Neuroimaging Biomarkers in Addiction.

As a neurobiological process, addiction involves pathological patterns of engagement with substances and a range of behaviors with a chronic and relapsing course. Neuroimaging technologies assess brain activity, structure, physiology, and metabolism at scales ranging from neurotransmitter receptors to large-scale brain networks, providing unique windows into the core neural processes implicated in substance use disorders. Identified aberrations in the neural substrates of reward and salience processing, response inhibition, interoception, and executive functions with neuroimaging can inform the development of pharmacological, neuromodulatory, and psychotherapeutic interventions to modulate the disordered neurobiology. Based on our systematic search, 409 protocols registered on ClinicalTrials.gov include the use of one or more neuroimaging paradigms as an outcome measure in addiction, with the majority (N=268) employing functional magnetic resonance imaging (fMRI), followed by positron emission tomography (PET) (N=71), electroencephalography (EEG) (N=50), structural magnetic resonance imaging (MRI) (N=35) and magnetic resonance spectroscopy (MRS) (N=35). Furthermore, in a PubMed systematic review, we identified 61 meta-analyses including 30 fMRI, 22 structural MRI, 8 EEG, 7 PET, and 3 MRS meta-analyses suggesting potential biomarkers in addictions. These studies can facilitate the development of a range of biomarkers that may prove useful in the arsenal of addiction treatments in the coming years. There is evidence that these markers of large-scale brain structure and activity may indicate vulnerability or separate disease subtypes, predict response to treatment, or provide objective measures of treatment response or recovery. Neuroimaging biomarkers can also suggest novel targets for interventions. Closed or open loop interventions can integrate these biomarkers with neuromodulation in real-time or offline to personalize stimulation parameters and deliver the precise intervention. This review provides an overview of neuroimaging modalities in addiction, potential neuroimaging biomarkers, and their physiologic and clinical relevance. Future directions and challenges in bringing these putative biomarkers from the bench to the bedside are also discussed.