Right Inferior Frontal Activation During Alcohol-Specific Inhibition Increases With Craving and Predicts Drinking Outcome in Alcohol Use Disorder

Alcohol use disorder (AUD) is characterized by enhanced cue-reactivity and the opposing control processes being insufficient. The ability to inhibit reactions to alcohol-related cues, alcohol-specific inhibition, is thus crucial to AUD; and trainings strengthening this ability might increase treatment outcome. The present study investigated whether neurophysiological correlates of alcohol-specific inhibition (I) vary with craving, (II) predict drinking outcome in AUD and (III) are modulated by alcohol-specific inhibition training. A total of 45 recently abstinent patients with AUD and 25 controls participated in this study. All participants underwent functional magnetic resonance imaging (fMRI) during a Go-NoGo task with alcohol-related as well as neutral conditions. Patients with AUD additionally participated in a double-blind RCT, where they were randomized to either an alcohol-specific inhibition training or an active control condition (non-specific inhibition training). After the training, patients participated in a second fMRI measurement where the Go-NoGo task was repeated. Percentage of days abstinent was assessed as drinking outcome 3 months after discharge from residential treatment. Whole brain analyses indicated that in the right inferior frontal gyrus (rIFG), activation related to alcohol-specific inhibition varied with craving and predicted drinking outcome at 3-months follow-up. This neurophysiological correlate of alcohol-specific inhibition was however not modulated by the training version. Our results suggest that enhanced rIFG activation during alcohol-specific (compared to neutral) inhibition (I) is needed to inhibit responses when craving is high and (II) fosters sustained abstinence in patients with AUD. As alcoholspecific rIFG activation was not affected by the training, future research might investigate whether potential training effects on neurophysiology are better detectable with other methodological approaches

Alcohol-Specific Computerized Interventions to Alter Cognitive Biases: A Systematic Review of Effects on Experimental Tasks, Drinking Behavior, and Neuronal Activation

Background: In patients with alcohol use disorder, novel interventions to increase abstinence have attracted growing attention. Interventions aimed at modifying cognitive biases linked to alcohol use [i.e. cognitive bias modification (CBM)] may serve as an add-on to standard therapy. This systematic review thoroughly aggregates existing data on the effects of three alcohol-specific computerized interventions, namely attentional bias modification (AtBM), approach bias modification (ApBM), and inhibition training (IT). In doing so, each CBM’s effects on experimental tasks assessing the relevant biases, drinking behavior, and neurophysiology are summarized. Also, the influence of drinking behavior severity and motivation to change drinking behavior are discussed. Methods: A literature search was conducted in four databases for original research articles published between 2000 and May 2019. Studies were eligible if investigating the effects of alcohol-specific computerized interventions (AtBM, ApBM, IT) on drinking behavior, bias change, and/or neurophysiology. Forty eligible articles were classified as being either a non-clinical experimental lab study (ELS) or clinical randomized-controlled trial (RCT) and summarized. Results: While AtBM seems to influence attentional bias, its effects on drinking behavior are inconsistent. As for ApBM, the best effects on drinking behavior are obtained in clinical samples. Effects of ApBM on approach bias are mixed. Interestingly, those clinical RCTs which investigated ApBM effects on bias change as well as on drinking outcome, reported consistent effects in both measures (i.e. either effects on bias and drinking or no effects). Studies on IT are limited to non-clinical samples and show inconsistent effects on drinking behavior. Considering ITs effects on implicit semantic associations, most studies do not support the conceptualization of IT as a form of memory bias modification, while reports on IT’s effects on inhibitory control are still incomplete. Conclusions about the overall influence of drinking behavior severity are hampered by the non-uniform use of sample descriptions. Conclusions: In clinical samples, ApBM has shown more consistent beneficial effects, while evidence on AtBM is more inconsistent, and data on IT still lacks important information. Conclusions about the influence of drinking behavior severity would be facilitated by a uniform use of clearly defined sample descriptions

Therapeutic relationship and concordance of client- and clinician-rated motivational goals in treatment of people with psychosis: an exploratory study

