Functional MRI and delay discounting in patients infected with hepatitis C

Abstract

Hepatitis C virus-infected (HCV+) adults evidence increased rates of psychiatric and cognitive difficulties. This is the first study to use functional magnetic resonance imaging (fMRI) to examine brain activation in untreated HCV+ adults. To determine whether, relative to non-infected controls (CTLs), HCV+ adults exhibit differences in brain activation during a delay discounting task (DDT), a measure of one's tendency to choose smaller immediate rewards over larger delayed rewards-one aspect of impulsivity. Twenty adults with HCV and 26 CTLs completed an fMRI protocol during the DDT. Mixed effects regression analyses of hard versus easy trials of the DDT showed that, compared with CTLs, the HCV+ group exhibited less activation in the left lateral occipital gyrus, precuneus, and superior frontal gyrus. There were also significant interactive effects for hard-easy contrasts in the bilateral medial frontal gyrus, left insula, left precuneus, left inferior parietal lobule, and right temporal occipital gyrus; the CTL group evidenced a positive relationship between impulsivity and activation, while the HCV+ group exhibited a negative relationship. Within the HCV+ group, those with high viral load chose immediate rewards more often than those with low viral load, regardless of choice difficulty; those with low viral load chose immediate rewards more often on hard choices relative to easy choices. Results show that HCV+ patients exhibit greater impulsive behavior when presented with difficult choices, and impulsivity is negatively related to activation in regions important for cognitive control. Thus, interventions that decrease impulsive choice may be warranted with some HCV+ patients.

Keywords: Cognition; Delay discounting; Hepatitis; Impulsivity; Neuroimaging; fMRI.

Fig. 1.. Representation of a typical subject’s answers on the delay discounting task.

As temporal delay increases, the number of immediate choices (green) increases, while the number of delayed choices (red) decreases. The indifference curve (black line) generated from subject responses reflects the points where subjects are equally likely to choose immediate or delayed options. The options near the indifference curve (pink) reflect Hard choices while options distant from the indifference curve reflect Easy choices.

Fig. 2.. By group, the percentage of times participants select immediate rewards over delayed rewards on Hard versus Easy Trials on the delayed discounting task (DDT).

Participants in both the hepatitis C virus (HCV) infected and non-infected control (CTL) groups have a significantly (p < 0.05) increased tendency to choose smaller immediate rewards over larger delayed rewards when choices are Hard versus when they are Easy. a. Results from the initial administration of the DDT outside the scanner. b. Results from the final administration of the DDT during functional magnetic resonance imaging (fMRI).

Fig. 3.. Whole-brain contrast comparing activation on Hard versus Easy trials on the delayed discounting task (DDT).

a. Contrast of Hard versus Easy decisions for all subjects combined. Significant regions of activation for Hard compared to Easy choices include anterior cingulate cortex, right middle frontal gyrus, right superior frontal gyrus, left insula and left inferior frontal gyrus. b. Group differences for the Hard versus Easy contrast. Compared to the hepatitis C positive (HCV) group, the control (CTL) group exhibits greater differences in activation between Hard and Easy choices in left lateral occipital gyrus, left precuneus and left superior frontal gyrus. (p < 0.05, whole-brain corrected).

Fig. 4.. Whole-brain Group by Impulsivity (IMP) interaction comparing activation on the Hard versus Easy trials on the delayed discounting task (DDT).

a. Clusters in which the Group by IMP interaction was significant for the Hard versus Easy contrast on the DDT. b. Within the clusters with a significant Group by IMP interaction, the relationship between IMP and activation on the Hard versus Easy trials is positive for controls (CTLs) but negative for the hepatitis C virus (HCV) infected group. (p < 0.05, whole-brain corrected).

Fig. 5.. By viral load, the percentage of times participants infected with the hepatitis C virus (HCV) select smaller immediate rewards over larger delayed rewards on Hard versus Easy trials on the delayed discounting task (DDT).

a. Participants with a High Viral Load choose immediate rewards significantly (p < 0.001) more often than those with a Low Viral Load. b. Participants with a High Viral Load choose immediate rewards significantly (p < 0.001) more often during both Hard trials and Easy trials, whereas participants in the Low Viral Load are more likely to choose immediate rewards during Hard trials relative to Easy trials.