Electroacupuncture ameliorates neuroinflammation by inhibiting TRPV4 channel in ischemic stroke.

AIMS: We investigated the potential mechanisms underlying the therapeutic efficacy of electroacupuncture (EA) at the Shuigou (GV26) and Baihui (GV20) acupoints in the treatment of ischemic stroke. METHODS: We assessed the therapeutic effects of EA on MCAO mice through behavioral studies and TTC staining. Various techniques, such as RT-PCR, immunofluorescence, and Western blots, were employed to evaluate the activation and polarization of microglia/macrophages, and changes in the TRPV4 ion channel. We used the TRPV4 antagonist GSK2193874 (GSK219) to verify the involvement of TRPV4 in the therapeutic effects of EA. RESULTS: EA effectively improved neurological impairments and reduced cerebral infarction volume in MCAO mice. It suppressed activated microglia/macrophages and inhibited their polarization toward the M1 phenotype post-MCAO. EA also downregulated the expression of pro-inflammatory cytokines, including Tnf-α, Il-6, Il-1ß, and Ccl-2 mRNA. Furthermore, EA reduced the elevated expression of TRPV4 following MCAO. Treatment with the TRPV4 antagonist GSK219 mirrored the effects of EA in MCAO mice. Notably, the combination of EA and GSK219 did not demonstrate an additive or synergistic effect. CONCLUSION: EA may inhibit neuroinflammation and exhibit a protective effect against ischemic brain injury by suppressing TRPV4 and the subsequent M1 polarization of microglia/macrophages.

Ginkgo biloba extract attenuates cisplatin-induced renal interstitial fibrosis by inhibiting the activation of renal fibroblasts through down-regulating the HIF-1α/STAT3/IL-6 pathway in renal tubular epithelial cells.

BACKGROUND: Activation of renal fibroblasts into myofibroblasts plays an important role in promoting renal interstitial fibrosis (RIF). Ginkgo biloba extract (EGb) can alleviate RIF induced by cisplatin (CDDP). PURPOSE: To elucidate the effect of EGb treatment on cisplatin-induced RIF and reveal its potential mechanism. METHODS: The two main active components in EGb were determined by high-performance liquid chromatography (HPLC) analysis. Rats were induced by CDDP and then treated with EGb, 2ME2 (HIF-1α inhibitor) or amifostine. After HK-2 cells and HIF-1α siRNA HK-2 cells were treated with CDDP, EGb or amifostine, the conditioned medium from each group was cultured with NRK-49F cells. The renal function of rats was detected. The renal damage and fibrosis were evaluated by H&E and Masson trichrome staining. The IL-6 content in the cell medium was detected by ELISA. The expression levels of indicators related to renal fibrosis and signaling pathway were examined by western blotting and qRT-PCR. RESULTS: HPLC analysis showed that the contents of quercetin and kaempferol in EGb were 36.0 µg/ml and 45.7 µg/ml, respectively. In vivo, EGb and 2ME2 alleviated renal damage and fibrosis, as well as significantly decreased the levels of α-SMA, HIF-1α, STAT3 and IL-6 in rat tissues induced by CDDP. In vitro, the levels of HIF-1α, STAT3 and IL-6 were significantly increased in HK-2 cells and HIF-1α siRNA HK-2 cells induced by CDDP. Notably, HIF-1α siRNA significantly decreased the levels of HIF-1α, STAT3 and IL-6 in HK-2 cells, as well as the IL-6 level in medium from HK-2 cells. Additionally, the α-SMA level in NRK-49F cells was significantly increased after being cultured with conditioned medium from HK-2 cells or HIF-1α siRNA HK-2 cells exposed to CDDP. Furthermore, exogenous IL-6 increased the α-SMA level in NRK-49F cells. Importantly, the expression levels of the above-mentioned indicators were significantly decreased after the HK-2 cells and HIF-1α siRNA HK-2 cells were treated with EGb. CONCLUSION: This study revealed that EGb improves CDDP-induced RIF, and the mechanism may be related to its inhibition of the renal fibroblast activation by down-regulating the HIF-1α/STAT3/IL-6 pathway in renal tubular epithelial cells.

