Effects of time-compressed speech training on multiple functional and structural neural mechanisms involving the left superior temporal gyrus

Time-compressed speech is an artificial form of rapidly presented speech. Training with time compressed speech in a second language leads to adaptation toward time-compressed speech in a second language and toward time compressed speech in different languages. However, the effects of training with time-compressed speech of a second language (TCSSL) on diverse cognitive functions and neural mechanisms beyond time compressed speech-related activation are unknown. We investigated the effects of 4 weeks of training with TCSSL on the fractional amplitude of spontaneous low-frequency fluctuations (fALFF) of 0.01–0.08 Hz, resting-state functional connectivity (RSFC) with the left superior temporal gyrus (STG), fractional anisotropy (FA), and regional gray matter volume (rGMV) of young adults by magnetic resonance imaging. There were no significant differences in change of performance of measures of cognitive functions or second language skills after training with TCSSL compared with that of the active control group. However, compared with the active control group, training with TCSSL was associated with increased fALFF, RSFC, and FA and decreased rGMV involving areas in the left STG. These results lacked evidence of a far transfer effect of time compressed speech training on a wide range of cognitive functions and second language skills in young adults. However, these results demonstrated effects of time compressed speech training on gray and white matter structures as well as on resting-state intrinsic activity and connectivity involving the left STG, which plays a key role in listening comprehension

Lenticular nucleus correlates of general self-efficacy in young adults

General self-efficacy (GSE) is an important factor in education, social participation, and medical treatment. However, the only study that has investigated the direct association between GSE and a neural correlate did not identify specific brain regions, rather only assessed brain structures, and included older adult subjects. GSE is related to motivation, physical activity, learning, the willingness to initiate behaviour and expend effort, and adjustment. Thus, it was hypothesized in the present study that the neural correlates of GSE might be related to changes in the basal ganglia, which is a region related to the abovementioned self-efficacy factors. This study aimed to identify the brain structures associated with GSE in healthy young adults (n = 1204, 691 males and 513 females, age 20.7 ± 1.8 years) using regional grey matter density and volume (rGMD and rGMV), fractional anisotropy (FA) and mean diffusivity (MD) analyses of magnetic resonance imaging (MRI) data. The findings showed that scores on the GSE Scale (GSES) were associated with a lower MD value in regions from the right putamen to the globus pallidum; however, there were no significant association between GSES scores and regional brain structures using the other analyses (rGMD, rGMV, and FA). Thus, the present findings indicated that the lenticular nucleus is a neural correlate of GSE

Regional homogeneity, resting-state functional connectivity and amplitude of low frequency fluctuation associated with creativity measured by divergent thinking in a sex-specific manner

Brain connectivity is traditionally thought to be important for creativity. Here we investigated the associations of creativity measured by divergent thinking (CMDT) with resting-state functional magnetic imaging (fMRI) measures and their sex differences. We examined these relationships in the brains of 1277 healthy young adults. Whole-brain analyses revealed a significant interaction between verbal CMDT and sex on (a) regional homogeneity within an area from the left anterior temporal lobe (b) on the resting state functional connectivity (RSFC) between the mPFC and the left inferior frontal gyrus and (c) on fractional amplitude of low frequency fluctuations (fALFF) in several distinct areas, including the precuneus and middle cingulate gyrus, left middle temporal gyrus, right middle frontal gyrus, and cerebellum. These interactions were mediated by positive correlations in females and negative correlations in males. These findings suggest that greater CMDT in females is reflected by (a) regional coherence (regional homogeneity) of brain areas responsible for representing and combining concepts as well as (b) the efficient functional connection (RSFC) between the key areas for the default state of cognitive activity and speech production, and (c) greater spontaneous neural activity (fALFF) during the resting of brain areas involved in frontal lobe functions, default cognitive activities, and language functions. Furthermore, these findings suggest that the associations between creativity and resting state brain connectivity patterns are different between males and females

Real time PCR confirms STATc-dependent transcriptional activation of selected genes.

