Abstract
D2-like dopamine receptors in animals and humans have been shown to be linked to impulsive behaviors that are highly relevant for several psychiatric disorders. Here, we investigate the relationship between the fronto-striatal D2/D3 dopamine receptor availability and response inhibition in a selected population of healthy OPRM1 G-allele carriers. Twenty-two participants successively underwent blood-oxygen level dependent functional magnetic resonance imaging (fMRI) while performing a stop-signal task and a separate positron emission tomography (PET) scan. Striatal and extrastriatal D2/D3 dopamine receptor availability was measured using the radiotracer [18F]fallypride. Caudate D2/D3 dopamine receptor availability positively correlated with stopping-related fronto-striatal fMRI activation. In addition, right prefrontal D2/D3 dopamine receptor availability correlated positively with stopping-related striatal fMRI BOLD signal. Our study partially replicates previous findings on correlations between striatal D2/D3 dopamine receptor availability and response inhibition in a population selected for its genetic determination of dopamine response to alcohol and as a modulator of impulse control via the endogenous opioid system. We confirm the important role of D2/D3 dopamine receptor availability in the fronto-striatal neural circuit for response inhibition. Moreover, we extend previous findings suggesting that dopamine receptor availability in the right inferior frontal cortex, a crucial region of the stopping network, is also strongly associated with stopping-related striatal fMRI activity in healthy OPRM1 G-allele carriers.
Highlights
Impulsive behavior is of high clinical relevance in psychiatric disorders such as substance use disorders, attentiondeficit/hyperactivity syndrome or personality disorders1 3 Vol.:(0123456789)Brain Imaging and Behavior (Chamberlain & Sahakian, 2007; Robbins et al, 2012; Sebastian et al, 2012, 2013, 2014; Stahl et al, 2014; Turner et al, 2017)
Applying functional magnetic resonance imaging studies, brain regions like right inferior frontal cortex (IFC) and anterior insula, pre-supplementary motor area, striatum, and the subthalamic nucleus have been identified as being critically involved in implementing response inhibition (e.g., Aron, 2011; Chambers et al, 2009; Sebastian et al, 2016)
For VOI-based correlations, following Buckholtz et al (2010) we calculated the first eigenvariate of the parameter estimate for the contrast 'successful stop > go' for each subject for the following anatomically defined VOIs: the right inferior frontal gyrus (IFG) pars opercularis from the Harvard–Oxford atlas included in FSL (Desikan et al, 2006) and the left and right striatum VOIs from the probabilistic atlas from Keuken et al (2014)
Summary
Impulsive behavior is of high clinical relevance in psychiatric disorders such as substance use disorders, attentiondeficit/hyperactivity syndrome or personality disorders. In line with Robertson et al (2015), Ghahremani et al (2012) reported that striatal dopamine D2/D3 receptor availability negatively correlated with stopping latency (i.e., SSRT). In the present study we assess the relationship of fMRI BOLD signal during response inhibition and D 2/D3 dopamine receptor availability in healthy male subjects. To this end, participants completed an SST during fMRI. Using a similar study design as Ghahremani et al (2012) the main aim of the present study was to replicate previous findings on D 2-like dopamine receptors and their relationship to fronto-striatal brain activation in the context of impulse control. In order to extend previous findings, we assessed the relationship of striatal D2/D3 receptor availability and of prefrontal D2-like dopamine receptors with stopping-related brain activity
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