ENIGMA Addiction: Mega-Analysis Results of Alcohol Cue Reactivity

1815 

Abstract Submission 

Anthony Juliano¹, Devarshi Pancholi¹, Scott Mackey², Patrick Bach³, Anne Beck⁴, Anneke Goudriaan⁵, Markus Heilig⁶, Andreas Heinz⁷, Falk Kiefer⁸, Freek Linders⁹, Kirsten Morley¹⁰, Irene Perini¹¹, Haoye Tan¹², Ellen Towers¹⁰, Ruth van Holst¹³, Sabine Vollstädt-Klein⁸, Adam Yngve⁶, Anna Zilverstand¹⁴, Hamed Ekhtiari¹⁵, Hugh Garavan¹

¹University of Vermont, Burlington, VT, ²The University of Vermont, Burlington, VT, ³Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health (CIMH), Mannheim, Germany, ⁴Health and Medical University Potsdam, Potsdam, Brandenburg, ⁵Amsterdam Institute for Addiction Research, Amsterdam University Medical Center, Amsterdam, Nether, Amsterdam, Netherlands, ⁶Center for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping, Sweden, ⁷Department of Psychiatry and Psychotherapy, Charité – Universitätsmedizin Berlin, Berlin, Germany, ⁸Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, Mannheim, Germany, ⁹Amsterdam University Medical Center, Amsterdam, Netherlands, ¹⁰Clinical School, Sydney Medical School, University of Sydney, Sydney, New South Whales, ¹¹Linköping University, Linköping, Linköping, ¹²Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical, Mannheim, Germany, ¹³1Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands, ¹⁴University of Minnesota, Minneapolis, MN, ¹⁵Laureate Institute for Brain Research, Tulsa, OK

Anthony Juliano, PsyD  
University of Vermont
Burlington, VT

Devarshi Pancholi  
University of Vermont
Burlington, VT

Scott Mackey  
The University of Vermont
Burlington, VT

Patrick Bach  
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health (CIMH)
Mannheim, Germany

Anne Beck, Prof. Dr.  
Health and Medical University Potsdam
Potsdam, Brandenburg

Anneke Goudriaan  
Amsterdam Institute for Addiction Research, Amsterdam University Medical Center, Amsterdam, Nether
Amsterdam, Netherlands

Markus Heilig  
Center for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences
Linköping, Sweden

Andreas Heinz  
Department of Psychiatry and Psychotherapy, Charité – Universitätsmedizin Berlin
Berlin, Germany

Falk Kiefer  
Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health
Mannheim, Germany

Freek Linders  
Amsterdam University Medical Center
Amsterdam, Netherlands

Kirsten Morley  
Clinical School, Sydney Medical School, University of Sydney
Sydney, New South Whales

Irene Perini  
Linköping University
Linköping, Linköping

Haoye Tan  
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical
Mannheim, Germany

Ellen Towers  
Clinical School, Sydney Medical School, University of Sydney
Sydney, New South Whales

Ruth van Holst  
1Department of Psychiatry, Amsterdam UMC, University of Amsterdam
Amsterdam, Netherlands

Sabine Vollstädt-Klein  
Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health
Mannheim, Germany

Adam Yngve  
Center for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences
Linköping, Sweden

Anna Zilverstand  
University of Minnesota
Minneapolis, MN

Hamed Ekhtiari  
Laureate Institute for Brain Research
Tulsa, OK

Hugh Garavan  
University of Vermont
Burlington, VT

Alcohol use disorder (AUD) is associated with disruption of reward, salience, and cognitive control networks. In cue reactivity paradigms, viewing alcohol cues elicits activation in the anterior cingulate cortex [ACC; Schacht et al., 2013], a primary region of interest (ROI) within the salience network [Seeley, 2019] that is implicated in reward processing[Marsh et al., 2007; Liu, et al., 2011]. Previous work has shown increased effective connectivity [EC] between the ACC and the ventral striatum (VS) and anterior insula in abstinent versus non-abstinent AUD individuals and decreased EC with increased subjective craving ratings [Strosche et al., 2020]. Here, we explored task-based activation and EC patterns in individuals who were diagnosed with an AUD as part of the ENIGMA Addiction Cue Reactivity Initiative (ACRI).

Datasets from 5 sites were curated by the ENIGMA Addiction working group according to a standardized protocol. Participants included 237 adults ages 18-68 years who were diagnosed with an AUD. Task-based fMRI Alcohol Cue Reactivity data were preprocessed using fMRIPrep version 20.2.5, which is based on Nipype 1.6.1. This pipeline encompasses anatomical (intensity non-uniformity correction, skull stripping, brain tissue segmentation, surface reconstruction, and spatial normalization) and functional (boundary-based registration using six degrees of freedom, estimation of head motion parameters, slice time correction, and generation of confound variables) data workflows. The BOLD time-series was then resampled into MNI152 2mm^3 standard space. Preprocessed data were then parcellated using the Brainnetome atlas (246 ROIs) to extract the timeseries signal for the physiological regressors in bilateral rostral ACC (rACC). Signal cleaning was performed with FSL functions and included the following nuisance covariates: acompcor, tcompcor, cerebrospinal fluid, white matter, three translations/rotations motion parameters and their derivatives, as well as censoring high motion timepoints (standardized DVARS ≥ 1.5). Psychophysiological Interactions (PPI) were tested between the psychological and physiological regressors for the contrast of interest [Alcohol cue vs Neutral cue], in addition to age- and sex-related effects. A linear, mixed-effects model was used to test group-level differences using FSL's PALM. Corrections for multiple comparisons were performed using False Discovery Rate [p ≤ 0.05].

One sample t-tests of the Alcohol Cue vs. Neutral Cue contrast showed significant BOLD activity in the rostral ACC. For the right rACC, decreased EC was found in the left precuneus and superior temporal gyrus, while the left rACC exhibited decreased EC with the right superior frontal gyrus and right VS. Decreased EC was shown between the right rACC and bilateral central opercula and between the left rACC and the left supramarginal gyrus and right parietal operculum when comparing males and females in the sample. Age-related effects were also found in EC with older individuals showing greater EC with the left anterior insula and bilateral rACC regions.

AUD disrupts EC of the rACC, notably when assessing the interaction effects between sex or age. Altered EC between rACC and the left anterior insula between older and younger individuals with AUD holds promise for intervention. Pharmacological [Morley et al., 2021] and psychological [Ewing et al., 2011] interventions have have shown some promise in attenuating the activation of the anterior insula in individuals with AUD, though other interventions, such as repetitive transcranial magnetic stimulation have not [Perini et al., 2020]. Given the need for larger sample sizes to assess interaction effects between sex and a given clinical condition [Galea et al., 2020], as well as interventions more broadly, ENIGMA: Addiction is uniquely positioned to answer the ever-evolving and complex questions being asked of the neuroimaging and healthcare communities.

Reward and Punishment ²

Activation (eg. BOLD task-fMRI)

fMRI Connectivity and Network Modeling ¹

Addictions

FUNCTIONAL MRI