<p>The differential expression of seven selected genes (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090025#pone-0090025-t003" target="_blank">Table 3</a>) in Ax2 wild-type (black bars) and STATc⁻ (white bars) cells in response to treatment with 200 mM sorbitol for 15 minutes was analysed by quantitative real time PCR. The data are expressed as means of fold change in comparison to untreated cells. Fold changes and standard deviations of six measurements from three independent experiments are shown. N/A: <i>not applicable.</i></p

Primer pairs used for quantitative Real-Time PCR analysis.

<p>Oligonucleotide primers were designed on the basis of sequence information and purchased from Metabion Corp. (Munich, Germany).</p

Model of STATc activation in response to hyperosmotic conditions.

<p>The model is based on results from previously published studies (green) and from results (blue) and educated assumptions (red) of the present work. In response to hyperosmolarity intracellular cGMP and Ca²⁺ act in parallel as second messengers in order to activate STATc. GbpC is downstream of cGMP and we postulate that it acts upstream of Pyk3 and an as yet unidentified STATc protein kinase (SPK). Phg2 inhibits PTP3 either directly or indirectly by phosphorylation of S747 and an unknown additional PTP3 serine/threonine protein kinase (PPK) must be responsible for phosphorylation of PTP3 at S448. These protein kinases are under control of the Ca²⁺ branch of the STATc signaling cascade <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090025#pone.0090025-Araki2" target="_blank">[7]</a>. The model does not satisfactorily explain all experimental results and we additionally propose a crosstalk between the two signaling branches (not shown). See the Discussion section for further details of this model.</p

<i>D. discoideum</i> mutant strains used in this study.

<p><i>D. discoideum</i> mutant strains used in this study.</p

Phg2 but not Pyk3 acts upstream of PTP3.

<p>(A) Upon hyperosmotic conditions, PTP3 becomes phosphorylated on two serine residues, S448 and S747, resulting in an inhibition of its phosphatase activity <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090025#pone.0090025-Araki2" target="_blank">[7]</a>. (B–E) Ax2/Myc-PTP3, pyk3⁻/Myc-PTP3 and phg2⁻/Myc-PTP3 cells were left untreated (−) or treated (+) with 200 mM sorbitol for 5 min (B, C) or 10 min (D, E). Myc-PTP3 was immunoprecipitated, separated by SDS-PAGE, transferred to nitrocellulose, and phosphorylated Myc-PTP3 was detected with PTP3 antibodies specific for phospho-serine 448 (B, D) and phospho-serine 747 (C, E). Total Myc-PTP3 was used as loading control and detected with an anti-Myc antibody (mAb 9E10). (F, G): Quantification of PTP3 phospho-serine 448 (F) and 747 (G) in either treated or untreated cells. Band intensities were determined densitometrically and normalised using the values for total Myc-PTP3. The amount of serine phosphorylated PTP3 of treated Ax2/Myc-PTP3 cells was set to 1 and relative values were calculated for untreated Ax2/Myc-PTP3 cells as well as for treated and untreated phg2^−/Myc-PTP3 cells. The error bars depict standard deviations of three independent experiments. (H, I): Pull-down assay to investigate the binding of Myc-PTP3 to bacterially expressed GST-Phg2. In the first approach (H) Myc-PTP3 was expressed in phg2⁻ cells, immunoprecipitated with anti-Myc Dynabeads, and eluted from the beads via a pH shift for binding to GST-Phg2 bound to glutathione beads. Lane 1: Total cell lysate of Myc-PTP3 expressing phg2⁻ cells; lane 2: Anti-Myc Dynabeads after immunoprecipitation of Myc-PTP3; lane 3: Myc-PTP3 after elution from anti-Myc Dynabeads; lane 4: GST, purified from bacteria and bound to glutathione-beads (GST-beads); lane 5: GST-Phg2, purified from bacteria and bound to glutathione-beads (GST-Phg2-beads); lane 6: supernatant after incubation of Myc-PTP3 with GST-beads; lane 7: pellet after incubation of Myc-PTP3 with GST-beads; lane 8: supernatant after incubation of Myc-PTP3 with GST-Phg2-beads; lane 9: pellet after incubation of Myc-PTP3 with GST-Phg2-beads. In the reverse approach (I) the binding of bacterially expressed GST-Phg2, which was eluted from glutathione-beads, to Myc-PTP3 bound to anti-Myc Dynabeads (Myc-PTP3-beads) was investigated. Lane 1: Total cell lysate of Myc-PTP3 expressing phg2⁻ cells; lane 2: lysate after immunoprecipitation of Myc-PTP3 with anti-Myc Dynabeads; lane 3: Anti-Myc Dynabeads with bound Myc-PTP3; lane 4: GST, purified from bacteria and eluted from glutathione-beads; lane 5: GST-Phg2, purified from bacteria and eluted from glutathione-beads; lane 6: supernatant after incubation of GST with Myc-PTP3-beads; lane 7: pellet after incubation of GST with Myc-PTP3-beads; lane 8: supernatant after incubation of GST-Phg2 with Myc-PTP3-beads; lane 9: pellet after incubation of GST-Phg2 with Myc-PTP3-beads. The order of lines from the same immunoblot were digitally re-arranged for illustration purposes to omit dispensable lines.</p