Addressing motives determining behavior and experiences of people in treatment for psychosis could improve the therapeutic relationship. This pilot study explored the association between the concordance of clients’ and clinicians’ ratings of clients’ motivational goals and the therapeutic relationship in the treatment of psychosis. Twenty in- and outpatients diagnosed with a psychotic disorder in a general psychiatric setting answered measures addressing motivational goals and the therapeutic relationship. Fifteen clinicians rated their clients’ motivational goals and psychopathology. The concordance between clients’ and clinicians’ ratings of approach goals was not associated with clients’ ratings of the therapeutic relationship. However, a higher concordance in avoidance goals ratings was significantly correlated with less satisfaction with the therapeutic relationship. This finding might be understood in light of explicit (i.e. conscious) and implicit (i.e. non-conscious) avoidance goals: The more difficulties clinicians had in recognizing their clients’ implicit goals, the more they may have only rated and considered the clients’ explicit goals. This could have resulted in both a higher concordance rating between clients and clinicians, and less client satisfaction with the therapeutic relationship (because of unintended threats for implicit avoidance goals). Future studies with larger samples are needed that separately examine explicit and implicit motivational goals of people in treatment for psychosis

The role of the orbitofrontal cortex and the nucleus accumbens for craving in alcohol use disorder.

This study aimed to investigate structural and functional alterations of the reward system and the neurobiology of craving in alcohol use disorder (AUD). We hypothesized reduced volume of the nucleus accumbens (NAcc), reduced structural connectivity of the segment of the supero-lateral medial forebrain bundle connecting the orbitofrontal cortex (OFC) with the NAcc (OFC-NAcc), and reduced resting-state OFC-NAcc functional connectivity (FC). Furthermore, we hypothesized that craving is related to an increase of OFC-NAcc FC. Thirty-nine recently abstinent patients with AUD and 18 healthy controls (HC) underwent structural (T1w-MP2RAGE, diffusion-weighted imaging (DWI)) and functional (resting-state fMRI) MRI-scans. Gray matter volume of the NAcc, white matter microstructure (fractional anisotropy (FA)) and macrostructure (tract length) of the OFC-NAcc connection and OFC-NAcc FC were compared between AUD and HC using a mixed model MANCOVA controlling for age and gender. Craving was assessed using the thoughts subscale of the obsessive-compulsive drinking scale (OCDS) scale and was correlated with OFC-NAcc FC. There was a significant main effect of group. Results were driven by a volume reduction of bilateral NAcc, reduced FA in the left hemisphere, and reduced tract length of bilateral OFC-NAcc connections in AUD patients. OFC-NAcc FC did not differ between groups. Craving was associated with increased bilateral OFC-NAcc FC. In conclusion, reduced volume of the NAcc and reduced FA and tract length of the OFC-NAcc network suggest structural alterations of the reward network in AUD. Increased OFC-NAcc FC is associated with craving in AUD, and may contribute to situational alcohol-seeking behavior in AUD

Neurophysiologie von impliziten Alkoholassoziationen bei Personen mit Alkoholkonsumstörungen

Hintergrund Die erhöhte automatische Anreizwirkung auf Alkoholreize ist bedeutend für die Entstehung und Aufrechterhaltung von Alkoholkonsumstörungen (AUD). Implizite Alkoholassoziationen sind ein Indikator dieser Anreizwirkung. Laut behavioralen Studien weisen sowohl Gesunde als auch Patient_innen mit AUD negative implizite Alkoholassoziationen auf, Patient_innen haben aber einen schwächeren negativen Bias. Studien zur Neurophysiologie bei Patient_innen mit einer AUD im Vergleich zu Gesunden ergänzen und erweitern bisherige Reaktionszeitanalysen. Methoden Die Hirnströme von 63 Patient_innen mit AUD und 21 Gesunden werden während der Durchführung eines Impliziten Assoziationstests (IAT) mit einem 64-Kanal-EEG abgeleitet. Darauf werden ereignisbezogene Potentiale (Alkohol-positiv und Alkohol-negativ) berechnet. Mittels Microstates werden quasi-stabile topografische Zustände von 0-1000ms nach Stimulus identifiziert. Innerhalb dieser wird analysiert, ob sich Patient_innen und Gesunde in der Verarbeitung positiver und negativer Alkoholzuordnungen unterscheiden. Ergebnisse/Diskussion Laut ersten Analysen weisen Patient_innen und Gesunde um 400ms nach Stimulus unterschiedliche Microstates mit divergenten zugrundeliegenden Netzwerken auf. Bei Patient_innen zeigen sich beim Vergleich der Alkohol-positiven mit den Alkohol-negativen ERPs eine signifikante Differenz in der Amplitude (meanGFP, p=0.002) sowie Trends in Dauer und Schwerpunkt. Gesunde unterscheiden sich nicht signifikant hinsichtlich der Alkohol-Valenz-Bedingung. Schlussfolgerung Anders als bei Gesunden wird bei Patient_innen in der Verarbeitung positiver Alkoholassoziationen rund 400ms nach Stimulus mehr Gehirnaktivität benötigt als bei negativen Zuordnungen. Bisherige Forschung verband höhere Amplituden in diesem Zeitfenster (N400) mit Mehraufwand in der semantischen Verarbeitung. So könnte bei Patient_innen während der Verarbeitung positiver Alkoholassoziationen höhere semantische Inkongruenz vorliegen

