Table 1.
Key demographic and clinical characteristics of participants.
Fig 1.
Go-No-Go task trial structure.
One of four abstract stimuli was presented, followed by a waiting period (+). This, as well as the inter-trial interval, were jittered as shown to aid fMRI analysis. The participant’s decision, either to ‘Go’ or to ‘not Go’, was implemented when the target (o) appeared. The best action was followed by the best outcome 80% of the time. For example, if the second stimulus down was a ‘Go to avoid loss’ one, then quickly pressing the button when the circle appeared would result in a null outcome (yellow horizontal line) 80% of the time, and a loss outcome (downward arrow) 20% of the time. The stimuli were randomized as to their best action and outcome across participants. Before scanning, in the ‘discovery’ version of the task, suboptimal action would attract 20% best outcomes, but during scanning suboptimal action never led to the best outcome. No deception was involved at any point.
Fig 2.
All clinical measures of motivation clearly separate the healthy control (HC, odd plots) from the depression (Dep, even plots) sample.
Shown are summed items ‘loss of interest’, ‘change in appetite’ and ‘loss of interest in sex’ from the Beck Depression Inventory BDI), ‘interest’ and ‘appetite’ items from the Patient Health Questionnaire– 9 (PHQ-9) and the total score of the Snaith-Hamilton Pleasure Scale (SHAPS). For each pairwise comparison, Wilcoxon p < 1e-06.
Fig 3.
Behavior in the ‘discovery’ version of the task closely replicates previous results regarding the effect of trial valence on the propensity to act.
a. Here, depressed and healthy groups are combined. Shaded bars: interquartile ranges; Notch: standard error of the median. During early trials participants perform much better in Go-to-Win than No-Go-to-Win, where they do worse than chance. b. Late trials, but otherwise as in a. All conditions show increased performance–each median has improved. However different abilities of participants to learn the optimal behavior results in greater spread of performance. This is particularly striking for the No-Go-to-Win condition. c. Performance in each quartile of trials for the Healthy Control group, showing learning across trials. Bars are +/- 1 standard error of the mean. d. As in c. but for the Depression group. Differences group differences between c. and d. are not significant.
Table 2.
Parameter comparison for the weak-prior MAP fit of the core model.
Fig 4.
Healthy participants had similar parameter distributions to the depressed.
Table 3.
Model comparison based on the Bayesian Information Criterion and random effects EM estimation.
Key: ‘b’ return sensitivity, so that ‘bb’ refers to a model with separate appetitive and aversive sensitivity; ‘a’ learning rate; ‘p’ Pavlovian bias; ‘l’ lapse rate; ‘g’ Go-bias (favoring action over inaction). Separate iBIC for the two groups, and also the total sample, are shown in columns. Using a single set of parameters to describe the group distributions for the healthy and control groups achieves a better score, by about 61 BIC units, than summing the best of each separate fit. Were one to fit the two groups separately, one would run a danger of over-fitting, here over-emphasizing differences between the groups.
Fig 5.
Significant activations for key contrasts, on which region-of-interest analysis was based, replicated previous findings.
a. Go > No-Go contrast showed significant bilateral midbrain (crosshairs), caudate, insula, primary motor and supplementary motor clusters (FWE p<0.001). b. No-Go > Go contrast, i.e. areas activated when action was to be withheld, showed highly significant bilateral inferior frontal, medial prefrontal, posterior cingulate and hippocampal clusters, as well as a prominent left parieto-occipital cluster (all FWE p<0.001).
Fig 6.
Comparisons of Healthy vs. Depression activations in specific ROIs hypothesized to be important for motivated action.
Means and standard errors are shown for each of the four sets of trials. No area showed differences between depression (blue) and control (black). a. Right Caudate region of interest defined as the cluster significant at 5% FWE for the main effect of action over the entire sample. The ‘Go’ conditions have greater activation by construction, but no other differences are seen. b. As an example, this ROI is an anatomically predefined mask for Substantia Nigra / Ventral Tegmental Area. It is a subset of the cluster indicated by cross-hairs in Fig 4A. The win–avoid-loss difference is not statistically significant. c. Inferior frontal ROI defined by functional criteria (as per a.) of greater activation for holding back (‘No-Go’). d. As per (c.) but for amygdala/hippocampal cluster.
Table 4.
In regions of a priori interest, as well as in functional ROIs, evidence was found that the same activation took place in depression and control groups.
The only exception was the bilateral supplementary motor area, where there was evidence for greater activation in the depression group upon action emission as contrasted with action withholding.