Corrigendum: Compound Dihuang Granule inhibits nigrostriatal pathway apoptosis in Parkinson's disease by suppressing the JNK/AP-1 pathway.

[This corrects the article DOI: 10.3389/fphar.2021.621359.].

Panax notoginseng saponins reduces the cisplatin-induced acute renal injury by increasing HIF-1α/BNIP3 to inhibit mitochondrial apoptosis pathway.

Cisplatin (CDDP) may induce apoptosis of renal tubular epithelial cells (RTEC) and cause CDDP-induced acute kidney injury (CAKI) during cancer treatment, but yet lack of preventive measures and effective treatment. As a new Chinese herbal preparation, Panax notoginseng saponins (PNS) has been found to mitigate CDDP-induced CAKI through elevating the expression of HIF-1α in the rat model, according to the data from our previous works. However, the underlying link between HIF-1α and apoptosis has not been well elucidated. The current study as a follow-up work, was aimed to reveal if PNS improves CAKI through HIF-1α-dependent apoptosis. A stably HIF-1α-knockdown human proximal tubular epithelial cell (HK-2) line was established by transfecting a HIF-1α-siRNA into HK-2 cells. Cell viability, mitochondrial function, cell apoptosis ratio and the expression of apoptosis-associated proteins (Cyt C, Bcl2, Bax, caspases 3) were determined. In order to elucidate the underlying mechanism, the expression of HIF-1α and BNIP3 were assessed. Our results showed that treatment of PNS rescued the cell viability of CDDP-injured HK-2 or HIF-1α-knockdown HK-2 cells, and increased the expression levels of ATP and MMP in HK-2 or HIF-1α-knockdown HK-2 cells which were reduced by CDDP. Moreover, PNS treatment decreased the CDDP or CDDP plus HIF-1α-knockdown-induced elevation of apoptosis and apoptosis-associated protein expressions. These findings demonstrate that PNS reduces CAKI through increasing HIF-1α to inhibit mitochondrial apoptosis pathway. Hence, we suggest PNS as a protective and therapeutic new drug for CDDP treatment of cancers, which might have significant meaning of further research and application potential.

Drug-containing serum of rhubarb-astragalus capsule inhibits the epithelial-mesenchymal transformation of HK-2 by downregulating TGF-ß1/p38MAPK/Smad2/3 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheum palmatum L; Astragalus membranaceus (Fisch.), is referred to as 'Dahuang, Huangqi' in China. As an important medicinal plant, the rhizome of rhubarb and astragalus is traditionally used in the treatment of kidney diseases associated with renal failure, inflammation and tumors. AIM OF THE STUDY: This study aimed to investigate the effect of a drug-containing serum of rhubarb-astragalus capsules (composed of rhubarb and astragalus) and to elucidate its mechanism in the epithelial-mesenchymal transformation of renal tubular epithelial cells. MATERIALS AND METHODS: Epithelial-mesenchymal transformation (EMT) of HK-2 cells was induced by TGF-ß1, and rhubarb-astragalus and losartan drug-containing serum from rats, as well as SB203580 (a specific inhibitor of p38 MAPK), were used. High-performance liquid chromatography analysis was performed to determine the main components of the drug-containing serum of rhubarb-astragalus from rats. Western blotting and immunofluorescence analysis were used to determine the levels of protein expression, and real-time quantitative PCR analysis was used to detect the levels of gene expression. RESULTS: The drug-containing serum of rhubarb-astragalus contained emodin (0.36 µg/ml) and danthraquinone (0.96 µg/ml). Rhubarb-astragalus significantly decreased the protein expression levels of α-SMA, FN, vimentin and N-cadherin in HK-2 cells that were increased by TGF-ß1, while it significantly increased the E-cadherin protein expression level that was decreased by TGF-ß1. Rhubarb-astragalus also significantly decreased the protein expression levels of TGF-ß1 and p38 MAPK and the mRNA expression levels of α-SMA, vimentin, TGF-ß1, p38 MAPK, Smad2 and Smad3 in HK-2 cells that were increased by TGF-ß1. It is worth noting that SB203580 (a p38 MAPK inhibitor) had similar effects as rhubarb-astragalus in this study. CONCLUSION: The drug-containing serum of rhubarb-astragalus can inhibit EMT in HK-2 cells by downregulating the TGF-ß1/p38 MAPK/Smad2/3 pathway.