Relevante Variablen für den Effekt eines computergesteuerten Inhibitionstrainings bei PatientInnen mit einer Alkoholkonsumstörung

Hintergrund Alkoholabhängigkeit stellt eine der häufigsten psychiatrischen Erkrankungen unserer Gesellschaft dar. Aktuelle Konzepte der Krankheit gehen von einem Ungleichgewicht zwischen einer erhöhten Anreizwirkung gegenüber alkoholspezifischen Reizen und einer verminderten Inhibitionskontrolle aus. Computergestützte Trainingsinterventionen können solche maladaptiven Inhibitionsprozesse verändern und letztendlich das Trinkverhalten reduzieren. Dies wurde jedoch bisher nur bei Personen mit hohem Alkoholkonsum, nie aber in klinischen Populationen untersucht. Möglicherweise hängen gewisse Variablen mit der Inhibitionskontrolle und/oder dem Trainingseffekt zusammen. Ziel Ein Hauptziel der Studie ist es zu untersuchen, ob das Inhibitionstraining zu einer erhöhten Inhibitionskontrolle und längerfristig weniger Rückfällen bei alkoholabhängigen PatientInnen führt. Um die Ausgangslage vor dem Training umfassend zu beschreiben, konzentriert sich die gegenwärtige Analyse auf Variablen, die möglicherweise mit der Inhibitionskontrollleistung zusammenhängen, wie beispielsweise Schweregrad der Abhängigkeit. Ziel ist zu eruieren, auf welche Eigenschaften von PatientInnen bei der Implementierung eines Inhibitionstrainings besonders geachtet werden sollte. Methode In dieser randomisiert-kontrollierten, doppelblinden Studie absolvieren alkoholabhängige PatientInnen entweder sechs Sitzungen eines computergesteuerten alkoholspezifischen Inhibitionstrainings mit dem Ziel, die alkoholspezifische Inhibitionskontrolle zu erhöhen, oder eine Kontrollbedingung. Zu Beginn der Studie werden eine Reihe von Fragebögen sowie Interviews durchgeführt. Vor und nach dem Inhibitionstraining wird die Inhibitionskontrolle anhand der Fehlerquote (Errors of Commission: EoC) in einen Go-NoGo-Task gemessen. Resultate Die Anzahl EoC vor dem Inhibitionstraining korreliert negativ mit dem Bildungsniveau (r = -0,305, p <0,01) und der Motivation, weniger zu trinken (r = -0,341, p <0,01). Eine Regressionsanalyse zeigt, dass 17,4% der Varianz vorausgesagt werden kann (R2 = 0,174, F = 8,001, df = 76, p <0,01). Weder Alter noch verschiedene Masse des Schweregrads (z.B. Anzahl DSM 5-Kriterien, Alkoholkonsum der letzten 3 Monate) korrelierten signifikant mit der Inhibitionskontrolle vor dem Inhibitionstraining . Schlussfolgerung Teilnehmer mit weniger Bildung und weniger Motivation, ihr Trinkverhalten zu ändern, zeigen weniger Inhibitionskontrolle vor dem Training. Dies könnte bedeuten, dass motivationale Interventionen zusätzlich zu einem potentiell gewinnbringenden Inhibitionstraining von Vorteil sein könnten. Entgegengesetzt der auf Literatur basierenden Annahmen, hängt der Schweregrad nicht mit der Inhibitionskontrollleistung vor dem Training zusammen. Weitere Berechnungen werden zeigen, ob der Schweregrad als Kovariate bei der Analyse der Trainingseffekte von Relevanz ist. Bei zukünftigen Analysen unserer Studie, in welchen wir Effekte des Inhibitionstrainings betrachten werden, sollen potentielle mediierende oder moderierende Einflüsse u.a. der genannten Variablen auf den Trainingseffekt berücksichtigt werden

