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  • Addiction, Drugs
  • Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation

    855—Behavioral Flexibility and Response Inhibition

    Wednesday, November 13, 2013, 1:00 pm - 5:00 pm

    855.02: A functional dissociation within the insular cortex contributes to the regulation of impulsive decision-making dependent on innate impulsive traits

    Location: Halls B-H

    *B. C. FINGER1, I. KUSUMOTO-YOSHIDA1, A. BONCI1,2,3;
    1Intramural Res. Program, Natl. Inst. On Drug Abuse, Baltimore, MD; 2Dept. of Neurol., Univ. of California San Francisco, San Francisco, CA; 3Solomon H. Snyder Neurosci. Institute, Johns Hopkins Sch. of Med., Baltimore, MD

    Abstract Body: Impulsivity is defined as the “predisposition toward rapid unplanned reactions to internal or external stimuli without regard to the negative consequences of these reactions to the impulsive individual or others“. In many psychiatric disorders including personality disorders, substance abuse disorders , attention-deficit hyperactivity and impulse control disorders, impulsive traits are a dominant symptom. So far, cortical and sub-cortical brain structures have been implicated in the control of impulsive behavior and decision-making in humans as well as in animals. However, a clear functional association of several anatomical regions that play a role in substance abuse disorders with impulsive traits remains elusive. One of these areas is the insular cortex. Studies have described a regulatory function of the insula in smoking cessation and craving but so far, to our knowledge, no functional cross-reference to the modulation of impulsive control has been investigated.
    Animal models are a well utilized tool to dissect these anatomical and functional aspects. Here we employ a classic delay-discounting task to investigate impulsive decision making. In this task rats choose between a small immediate and a large, delayed food reward (reward ratio 1:4). Across trials the delay to obtain the large reward increases (delay 0s, 10s, 20s, 40s and 60s). As in humans, outbred rats show innate differences in impulsive traits, with 2/3 being innately impulsive. Using pharmacological and anatomical techniques our study describes a modulatory role of the insular cortex in impulsive decision making. We show a regional functional dissociation with anterior and posterior insula playing an opposing role in impulse control that is dependent on the innate level of impulsivity of the individual.
    These studies describe, to our knowledge, for the first time a direct functional association of the insular cortex with impulsive behavior. Future studies will investigate the functional link between impulse modulation by the insular cortex and intake and craving for addictive substances.

    Lay Language Summary: This study identifies the insular cortex as a modulator of impulsive behavior, where anterior and posterior parts of the structure play an opposing role in impulse control that is dependent on the innate level of impulsivity of the individual.
    Decision-making is one of the most frequent challenges in our daily life. When making an economic decision one has to consider the potential outcomes and consequences of this decision by evaluating the required costs and benefits. However, this process varies greatly among individuals and these differences between subjects can be explained by several contributing factors. Our prior life experiences, genetic background and development will all shape the individual pattern of decision-making. Among subjects some individuals tend to show impulsive traits, not considering the potential cost or negative outcome that is associated with their decision and also not learning from the negative consequence that resulted from prior decision for future challenges. These impulsive traits are a dominant symptom found in many psychiatric disorders including personality disorders, substance abuse disorders, attention-deficit hyperactivity and impulse control disorders.
    So far, several brain structures have been implicated in the control of impulsive behavior and decision-making in humans as well as in animals. However, a clear association of brain regions that play a role in substance abuse disorders with impulsive traits remains elusive. One of these areas is the insular cortex, often also called “insula”, which is part of the cerebral cortex. Anatomically the insular cortex can be divided into an anterior and posterior part; however, so far not many studies have identified clear functions for these sub-regions.
    Interestingly, studies have described a regulatory function of the insula in smoking cessation and craving but, to our knowledge, no association to impulsive behavior has been investigated.
    To study a potential involvement of the insular cortex in impulsive decision-making for reward we use a well-established rat model of delay discounting. In this task the rat can choose between pressing a lever that gives one food reward pellet or a lever that gives four food reward pellets. Naturally, animals will choose the side of the big reward. To mimic the economic decision process observed in humans, we then increase the cost of the big reward by introducing a delay. Now, when choosing the big-reward lever, rats have to wait for either 10s, 20s, 40s and 60s before they receive the food. On the other hand, if they choose the small reward lever they receive the food immediately. An animal with strong impulsive traits will not wait during the delay to obtain the big reward later, but will most of the time take the immediate reward. As in humans, outbred rats show individual differences in impulsive traits, with 2/3 being innately impulsive.
    To investigate if the insula cortex is modulating this impulsive decision-making process, we pharmacologically inactivate the brain area for a short period of time. Now, animals that innately tend to make more impulsive decisions become less impulsive, however, those that were initially less impulsive become more impulsive. These results clearly suggest a modulatory function of the insular cortex in impulsive behavior. Furthermore, we found that this described impulse control function also depends on the anatomical part, with anterior and posterior regions, of the insular cortex that is inactivated.These studies describe, to our knowledge, for the first time a direct functional association of the insular cortex with impulsive behavior. Future studies will investigate the functional link between impulse modulation by the insular cortex and intake and craving for addictive substances.