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The Use of Functional Magnetic Resonance Imaging to Test Pharmacotherapies for Alcohol Use Disorder: A Systematic Review.

ABSTRACT: Alcohol use disorder (AUD) is a chronic relapsing condition that represents a significant public health concern. Pharmacological treatment development for AUD is a top research priority, and many studies are being conducted to evaluate potential AUD treatments. Understanding the brain circuitry impacted by addiction is crucial for the development of efficacious pharmacological interventions. These neuroadaptations can be probed noninvasively using functional magnetic resonance neuroimaging (fMRI). fMRI may be an effective tool to identify biomarkers for AUD pharmacotherapies, evaluating changes associated with pharmacological treatment. Thus, the present qualitative review of the literature focuses on the role of fMRI as a tool for medication development for AUD. The aim of this review was to assemble research across a range of fMRI paradigms to study the effectiveness of pharmacological treatments of adult AUD. First, we present a qualitative review of fMRI AUD pharmacotherapy studies, differentiating studies based on their dosing regimen. Second, we provide recommendations for the field to improve the use of fMRI as a biomarker for AUD pharmacotherapy.

SUBMITTER: Grodin EN

PROVIDER: S-EPMC6779480 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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The Use of Functional Magnetic Resonance Imaging to Test Pharmacotherapies for Alcohol Use Disorder: A Systematic Review.

Grodin Erica N EN Ray Lara A LA

Alcoholism, clinical and experimental research 20190823 10

Alcohol use disorder (AUD) is a chronic relapsing condition that represents a significant public health concern. Pharmacological treatment development for AUD is a top research priority, and many studies are being conducted to evaluate potential AUD treatments. Understanding the brain circuitry impacted by addiction is crucial for the development of efficacious pharmacological interventions. These neuroadaptations can be probed noninvasively using functional magnetic resonance neuroimaging (fMRI ...[more]

PMID: 31386215

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Project description:Impaired cognitive-motivational functioning is present in many psychiatric disorders, including alcohol use disorder (AUD). Emotion regulation is a key intermediate factor, relating to the (cognitive) regulation of emotional and motivational states, such as in regulation of craving or negative emotions that may lead to relapse in alcohol use. These cognitive-motivational functions, including emotion regulation, are a target in cognitive behavioral therapy and may possibly be improved by neurostimulation techniques. The present between-subjects, single-blind study assesses the effects of sham-controlled high-frequency neuronavigated repetitive transcranial magnetic stimulation (10 Hz) of the right dorsolateral prefrontal cortex (dlPFC) on several aspects relevant for emotion regulation (emotion processing and reappraisal abilities) and related brain activity, as well as self-reported craving in a sample of alcohol use disorder patients (AUD; n = 39) and healthy controls (HC; n = 36). During the emotion reappraisal task, participants were instructed to either attend or reappraise their emotions related to the negative, positive, neutral, and alcohol-related images, after which they rated their experienced emotions. We found that repetitive transcranial magnetic stimulation (rTMS) reduces self-reported experienced emotions in response to positive and negative images in AUD patients, whereas experienced emotions were increased in response to neutral and positive images in HCs. In the functional magnetic resonance imaging (fMRI) analyses, we found that rTMS reduces right dlPFC activity during appraisal of affective images relative to sham stimulation only in AUD patients. We could not confirm our hypotheses regarding the effect of rTMS craving levels, or on reappraisal related brain function, since no significant effects of rTMS on craving or reappraisal related brain function were found. These findings imply that rTMS can reduce the emotional impact of images as reflected in blood oxygenation level-dependent (BOLD) response, especially in AUD patients. Future studies should replicate and expand the current study, for instance, by assessing the effect of multiple stimulation sessions on both explicit and implicit emotion regulation paradigms and craving, and assess the effect of rTMS within subgroups with specific addiction-relevant image preferences. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02557815.

Project description:ContextCurrent behavioral measures poorly predict treatment outcome in social anxiety disorder (SAD). To our knowledge, this is the first study to examine neuroimaging-based treatment prediction in SAD.ObjectiveTo measure brain activation in patients with SAD as a biomarker to predict subsequent response to cognitive behavioral therapy (CBT).DesignFunctional magnetic resonance imaging (fMRI) data were collected prior to CBT intervention. Changes in clinical status were regressed on brain responses and tested for selectivity for social stimuli.SettingPatients were treated with protocol-based CBT at anxiety disorder programs at Boston University or Massachusetts General Hospital and underwent neuroimaging data collection at Massachusetts Institute of Technology.PatientsThirty-nine medication-free patients meeting DSM-IV criteria for the generalized subtype of SAD.InterventionsBrain responses to angry vs neutral faces or emotional vs neutral scenes were examined with fMRI prior to initiation of CBT.Main outcome measuresWhole-brain regression analyses with differential fMRI responses for angry vs neutral faces and changes in Liebowitz Social Anxiety Scale score as the treatment outcome measure.ResultsPretreatment responses significantly predicted subsequent treatment outcome of patients selectively for social stimuli and particularly in regions of higher-order visual cortex. Combining the brain measures with information on clinical severity accounted for more than 40% of the variance in treatment response and substantially exceeded predictions based on clinical measures at baseline. Prediction success was unaffected by testing for potential confounding factors such as depression severity at baseline.ConclusionsThe results suggest that brain imaging can provide biomarkers that substantially improve predictions for the success of cognitive behavioral interventions and more generally suggest that such biomarkers may offer evidence-based, personalized medicine approaches for optimally selecting among treatment options for a patient.

Project description:The early abstinence period is a crucial phase in alcohol use disorder (AUD) in which patients have to find a new equilibrium and may start recovery, or conversely, relapse. However, the changes in brain functions during this key period are still largely unknown. We set out to study longitudinal changes in large-scale brain networks during the early abstinence period using resting-state scans. We scanned AUD patients twice in a well-controlled inpatient setting, with the first scan taking place shortly after admission and the second scan 4 weeks (±9 days) later near the end of the treatment period. We studied 37 AUD patients (22 males) and 27 healthy controls (16 males). We focused on three networks that are affected in AUD and underly core symptom dimensions in this disorder: the frontoparietal networks (left and right FPN) and default mode network (DMN). Both the whole brain and within network connectivity of these networks were studied using dual regression. Finally, we explored correlations between these brain networks and various neuropsychological and behavioral measures. In contrast to the controls (Z = -1.081, p = 0.280), the AUD patients showed a decrease in within left FPN connectivity (Z = -2.029, p = 0.042). However, these results did not survive a strict Bonferroni correction. The decrease in left FPN connectivity during the early abstinence period in AUD may reflect an initially upregulated FPN, which recovers to a lower resting-state connectivity level during subsequent weeks of abstinence. The AUD patients showed a trend for a positive association between the change in left FPN connectivity and trait anxiety (rs = 0.303, p = 0.068), and a trend for a negative association between the change in left FPN connectivity and delay discounting (rs = -0.283, p = 0.089) (uncorrected for multiple comparisons). This suggests that the FPN might be involved in top-down control of impulsivity and anxiety, which are important risk factors for relapse. Although there were no statistically significant results (after multiple comparison correction), our preliminary findings encourage further research into the dynamic neuroadaptations during the clinically crucial early abstinence period and could inform future study designs.

Dataset Information

The Use of Functional Magnetic Resonance Imaging to Test Pharmacotherapies for Alcohol Use Disorder: A Systematic Review.

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The Use of Functional Magnetic Resonance Imaging to Test Pharmacotherapies for Alcohol Use Disorder: A Systematic Review.

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