Contextual prediction modulates musical tension: Evidence from behavioral and neural responses.

Tension is a bridge between music structure and emotion. It is known that tension is affected by prediction in music listening as music unfolds. Combining behavioral and neural responses, the current research investigated how musical predictions influence tension in the process of prediction build-up based on musical context (anticipatory stage) and its integration with upcoming stimuli (integration stage). The results showed that, at the anticipatory stage, compared with high-prediction conditions, in low-prediction conditions tension curve changed faster and unstable, and a larger N5 in ERP response was elicited. Furthermore, at the integration stage, compared with congruent conditions, in incongruent conditions the behavioral rating of tension were higher regardless of the predictability of the final chord; a right negativity and P600 were elicited, and the amplitude of P600 was modulated by the predictability of the final chord. These results indicated that the effect of prediction on tension was modulated by contextual predictability. The findings provide a more comprehensive view on how musical prediction affects musical tension.

Compound Dihuang Granule Inhibits Nigrostriatal Pathway Apoptosis in Parkinson's Disease by Suppressing the JNK/AP-1 Pathway.

Compound Dihuang Granule (CDG) is widely used in traditional Chinese medicine (TCM) for the treatment of Parkinson's disease (PD). It has been shown to alleviate PD symptoms. However, the molecular mechanisms of its action have not been established. To establish the molecular mechanisms of CDG against PD, we used TCM network pharmacology methods to predict its molecular targets and signaling pathways, followed by experimental validation. The Core Protein protein interaction (PPI) network of the 150 intersections between CDG and PD-related genes, comprising 23 proteins, including CASP3 (caspase-3), MAPK8 (JNK), FOS (c-Fos), and JUN (c-Jun). KEGG and GO analyses revealed that apoptotic regulation and MAPK signaling pathways were significantly enriched. Since c-Jun and c-Fos are AP-1 subunits, an important downstream JNK effector, we investigated if the JNK/AP-1 pathway influences CDG against apoptosis through the nigrostriatal pathways in PD rat models. Molecular docking analysis found that the top three bioactive compounds exhibiting the highest Degree Centrality following online database and LC-MS analysis had high affinities for JNK. Experimental validation analysis showed that CDG decreased the number of rotating laps and suppressed the levels of phosphorylated c-Jun, c-Fos, and JNK, as well as the number of TUNEL positive cells and the cleaved caspase-3 level in the nigrostriatal pathway. Furthermore, CDG treatment elevated the number of TH neurons, TH expression level, and Bcl-2/Bax protein ratio in a 6-OHDA-induced PD rat. These findings are in tandem with those obtained using SP600125, a specific JNK inhibitor. In conclusion, CDG suppresses the apoptosis of the nigrostriatal pathway and relieves PD symptoms by suppressing the JNK/AP-1 signaling pathway.

Electroacupuncture alleviates ischaemic brain injury by regulating the miRNA-34/Wnt/autophagy axis.

Electroacupuncture (EA), a modern form of acupuncture therapy, has been widely used for the treatment of ischaemic brain injury. However, the molecular mechanism by which EA improves ischaemic brain injury remains unclear. In the current study, middle cerebral artery occlusion (MCAO) rats were treated with EA. The infarct volumes and apoptosis of neurocytes were assessed to determine the therapeutic effect of EA. The differentially expressed miRNAs between the control, MCAO and MCAO treated with EA groups were detected by high-throughput sequencing. The results indicated that EA treatment decreased neurocyte apoptosis and ischaemic infarct volume. Between the three groups, miR-34, miR-235 and miR-275 were found to be significantly different. Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway data suggest that the Wnt pathway may play an important role in ischaemic brain injury and in the treatment of EA. Our data documented that miR-34 was obviously increased in the MCAO group, while EA treatment decreased miR-34 expression. WNT1 was the target of miR-34 and was confirmed by a luciferase reporter assay. A previous study suggested that the Wnt pathway mediates autophagy in EA-pretreated MCAO mice. Our data further confirmed that EA treatment after MCAO also alleviated autophagy in the MCAO group. Our results suggest that EA treatment alleviates ischaemic brain injury by inhibiting autophagy through the miR-34/Wnt pathway.

