Striatal sensitivity to reward deliveries and omissions in substance dependent patients

Abstract

Some motivational theories of substance dependence (SD) posit either pathologically increased or decreased ventral striatum (VS) recruitment by cues for nondrug rewards. The incentive-sensitization hypothesis, alternatively, attributes SD to enhanced incentive salience of drug-predictive cues specifically, with no requirement for altered nondrug incentive processing. We assessed whether individuals undergoing inpatient therapy for SD are characterized by altered recruitment of mesolimbic incentive neurocircuitry by cues and deliveries of nondrug rewards. During functional magnetic resonance imaging, substance-dependent patients (SDP) and controls performed a modified monetary incentive delay task featuring: a) anticipatory cues that signaled opportunities to respond to a target to either win money or avoid losing money, b) notifications of wins and losses, and c) unexpected replacement of reward trial outcomes with a demand to repeat the trial. Both anticipatory reward cues and loss cues elicited similar mood responses and VS activation between SDP and controls. However, in SDP (but not controls), reward notifications also activated VS and mesial frontal cortex, and loss notifications activated anterior insula. Finally, substitution of expected outcomes in reward trials with notifications to repeat the trial deactivated the VS in SDP but not in controls. These data do not suggest that SD is characterized by altered recruitment of VS circuitry by cues for nondrug incentives. Rather, SD may instead have increased limbic system sensitivity to reward and loss delivery, consistent with the role of impulsivity in SD.

Dietary Tyrosine/Phenylalanine Depletion Effects on Behavioral and Brain Signatures of Human Motivational Processing

“…In a degraded-stimulus signal-detection task, however, His depletion only mildly affected some taskelicited EEG signatures, but did not significantly affect RTs or accuracy of signal detection (van Ruitenbeek et al, 2009). Similarly, RTs in this experiment were substantially similar to those of controls in the previous study with this MID variant (Bjork et al, 2008) that featured no pharmacological manipulation. However, it cannot be ruled out that some effects may have resulted from reduced histamine signaling (on both mixture days).…”

“…Taken together with the presence of VS activation by gain notification under DEP (but not BAL) conditions, it is tempting to speculate that TPD may have increased limbic sensitivity to acute valenced instrumental outcomes through some other mechanism, to essentially mimic the responses of groups (eg, alcoholics) ostensibly characterized by impaired monoaminergic functioning. In the previous experiment with this MID task (Bjork et al, 2008), both left anterior insula activation by losses and VS activation by gains were greater in alcoholics. As we did not probe affective responses to gain and loss notifications, this question will require additional studies, where mood could be probed during the task.…”

“…In the MID task used here, some reward trial outcomes were replaced by a demand to repeat the trial (Bjork et al, 2008). Trials consisted of: cue presentation, target presentation, and either success-dependent feedback or notification of the requirement to repeat the trial (Figure 1).…”

“…Because NAcc recruitment during reward anticipation has correlated with self-reported positive affect (Bjork et al, 2004;Knutson et al, 2001), we further hypothesized that blunted NAcc recruitment by rewards following TPD would be specific to those subjects who showed worsened mood. Finally, because mesolimbic DA neurons show phasic decreases in response to omissions of expected reward (Schultz, 2007), we hypothesized that occasional replacement of reward outcomes with a demand to repeat the trial would deactivate the NAcc (Bjork et al, 2008), but that this would be blunted following TPD owing to reduction in DA tone.…”

Neural Correlates of Impulsivity in Healthy Males and Females with Family Histories of Alcoholism

“…Previous findings of abnormal ventral-striatal activity in adolescent/young adult FHP or alcohol-dependent individuals were often associated with high impulsivity or alcohol use (Beck et al, 2009;Bjork et al, 2008a;Bjork et al, 2008b;Heitzeg et al, 2008;Heitzeg et al, 2010;Wrase et al, 2007). The lack of ventral-striatal findings in this sample may have been due to the FHP and FHN groups' similar impulsivity and alcohol use levels.…”