Asymmetric representation of aversive prediction errors in Pavlovian threat conditioning

Learning to predict threat is important for survival. Such learning may be driven by differences between expected and encountered outcomes, termed prediction errors (PEs). While PEs are crucial for reward learning, the role of putative PE signals in aversive learning is less clear. Here, we used functional magnetic resonance imaging in humans to investigate neural PE signals. Four cues, each with a different probability of being followed by an aversive outcome, were presented multiple times. We found that neural activity only at omission - but not at occurrence - of predicted threat related to PEs in the medial prefrontal cortex. More expected omission was associated with higher neural activity. In no brain region did neural activity fulfill necessary computational criteria for full signed PE representation. Our result suggests that, different from reward learning, aversive learning may not be primarily driven by PE signals in one single brain region

Oncogenic Herpesvirus Utilizes Stress-Induced Cell Cycle Checkpoints for Efficient Lytic Replication

Kaposi's sarcoma herpesvirus (KSHV) causes Kaposi's sarcoma and certain lymphoproliferative malignancies. Latent infection is established in the majority of tumor cells, whereas lytic replication is reactivated in a small fraction of cells, which is important for both virus spread and disease progression. A siRNA screen for novel regulators of KSHV reactivation identified the E3 ubiquitin ligase MDM2 as a negative regulator of viral reactivation. Depletion of MDM2, a repressor of p53, favored efficient activation of the viral lytic transcription program and viral reactivation. During lytic replication cells activated a p53 response, accumulated DNA damage and arrested at G2-phase. Depletion of p21, a p53 target gene, restored cell cycle progression and thereby impaired the virus reactivation cascade delaying the onset of virus replication induced cytopathic effect. Herpesviruses are known to reactivate in response to different kinds of stress, and our study now highlights the molecular events in the stressed host cell that KSHV has evolved to utilize to ensure efficient viral lytic replication.Peer reviewe

Code

All of the MATLAB scripts necessary for reproducing the parameter estimates and plots in our study<br><br>Each script includes a description of its function and is commented throughout in most cases<br><br><div><b>Main script for Prospect Theory parameter estimates:</b></div><div>Certainty_equivalent_task.m<br><br><b>Parameter recovery:</b><br>Certainty_equivalent_simanalysis.m<br><br><b>Checking quality of model fitting:</b><br>getCovarianceMatrix.m<br>plotModelFitCovarSdErr.m<br>plotResnorm.m<br>weightedParameterEstimates.m<br><br><b>Probability Weighting Function plots (manuscript Figure 1B, 2C, 3):</b><br>Certainty_equivalent_plots_withmedians.m<br><br><b>Boxplot and stripchart (Figure 2A,B) - in R:</b><br>figures_boxplot_stripchart.R<br>(requires transformation of MATLAB data into Excel format)</div

Inhibiting human aversive memory by transcranial theta-burst stimulation to the primary sensory cortex

BACKGROUND: Predicting adverse events from past experience is fundamental for many biological organisms. However, some individuals suffer from maladaptive memories that impair behavioral control and well-being, e.g., after psychological trauma. Inhibiting the formation and maintenance of such memories would have high clinical relevance. Previous preclinical research has focused on systemically administered pharmacological interventions, which cannot be targeted to specific neural circuits in humans. Here, we investigated the potential of noninvasive neural stimulation on the human sensory cortex in inhibiting aversive memory in a laboratory threat conditioning model. METHODS: We build on an emerging nonhuman literature suggesting that primary sensory cortices may be crucially required for threat memory formation and consolidation. Immediately before conditioning innocuous somatosensory stimuli (conditioned stimuli [CS]) to aversive electric stimulation, healthy human participants received continuous theta-burst transcranial magnetic stimulation (cTBS) to individually localized primary somatosensory cortex in either the CS-contralateral (experimental) or CS-ipsilateral (control) hemisphere. We measured fear-potentiated startle to infer threat memory retention on the next day, as well as skin conductance and pupil size during learning. RESULTS: After overnight consolidation, threat memory was attenuated in the experimental group compared with the control cTBS group. There was no evidence that this differed between simple and complex CS or that CS identifi- cation or initial learning were affected by cTBS. CONCLUSIONS: Our results suggest that cTBS to the primary sensory cortex inhibits threat memory, likely by an impact on postlearning consolidation. We propose that noninvasive targeted stimulation of the sensory cortex may provide a new avenue for interfering with aversive memories in humans

Asymmetric representation of aversive prediction errors in Pavlovian threat conditioning

Survival in biological environments requires learning associations between predictive sensory cues and threatening outcomes. Such aversive learning may be implemented through reinforcement learning algorithms that are driven by the signed difference between expected and encountered outcomes, termed prediction errors (PEs). While PE-based learning is well established for reward learning, the role of putative PE signals in aversive learning is less clear. Here, we used functional magnetic resonance imaging in humans (21 healthy men and women) to investigate the neural representation of PEs during maintenance of learned aversive associations. Four visual cues, each with a different probability (0, 33, 66, 100%) of being followed by an aversive outcome (electric shock), were repeatedly presented to participants. We found that neural activity at omission (US-) but not occurrence of the aversive outcome (US+) encoded PEs in the medial prefrontal cortex. More expected omission of aversive outcome was associated with lower neural activity. No neural signals fulfilled axiomatic criteria, which specify necessary and sufficient components of PE signals, for signed PE representation in a whole-brain search or in a-priori regions of interest. Our results might suggest that, different from reward learning, aversive learning does not involve signed PE signals that are represented within the same brain region for all conditions

Dopaminergic Drug Effects on Probability Weighting during Risky Decision Making

Contains fulltext : 191053.pdf (publisher's version ) (Open Access

PCF05: fMRI data in a Pavlovian delay threat conditioning task with four visual CS with different rates of electrical US

This data set includes selected functional magnetic resonance imaging (fMRI) data supplementing an article. The data include: 1. Untresholded Statistical Parametric Maps (SPMs) and beta images (BOLD signal estimates) for relevant contrasts for the GLMs reported in the article 2. Region-of-interest (ROI) masks: anatomical ROIs with combined hemispheres, and masks created from significant BOLD signal clusters from the whole-brain analyses 3. Summary data files for mean beta (BOLD signal estimate) values and their within-subject errors for each ROI Details of the experimental paradigm as well as of the fMRI data acquisition and analysis can be found in the associated article