Rhubarb and Astragalus Capsule Attenuates Renal Interstitial Fibrosis in Rats with Unilateral Ureteral Obstruction by Alleviating Apoptosis through Regulating Transforming Growth Factor beta1 (TGF-ß1)/p38 Mitogen-Activated Protein Kinases (p38 MAPK) Pathway.

BACKGROUND Rhubarb and astragalus capsule (RAC) has been used in the clinical treatment of chronic kidney disease for decades. However, the mechanism of RAC has not been fully elucidated. This study aimed to investigate the protective effect and mechanisms of RAC on unilateral ureteral obstruction (UUO)-induced renal interstitial fibrosis. MATERIAL AND METHODS The main components of RAC are detected by high-performance liquid phase (HPLC). A rat model of UUO was established, and a subset of rats underwent treatment with RAC. Renal function and renal pathology were examined at 14 days and 21 days after the UUO operation. Renal cell apoptosis was detected by TUNEL staining. The levels of Bcl-2 and Bax in the kidney were examined by western blotting, and the levels of collagen I, alpha-SMA, transforming growth factor (TGF)-ß1, and p38 MAPK in the kidneys were detected by immunohistochemistry. RESULTS High-performance liquid phase chromatography showed that RAC contained 1.12 mg/g aloe-emodin, 2.25 mg/g rhein, 1.75 mg/g emodin, and 4.50 mg/g chrysophanol. Administration of RAC significantly decreased the levels of urinary N-acetyl-ß-D-glucosaminidase (NAG), serum blood urea nitrogen (BUN), and creatinine (Scr) and also reduced renal tissue damages and interstitial fibrosis induced by UUO in rats. Moreover, the increased levels of collagen I, alpha-SMA, TGF-ß1, p38 MAPK, and the Bax/Bcl-2 ratio, as well as cell apoptosis in the kidney, were induced by UUO, and were all found deceased by RAC treatment. CONCLUSIONS RAC can improve the renal interstitial fibrosis induced by UUO, and the mechanism may be related to inhibition of renal tubular cell apoptosis via TGF-ß1/p38 MAPK pathway.

Effects of global and local contexts on chord processing: An ERP study.

In real life, the processing of an incoming event is continuously influenced by prior information at multiple timescales. The present study investigated how harmonic contexts at both local and global levels influence the processing of an incoming chord in an event-related potentials experiment. Chord sequences containing two phrases were presented to musically trained listeners, with the last critical chord either harmonically related or less related to its preceding context at local and/or global levels. ERPs data showed an ERAN-like effect for local context in early time window and a N5-like component for later interaction between the local context and global context. These results suggest that both the local and global contexts influence the processing of an incoming music event, and the local effect happens earlier than the global. Moreover, the interaction between the local context and global context in N5 may suggest that music syntactic integration at local level takes place prior to the integration at global level.

THE ANTIBACTERIAL EFFECT OF URENA LOBATA L. FROMV GUANGXI ON MICE WITH STAPHYLOCOCCUS AUREUS PNEUMONIA.

BACKGROUND: Alcohol extract from the root of Urena lobata L. (ULL) had broad spectrum antimicrobial activity. Studies in vitro have sho that ULL aqueous extract has antibacterial effect on S. aureusis, and the combination therapy of the ULL aqueous extract with cefazolin sodium showed additive effect. MATERIALS AND METHODS: The mice underwent nasal inhalation with S. aureus, a subset of mice were intra-gastric gavage with ULL and/or intravenous injection cefazolin sodium twice daily. After being exposed to S. aureus for 5 days, 10 days and 14 days respectively, the white blood cells count (WBC), neutrophils absolute value (NEU) and the neutrophil percentage (NEU%) in peripheral blood, as well as the levels of serum immunoglobulin (Ig) G and IgM were determined using commercial kits. The colony count of S. aureus, the levels of interleukin (IL) -6 and IL-10 of mice lung tissue were detected, and the pathological changes of lung tissue were examined using H & E staining. RESULTS: ULL significantly protected against S. aureus pneumonia, as evidenced by the remarkable decrease in the rate of S. aureus colony count/lung weight, WBC, NEU and NEU% in peripheral blood, as well as the attenuation of lung histopathological damage. Additionally, ULL+cefazolin could have markedly reduced the rate of S. aureus colony count/lung weight when compared with cefazolin. Furthermore, ULL and ULL+cefazolin both could significantly decrease the serum levels of IgG and IgM, and the levels of IL-6, IL-10 in mice lung tissue. CONCLUSION: This study first demonstrated that ULL may have potential use as a therapeutic agent for S. aureus pneumonia, and the roles of IgG, IgM, IL-6 and IL-10 in ULL protection against S. aureus pneumonia remain to be further studied.

