Clinical trial NCT05843435: Brain Connectivity Between Networks Implied in Inhibition and Cue-reactivity in Alcohol Use Disorder
Official title: Brain Connectivity Between Networks Implied in Inhibition and Cue-reactivity in Alcohol Use Disorder
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Alcohol Use Disorder
Keywords: Inhibition, Psychology
Magnetic Resonance Imaging
Drinking Behavior
Lead sponsor: University of Bern
Sponsor class: OTHER
Collaborators: name: Clinic Suedhang
First posted: 2023-05-06
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: AUD patients are detoxified and will be recruited upon entry to specialized residential treatment program at the Clinic Südhang in Kirchlindach in Switzerland.

HC subjects will be recruited via advertisement in social media and local newspapers in the area of Bern in Switzerland.

Brief summary: Research about patients with alcohol use disorder has shown that task-related brain activation patterns as well as resting-state connectivity (measured with functional magnetic resonance imaging) change with clinical parameters such as the extent of craving and duration of abstinence during treatment. These brain activation alterations are related to treatment success. Although an imbalance between increased cue-reactivity and impaired counteracting inhibitory control processes are at the core of most neuropsychological conceptualizations of alcohol use disorder, the direct interaction between these two processes has not yet been investigated. Therefore, the investigators aim to study patients with alcohol use disorder in an ultra-high-field 7 Tesla magnetic resonance imaging scanner to identify fine-grained activation and connectivity patterns. The investigators would like to improve the knowledge of the interplay between the brain networks for inhibition and cue-reactivity, as well as to explore its influence on craving and treatment success. The investigators hypothesize that a more pronounced negative relationship between increased cue-reactivity and reduced inhibitory control processes in the brain is linked to higher craving and worse relapse probability.

Detailed description: Even if an imbalance between enhanced cue-reactivity and impaired opposing control processes is at the center of most neuroscientific conceptualizations of alcohol use disorder (AUD), these two processes are still rarely investigated in direct interaction.

Attempting to target both processes in one design, initial studies reported enhanced brain activation in anterior cingulate cortex (ACC) and ventrolateral prefrontal cortex (vlPFC), when control processes had to be carried out in the context of alcohol-related cues, and linked this altered brain activation to relapse risk. Hence, the proposed study will take advantage of the higher spatial resolution and signal-to-noise ratio of a 7 Tesla fMRI scanner to investigate more subtle effects and the involvement of subregions of vlPFC and ACC during alcohol-related inhibition.

Of special interest, particularly when it comes to explaining an imbalance between brain systems related to cue-reactivity and inhibitory control, are concurrent measures of functional brain connectivity. Aberrant resting-state functional connectivity in networks involved in reward prediction, motivation, salience attribution and executive control have been reported in AUD. Also, altered task-related connectivity was observed during cue-reactivity as well as during executive control. However, functional connectivity measures during a task combining both aspects are still missing. Therefore, this study examines the mutual interplay between cue-responsive regions and opposing inhibitory control networks. To this aim, task-related functional connectivity are measured in a specifically tailored experimental design allowing for the assessment of effects related to cue-reactivity, inhibition, as well as their interaction.

Besides, this study assesses whether possible interaction effects of task-related functional connectivity between cue-reactivity and inhibitory control vary with craving, change with prolonged abstinence or predicts drinking outcome.

Taken together, this study will deepen the understanding of the interplay between neuronal networks central to AUD, cue-reactivity and inhibitory control. The (im)balance between these processes is crucial for recently abstinent patients striving to control drinking habits and urges in an environment infused with alcohol-related cues. As such, markers capturing the interaction between these processes are of high conceptual and clinical relevance and might pave the way towards a potential biomarker indicating enhanced relapse risk.

Eligibility criteria: Inclusion Criteria:

* Abstained from alcohol for at least 4 weeks prior to fMRI measurement (AUD only)
* Diagnosis of AUD according to ICD-11 (AUD only)
* Written informed consent
* Mother tongue German (or Swiss German)
* Right-handedness
* AUDIT ≤ 7 (HC only)
* AUD-S \< 2 (HC only)
* BSCL GSI ≤ 63 (T-value, HC only)
* DUDIT \< 7 (HC only)

Exclusion Criteria:

* Other main psychiatric diagnosis than AUD (comorbidity allowed, but AUD has to be considered the main diagnosis, AUD only)
* Neurocognitive problems
* Current medical conditions excluding participation (e.g. acute infectious disease)
* Inability to understand the participant information
* Contraindication to Magnetic Resonance Imaging (e.g. metallic objects, pregnancy, claustrophobia)
* History of alcohol and other substance use disorder (HC only)
* Being staff or student of the project leader and other persons involved in the project

Primary outcomes:
measure: BOLD contrast alcohol vs. neutral inhibition
timeFrame: 3-4 weeks after study inclusion
measure: BOLD contrast covariance with craving
timeFrame: 3-4 weeks after study inclusion
Secondary outcomes:
measure: BOLD task-related connectivity
timeFrame: 3-4 weeks after study inclusion
measure: BOLD task-related connectivity covariance with craving and drinking outcome
timeFrame: 3 months after GNG-task in fMRI
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: University Hospital for Psychiatry and Psychotherapy Bern
Study officials:
affiliation: University Hospital for Psychiatry and Psychotherapy Bern
name: Matthias Grieder, PhD
role: PRINCIPAL_INVESTIGATOR
References: