutic and pharamacological interventions is a promising new line of reseach. According to the theory of incentive sensitization, stimuli previously associated with substance consumption acquire incentive properties, are able to capture attention (attentional bias) and trigger relapse in alcohol dependent patients. Thus, treatments aiming at the extinction of conditioned reactions, i.e. cue exposure treatment, are of special importance. In the treatment of anxiety disorders, some studies demonstrated that the application of D-Cycloserine (50 mg) prior to cue exposure training is associated with better treatment outcome (e.g., 1). At present, we are investigating the effects of such a combined treatment approach in the case of alcohol dependence and are evaluating the attentional bias to alcohol associated cues as a measure of treatment effects. Thus, the objective of the present study was to investigate, whether different presentation times of the alcohol-associated pictures have an impact of attentional bias, and whether the duration of abstinence prior to the measurement of attentional bias influences the results. Methods: Alcohol-dependent patients according to DSM-IV criteria (N = 30) were recruited from an inpatient detoxification treatment facility. Attentional bias to alcohol-associated cues was assessed with the dot-probe task using two different presentation times of the stimuli (i.e., 500 ms vs. 50 ms). The dot-probe task measures the reaction time to a dot which either replaces an alcohol associated stimuli or a neutral one. Testing was performed after cessation of medically supervised detoxification and patients were free of any psychopharmacological agents for at least 5 days. Results: Our results show that when alcohol-associated and neutral picture pairs are presented for 500 ms, alcohol-dependent patients show an avoidance of alcohol-associated stimuli as indicated by a longer reaction time when the dot replaces alcoholassociated stimuli in contrast to neutral ones. In contrast, when pictures were presented for only 50 ms, we found an attentional bias to the alcohol-associated stimuli in recently abstinent patients, but not in patients who had no relapse without further treatment for at least 4 weeks Conclusions: These results suggest that when pictures are presented for longer time durations, processes of active avoidance are influencing the attentional bias of patients in treatment for their dependence as previously reported [2]. In contrast, shorter presentation times allow the assessment of unconscious incentive
P.6.a Addiction – Alcohol (clinical)
P.6.a.002 Cue-induced activation in alcohol-dependent patients pre and post treatment with and without cue-exposure based training S. Vollst¨adt-Klein1 , S. L¨ober1 , R. Stadelmann1 , C. von der Goltz1 , K. Mann1 , F. Kiefer1 ° . 1 Central Institute of Mental Health, Dept. of Addictive Behavior & Addiction Medicine, Mannheim, Germany Purpose of the study: Cue-exposure based extinction training of conditioned drug-related responses has been advocated as potentially effective treatment of addiction, based on the importance of classical and instrumental conditioning in the development and maintenance of addictive disorders, e.g. [1]. Using functional magnetic resonance imaging (fMRI) techniques exposure to alcohol related visual cues to alcohol dependent volunteers results in a cue-induced activation of regions tightly associated with mesolimbic dopaminergic pathways, e.g. [2]. Therefore fMRI cue-reactivity could be a potential measure of therapy outcome of cue-exposure based extinction training. In an own study we already found an association between fMRI cue-reactivity and therapy outcome during standard clinical treatment: the magnitude of the neural response in reward-related areas predicted the amount of alcohol intake during a three-month follow-up period [3]. Methods: In an ongoing study we used functional magnetic resonance imaging (fMRI) to measure the effects of cue-exposure based intervention on cue-reactivity and the processing of alcoholrelated cues in abstinent alcohol-dependent patients. Day clinic patients with alcohol-dependence were treated with cue exposure based extinction training (3 weeks, 3 sessions per week). fMRI cue reactivity was measured pre and post treatment. Control subjects who were also day clinic patients but did not take part in the extinction training also underwent these 2 fMRI measurements. Subjects’ first fMRI session took place during an early stage of abstinence during the first three weeks after detoxification. The fMRI paradigm consisted of 30 stimulation blocks alternating with a fixation condition. Alcohol-associated visual stimuli were drawn from an own picture series with alcoholic beverages, separated into blocks with beer, wine and spirits. Neutral pictures from the International Affective Picture System IAPS were selected as neutral control stimuli. Images were presented via MR compatible goggles. After each block presentation the volunteers assessed their subjective craving on a visual analogue scale (VAS) using MR compatible response pads. The total duration of the experiment was 18 minutes. Scanning was performed with a 3 T whole-body tomograph (MAGNETOM Trio with TIM technology; Siemens, Erlangen, Germany). T2* weighted echo-planar images were acquired covering the whole brain. In addition a T1-weighted 3D MPRAGE dataset was acquired. Data were analyzed with SPM5. Group analyses were done by including individual contrast images (alcohol vs. neutral cues) of all subjects in second-level random effects analyses. Results: In accordance with previous studies we found cueinduced fMRI activation of limbic, reward-related and attentionassociated areas in a preliminary alcohol-dependent patient group of our ongoing study. These activations were decreased post treatment but still prominent. Conclusions: During the phase of early alcohol abstinence cueinduced fMRI activation seems to decrease. Conclusions about the effect of cue-exposure based extinction training can be made with increasing sample size at the date of the poster presentation.