Perception of hierarchical boundaries in music and its modulation by expertise.

Hierarchical structure with units of different timescales is a key feature of music. For the perception of such structures, the detection of each boundary is crucial. Here, using electroencephalography (EEG), we explore the perception of hierarchical boundaries in music, and test whether musical expertise modifies such processing. Musicians and non-musicians were presented with musical excerpts containing boundaries at three hierarchical levels, including section, phrase and period boundaries. Non-boundary was chosen as a baseline condition. Recordings from musicians showed CPS (closure positive shift) was evoked at all the three boundaries, and their amplitude increased as the hierarchical level became higher, which suggest that musicians could represent music events at different timescales in a hierarchical way. For non-musicians, the CPS was only elicited at the period boundary and undistinguishable negativities were induced at all the three boundaries. The results indicate that a different and less clear way was used by non-musicians in boundary perception. Our findings reveal, for the first time, an ERP correlate of perceiving hierarchical boundaries in music, and show that the phrasing ability could be enhanced by musical expertise.

Conveying the concept of movement in music: An event-related brain potential study.

This study on event-related brain potential investigated whether music can convey the concept of movement. Using a semantic priming paradigm, natural musical excerpts were presented to non-musicians, followed by semantically congruent or incongruent pictures that depicted objects either in motion or at rest. The priming effects were tested in object decision and implicit recognition tasks to distinguish the effects of automatic conceptual activation from response competition. Results showed that in both tasks, pictures that were incongruent to preceding musical excerpts elicited larger N400 than congruent pictures, suggesting that music can prime the representations of movement concepts. Results of the multiple regression analysis showed that movement expression could be well predicted by specific acoustic and musical features, indicating the associations between music per se and the processing of iconic musical meaning.

Possible mechanism of PNS protection against cisplatin-induced nephrotoxicity in rat models.

This study investigates the mechanism of the protective effect of Panax notoginsenosides (PNS) against cisplatin-induced nephrotoxicity via the hypoxia inducible factor 1 (HIF-1)/Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) pathway of autophagy. The rats underwent intraperitoneal injection with a single dose of cisplatin and a subset of rats were also intraperitoneally injected with 31.35 mg/kg PNS once a day. After 24 h exposure to cisplatin, the concentrations of urinary N-acetyl-ß-D-glucosaminidase (NAG), blood urea nitrogen (BUN) and serum creatinine (Scr) were determined. The rat renal tissue was examined using H&E-staining, and the mitochondria of renal tubular epithelial cells were observed using transmission electron microscopy. The expressions of microtubule-associated protein-1 light chain (LC)3, autophagy-related gene (Atg)5, Beclin-1 and BNIP3 in rat renal tissue were detected using western blotting. The expression of HIF-1 was detected by immunohistochemistry. The results showed that PNS significantly protected against cisplatin-induced nephrotoxicity, as evidenced by decreasing the concentration of blood BUN and Scr, the attenuation of renal histopathological changes and the mitochondrial damages of renal cells, and the increase of mitochondria autophagosome in renal tubular epithelial cells. Additionally, PNS significantly increased the expression of LC3 and the ratio of LC3II/LC3I in rat renal tissue. Moreover, PNS significantly increased the expression of HIF-1α, BNIP3, Atg5 and Beclin-1 in rat renal tissue. In conclusion, the protective effect of PNS on cisplatin-induced nephrotoxicity was mainly due to its ability to enhancing the mitochondrial autophagy of renal tissue via the HIF-1α/BNIP3 pathway, and here is the first demonstration about it.

