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Deserno, L.

Publications and source records attributed to Deserno, L..

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Overestimating environmental volatility increases switching behavior and is linked to activation of dorsolateral prefrontal cortex in schizophrenia

BackgroundReward-based decision-making is impaired in patients with schizophrenia (PSZ) as reflected by increased choice switching. The underlying cognitive and motivational processes as well as associated neural signatures remain unknown. Reinforcement Learning (RL) and hierarchical Bayesian learning account for choice switching in different ways. We hypothesized that enhanced choice switching, as seen in PSZ during reward-based decision-making, relates to higher-order beliefs about environmental volatility and examined the associated neural activity.\n\nMethods46 medicated PSZ and 43 healthy controls (HC) performed a reward-based decision-making task requiring flexible responses to changing action-outcome contingencies during functional Magnetic Resonance Imaging (fMRI). Detailed computational modeling of choice data was performed, including RL and the hierarchical Gaussian filter (HGF). Trajectories of learning from computational modeling informed the analysis of fMRI data.\n\nResultsA three-level HGF accounted best for the observed choice data. This model revealed a heightened initial belief about environmental volatility and a stronger influence of volatility on lower-level learning of action-outcome contingencies in PSZ as compared to HC. This was replicated in an independent sample of non-medicated PSZ. Beliefs about environmental volatility were reflected by higher activity in dorsolateral prefrontal cortex of PSZ as compared to HC.\n\nConclusionsOur study suggests that PSZ inferred the environment as overly volatile, which may explain increased choice switching. In PSZ, activity in dorsolateral prefrontal cortex was more strongly related to beliefs about environmental volatility. Our computational phenotyping approach may provide useful information to dissect clinical heterogeneity and could improve prediction of outcome.

neuroscience

Dopaminergic Modulation Of Brain Signal Variability And The Functional Connectome During Cognitive Performance

Dopamine underlies important aspects of cognition, and has been suggested to boost cognitive performance. However, how dopamine modulates the large-scale cortical dynamics during cognitive performance has remained elusive. Using functional MRI during a working memory task in healthy young human listeners (N=22), we investigated the effect of levodopa (L-dopa) on two aspects of cortical dynamics, blood oxygen-level-dependent (BOLD) signal variability and the functional connectome of large-scale cortical networks. We here show that enhanced dopaminergic signaling modulates the two potentially interrelated aspects of large-scale cortical dynamics during cognitive performance, and the degree of these modulations is able to explain inter-individual differences in L-dopa-induced behavioral benefits. Relative to placebo, L-dopa increased BOLD signal variability in task-relevant temporal, inferior frontal, parietal and cingulate regions. On the connectome level, however, L-dopa diminished functional integration across temporal and cingulo-opercular regions. This hypo-integration was expressed as a reduction in network efficiency and modularity in more than two thirds of the participants and to different degrees. Hypo-integration co-occurred with relative hyper-connectivity in paracentral lobule and precuneus, as well as posterior putamen. Both, L-dopa-induced BOLD signal variability modulation and functional connectome modulations proved predictive of an individuals L-dopa-induced gain in behavioral performance, namely response speed and perceptual sensitivity. Lastly, L-dopa-induced modulations of BOLD signal variability were correlated with L-dopa-induced modulation of nodal connectivity and network efficiency. Our findings underline the role of dopamine in maintaining the dynamic range of, and communication between, cortical systems, and their explanatory power for inter-individual differences in benefits from dopamine during cognitive performance.

neuroscience