Lying about the Valence of Affective Pictures: An fMRI Study

The neural correlates of lying about affective information were studied using a functional magnetic resonance imaging (fMRI) methodology. Specifically, 13 healthy right-handed Chinese men were instructed to lie about the valence, positive or negative, of pictures selected from the International Affective Picture System (IAPS) while their brain activity was scanned by a 3T Philip Achieva scanner. The key finding is that the neural activity associated with deception is valence-related. Comparing to telling the truth, deception about the valence of the affectively positive pictures was associated with activity in the inferior frontal, cingulate, inferior parietal, precuneus, and middle temporal regions. Lying about the valence of the affectively negative pictures, on the other hand, was associated with activity in the orbital and medial frontal regions. While a clear valence-related effect on deception was observed, common neural regions were also recruited for the process of deception about the valence of the affective pictures. These regions included the lateral prefrontal and inferior parietal regions. Activity in these regions has been widely reported in fMRI studies on deception using affectively-neutral stimuli. The findings of this study reveal the effect of valence on the neural activity associated with deception. Furthermore, the data also help to illustrate the complexity of the neural mechanisms underlying deception

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

Phase I/II Trial of Sorafenib in Combination with Vinorelbine as First-Line Chemotherapy for Metastatic Breast Cancer

<div><p>Background</p><p>Preclinical models have reported a synergistic interaction between sorafenib and vinorelbine. We investigated the toxicity, efficacy, and pharmacokinetics interaction of this combination as first-line treatment for patients with metastatic breast cancer.</p><p>Methods</p><p>Patients were HER2-negative and treated with vinorelbine 30 mg/m² IV days 1,8 every 21 plus daily oral sorafenib. In the phase I portion (3+3 design) patients received sorafenib 200 mg BID (cohort 1) or 400 mg BID (cohort 2). In the phase II expansion, 21 more evaluable patients were planned to receive the maximum tolerated dose (MTD). Pharmacokinetic analysis was performed in 6 patients: blood concentrations were compared for each drug in the presence or absence of the other drug.</p><p>Results</p><p>In cohort 1, one patient experienced a dose-limiting toxicity (DLT) (grade 3 pancreatitis), requiring the expansion of this cohort to 6 patients, without further documented DLTs. In cohort 2, one patient of six experienced a grade 4 DLT (asymptomatic rise in amylase not requiring drug discontinuation), establishing this dose level as the MTD (sorafenib 400 mg BID). After expansion at the MTD, a total of 27 patients (median age 57) were treated for a median of 8 cycles. One grade 5 febrile neutropenia occurred. With repeated cycles, 52% of patients required at least 1 dose reduction of either drug. One patient experienced a sustained grade 3 fatigue resulting in treatment discontinuation. The response rate was 30%. Median PFS was 5.7 months (95% CI 4.4–7.6), and clinical benefit (absence of disease progression at 6 months) was 48%. PK analysis showed a significant interaction between the two drugs, resulting in a higher Cmax of vinorelbine in the presence of sorafenib.</p><p>Conclusion</p><p>The combination of sorafenib and vinorelbine at full doses is feasible but not devoid of toxicity, likely also due to a significant PK interaction.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT00764972" target="_blank">NCT00764972</a></p></div

Progression-free survival of the VS combination

<p>Progression-free survival of the VS combination</p

Mean plasma concentrations of vinorelbine when administered as a single agent (cycle 1 day 1, blue curve) or in the presence of steady-state concentrations of sorafenib (cycle 2 day 1, red curve).

<p>Mean plasma concentrations of vinorelbine when administered as a single agent (cycle 1 day 1, blue curve) or in the presence of steady-state concentrations of sorafenib (cycle 2 day 1, red curve).</p

Mean pharmacokinetic parameters in all 6 patients with SD.

<p>Mean pharmacokinetic parameters in all 6 patients with SD.</p

Flow diagram of the patients enrolled in the study.

<p>Flow diagram of the patients enrolled in the study.</p