The insula in nicotine use disorder: Functional neuroimaging and implications for neuromodulation.

Insula dysfunction contributes to nicotine use disorders. Yet, much remains unknown about how insular functions promote nicotine use. We review current models of brain networks in smoking and propose an extension to those models that emphasizes the role of the insula in craving. During acute withdrawal, the insula provides the sensation of craving to the cerebrum and is thought to negotiate craving sensations with cognitive control to guide behavior - either to smoke or abstain. Recent studies have shown that insula processing is saturable, such that different insular functions compete for limited resources. We propose that this saturability explains how craving during withdrawal can overload insular processing to the exclusion of other functions, such as saliency and network homeostasis. A novel signal flow model illustrates how limited insular capacity leads to breakdown of normal function. Finally, we discuss suitability of insula as a neuromodulation target to promote cessation. Given the limited efficacy of standard-of-care treatments for nicotine use disorder, insular neuromodulation offers an innovative, potentially therapeutic target for improving smoking cessation.