Phosphorylation of STATc is reduced in the absence of Pyk3 and Phg2.

<p>Ax2 wild-type, pyk3⁻, phg2⁻, and pyk3⁻/phg2⁻cells were either treated (+) for 15 minutes with 200 mM sorbitol (A), 20 mM 8-Br-cGMP (B), 30 µM BHQ (C) or left untreated (−). Total cell lysates were prepared, proteins were separated by 10% SDS-PAGE and transferred to nitrocellulose. Total and tyrosine phosphorylated STATc were detected with the CP22 and 7H3 antibodies, respectively. (D–F): Quantification of phosphorylated STATc in either treated or untreated cells. Band intensities were determined densitometrically and normalised using the values for total STATc. The amount of phosphorylated STATc of treated Ax2 cells was set to 1 and relative values were calculated for untreated Ax2 cells as well as treated and untreated mutants. The error bars depict standard deviations of three (D, E) and six (F) independent experiments. (G–I): Staple diagrams depicting the relative amount of phosphorylated STATc from treated (black part) versus untreated (white part) cells. The total amount of phosphorylated STATc was set to 1 for each comparison and relative values were calculated.</p

Nuclear translocation of STATc is delayed in pyk3⁻, phg2⁻, and pyk3⁻/phg2⁻ cells.

<p>(A) Ax2 wild-type, pyk3⁻, phg2⁻, and pyk3⁻/phg2⁻ cells expressing GFP-STATc were treated with 100 mM sorbitol for the indicated times to induce GFP-STATc nuclear translocation, fixed with ice-cold methanol, and observed under the fluorescence microscope. Exemplary images of GFP-STATc expressing cells after 0, 3, and 8 min of treatment are shown and the insets at 3 min show a single exemplary cell for each strain to show prominent nuclear (Ax2), transition i.e. beginning nuclear (pyk3⁻ and phg2⁻) and clear cytosolic (pyk3⁻/phg2⁻) localisation of GFP-STATc. (B) Quantification of GFP-STATc nuclear translocation in Ax2 wild-type and mutant cells. For each time point, we analysed 150 cells per experiment and determined the number of cells showing either clear cytosolic (black bar), transition i.e. beginning nuclear (grey bar) or prominent nuclear (white bar) localisation of GFP-STATc. The percentage of cells in each of these three categories was calculated. Error bars depict standard deviations of two independent experiments.</p