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. 2020:26:102193.
doi: 10.1016/j.nicl.2020.102193. Epub 2020 Jan 22.

Striatal reactivity to reward under threat-of-shock and working memory load in adults at increased familial risk for major depression: A preliminary study

Claudie Gaillard  1 , Matthias Guillod  2 , Monique Ernst  3 , Andrea Federspiel  4 , Dominik Schoebi  5 , Romina Evelyn Recabarren  2 , Xinyi Ouyang  6 , Christoph Mueller-Pfeiffer  7 , Antje Horsch  8 , Philipp Homan  9 , Roland Wiest  10 , Gregor Hasler  11 , Chantal Martin-Soelch  2
Affiliations

Striatal reactivity to reward under threat-of-shock and working memory load in adults at increased familial risk for major depression: A preliminary study

Claudie Gaillard et al. Neuroimage Clin. 2020.

Abstract

Introduction: Anhedonia, a core symptom of Major Depressive Disorder (MDD), manifests as a lack or loss of motivation as reflected by decreased reward responsiveness, at both behavioral and neural (i.e., striatum) levels. Exposure to stressful life events is another important risk factor for MDD. However, the mechanisms linking reward-deficit and stress to MDD remain poorly understood. Here, we explore whether the effects of stress exposure on reward processing might differentiate between Healthy Vulnerable adults (HVul, i.e., positive familial MDD) from Healthy Controls (HCon). Furthermore, the well-described reduction in cognitive resources in MDD might facilitate the stress-induced decrease in reward responsiveness in HVul individuals. Accordingly, this study includes a manipulation of cognitive resources to address the latter possibility.

Methods: 16 HVul (12 females) and 16 gender- and age-matched HCon completed an fMRI study, during which they performed a working memory reward task. Three factors were manipulated: reward (reward, no-reward), cognitive resources (working memory at low and high load), and stress level (no-shock, unpredictable threat-of-shock). Only the reward anticipation phase was analyzed. Imaging analyses focused on striatal function.

Results: Compared to HCon, HVul showed lower activation in the caudate nucleus across all conditions. The HVul group also exhibited lower stress-related activation in the nucleus accumbens, but only in the low working memory (WM) load condition. Moreover, while stress potentiated putamen reactivity to reward cues in HVul when the task was more demanding (high WM load), stress blunted putamen reactivity in both groups when no reward was at stake.

Conclusion: Findings suggest that HVul might be at increased risk of developing anhedonic symptoms due to weaker encoding of reward value, higher difficulty to engage in goal-oriented behaviors and increased sensitivity to negative feedback, particularly in stressful contexts. These findings open new avenues for a better understanding of the mechanisms underlying how the complex interaction between the systems of stress and reward responsiveness contribute to the vulnerability to MDD, and how cognitive resources might modulate this interaction.

Keywords: Major depressive disorder; Reward; Stress; Striatum; Vulnerability; fMRI.

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Conflict of interest statement

Declaration of Competing Interest None

Figures

Fig 1
Fig. 1
Fribourg reward task. Illustration of the four types of trials (reward × load) randomly distributed in the no-shock and unpredictable threat-of-shock conditions. The anticipation phase corresponds to the presentation of the reward-cue (1500 ms).
Fig 2
Fig. 2
Effect of stress induction and reward on the working memory performance and self-reported mood ratings during the Fribourg reward task across groups. Mean and standard error as a function of stress induction (unpredictable threat-of-shock vs no-shock) and reward (reward vs no-reward) for the (A) response accuracy, (B) reaction times, and (C) self-reported mood scaled from 0 ‘very negative mood’ to 9 ‘very positive mood’. Lines with brackets above the data-mean indicate a main effect of reward (i.e., significant differences between the reward vs not-reward trials, represented by a dark gray bar and a light gray bar, respectively. Line without brackets above the data-mean indicate a main effect of stress (i.e., unpredictable threat-of-shock vs no-shock). Tpone-tailed < 0.05, ★★p < 0.01, ★★★p < 0.001.
Fig 3
Fig. 3
Illustration of the main effect of group comparing the healthy adults without (HCon, healthy control) and with (HVul, healthy vulnerable) increased familial risk for major depression, and threefold interaction effect (group × stress × load). (A) Significant reduced recruitment of the bilateral caudate nucleus in the HVul across conditions, irrespective of stress, reward and WM load. (B) Significant reduced activation in the bilateral nucleus accumbens in the HVul during the unpredictable threat-of-shock condition vs no-shock condition, but only in the low load compared to high load conditions. Parameter estimates (βeta weights) mean with standard errors and ROI's masks from which parameter estimates were extracted are presented at the top of the figure. Statistical parametric maps corresponding to the contrasts of interest are presented below. These whole-brain activations are corrected for multiple comparisons, but thresholded here at 0.05 for visualization purpose. ★p < 0.05.
Fig 4
Fig. 4
Illustration of the fourfold interaction effect (group × stress × reward x load) in the bilateral putamen. (A) Post-hoc comparisons evidenced a significant stress-induced reduction in the bilateral putamen activation in response to no-reward cues in the unpredictable threat-of-shock compared to no-shock conditions in healthy control (HCon) adults without increased familial risk for major depression, but exclusively in the low cognitive load condition. (B) In healthy adults with increased familial risk for major depression (HVul, healthy vulnerable), threat-of-shock potentiated the bilateral putamen reactivity in response to reward compared to no-reward cues, in particular when the task was more demanding (i.e., high working memory load). In turn, threat-of-shock resulted in a deactivation in response to both reward and no-reward cues in the low cognitive load condition, with stronger deactivation in response to no-reward compared to reward cues. Parameter estimates (βeta weights) mean with standard errors and ROI's masks from which parameter estimates were extracted are presented at the top of the figure. Statistical parametric map corresponding to the fourfold interaction effect (group × stress × reward × load) is presented below These whole-brain activations are corrected for multiple comparisons, but thresholded here at 0.05 for visualization purpose. ★p ≤ 0.05, ★★p ≤ 0.01, ★★★p ≤ 0.001.
Fig 5
Fig. 5
Illustration of the main effect of reward and the twofold interaction effect (stress × reward) that occurred in striatal ROIs during the anticipation phase in the healthy adults without (HCon, healthy control) and with (HVul, healthy vulnerable) increased familial risk for major depression. Significant increased reactivity to cued rewards (reward vs no-reward) in the bilateral (A) nucleus accumbens, (B) caudate nucleus, and (C) putamen. (D) Significant reduced activation in the bilateral putamen during the unpredictable threat-of-shock condition vs no-shock condition, but only in no-reward trials. Parameter estimates (βeta weights) mean with standard errors and ROI's masks from which parameter estimates were extracted are presented at the top of the figure. Statistical parametric maps corresponding to the contrasts of interest during anticipation are presented below. These whole-brain activations are corrected for multiple comparisons, but thresholded here at 0.05 for visualization purpose. ★★p < 0.01, ★★★p < 0.001.
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