Gender Effects in Inhibition in Patients with Alcohol Use Disorder: Preliminary Results

Background • Current neuroscientific theories postulate deficits in inhibition as a significant factor in the development and maintenance of alcohol use disorders (AUD). • Preclinical behavioral studies indicate that deficits in contextunspecific inhibition are more pronounced in women than in men. • Neurophysiological findings show alterations in the N2- and P3-components (EEG) in AUD patients. • Only one preclinical EEG-study investigated gender effects. No neurophysiological effects were observed. • Studies investigating gender effects in (alcohol-specific) inhibition in clinical samples are missing. Methods A total of 31 abstinent inpatients with AUD, attending a specialized treatment program (Clinic Südhang or Forel Clinic) were measured with a 64-channel EEG. All subjects completed a Go-NoGo Task (with 75/25 ratio) to assess inhibition in alcohol-related (alcoholic beverages) and neutral context (mineral water). After preprocessing (i.e. artefact removal), all data was re-referenced to average reference and four ERPs were obtained for each subject over all correct trials using BrainVision Analyzer: Alcohol-related (alcNoGo) and neutral NoGo (neuNoGo) as well as alcohol-related (alcGo) and neutral Go (neuGo). Finally, the ERPs were filtered (1-20Hz, 50Hz notch). All further analyses were performed with Ragu. After identifying data outliers (n=1), the time windows for N2- and P3 components were defined using microstates. They were defined according to the minimal onset and maximal offset times of the identified microstates in the four ERPs: N2a (150-220ms), N2b (220-330ms) and P3 (330-550ms). Furthermore, differences in map topography and map strength were examined in these microstates: First, a 2x2x2 TANOVA (not normalized) with the between-factor gender (male, female) and the within-factors response-type (Go, NoGo) and stimulus-type (alcohol, neutral) was performed for the time windows of the N2- and P3 microstates to test for interactions. Second, GFP analyses were performed for the same interactions. Descriptives Men and women did not differ regarding age, education (years) and severity of AUD (number of DSM-5 criteria / standard drinks (SD) in the last 90 days before detoxification). Results The TANOVA the with the factors gender, response- and stimulus-type in the time windows (N2a, N2b, P3) showed the following results: 1) For N2a and N2b, no significant interactions were found. 2) A significant gender by stimulus-type interaction occurred in the P3 microstate (p=0.01): Women showed an extended fronto-parietal positivity compared to men, which seems to be more extended towards the back during processing of neutral compared to alcohol-related stimuli. Corresponding to this, differences (alcohol vs. neutral stimuli ) for men did not vary significantly (p=0.44), whereas the maps for women showed a significant difference (p=0.02). GFP analyses with the same factors in the same microstates showed: 1) In N2a and P3 no significant interactions. 2) For the N2b microstate, a trend to a significant threefold interaction was found (p=0.06): Women had higher GFP in neutral NoGos than men. Discussion This study examines neurophysiological gender effects of (context-specific) inhibition in AUD patients for the first time. Preliminary GFP-analyses revealed a trend for the threefold interaction with the factors gender, response- and stimulus-type in late N2. This indicates that female patients have a higher N2b in NoGos, a difference that is even more enhanced in neutral NoGos. As the N2 component reflects the monitoring of a response conflict, females thus tend to have a greater conflict in neutral inhibition. Thus, inhibition (of neutral stimuli) could be more difficult for women than for men as it was shown in behavioral studies. During P3 microstate, women differed between alcohol-related and neutral stimuli whereas men did not. Further, analyses are needed to elaborate the underlying processes in inhibition. Especially the comparison of the (full) patient sample to healthy controls, the inclusion of other inhibition-tasks (SST) and the analyses of errors of commissions (EOC) will help to understand the gender-specific effects in patients with AUD

Neurophysiological correlates of alcohol-specific inhibition in alcohol use disorder and its association with craving and relapse

