Abstract
Cognitive deficits associated with Huntington disease (HD) are generally dominated by executive function disorders often associated with disinhibition and impulsivity/compulsivity. Few studies have directly examined symptoms and consequences of behavioral disinhibition in HD and its relation with decision-making. To assess the different forms of impulsivity in a transgenic model of HD (tgHD rats), two tasks assessing cognitive/choice impulsivity were used: risky decision-making with a rat gambling task (RGT) and intertemporal choices with a delay discounting task (DD). To assess waiting or action impulsivity the differential reinforcement of low rate of responding task (DRL) was used. In parallel, the volume as well as cellular activity of the amygdala was analyzed. In contrast to WT rats, 15 months old tgHD rats exhibited a poor efficiency in the RGT task with difficulties to choose advantageous options, a steep DD curve as delays increased in the DD task and a high rate of premature and bursts responses in the DRL task. tgHD rats also demonstrated a concomitant and correlated presence of both action and cognitive/choice impulsivity in contrast to wild type (WT) animals. Moreover, a reduced volume associated with an increased basal cellular activity of the central nucleus of amygdala indicated a dysfunctional amygdala in tgHD rats, which could underlie inhibitory dyscontrol. In conclusion, tgHD rats are a good model for impulsivity disorder that could be used more widely to identify potential pharmacotherapies to treat these invasive symptoms in HD.
Highlights
Impulsiveness refers to the tendency to engage in inappropriate or maladaptive behaviors, without weighing consequences of actions
No significant between group difference (F(1,16) = 2.40, ns) and genotype × period interaction (F(5,80) = 1.24, ns) were found, wild type (WT) rats showed a progressive improvement of performance reaching 90% of correct choices during the last 10 min period (p = 0.001 from random on this last period), whereas transgenic model of HD (tgHD) rats reached only 64% of correct responses (p = 0.13 from random)
The percentage of low impulsive rats was significantly lower for the tgHD group than for the WT group (p = 0.05; Figure 1B), which was not reflected in different percentage of high impulsive rats (Figure 1B; p = 0.17)
Summary
Impulsiveness refers to the tendency to engage in inappropriate or maladaptive behaviors, without weighing consequences of actions. Self-control is thought to emerge from the dynamic interaction between an impulsive system, in which the amygdala is a neural structure critical in processing the affective and emotional signals of immediate outcomes, and a reflective system, in which the prefrontal (PFC) and orbitofrontal cortices are crucial in triggering the affective and emotional signals of long-term outcomes (Bechara, 2005). A high level of impulsivity in a delay discounting task (DD) was associated with higher amygdala activation for winning immediate rewards (Ludwig et al, 2015). Trait impulsivity was positively correlated with the level of activity in response to reward cues in the anterior cingulate cortex (ACC) and amygdala (Kerr et al, 2015). Disconnection of the medial PFC and basolateral amygdala induces high level of impulsivity assessed in a DD task (Churchwell et al, 2009). Patients with selective amygdala damage (Urbach-Wiethe syndrome) have lower scores in decision-making under ambiguity and under risk (Brand et al, 2007), and lack of autonomic responses to reward and punishment used as ‘‘somatic markers’’ to guide future decision (Gupta et al, 2011)
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