Shared Neural Correlates Underlying Addictive Disorders and Negative Urgency.

brain sciences Review Shared Neural Correlates Underlying Addictive Disorders and Negative Urgency Miji Um *, Zachary T. Whitt, Rebecca Revilla, Taylor Hunton and Melissa A. Cyders Department of Psychology, Indiana University–Purdue University Indianapolis, Indianapolis, IN 46202, USA; (Z.T.W.); (R.R.); (T.H.); (M.A.C.) * Correspondence: ; Tel.: +1-317-274-6752 Received: 31 January 2019; Accepted: 6 February 2019; Published: 8 February 2019



 Abstract: Negative urgency is a personality trait reflecting the tendency to act rashly in response to extreme negative emotions and is considered a transdiagnostic endophenotype for problematic levels of addictive behaviors. Recent research has begun to identify the neural correlates of negative urgency, many of which appear to overlap with neural circuitry underlying addictive disorders associated with negative urgency. The goal of this qualitative review is to summarize the extant literature concerning the neural correlates of negative urgency, to compare these correlates with those implicated with addictive disorders, and to propose new ways to begin to leverage such findings in treatment and intervention approaches. We also address current limitations in the field and make recommendations for areas for future growth in this research domain. Patterns of structure and function in the ventral striatum, frontal regions, such as the prefrontal cortex (PFC) and orbitofrontal cortex (OFC), and amygdala are common across addictive disorders and are related to both real-world risky behaviors and self-report measures of negative urgency. We propose that the time has come to move past considering this trait and these disorders as completely separate entities, and instead for the field to consider how general patterns of convergence across these disorders can lead to a more transdiagnostic approach to treatment and intervention. We suggest future work utilize these convergent patterns in the development of animal models of negative urgency, in the identification and testing of prime pharmacological and physiological interventions, and as objective biomarkers to be used when testing behavioral, pharmacological, and physiological intervention effectiveness. Little empirical work has been done to date in these areas and advances in these nascent fields would advance understanding and applications of the neuroscience of negative urgency. Keywords: negative urgency; addictive disorders; substance use disorders; pathological gambling; disordered eating 1. Shared Neural Correlates Underlying Addictive Disorders and Negative Urgency Negative urgency, a personality trait defined as the tendency to act rashly in response to extreme negative emotions [1,2], is one of the personality traits from the UPPS-P model of impulsive behavior, a multidimensional model of impulsivity [3]. The multidimensional model of impulsivity consists of five traits: negative urgency, lack of premeditation (a tendency to act without thinking), lack of perseveration (an inability to stay focused on a task that may be boring or difficult), sensation seeking (a tendency to seek out novel and exciting experiences), and positive urgency (a tendency to act rashly in response to extreme positive emotion). Among them, negative urgency is the personality trait that has been most extensively studied and linked to various addictive disorders, including tobacco use [4–7], problematic alcohol and drug use [8–10], pathological gambling [11], and disordered eating [12]. Therefore, negative urgency is proposed as a transdiagnostic endophenotype for problematic levels of risk-taking behaviors, such as addictive disorders [13]. Brain Sci. 2019, 9, 36; doi:10.3390/brainsci9020036 www.mdpi.com/journal/brainsci Brain Sci. 2019, 9, 36 2 of 17 Because of the clinical implications, recent research has begun to identify the neural correlates of negative urgency in the hopes of designing better treatment and intervention approaches. Existing neuroimaging studies have primarily focused on neural correlates of negative urgency implicated in healthy and various at-risk populations, such as individuals across the drug use spectrum, individuals who engage in pathological gambling, patients with schizophrenia, individuals engaged in risky sexual practices, and individuals with obesity. Most of the previous work has focused on neural correlates of negative urgency using segregated, localized brain regions and has failed to consider functional connectivity or interactions between separate brain regions or large-scale brain networks, which is necessary for more effective pharmacological or physiological treatment design. So far, studies examining negative urgency as related to functional connectivity in the brain are still growing and studies examining how negative urgency relates to structural characteristics or task-based localized blood-oxygen level dependent (BOLD) response are more abundant. Many of the regions identified as related to negative urgency appear to overlap with neurocircuitry underlying addictive disorders. The goal of this qualitative review is to summarize the extant literature concerning the neural correlates of negative urgency and to compare these findings with regions and circuits implicated in addictive disorders. We propose four key ways in which convergent brain evidence for negative urgency and addictive disorders can improve the treatment and intervention process. These proposed areas of future growth are, to date, understudied and require empirical study and support; we hope this review catalyzing research in these domains. 2. Neural Correlates of Negative Urgency Despite the need to understand how negative urgency relates to addictive disorders in the brain, the neural correlates of negative urgency, in general, are not yet well understood. Here, we review brain regions related to negative urgency from existing neuroimaging work that has investigated negative urgency in the human brain using various imaging modalities. We report those regions that showed converging evidence from at least two or more studies. 2.1. Insula The insula is involved in emotional decision making [14] and drug addiction (see a review [15]). Also, the insula is a key brain structure for salience network that detects a personally relevant and salient stimulus from a host of stimuli in one’s environment to subsequently act upon [16,17]. One main function of the salience network is visceral interoception [18]. This function is critical to negative urgency, as it may suggest that urgent individuals exhibit aberrant patterns of connections to their own feelings and this may help us understand their rash responses to affective stimuli. The right insula is the most reported region in relation to negative urgency, although some studies also report the bilateral insula as related to negative urgency. In studies with response inhibition tasks, the relationship between negative urg (...truncated)