Brain Functional Magnetic Resonance Imaging Cue-reactivity Can Predict Baclofen Response in Alcohol Use Disorders

Abstract

ObjectiveBaclofen is a promising treatment for alcohol use disorders (AUD), although its clinical response in humans is mixed. The present study aimed at investigating the impact of baclofen treatment on cue-induced brain activation pattern and its relationship with relapse outcomes.MethodsTwenty-three inpatients with AUD underwent a functional magnetic resonance imaging cue-reactivity task before beginning medication with baclofen and 2 weeks later. Twelve additional inpatients with AUD, who did not receive any anticraving medications, formed the control group. All subjects were prospectively followed up for 90 days post-discharge or until lapse to first alcohol use.ResultsWhole-brain linear mixed effects analysis revealed a significant group-by-time interaction with greater activation of the bilateral dorsolateral pre-frontal cortex and right anterior cingulate cortex (ACC) following baclofen treatment in comparison with the control group. Further, cox regression analysis revealed that increased activation of ACC and deactivation of insular cortex (IC) was associated with longer time to first alcohol use only in the baclofen treatment group but not in the control group.ConclusionThis study provides preliminary evidence for the neural predictors of baclofen treatment response in AUD. Baclofen treatment in AUD was associated with changes in cue-reactivity at critical brain regions within the incentive-salience network. Importantly, baclofen treatment-related specific activation of regions involved in cognitive control (ACC) and deactivation of regions involved in reward anticipation (IC) prolonged the time to first alcohol drink.

Baclofen-induced Changes in the Resting Brain Modulate Smoking Cue Reactivity: A Double-blind Placebo-controlled Functional Magnetic Resonance Imaging Study in Cigarette Smokers

“…In the present study, we seek to extend the findings of ourselves and others by determining whether baclofen-related changes in the resting brain are associated with SC-reactivity within cigarette smokers. Based on our previous findings and those of Holla et al [24], 2018 and Janes et al [12], 2010, described above, we hypothesized (1) that baclofen would increase CBF in the bilateral dlPFC and the ACC in the resting brain, and (2) that the increases observed in resting CBF would be associated with decreases in CBF during SC exposure in our a priori reward regions (i.e., ventromedial prefrontal cortex/medial orbitofrontal cortex [vmPFC/mOFC], VS, and avInsula) [9,11,12,24,29,30].…”

“…Baclofen increased activity of the anterior cingulate cortex (ACC) and bilateral dlPFC while decreasing responses in the ventral striatum (VS) and orbitofrontal and insular cortices. Responses in the ACC and insula predicted time to relapse [24]. Collectively, these studies suggest a common mechanism whereby baclofen blunts the neural response to drug cues, which could be a useful/necessary mechanism of blunting cue-induced craving in cue-vulnerable substance use disorder patients.…”

“…For hypothesis 1, that baclofen would increase CBF in cognitive control regions at rest, all participant's mean resting images were included in a full factorial analysis, to determine a group-by-timepoint interaction. Based on the literature, ROIs for examining the effects of baclofen on the resting brain were the ACC (−8, −14, 40) and right and left dlPFC (±51, 24, 33) [12,24,25].…”

“…For hypothesis 2, that the baclofen-induced increase in ROIs at rest would be associated with a decrease in the reward response during SC-exposure, we calculated a change value from the resting data (T2-T1) in the ROIs and entered them independently as covariates in the SC-model at T2, as previously described [26]. Based on the literature and our significant experience examining the brain substrates of SC-induced brain activity, ROIs included the VS, vmPFC, and avInsula [9,24,29,56,57].…”

“…One functional magnetic resonance imaging (fMRI) study showed that baclofen reduced reward-related neural responses to cocaine cues in abstinent, treatment-seeking cocaine participants, however baclofen-induced changes from baseline could not be determined from that study [23]. Another recent neuropharmacological study examined baclofen's effects on alcohol cue reactivity in abstinent alcohol use disorder (AUD) treatment-seeking patients relapse [24]. Authors examined cue reactivity prior to and after two weeks of medication.…”