The Insula: A Brain Stimulation Target for the Treatment of Addiction

Abstract

Substance use disorders (SUDs) are a growing public health concern with only a limited number of approved treatments. However, even approved treatments are subject to limited efficacy with high long-term relapse rates. Current treatment approaches are typically a combination of pharmacotherapies and behavioral counselling. Growing evidence and technological advances suggest the potential of brain stimulation techniques for the treatment of SUDs. There are three main brain stimulation techniques that are outlined in this review: transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS). The insula, a region of the cerebral cortex, is known to be involved in critical aspects underlying SUDs, such as interoception, decision making, anxiety, pain perception, cognition, mood, threat recognition, and conscious urges. This review focuses on both the preclinical and clinical evidence demonstrating the role of the insula in addiction, thereby demonstrating its promise as a target for brain stimulation. Future research should evaluate the optimal parameters for brain stimulation of the insula, through the use of relevant biomarkers and clinical outcomes for SUDs.

After the Honeymoon: Neural and Genetic Correlates of Romantic Love in Newlywed Marriages

“…The human insula has also become a target for treatment in a variety of disorders such as substance abuse, depression, anxiety disorders, schizophrenia, and autism. Specifically, dopamine and opioid receptors in the insular cortex are thought to influence addiction (Ibrahim et al, 2019). Our findings highlight the role of attachment in sustained romantic love and are consistent with theories suggesting that romantic love is a "natural addiction" (Fischer et al, 2016).…”

Continuous High Frequency Deep Brain Stimulation of the Rat Anterior Insula Attenuates the Relapse Post Withdrawal and Strengthens the Extinction of Morphine Seeking

“…The insular cortex is a part of the cerebral cortex, and connects with addiction-related areas to form a wide range of addictive brain network, and plays an important role in the three stages of substance use disorder cycle ( 23 ). Through its projections to the pre-frontal cortex, the amygdala and the ventral striatal nodes of the corticostriatal circuitry, the anterior insula influences executive functions and reward-related behavior ( 50 ).…”

“…For example, morphine-induced conditioned place preference (CPP) in rats were attenuated in studies using administration of muscarinic acetylcholine receptor antagonists and nitric oxide inhibitors into insula ( 21 , 22 ). Previous work has also confirmed that insula is involved in the neurocircuitry underlying all stages of substance use disorder, and clearly suggested that insula is a fundamental brain region in the maintenance and relapse to addictive drugs ( 23 ).…”

Choosing the Optimal Brain Target for Neuromodulation Therapies as Alcohol Addiction Progresses—Insights From Pre-Clinical Studies

“…However, these effects are only temporary and generally do not prevent relapse. The insula has been suggested as a potential new brain stimulation target for treating addiction, including alcohol use disorder [100]. Recently, it was reported that repeated TMS treatment (5 days a week for 3 weeks) had no effect on alcohol drinking and relapse, as compared with sham treatment [86••].…”