Impulsive personality predicts dopamine-dependent changes in frontostriatal activity during component processes of working memory

Abstract

Dopaminergic drugs affect a variety of cognitive processes, but the direction and extent of effects vary across individuals and tasks. Paradoxical effects are observed, by which the same drug causes cognitive enhancing as well as adverse effects. Here, we demonstrate that individual differences in impulsive personality account for the contrasting effects of dopaminergic drugs on working memory and associated frontostriatal activity. We observed that the dopamine D2 receptor agonist bromocriptine improved the flexible updating (switching) of relevant information in working memory in high-impulsive subjects, but not in low-impulsive subjects. These behavioral effects in high-impulsive subjects accompanied dissociable effects on frontostriatal activity. Bromocriptine modulated the striatum during switching but not during distraction from relevant information in working memory. Conversely, the lateral frontal cortex was modulated by bromocriptine during distraction but not during switching. The present results provide a key link between dopamine D2 receptor function, impulsivity, and frontostriatal activity during component processes of working memory.

Figure 1.

Example trial from the experimental paradigm. In this trial, a blue fixation cross instructed subjects to attend to the faces and ignore the scenes. The encoding period (1000 ms) was followed by an 8000 ms delay period, after which a scrambled distractor was presented. After a second delay (8000 ms), subjects were probed to make a left/right button press depending on whether or not the probe face matched one of the two encoding faces.

Figure 2.

Encoding-related suprathreshold clusters (p_FWE < 0.00001). Left, Right hemisphere (R); right, left hemisphere (L). Note that the small clusters that appear to be located in the posterior/inferior portions of the inferior frontal gyrus were in fact located in the insulae/superior temporal gyri.

Figure 3.

Behavioral switch costs as a function of trait impulsivity and drug. Switch costs represent the mean proportion of errors on switch trials minus the mean proportion of errors on nonswitch trials. Error bars represent SEs of the difference between treatment sessions.

Figure 4.

Signal change during switch trials minus nonswitch trials in the putamen. Data represent mean percentage signal change and are collapsed across the right and left putamen. Error bars represent SEs of the difference between treatment sessions.

Figure 5.

Effect of bromocriptine during switching as a function of trait impulsivity. Statistical parametric map superimposed on five axial sections [numbers below sections represent MNI z-coordinates (millimeters from the anterior commissure)] from the MNI template brain (the average of 27 scans from 1 subject to create the image known as “colin27”) for the group × drug × switch interaction contrast. A significant peak was observed in the right putamen [at coordinates 24, 4, 2 (x, y, z); all t values >2.5 are shown]. L, Left; R, right.

Figure 6.

Signal change as a function of process, drug, and region of interest. Data represent mean percentage signal change in the striatum (collapsed across the four subregions) and the lateral frontal cortex (collapsed across the three subregions) for the high-impulsive subjects. Error bars represent SEs of the difference between drug sessions.

Figure 7.

Effect of bromocriptine during distraction as a function of trait impulsivity. Statistical parametric map superimposed on five axial sections [numbers below sections represent MNI z-coordinates (millimeters from the anterior commissure)] from the MNI template brain (the average of 27 scans from 1 subject to create the image known as “colin27”) for the group × drug × distractor interaction contrast. A significant peak was observed in the inferior frontal junction [i.e., the border of the left inferior frontal gyrus and left precentral gyrus; at coordinates 46, 4, 28 (x, y, z); all t-values >3.0 are shown]. L, Left; R, right.