References [1] Drummond, D.C., Cooper, T., & Glautier, S.P., 1990 Conditioned learning in alcohol dependence: Implications for cue exposure treatment. British Journal of Addiction, 85, 725–743. [2] Myrick, H., Anton R.F., Li X., Henderson S., Drobes D., Voronin K., George MS, 2004 Differential brain activity in alcoholics and social drinkers to alcohol cues: relationship to craving. Neuropsychopharmacology, 29, 393–402. [3] Gr¨usser, S.M., Wrase, J., Klein, S., Hermann, D., Smolka, M.N., Ruf, M., Weber-Fahr, W., Flor, H., Mann, K., Braus, D.F., Heinz, A., 2004 Cue-induced activation of the striatum and medial prefrontal cortex is associated with subsequent relapse in abstinent alcoholics. Psychopharmacology (Berl), 175, 296–302.
P.6.a.003 Is attentional bias a good measure of incentive properties of alcohol-associated stimuli in alcohol-dependent patients? S. Loeber1 ° , S. Vollstaedt-Klein1 , C. von der Goltz1 , K. Mann1 , F. Kiefer1 . 1 Central Institute of Mental Health, Department of Addictive Behavior and Addiction Medicine, Mannheim, Germany Purpose of the study: Within the treatment of alcohol dependence the combination of psychotherapeutic and pharamacological interventions is a promising new line of reseach. According to the theory of incentive sensitization, stimuli previously associated with substance consumption acquire incentive properties, are able to capture attention (attentional bias) and trigger relapse in alcohol dependent patients. Thus, treatments aiming at the extinction of conditioned reactions, i.e. cue exposure treatment, are of special importance. In the treatment of anxiety disorders, some studies demonstrated that the application of D-Cycloserine (50 mg) prior to cue exposure training is associated with better treatment outcome (e.g., 1). At present, we are investigating the effects of such a combined treatment approach in the case of alcohol dependence and are evaluating the attentional bias to alcohol associated cues as a measure of treatment effects. Thus, the objective of the present study was to investigate, whether different presentation times of the alcohol-associated pictures have an impact of attentional bias, and whether the duration of abstinence prior to the measurement of attentional bias influences the results. Methods: Alcohol-dependent patients according to DSM-IV criteria (N = 30) were recruited from an inpatient detoxification treatment facility. Attentional bias to alcohol-associated cues was assessed with the dot-probe task using two different presentation times of the stimuli (i.e., 500 ms vs. 50 ms). The dot-probe task measures the reaction time to a dot which either replaces an alcohol associated stimuli or a neutral one. Testing was performed after cessation of medically supervised detoxification and patients were free of any psychopharmacological agents for at least 5 days. Results: Our results show that when alcohol-associated and neutral picture pairs are presented for 500 ms, alcohol-dependent patients show an avoidance of alcohol-associated stimuli as indicated by a longer reaction time when the dot replaces alcoholassociated stimuli in contrast to neutral ones. In contrast, when pictures were presented for only 50 ms, we found an attentional bias to the alcohol-associated stimuli in recently abstinent patients, but not in patients who had no relapse without further treatment for at least 4 weeks Conclusions: These results suggest that when pictures are presented for longer time durations, processes of active avoidance are influencing the attentional bias of patients in treatment for their dependence as previously reported [2]. In contrast, shorter presentation times allow the assessment of unconscious incentive