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Neural mechanisms for integrating consecutive and interleaved natural events.

ABSTRACT: To understand temporally extended events, the human brain needs to accumulate information continuously across time. Interruptions that require switching of attention to other event sequences disrupt this process. To reveal neural mechanisms supporting integration of event information, we measured brain activity with functional magnetic resonance imaging (fMRI) from 18 participants while they viewed 6.5-minute excerpts from three movies (i) consecutively and (ii) as interleaved segments of approximately 50-s in duration. We measured inter-subject reliability of brain activity by calculating inter-subject correlations (ISC) of fMRI signals and analyzed activation timecourses with a general linear model (GLM). Interleaving decreased the ISC in posterior temporal lobes, medial prefrontal cortex, superior precuneus, medial occipital cortex, and cerebellum. In the GLM analyses, posterior temporal lobes were activated more consistently by instances of speech when the movies were viewed consecutively than as interleaved segments. By contrast, low-level auditory and visual stimulus features and editing boundaries caused similar activity patterns in both conditions. In the medial occipital cortex, decreases in ISC were seen in short bursts throughout the movie clips. By contrast, the other areas showed longer-lasting differences in ISC during isolated scenes depicting socially-relevant and suspenseful content, such as deception or inter-subject conflict. The areas in the posterior temporal lobes also showed sustained activity during continuous actions and were deactivated when actions ended at scene boundaries. Our results suggest that the posterior temporal and dorsomedial prefrontal cortices, as well as the cerebellum and dorsal precuneus, support integration of events into coherent event sequences. Hum Brain Mapp 38:3360-3376, 2017. © 2017 Wiley Periodicals, Inc.

SUBMITTER: Lahnakoski JM

PROVIDER: S-EPMC6866821 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Neural mechanisms for integrating consecutive and interleaved natural events.

Lahnakoski Juha M JM Jääskeläinen Iiro P IP Sams Mikko M Nummenmaa Lauri L

Human brain mapping 20170405 7

To understand temporally extended events, the human brain needs to accumulate information continuously across time. Interruptions that require switching of attention to other event sequences disrupt this process. To reveal neural mechanisms supporting integration of event information, we measured brain activity with functional magnetic resonance imaging (fMRI) from 18 participants while they viewed 6.5-minute excerpts from three movies (i) consecutively and (ii) as interleaved segments of approx ...[more]

PMID: 28379608

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Project description:ObjectiveTo integrate pharmacovigilance and network toxicology methods to explore the potential adverse drug events (ADEs) and toxic mechanisms of selumetinib, and to provide a reference for quickly understanding the safety and toxicological mechanisms of newly marketed drugs.MethodsTaking selumetinib as an example, this study integrated pharmacovigilance methods based on real-world data and network toxicology methods to analyze its ADE and its potential toxicological mechanism. First, the ADE reports of selumetinib were extracted from the US Food and Drug Administration (FDA) adverse event reporting system (FAERS), and the ADE signals were detected by reporting odds ratio (ROR) and UK medicines and healthcare products regulatory agency (MHRA) methods. The ADE signals were classified and described according to the preferred terms (PTs) and system organ class (SOC) derived from the Medical Dictionary for Regulatory Activities (MedDRA). The network toxicology method was used to analyze the toxicological mechanism of the interested SOCs. The specific steps included predicting the potential targets of selumetinib using TOXRIC, STITCH, ChEMBL, CTD, SwissTargetPreditcion, and Super-PRED databases, collecting the targets of SOC using GeneCards database, conducting protein-protein interaction (PPI) analysis through STRING database, conducting gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis through DAVID database, and testing the molecular affinity using AutoDock software.ResultsA total of 1388 ADE reports related to selumetinib were extracted, and 53 positive signals were detected by ROR and MHRA methods, of which 20 signals were not mentioned in the package insert, including ingrowing nail, hyperphosphatemia, cardiac valve disease, hematuria, neutropenia, etc. Analysis of the toxicological mechanism of six SOCs involved in positive ADE signals revealed that the key targets included EGFR, STAT3, AKT1, IL6, BCL2, etc., and the key pathways included PI3K/Akt pathway, apoptosis, ErbB signaling pathway, and EGFR tyrosine kinase inhibitor resistance, etc. Molecular docking assays showed spontaneous binding of selumetinib to key targets in these pathways.ConclusionThe pharmacovigilance analysis identified some new potential ADEs of selumetinib, and the network toxicology analysis showed that the toxic effects of selumetinib may be related to PI3K/Akt pathway, apoptosis, ErbB signaling pathway, EGFR tyrosine kinase inhibitor resistance and other pathways.

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Neural mechanisms for integrating consecutive and interleaved natural events.

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Neural mechanisms for integrating consecutive and interleaved natural events.

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