Objective: This study investigates neurophysiological correlates of general and alcohol-specific inhibitory control in patients with Alcohol Use Disorder (AUD), focusing on its association with individual craving levels and with relapse at three-month follow-up. Methods: 59 abstinent AUD patients and 20 healthy controls performed a Go/NoGo task incorporating alcohol-related and neutral stimuli during 64-channel electroencephalography (EEG) recording, yielding four event-related potentials (ERP) per participant (NoGo-Alcohol, Go-Alcohol, NoGo-Neutral, Go-Neutral). Whole-scalp randomization-based statistics assessed effects of the factors group (patients/controls or relapsers/abstainers), craving level, response type (NoGo/Go) and picture type (alcohol/neutral) on topography and signal strength of the ERP components N2 and P3. Results: No differences on group level were observed between patients and controls. However, analyses incorporating individual craving indicated that the topographic difference between alcohol-related and neutral NoGo-N2 components increased with craving. Moreover, topographic differences in the alcohol-related and neutral NoGo-P3 component allowed for differentiation between relapsers and abstainers. Conclusions: In alcohol-related contexts, the response inhibition conflict reflected in the NoGo-N2 seems enhanced in patients with high craving. The inhibition-sensitive NoGo-P3 varies in relapsers but not in abstainers between neutral and alcohol-related contexts. Significance: In AUD patients, neurophysiological correlates of inhibition vary with alcohol-related contexts and craving, and might be indicative of relapse ris

Inhibitionstraining für Patienten mit einer Alkoholkonsumstörung (INTRA)

Hintergrund Behandlungen für Alkoholkonsumstörungen sind im Wesentlichen auf explizite Erlebens- und Verhaltensprozesse ausgerichtet. Jüngste Studien zeigen, dass Trainingsverfahren, die bei impliziten Prozessen ansetzen, die Rückfallhäufigkeit zusätzlich zu verringern scheinen. Methoden Das Projekt untersucht in einer randomisiert kontrollierten Doppelblindstudie die Wirkung eines computergestützten Inhibitionstrainings zusätzlich zur stationären Standardbehandlung von Patienten mit Alkoholkonsumstörungen. Dabei üben die Patienten, ihre Reaktionen auf alkoholbezogene Reize zu inhibieren. In den beiden Experimentalgruppen wird alkoholspezifische Inhibition, in der Kontrollgruppe unspezifische Inhibition trainiert. Untersucht wird die Häufigkeit und Intensität des Alkoholkonsums vor, während und nach der Standardbehandlung. Indem die Tageszeit des Trainings variiert wird, wird zudem die mediierende Wirkung körpereigenen Cortisols auf den Lerneffekt gemessen. Bei einem Teil der Teilnehmenden wird vor und nach dem Training zusätzlich eine EEG-Messung durchgeführt. Ergebnisse Von den angestrebten 246 Patienten wurden in zwei Suchtkliniken bis dato 82 rekrutiert. Die Patienten absolvieren vier Erhebungen sowie sechs Trainings während der stationären Therapie und werden 3, 6 und 12 Monate nach Austritt nachbefragt. Schlussfolgerung Die Datenerhebung wird voraussichtlich im Frühjahr 2018 abgeschlossen und die Präsentation erster Ergebnisse ist für nächsten SGPP Kongress geplant

Effects of computerized inhibition training on inhibitory control in patients attending residential treatments for severe alcohol use disorders: a multicenter, randomized controlled trial

Objectives: Alcohol use disorders (AUD) represent one of the most frequent and significant psychiatric disorders in developed countries. Patients suffering from AUD show enhanced cue reactivity towards alcohol associated stimuli and deficits in inhibition to control alcohol use behavior. Recent evidence has shown that computerized training interventions may be able to alter some of these maladaptive processes and eventually reduce drinking behavior in heavy drinkers. However, this has not yet been examined in clinical populations in sufficient detail to implement it as an additional intervention in standard treatment. Methods: In an ongoing randomized control trial in two Swiss clinics specialized in the treatment of AUD, patients attending inpatient treatment complete six sessions of a computerized alcohol-specific inhibition training. This inhibition training aims to increase inhibitory control (experimental group), while the control version consists of an unspecific training (one control group). At pre- and post-training, a Go-NoGo task measures inhibitory control. Rate of commission errors (failure to inhibit the response to NoGo targets, i.e. “false alarms”) will be compared between the two groups and the two time points with a 2x2 AN(C)OVA with repeated measures. Because slower reaction times might indicate prospective inhibition, an additional analysis including reaction times for Go stimuli as a covariate will be performed. Results/Conclusion: Preliminary results of a sample size of approximately 60 will be presented and discussed. Compared to the control condition, we expect inhibition training to have a significant positive effect on inhibitory control, reflected by fewer commission errors. The results may contribute to the understanding of the mechanism of action at work during inhibition training and elucidate its potential as a therapeutic add-on