From impulses to maladaptive actions: the insula is a neurobiological gate for the development of compulsive behavior

Abstract

Impulsivity is an endophenotype of vulnerability for compulsive behaviors. However, the neural mechanisms whereby impulsivity facilitates the development of compulsive disorders, such as addiction or obsessive compulsive disorder, remain unknown. We first investigated, in rats, anatomical and functional correlates of impulsivity in the anterior insular (AI) cortex by measuring both the thickness of, and cellular plasticity markers in, the AI with magnetic resonance imaging and in situ hybridization of the immediate early gene zif268, respectively. We then investigated the influence of bilateral AI cortex lesions on the high impulsivity trait, as measured in the five-choice serial reaction time task (5-CSRTT), and the associated propensity to develop compulsivity as measured by high drinking levels in a schedule-induced polydipsia procedure (SIP). We demonstrate that the AI cortex causally contributes to individual vulnerability to impulsive-compulsive behavior in rats. Motor impulsivity, as measured by premature responses in the 5-CSRTT, was shown to correlate with the thinness of the anterior region of the insular cortex, in which highly impulsive (HI) rats expressed lower zif268 mRNA levels. Lesions of AI reduced impulsive behavior in HI rats, which were also highly susceptible to develop compulsive behavior as measured in a SIP procedure. AI lesions also attenuated both the development and the expression of SIP. This study thus identifies the AI as a novel neural substrate of maladaptive impulse control mechanisms that may facilitate the development of compulsive disorders.

Intertemporal Decision Making After Brain Injury: Amount-Dependent Steeper Discounting after Frontal Cortex Damage

“…Also, the lack of strong evidence for different rates of discounting between the POC and PFC groups (only statistical trend) might be due to involvement of insula damage in the POC group. The anterior insular cortex (AI) has been reported to be causally related to impulsive-compulsive decision making in rats (Belin-Rauscent et al, 2016). This is supported by results from human studies and the involvement of insula areas in decision making (Mohammadi et al, 2016).…”

Role of the agranular insular cortex in contextual control over cocaine-seeking behavior in rats

“…Cocaine users exhibit decreases in insular cortex gray matter density (Franklin et al 2002). Insular cortex gray matter volume reduction in cocaine users (Moreno-López et al 2012), AI cortical thinness in rats (Belin-Rauscent et al 2016), as well as insular cortex lesions in drug naïve individuals (Clark et al 2008) and AI lesions in rats (Belin-Rauscent et al 2016) positively correlate with measures of risky decision making and trait impulsivity. Furthermore, diminished insular cortex activation during a drug-unrelated decision-making task in methamphetamine users (Paulus et al 2005) and reduced resting functional connectivity between the insular cortex and sensorimotor cortices in smokers (Addicott et al 2015) are associated with increased probability of drug relapse.…”

Adenosine A2A receptor and ERK-driven impulsivity potentiates hippocampal neuroblast proliferation

“…Therefore, given the complexity of the overlapping cortical, striatal, sub-thalamic and amygdalar neural substrates, the molecular regulation of waiting versus decisional impulsivity may be differentially affected by behavioral task (that is, DRL versus delay discounting). 27, 69, 70 …”