Selective and divided attention modulates auditory–vocal integration in the processing of pitch feedback errors

Speakers rapidly adjust their ongoing vocal productions to compensate for errors they hear in their auditory feedback. It is currently unclear what role attention plays in these vocal compensations. This event‐related potential (ERP) study examined the influence of selective and divided attention on the vocal and cortical responses to pitch errors heard in auditory feedback regarding ongoing vocalisations. During the production of a sustained vowel, participants briefly heard their vocal pitch shifted up two semitones while they actively attended to auditory or visual events (selective attention), or both auditory and visual events (divided attention), or were not told to attend to either modality (control condition). The behavioral results showed that attending to the pitch perturbations elicited larger vocal compensations than attending to the visual stimuli. Moreover, ERPs were likewise sensitive to the attentional manipulations: P2 responses to pitch perturbations were larger when participants attended to the auditory stimuli compared to when they attended to the visual stimuli, and compared to when they were not explicitly told to attend to either the visual or auditory stimuli. By contrast, dividing attention between the auditory and visual modalities caused suppressed P2 responses relative to all the other conditions and caused enhanced N1 responses relative to the control condition. These findings provide strong evidence for the influence of attention on the mechanisms underlying the auditory–vocal integration in the processing of pitch feedback errors. In addition, selective attention and divided attention appear to modulate the neurobehavioral processing of pitch feedback errors in different ways.     

Sub‐hubs of baseline functional brain networks are related to early improvement following two‐week pharmacological therapy for major depressive disorder

Accumulating evidence suggests that early improvement after two‐week antidepressant treatment is predictive of later outcomes of patients with major depressive disorder (MDD); however, whether this early improvement is associated with baseline neural architecture remains largely unknown. Utilizing resting‐state functional MRI data and graph‐based network approaches, this study calculated voxel‐wise degree centrality maps for 24 MDD patients at baseline and linked them with changes in the Hamilton Rating Scale for Depression (HAMD) scores after two weeks of medication. Six clusters exhibited significant correlations of their baseline degree centrality with treatment‐induced HAMD changes for the patients, which were mainly categorized into the posterior default‐mode network (i.e., the left precuneus, supramarginal gyrus, middle temporal gyrus, and right angular gyrus) and frontal regions. Receiver operating characteristic curve and logistic regression analyses convergently revealed excellent performance of these regions in discriminating the early improvement status for the patients, especially the angular gyrus (sensitivity and specificity of 100%). Moreover, the angular gyrus was identified as the optimal regressor as determined by stepwise regression. Interestingly, these regions possessed higher centrality than others in the brain (P < 10^?3) although they were not the most highly connected hubs. Finally, we demonstrate a high reproducibility of our findings across several factors (e.g., threshold choice, anatomical distance, and temporal cutting) in our analyses. Together, these preliminary exploratory analyses demonstrate the potential of neuroimaging‐based network analysis in predicting the early therapeutic improvement of MDD patients and have important implications in guiding earlier personalized therapeutic regimens for possible treatment‐refractory depression. Hum Brain Mapp 36:2915–2927, 2015. © 2015 Wiley Periodicals, Inc.     

Expression of Hsp72 in lymphocytes in patients with febrile convulsion

The pathophysiology of febrile convulsion, the most common childhood neurologic disease, remains unclear. In this study, we investigated what role a heat shock protein plays in this disease. We enrolled eight boys and two girls with febrile convulsion and 10 age-matched healthy controls. We did a biosynthetic evaluation of both groups by separating lymphocytes and measuring the expression of heat shock protein 72 before and after heat shock treatment. Before the treatment, both groups were found to have small amounts of constitutive heat shock protein 72. Afterwards, its expression increased in both groups, and no statistical difference was found between the increases in the two groups. In addition, there was no obvious difference in the susceptibility to produce heat shock proteins. However, the febrile convulsion group was found to have a significant decrease in phosphorylation of heat shock protein 72. These results suggest the possible involvement of post-translational modification of heat shock proteins, most likely phosphorylation, in the pathogenesis of febrile convulsion.     

Extraskeletal intracranial mesenchymal chondrosarcoma: case report and literature review

We present the case of a 13-year-old girl with a huge intracranial mesenchymal chondrosarcoma. She had suffered from severe headache, diplopia, intermittent nausea and vomiting for 1 month. Neurologic examination revealed bilateral blurred optic disc margins and abducens paresis. Magnetic resonance imaging demonstrated a giant, heterogeneous, intensely enhancing mass of 7 x 8 x 6 cm, occupying the bilateral frontal and left high parietal regions and based on the anterior cerebral falx. A presumptive diagnosis of aggressive meningioma was made. The patient underwent bicoronal craniotomy and gross total resection of the tumor. Pathologic examination revealed an extraskeletal mesenchymal chondrosarcoma. She was under regular follow-up and remained free of recurrence after surgery. In addition to the current case, we review previously reported cases of extraskeletal intracranial mesenchymal chondrosarcoma and discuss treatment strategies and outcomes.     

A novel system to identify Myb target promoters in friend murine erythroleukemia cells

Friend murine erythroleukemia (MEL) cells provide an early erythroid precursor model that can be induced to terminally differentiate in cell culture and has been used to study erythroid differentiation as well as multistage tumorigenesis. During the chemically induced differentiation of MEL cells, expression of the c-myb protooncogene is downregulated in a biphasic fashion and forced expression of c-myb is able to block the differentiation process, suggesting that c-myb activity may be limiting for differentiation in MEL cells. We have recently produced stable transfectants in the C19 MEL cell line that carry a dominant interfering myb allele (MEnT) under the control of an inducible mouse metallothionein I (MTH) promoter. Upon inducing expression of MEnT, transfected cells enter a differentiation program and begin to produce alpha-globin mRNA, assemble hemoglobin, and stop proliferating. Differential display was used to compare mRNA expression between parental C19 MEL cells induced to differentiate with hexamethylene bisacetamide (HMBA) and stable transfectants induced to differentiate via expression of MEnT to identify potential Myb target promoters. We identified six candidate cDNAs in this fashion and present evidence that two of these represent genes that are dependent on c-Myb activity for maximal expression in MEL cells.     

Hybrid Molecule from Farnesylthiosalicylic Acid-diamine and Phenylpropenoic Acid as Ras-related Signaling Inhibitor with Potent Antitumor Activities

Novel series of Farnesylthiosalicylic acid-diamine/phenylpropenoic acid hybrids were designed and synthesized. Their in vitro growth inhibitory assays showed that most compounds displayed strong antiproliferation activity against seven cancer cells. Especially, the new hybrid 12f , by the conjugation of 10a with ferulic acid, could selectively suppress the proliferation of tumor cells and display significantly lower toxicities to normal cells than its intermediate 10a . Furthermore, 12f dose-dependently induced SMMC-7721 cell apoptosis. Additionally, our observations demonstrated that 12f inhibited both Ras-related signaling and phosphorylated NF-κB synergistically, which may be advantageous to the strong antitumor activities of 12f . Our findings suggest that these novel hybrids may hold a great promise as therapeutic agents for the intervention of human cancers.     

Discovery of Novel Multiacting Topoisomerase I/II and Histone Deacetylase Inhibitors

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Structure-Based Design of GNE-495, a Potent and Selective MAP4K4 Inhibitor with Efficacy in Retinal Angiogenesis

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Discovery of Imidazo[1,2-α][1,8]naphthyridine Derivatives as Potential HCV Entry Inhibitor

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