Distinct Mindfulness States Produce Dissociable Effects on Neural Markers of Emotion Processing: Evidence From the Late Positive Potential.

Background: Mindfulness has long been theorized to benefit emotion regulation, but despite the ubiquity of the claim, there is little empirical evidence demonstrating how mindfulness modulates the neurophysiology of emotion processing. The current study aimed to fill this gap in knowledge by leveraging a novel research approach capable of discretizing mindfulness into distinct states of open monitoring (OM) and focused attention (FA) to distinguish their influence on multimodal subjective and objective measures of emotion processing. Methods: Utilizing a fully within-participant picture viewing state induction protocol (N = 30), we compared the effects of OM and FA, rigorously contrasted against an active control, on the visually evoked late positive potential (LPP), a neural index of motivated attention. Bayesian mixed modeling was used to distinguish OM versus FA effects on the early and late sustained LPP while evaluating the influence of subjective arousal ratings as a within-participant moderator of the state inductions. Results: When negative picture trials were retrospectively rated as more subjectively arousing, the OM induction reduced the late sustained LPP response, whereas the FA induction enhanced the LPP. Conclusions: Acute manipulation of OM and FA states may reduce and enhance motivated attention to aversive stimuli during conditions of high subjective arousal, respectively. Functional distinctions between different mindfulness states on emotion processing may be most dissociable after accounting for within-participant variability in how stimuli are appraised. These results support the future potential of the state induction protocol for parsing the neural affective mechanisms that underlie mindfulness training programs and interventions.

Mindfulness, defined as a nonjudgmental awareness of present moment experience, is widely thought to benefit emotional well-being. Despite substantial research in this area, it remains unclear how mindfulness influences emotion-related processes at the level of brain functioning. The current study utilized an EEG picture viewing task to examine how open monitoring (OM) and focused attention (FA), 2 distinct mindfulness states, influence the late positive potential (LPP), a neural marker of motivated attention. The results show that when participants rated negatively valenced pictures as more subjectively arousing, the OM state decreased the LPP response, whereas the FA state increased the LPP. These findings suggest that OM and FA states may reduce and enhance motivated attention to unpleasant high arousing stimuli, respectively. At a broader level, the study shows that the effects of experientially distinct mindfulness states are distinguishable and provides a methodological foundation for future studies to disentangle the neural mechanisms of mindfulness programs and interventions.

Small molecule inhibitor agerafenib effectively suppresses neuroblastoma tumor growth in mouse models via inhibiting ERK MAPK signaling.

Neuroblastoma (NB) is the most common extracranial solid tumor in early childhood. Despite intensive multimodal therapy, nearly half of children with high-risk disease will relapse with therapy-resistant tumors. Dysregulation of MAPK pathway has been implicated in the pathogenesis of relapsed and refractory NB patients, which underscores the possibility of targeting MAPK signaling cascade as a novel therapeutic strategy. In this study, we found that high expressions of RAF family kinases correlated with advanced tumor stage, high-risk disease, tumor progression, and poor overall survival. Targeted inhibition of RAF family kinases with the novel small molecule inhibitor agerafenib abrogated the activation of ERK MAPK pathway in NB cells. Agerafenib significantly inhibited the cell proliferation and colony formation ability of NB cells in vitro, and its combination with traditional chemotherapy showed a synergistic pro-apoptotic effect. More importantly, agerafenib exhibited a favorable toxicity profile, potently suppressed tumor growth, and prolonged survival in NB mouse models. In conclusion, our preclinical data suggest that agerafenib might be an effective therapeutic agent for NB treatment, both as a single-agent and in combination with chemotherapy.