Reduced activation in ventral striatum and ventral tegmental area during probabilistic decision-making in schizophrenia

Abstract

Patients with schizophrenia suffer from deficits in monitoring and controlling their own thoughts. Within these so-called metacognitive impairments, alterations in probabilistic reasoning might be one cognitive phenomenon disposing to delusions. However, so far little is known about alterations in associated brain functionality. A previously established task for functional magnetic resonance imaging (fMRI), which requires a probabilistic decision after a variable amount of stimuli, was applied to 23 schizophrenia patients and 28 healthy controls matched for age, gender and educational levels. We compared activation patterns during decision-making under conditions of certainty versus uncertainty and evaluated the process of final decision-making in ventral striatum (VS) and ventral tegmental area (VTA). We replicated a pre-described extended cortical activation pattern during probabilistic reasoning. During final decision-making, activations in several fronto- and parietocortical areas, as well as in VS and VTA became apparent. In both of these regions schizophrenia patients showed a significantly reduced activation. These results further define the network underlying probabilistic decision-making. The observed hypo-activation in regions commonly associated with dopaminergic neurotransmission fits into current concepts of disrupted prediction error signaling in schizophrenia and suggests functional links to reward anticipation. Forthcoming studies with patients at risk for psychosis and drug-naive first episode patients are necessary to elucidate the development of these findings over time and the interplay with associated clinical symptoms.

Polygenic Risk of Psychosis and Ventral Striatal Activation During Reward Processing in Healthy Adolescents

“…1 We recently found that a schizophrenia RPS was associated with an attenuated VS BOLD response during a probabilistic learning task, 15 suggesting that the cumulative effect of risk single-nucleotide polymorphisms was associated with the VS BOLD alterations previously observed in patients with psychosis [16][17][18] and unaffected relatives. 19 However, it is currently not known whether polygenic risk of psychotic disorders is associated with reward processes, such as anticipation and receipt, as assayed using the monetary incentive delay (MID) task.…”

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

“…34 We note that our results are constrained to ARMS without regard to prepsychot ic stages owing to the lack of transition data for our sample and to the generally low rates of psychotic transitions (22%) reported in the literature. However, our findings could indicate that alterations in the striatal system represent an early state in the development of psychosis.…”

“…33 Applying this task to patients with schizophrenia, a hypoactivation in the VTA and right VS during probabilistic decision-making was found, while the above-mentioned broad cortical activation pattern could be replicated. 34 Other authors assessing patients with schizophrenia also found differential activation patterns in frontal-striatal-thalamic regions during probabilistic learning or reward prediction tasks. [35][36][37] Imaging techniques in general might be able to unravel the neurobiological alteration during ARMS.…”

“…We applied a predescribed fMRI task 33,34 to ARMS patients and healthy controls to determine whether differential activation patterns in the VTA and VS can be identified, which might indicate a mechanism for the emergence of brief limited psychotic symptoms and disturbed cognition during prodromal states. Furthermore, we hypothesized that we would find an impaired capability to weigh information effectively along with a JTC bias, mirroring findings in patients with manifest illness.…”

Metamemory in schizophrenia: Retrospective confidence ratings interact with neurocognitive deficits

“…It was approved by the ethical board of the Ruprecht-Karls-University Heidelberg (accession number: 2009-296 N-MA). Analyses of endpoints beyond metamemory included partially overlapping participants Rausch et al, 2014). All participants were informed about aims and procedures of the study and provided their written consent after a sufficient period of consideration and resolving open questions.…”