Abstract:

Located deep in the lateral sulcus, the insula is associated with a variety of psychological functions such as emotions and interoception. As an important nerve center of the interoception, the insula plays a critical role in the formation, maintenance, withdrawal and relapse of addiction.
The function and structure of the insula show distinctive heterogeneity and anterior-posterior distribution. The differentiation of the anterior and posterior insula is mainly reflected in the posterior insula being more responsible for perceptual activities such as sensory motor, pain and language processing, while the anterior insula is more involved in cognitive and executive functions.
In addicted individuals, the structure of the insula has changed, most of the findings point to a decrease in the volume and density of the insula gray matter, and this change is correlates with the length of time the addictive substance was used. Addiction has also led to changes in salience network function and connectivity between insula and executive function areas. In various types of addiction, the insula-centric network function and its functional connection are generally weakened.
Therefore, how stimulations in the insula could lead to changes in addictive behaviors becomes the focus of ongoing research. A large number of studies have shown that insula is a highly promising target area for intervention in addiction. Deep brain stimulation (DBS) and repetitive transcranial magnetic stimulation (rTMS) are both effective methods of brain stimulation. Currently, published human experience with DBS for drug addiction is limited to a few promising case series or case reports, and further animal and human studies are needed to determine the role of DBS in drug addiction treatment. High-frequency rTMs targeting insula regions have been beneficial for craving associated with nicotine use disorder, but the available evidence does not adequately support the effectiveness of rTMs in the treatment of alcoholism. In terms of behavioral addiction, although there are no stimulation studies that target the insula, it is worthwhile to explore the cognitive and neurophysiological characteristics unique to behavioral addiction, and to establish separate brain stimulation methods targeting the areas related to behavioral addiction. Brain stimulation technology is progressing, which also allows researchers to use the insula as the direction of treatment of addiction, to provide promising treatment results for addicts.
Although most studies have shown a decrease in the volume and density of the insula gray matter and the function of the network centered on the insula and its functional connections were generally weakened, some studies have shown the opposite conclusion. On the one hand, the contradictory results of the insula may be related to the functional and structural heterogeneity of the insula itself, the different sub-regions of the insula have different functions and participate in different functional networks, and some of the above conclusions do not distinguish the sub-regions of the insula. On the other hand, the insula is a typical region with dynamic functional changes, and changes in the interoceptive state (such as whether the patient is in a state of withdrawal or craving) are critical to the functional response of the insula. In addition, the commonalities and characteristics of different addictions also need to be considered. A large number of studies have shown that long-term adaptive changes in the nervous system under the action of addictive drugs are the basis for the formation of substance addiction behavior. Compared with the addictive behavior of substance dependence, behavioral addiction is not affected by any intake of substances, so the formation of its dependence state is mainly due to psychological mechanisms. Even different substance addictions have different characteristics. Therefore, future research should further investigate the specific role of insula in addiction through fine segmentation and a combination of multiple methods, and explore the commonalities and characteristics of different types of addiction in order to better carry out brain-based addiction intervention.

Key words: insula, addiction, intervention, functional connectivity, brain imaging