A preliminary study of longitudinal neuroadaptation associated with recovery from addiction

Abstract

Background: Few studies have explored longitudinal change in event-related brain responses during early recovery from addiction. Moreover, existing findings yield evidence of both increased and decreased signaling within reward and control centers over time. The current study explored reward- and control-related signals in a risky decision-making task and specifically investigated parametric modulations of the BOLD signal, rather than signal magnitude alone. It was hypothesized that risk-related signals during decision-making and outcome evaluation would reflect recovery and that change in specific signals would correspond with improved treatment outcomes.

Methods: Twenty-one substance dependent individuals were recruited upon enrollment in community-based substance use treatment programs, wherein they received treatment-as-usual. Participants completed functional neuroimaging assessments at baseline and 3-month follow-up while performing the Balloon Analogue Risk Task (BART). Risk- and reward-sensitive signals were identified using parametric modulators. Substance use was tracked throughout the 3-month study interval using the timeline follow-back procedure.

Results: Longitudinal contrasts of parametric modulators suggested improved formation of risk-informed outcome expectations at follow-up. Specifically, a greater response to high risk (low-likelihood) positive feedback was identified in caudal anterior cingulate cortex (ACC) and a greater response to low risk (low-likelihood) negative feedback was identified in caudal ACC and inferior frontal gyrus. In addition, attenuation of a ventromedial prefrontal cortex (vmPFC) "reward-seeking" signal (i.e., increasing response with greater reward) during risky decisions at follow-up was associated with less substance use during the study interval.

Conclusions: Changes in risk- and reward-related signaling in ACC/vmPFC appear to reflect recovery and may support sobriety.

Keywords: Anterior cingulate cortex; Balloon analogue risk task; Decision-making; Monetary reward; Treatment outcome; Ventromedial prefrontal cortex; fMRI.

Fig. 1

Schematic representation of the Balloon Analogue Risk Task (BART). Adapted, with permission, from Fukunaga et al. (2012).

Fig. 2

Regions demonstrating longitudinal recovery of prediction error effects, as a change in signaling to positive and negative BART outcomes. A greater increasing activation to successful inflation feedback with increasing explosion probability (i.e., 'Success*p(Explode)') was identified at follow-up in right caudal ACC (peak voxel: 8, 4, 34) and a greater decreasing signal to explosion feedback with increasing explosion probability ('Explode*p(Explode)') was identified at follow-up in right IFG (peak voxel: 32, 20, −14) and left caudal ACC/cingulum (peak voxel: −18, 12, 32). Results suggest more robust signaling of unexpected (low likelihood) outcomes at follow-up which is consistent with stronger formation of risk-informed outcome expectations. Line plots at the right side of the figure are included to conceptually illustrate longitudinal parametric modulator contrasts. For the Success*p(Explode) contrast (green), there was a greater positive relationship between trial-to-trial variation in p(Explode) and the magnetic resonance (MR) signal at follow-up (i.e., stronger signal with a higher probability of an explosion (or magnitude of reward) at follow-up. For the Explode*p(Explode) contrast (red), there was a greater negative relationship between trial-to-trial variation in p(Explode) and the magnetic resonance (MR) signal at follow-up (i.e., stronger signal with a lower probability of an explosion (or magnitude of reward) at follow-up. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

Longitudinal attenuation of the “risk-seeking” signal in dACC/vmPFC during 'Inflate' decisions corresponded with decreased substance use during the study interval. Overlapping clusters were identified with (peak voxel: −2, 44, 10) and without (peak voxel: −6, 36, 10) inclusion of two participants with the heaviest reported substance use, indicating the effect was robust to the exclusion of potential outliers. A positive longitudinal contrast, indicating increased signal with increasing reward at follow-up, was associated with increased substance use. A negative longitudinal contrast, indicating decreased signal with increasing reward at follow-up, was associated with less substance use. A vmPFC-based reward-seeking signal was previously described in association with BART inflation events in healthy participants (Fukunaga et al., 2012). Longitudinal attenuation of this signal in successful early recovery may reflect improved inhibition of reward-seeking and may, in turn, be mediated by restoration of control-related functioning in other prefrontal regions.