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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.

SUBMITTER: Ibrahim C

PROVIDER: S-EPMC6614510 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Ibrahim Christine C Rubin-Kahana Dafna S DS Pushparaj Abhiram A Musiol Martin M Blumberger Daniel M DM Daskalakis Zafiris J ZJ Zangen Abraham A Le Foll Bernard B

Frontiers in pharmacology 20190702

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 ...[more]

PMID: 31312138

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Project description:BackgroundUntil now, the treatment of patients with autism spectrum disorder (ASD) remain a difficult problem. The insula is involved in empathy and sensorimotor integration, which are often impaired in individuals with ASD. Deep brain stimulation, modulating neuronal activity in specific brain circuits, has recently been considered as a promising intervention for neuropsychiatric disorders. Valproic acid (VPA) is a potential teratogenic agent, and prenatal exposure can cause autism-like symptoms including repetitive behaviors and defective sociability. Herein, we investigated the effects of continuous high-frequency deep brain stimulation in the anterior insula of rats exposed to VPA and explored cognitive functions, behavior, and molecular proteins connected to autism spectrum disorder.MethodsVPA-exposed offspring were bilaterally implanted with electrodes in the anterior insula (Day 0) with a recovery period of 1 week. (Day 0-7). High-frequency deep brain stimulation was applied from days 11 to 29. Three behavioral tests, including three-chamber social interaction test, were performed on days 7, 13, 18, 25 and 36, and several rats were used for analysis of immediate early genes and proteomic after deep brain stimulation intervention. Meanwhile, animals were subjected to a 20 day spatial learning and cognitive rigidity test using IntelliCage on day 11.ResultsDeep brain stimulation improved the sociability and social novelty preference at day 18 prior to those at day 13, and the improvement has reached the upper limit compared to day 25. As for repetitive/stereotypic-like behavior, self- grooming time were reduced at day 18 and reached the upper limit, and the numbers of burried marbles were reduced at day 13 prior to those at day 18 and day 25. The improvements of sociability and social novelty preference were persistent after the stimulation had ceased. Spatial learning ability and cognitive rigidity were unaffected. We identified 35 proteins in the anterior insula, some of which were intimately linked to autism, and their expression levels were reversed upon administration of deep brain stimulation.ConclusionsAutism-like behavior was ameliorated and autism-related proteins were reversed in the insula by deep brain stimulation intervention, these findings reveal that the insula may be a potential target for DBS in the treatment of autism, which provide a theoretical basis for its clinical application., although future studies are still warranted.

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

Publications

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

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