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Dorsolateral prefrontal cortex plays causal role in probability weighting during risky choice.

ABSTRACT: In this study, we provide causal evidence that the dorsolateral prefrontal cortex (DLPFC) supports the computation of subjective value in choices under risk via its involvement in probability weighting. Following offline continuous theta-burst transcranial magnetic stimulation (cTBS) of the DLPFC subjects (N = 30, mean age 23.6, 56% females) completed a computerized task consisting of 96 binary lottery choice questions presented in random order. Using the hierarchical Bayesian modeling approach, we then estimated the structural parameters of risk preferences (the degree of risk aversion and the curvature of the probability weighting function) and analyzed the obtained posterior distributions to determine the effect of stimulation on model parameters. On a behavioral level, temporary downregulation of the left DLPFC excitability through cTBS decreased the likelihood of choosing an option with higher expected reward while the probability of choosing a riskier lottery did not significantly change. Modeling the stimulation effects on risk preference parameters showed anecdotal evidence as assessed by Bayes factors that probability weighting parameter increased after the left DLPFC TMS compared to sham.

SUBMITTER: Panidi K

PROVIDER: S-EPMC9515118 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Dorsolateral prefrontal cortex plays causal role in probability weighting during risky choice.

Panidi Ksenia K Vorobiova Alicia Nunez AN Feurra Matteo M Klucharev Vasily V

Scientific reports 20220927 1

In this study, we provide causal evidence that the dorsolateral prefrontal cortex (DLPFC) supports the computation of subjective value in choices under risk via its involvement in probability weighting. Following offline continuous theta-burst transcranial magnetic stimulation (cTBS) of the DLPFC subjects (N = 30, mean age 23.6, 56% females) completed a computerized task consisting of 96 binary lottery choice questions presented in random order. Using the hierarchical Bayesian modeling approach, ...[more]

PMID: 36167703

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Project description:Previous literature suggests that a balance between Pavlovian and instrumental decision-making systems is critical for optimal decision-making. Pavlovian bias (i.e., approach toward reward-predictive stimuli and avoid punishment-predictive stimuli) often contrasts with the instrumental response. Although recent neuroimaging studies have identified brain regions that may be related to Pavlovian bias, including the dorsolateral prefrontal cortex (dlPFC), it is unclear whether a causal relationship exists. Therefore, we investigated whether upregulation of the dlPFC using transcranial current direct stimulation (tDCS) would reduce Pavlovian bias. In this double-blind study, participants were assigned to the anodal or the sham group; they received stimulation over the right dlPFC for 3 successive days. On the last day, participants performed a reinforcement learning task known as the orthogonalized go/no-go task; this was used to assess each participant's degree of Pavlovian bias in reward and punishment domains. We used computational modeling and hierarchical Bayesian analysis to estimate model parameters reflecting latent cognitive processes, including Pavlovian bias, go bias, and choice randomness. Several computational models were compared; the model with separate Pavlovian bias parameters for reward and punishment domains demonstrated the best model fit. When using a behavioral index of Pavlovian bias, the anodal group showed significantly lower Pavlovian bias in the punishment domain, but not in the reward domain, compared with the sham group. In addition, computational modeling showed that Pavlovian bias parameter in the punishment domain was lower in the anodal group than in the sham group, which is consistent with the behavioral findings. The anodal group also showed a lower go bias and choice randomness, compared with the sham group. These findings suggest that anodal tDCS may lead to behavioral suppression or change in Pavlovian bias in the punishment domain, which will help to improve comprehension of the causal neural mechanism.

Project description:BackgroundMethamphetamine (MA), is an extremely addictive stimulant that adversely affects the central nervous system. Accumulating evidence indicates that molecular mechanisms such as oxidative stress, apoptosis, and autophagy are involved in the toxicity of MA. Considering experimental animal studies exhibiting MA-induced neurotoxicity, the relevance of these findings needs to be evidently elucidated in human MA users. It is generally assumed that multiple chemical substances released in the brain following MA-induced metabolic activation are primary factors underlying damage of neural cells. Hence, this study aimed to investigate the role of autophagy and apoptosis as well as oxidative stress in the brain of postmortem MA-induced toxicity.Materials and methodsIn this study, we determine the gene expression of autophagy and apoptosis, including BECN1, MAP1ALC3, CASP8, TP53, and BAX genes in ten healthy controls and ten chronic users of MA postmortem dorsolateral prefrontal cortex (DLPFC) by real-time polymerase chain reaction. Also, we applied immunohistochemistry in formalin-fixed and paraffin-embedded human brain samples to analyze brain-derived neurotrophic factor (BDNF). Also, spectrophotometry was performed to measure glutathione (GSH) content.ResultsThe expression level of apoptotic and autophagic genes (BECN1, MAP1ALC3, CASP8, TP53, and BAX) were significantly elevated, while GSH content and BDNF showed substantial reductions in DLPFC of chronic MA users. Discussion: Our data showed that MA addiction provokes transduction pathways, namely apoptosis and autophagy, along with oxidative mechanisms in DLPFC. Also, MA induces multiple functional and structural perturbations in the brain, determining its toxicity and possibly contributing to neurotoxicity.DiscussionOur study showed BDNF-positive cells as well as GSH amount, displayed significant declines in DLPFC of MA user. MA addiction provokes transduction pathways, namely apoptosis and autophagy, along with oxidative mechanisms in DLPFC. However, further investigations are needed to throw light on the cellular and molecular mechanisms that act in the various regions of the addicted brain, especially in DLPFC.

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Dorsolateral prefrontal cortex plays causal role in probability weighting during risky choice.

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Dorsolateral prefrontal cortex plays causal role in probability weighting during risky choice.

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