Electrophysiology and Functional Magnetic Resonance Imaging of Cue Craving: Potential Biomarkers for Therapeutic Neuromodulation in Addiction.

A major goal for substance use disorder (SUD) treatment is the reduction of drug craving, which contributes to continued drug use and relapse. Pathological craving is thought to reflect dysfunction in neural networks, sparking a growing interest in modulating the mesocorticolimbic reward and related networks to decrease craving and improve outcomes. Although initial studies of neuromodulation in SUDs have produced promising results, biomarkers for craving remain elusive. Advances in deep brain stimulation (DBS) now allow recording of local field potentials (LFPs) in the nucleus accumbens (NAc), the central hub of the reward circuit, thus paving the way for a novel LFP biomarker for craving. Insights into mechanistic models of craving that relate localized electrophysiology to distributed circuit activity are in the earliest stages. At the same time, performing invasive DBS surgery on individuals with SUD is a formidable challenge and underscores the need to refine our understanding of noninvasive functional magnetic resonance imaging (fMRI)-defined network biomarkers of craving. Here, we review the literature on LFPs and single-unit neural activity during craving and reward, highlighting recent findings of craving-related NAc LFPs in humans. Next, we review fMRI studies of cue craving in the context of potential neuromodulation targets based on a triple network model. Third, we briefly review relationships between electrophysiology and fMRI in general. Lastly, we suggest future research directions that integrate neuromodulation, electrophysiological recording, and neuroimaging to improve our understanding of craving in SUD.