Reduced activation in the ventral striatum during probabilistic decision-making in patients in an at-risk mental state

Abstract

Background: Patients with schizophrenia display metacognitive impairments, such as hasty decision-making during probabilistic reasoning - the "jumping to conclusion" bias (JTC). Our recent fMRI study revealed reduced activations in the right ventral striatum (VS) and the ventral tegmental area (VTA) to be associated with decision-making in patients with schizophrenia. It is unclear whether these functional alterations occur in the at-risk mental state (ARMS).

Methods: We administered the classical beads task and fMRI among ARMS patients and healthy controls matched for age, sex, education and premorbid verbal intelligence. None of the ARMS patients was treated with antipsychotics. Both tasks request probabilistic decisions after a variable amount of stimuli. We evaluated activation during decision-making under certainty versus uncertainty and the process of final decision-making.

Results: We included 24 AMRS patients and 24 controls in our study. Compared with controls, ARMS patients tended to draw fewer beads and showed significantly more JTC bias in the classical beads task, mirroring findings in patients with schizophrenia. During fMRI, ARMS patients did not demonstrate JTC bias on the behavioural level, but showed a significant hypoactivation in the right VS during the decision stage.

Limitations: Owing to the cross-sectional design of the study, results are constrained to a better insight into the neurobiology of risk constellations, but not prepsychotic stages. Nine of the ARMS patients were treated with antidepressants and/or lorazepam.

Conclusion: As in patients with schizophrenia, a striatal hypoactivation was found in ARMS patients. Confounding effects of antipsychotic medication can be excluded. Our findings indicate that error prediction signalling and reward anticipation may be linked to striatal dysfunction during prodromal stages and should be examined for their utility in predicting transition risk.

Fig. 1

(A) Illustration of the classical beads task. (B) Comparison of draws to decision (DTD) between patients in the at-risk mental state (ARMS) and controls. Results are reported as means and standard errors. (C) Comparison of jumping to conclusions bias (JTC; defined as 1 or 2 beads) between ARMS patients and controls (Fisher exact test, p = 0.015).

Fig. 2

(A) Main effect of the lake decision (lake decision > colour decision). Significance threshold is p < 0.05, family-wise error [FWE]–corrected. (B) Final decision-making, indicating enhanced activation for the last fish (last fish > all previous fish). Significance threshold set at p < 0.05, FWE-corrected. (C) Final decision-making, indicating average signal change for the last fish in comparison to all previous fish in the right ventral striatum. Displayed is the first Eigenvariate of the right ventral striatal activation extracted for a mask of the right nucleus accumbens, with a significance threshold set to 1. ARMS = at-risk mental state.