Regulation of addiction by the insular cortex: The interplay between interoception and cognitive function

The insular cortex (IC) functions as a pivotal core for interoception. Functional magnetic resonance imaging reveals how the IC integrates internal and external stimuli by observing its neural activation patterns. It facilitates interactions among sensory, emotional, and cognitive inputs via specific neural circuits. The finding that IC injury can reduce nicotine intake and the pioneering research on the involvement of the IC in addiction. Subsequently, human studies discovered that the IC amplifies drug-derived pleasure, strengthening the link between cravings and drug use, thus increasing compulsive drug-seeking behavior. During withdrawal, the IC processes negative emotions, prompting animals to increase drug intake to alleviate distress and other withdrawal symptoms, thus promoting continued drug abuse and relapse via negative reinforcement. Moreover, it participates in the consolidation/reconsolidation of drug memories, which may be linked to synaptic plasticity. The dysfunction of the IC leads to cognitive deficits, which influence decision-making and motivation and indirectly regulate drug-driven behaviors. Despite growing interest in the role of the IC in addiction, the precise mechanisms are still not fully understood. This article reviews the IC's role in addiction, highlighting its direct impact on behaviors like craving and drug-seeking via interoception and its influence on addiction memory. It also examines the IC's indirect effects on decision-making and motivation through cognitive functions in risk assessment and maintaining motivation. To advance addiction neurobiology research, future studies must explore the interaction between environmental factors and neural mechanisms in driving addiction. Including observable behaviors in research will facilitate the translation of findings into effective substance use disorder treatments.