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.

Keywords: Alcohol Use Disorder; Functional Magnetic Resonance Imaging; Medication Development; Pharmacotherapy; Treatment.

Figure 1:. Brain Circuits Implicated in AUD

Three domains implicated in AUD are displayed (purple = reward processing; green = negative emotionality; blue = inhibitory control). fMRI tasks used to probe these domains are listed below the domain and major brain regions targeted within these tasks are highlighted. Brain regions that are involved in multiple domains are listed in two-colors. Abbreviations: dlPFC = dorsolateral prefrontal cortex; vlPFC = ventrolateral prefrontal cortex; ACC = anterior cingulate cortex; OFC = orbitofrontal cortex; VS = ventral striatum

Figure 2:. PRISMA Flow Diagram

The Pubmed search identified 678 studies. Of these studies, 71 were initially screening, and 39 articles were assessed for eligibility. Thirty-two studies combining fMRI and AUD pharmacotherapy were included in this review, which were then further divided based on their pharmacological dosing regimen into 22 studies which employed a chronic dosing approach and 10 studies which employed an acute, single dosing approach

Figure 3:. Brain Circuits Modulated by AUD Pharmacotherapies Administered Chronically

The summarized findings of the review are presented for each pharmacotherapy that was investigated using a chronic dosing approach, ↓ = attenuated activation in targeted brain circuitry; ↑ = potentiated activation in targeted brain circuity; - = mixed findings in targeted brain circuitry (attenuation, potentiation, and/or null); ? = has not yet been investigated.

Figure 4:. Brain Circuits Modulated by AUD Pharmacotherapies Administered Acutely

The summarized findings of the review are presented for each pharmacotherapy that was investigated using a single dosing approach. ↓ = attenuated activation in targeted brain circuitry; ↑ = potentiated activation in targeted brain circuity; - = mixed findings in targeted brain circuitry (attenuation, potentiation, and/or null); ? = has not yet been investigated.