Presentation_1_Cortical Gray Matter Loss, Augmented Vulnerability to Speech-on-Speech Masking, and Delusion in People With Schizophrenia.pdf

<p>People with schizophrenia exhibit impairments in target-speech recognition (TSR) against multiple-talker-induced informational speech masking. Up to date, the underlying neural mechanisms and its relationships with psychotic symptoms remain largely unknown. This study aimed to investigate whether the schizophrenia-associated TSR impairment contribute to certain psychotic symptoms by sharing underlying alternations in cortical gray-matter volume (GMV) with the psychotic symptoms. Participants with schizophrenia (N = 34) and their matched healthy controls (N = 29) were tested for TSR against a two-talker-speech masker. Psychotic symptoms of participants with schizophrenia were evaluated using the Positive and Negative Syndrome Scale. The regional GMV across various cortical regions was assessed using the voxel-based morphometry. The results of partial-correlation and mediation analyses showed that in participants with schizophrenia, the TSR was negatively correlated with the delusion severity, but positively with the GMV in the bilateral superior/middle temporal cortex, bilateral insular, left medial orbital frontal gyrus, left Rolandic operculum, left mid-cingulate cortex, left posterior fusiform, and left cerebellum. Moreover, the association between GMV and delusion was based on the mediating role played by the TSR performance. Thus, in people with schizophrenia, both delusions and the augmented vulnerability of TSR to informational masking are associated with each other and share the underlying cortical GMV reduction, suggesting that the origin of delusion in schizophrenia may be related to disorganized or limited informational processing (e.g., the incapability of adequately filtering information from multiple sources at the perceptual level). The TSR impairment can be a potential marker for predicting delusion severity.</p

CHA structure and its effect on RD cell viability.

<p>(A) The structure of CHA. (B) Control: control ; DMSO: 0.1% DMSO was added in RD cells. CHA was serially diluted as different concentrations (160,80,40,20,10,5 and 2.5 µg/mL) in triplicate. After 2 days of incubation, the cytotoxicity of CHA was determined by MTT assay. Data were presented as mean ± S.D. of three independent experiments.</p

CHA inhibits EV71 replication in RD cells.

<p>RD cells (5×10⁶) were infected with EV71 at a MOI of 5 in the presence or absence of CHA (20 µg/ml) and ribavirin (40 µg/ml). CHA and ribavirin were added with EV71 at the same time or absorbation for 1 h. Then cell supernatants were collected at 0, 4, 8,12, 16, 20, 24,28, 32 and 36 h p.i. and the viral titers were determined by a plaque forming assay. Each point represents the mean ± S.D. of three independent experiments (*** <i>p</i> < 0.001).</p

Effects of CHA on EV71 replication before or after viral infection.

<p>DMSO: EV71 infection with DMSO. CHA: EV71 infection with DMSO and CHA RD cells (5 × 10⁶) were infected with EV71 (5 MOI) and CHA (20 µg/ml) was added at the indicated time. Cell supernatants were collected at 25 h p.i. and EV71 titers were determined by a plaque forming assay. Each bar represents the mean ± S.D. of three independent experiments（** <i>p</i> < 0.01, *** <i>p</i> < 0.001).</p

Effects of CHA on EV71 replication.

<p>Ribavirin was used as positive control and 0.1% DMSO as negative control. Inhibitory effects of ribavirin and indicated concentration of CHA on EV71 replication were determined by a plaque reduction assay. Data were represented as mean ± S.D. of three independent experiments.</p

EV71 infection stimulates cytokine secretion.

<p>Control: Uninfected RD cells; EV71: RD cell-infected with EV71 (MOI = 5); CHA: EV71 infection in the presence of CHA (20 µg/ml). RD cells were absorbed with EV71 for 1h, and then treated with or without CHA(20 µg/ml). Culture supernatants were collected at 8h, 12h, and 20h. The concentrations of IL-2, IL-6, IL-10, TNF-α, IFN-γ and MCP-1 were detected by luminex fluorescent technique. The data were expressed as mean ± SE from 3 independent experiments. ** <i>P</i> < 0.01 and ***<i>P</i> < 0.001 by two-way ANOVA.</p

Effects of CHA on EV71 protein expression.

<p>EV71 infection: RD cell-infected with EV71 (MOI = 5). CHA treatment: EV71 infection in the presence of CHA (20 µg/ml). DMSO: EV71 infection treated with 0.1% DMSO. At 4 and 8h, the cell lysates were subjected to 10% SDS-PAGE and transferred to PVDF membrane to determine the level of EV71 VP1, 2A, 3C, and 3D.</p