Cortical dopamine release during a behavioral response inhibition task

Abstract

Dopamine (DA) dysregulation within fronto-striatal circuitry may underlie impulsivity in alcohol and other substance use disorders. To date, no one has directly demonstrated DA release during a task requiring the control of impulsive behavior. The current study was conducted to determine whether a response inhibition task (stop signal task; SST) would elicit detectable extrastriatal DA release in healthy controls. We hypothesized that DA release would be detected in regions previously implicated in different aspects of inhibitory control. [18F]Fallypride (FAL) PET imaging was performed in nine healthy males (24.6 ± 4.1 y.o.) to assess changes in cortical DA during a SST relative to a baseline “Go” task. On separate days, subjects received one FAL scan during the SST, and one FAL scan during a “Go” control; task-order was counter-balanced across subjects. Parametric BPND images were generated and analyzed with SPM8. Voxel-wise analysis indicated significant SST-induced DA release in several cortical regions involved in inhibitory control, including the insula, cingulate cortex, orbitofrontal cortex, precuneus, and supplementary motor area. There was a significant positive correlation between stop signal reaction time and DA release in the left orbitofrontal cortex, right middle frontal gyrus, and right precentral gyrus. These data support the feasibility of using FAL PET to study DA release during response inhibition, enabling investigation of relationships between DA function and impulsive behavior.

Dissociable Effects of Dopamine on the Initial Capture and the Reactive Inhibition of Impulsive Actions in Parkinson's Disease

“…For example, imaging studies show that dopamine release and dopamine receptor availability predict individual differences in reactive inhibitory control processes (Albrecht, Kareken, Christian, Dzemidzic, & Yoder, 2014; Ghahremani et al, 2012). Moreover, genetic variations in dopamine transporter genes and COMT also vary with inhibitory control in the stop-signal paradigm (Cummins et al, 2012; Congdon, Constable, Lesch, & Canli, 2009).…”

Adolescent methylphenidate treatment differentially alters adult impulsivity and hyperactivity in the Spontaneously Hypertensive Rat model of ADHD

“…Thus, elevated NET function in the absence of MPH treatment may contribute to decreased extracellular DA and/or decreased DA receptor signaling in OFC. Reduction in DA receptor availability in the OFC was negatively correlated with response inhibition capacity in humans (Albrecht, Kareken et al 2014). Inhibition of NET by local infusion of atomoxetine into OFC improved response inhibition capacity in rats (Bari, Mar et al 2011).…”

Neuroscience of inhibition for addiction medicine

“…For example, in a preliminary sample of cocaine-addicted individuals and healthy controls, we showed that dopamine D2 receptor availability, measured by positron emission tomography (PET) with [ 11 C]raclopride, correlated with fMRI midbrain response to errors during the color-word Stroop task when cognitive resources were presumably most depleted (during the final versus the first task repetition) (Moeller, Tomasi, Honorio, et al, 2012). In addition, studies administering the stop-signal tasks during PET with [ 18 F]fallypride in healthy individuals revealed correlations between SSRT and D2/D3 receptor availability in the left OFC, right MFG, and right precentral gyrus (Albrecht, Kareken, Christian, Dzemidzic, & Yoder, 2014) and the striatum (Ghahremani et al, 2012). Accordingly, therapeutic agents that act on this system, such as the indirect dopamine agonist methylphenidate, could be used to modulate the neural correlates of response inhibition in drug addiction as indeed previously demonstrated (Goldstein et al, 2010; Li et al, 2010; Moeller et al, 2014; Sofuoglu, Devito, Waters, & Carroll, 2013).…”