How long-term memory and accentuation interact during spoken language comprehension.

Spoken language comprehension requires immediate integration of different information types, such as semantics, syntax, and prosody. Meanwhile, both the information derived from speech signals and the information retrieved from long-term memory exert their influence on language comprehension immediately. Using EEG (electroencephalogram), the present study investigated how the information retrieved from long-term memory interacts with accentuation during spoken language comprehension. Mini Chinese discourses were used as stimuli, with an interrogative or assertive context sentence preceding the target sentence. The target sentence included one critical word conveying new information. The critical word was either highly expected or lowly expected given the information retrieved from long-term memory. Moreover, the critical word was either consistently accented or inconsistently de-accented. The results revealed that for lowly expected new information, inconsistently de-accented words elicited a larger N400 and larger theta power increases (4-6 Hz) than consistently accented words. In contrast, for the highly expected new information, consistently accented words elicited a larger N400 and larger alpha power decreases (8-14 Hz) than inconsistently de-accented words. The results suggest that, during spoken language comprehension, the effect of accentuation interacted with the information retrieved from long-term memory immediately. Moreover, our results also have important consequences for our understanding of the processing nature of the N400. The N400 amplitude is not only enhanced for incorrect information (new and de-accented word) but also enhanced for correct information (new and accented words).

The contribution of sound intensity in vocal emotion perception: behavioral and electrophysiological evidence.

Although its role is frequently stressed in acoustic profile for vocal emotion, sound intensity is frequently regarded as a control parameter in neurocognitive studies of vocal emotion, leaving its role and neural underpinnings unclear. To investigate these issues, we asked participants to rate the angry level of neutral and angry prosodies before and after sound intensity modification in Experiment 1, and recorded electroencephalogram (EEG) for mismatching emotional prosodies with and without sound intensity modification and for matching emotional prosodies while participants performed emotional feature or sound intensity congruity judgment in Experiment 2. It was found that sound intensity modification had significant effect on the rating of angry level for angry prosodies, but not for neutral ones. Moreover, mismatching emotional prosodies, relative to matching ones, induced enhanced N2/P3 complex and theta band synchronization irrespective of sound intensity modification and task demands. However, mismatching emotional prosodies with reduced sound intensity showed prolonged peak latency and decreased amplitude in N2/P3 complex and smaller theta band synchronization. These findings suggest that though it cannot categorically affect emotionality conveyed in emotional prosodies, sound intensity contributes to emotional significance quantitatively, implying that sound intensity should not simply be taken as a control parameter and its unique role needs to be specified in vocal emotion studies.

Immediate integration of different types of prosodic information during on-line spoken language comprehension: an ERP study.

An event-related brain potentials (ERP) experiment was carried out to investigate the role of prosodic prominence and prosodic boundary as well as their interaction in spoken discourse comprehension. Chinese question-answer dialogues were used as stimuli. The answer sentence is a syntactically ambiguous phrase, with a prosodic phrase boundary at the immediate left side of the critical word in the carrier sentence. Meanwhile, the critical word was accented. We manipulated the question context while keeping the speech signal of the answer sentence constant, which gives rise to congruent and in-congruent question-answer pairs with violations of prosodic prominence, prosodic boundary, or both. Results showed that prosodic prominence violation evoked a frontal-central negative effect (270-510ms), while prosodic boundary violation elicited a broadly distributed negative effect (270-510ms and 510-660ms). The effect of combined prominence-boundary violation was similar to that of the single prosodic prominence violation. Furthermore, there was an interaction between the effect of prosodic prominence violation and the effect of prosodic boundary violation in the window latency of 270-510ms, which suggests an immediate interaction between the semantic processing of prosodic prominence and the syntactic processing of prosodic boundary during spoken language comprehension. In addition, a detailed analysis of the obtained negativity effects showed that the size of the negative effect to the prosodic boundary violation was increased by an additional prosodic prominence violation, but the size of the negative effect to the prosodic prominence violation was not affected by an additional prosodic boundary violation, which suggests an asymmetry between the effects of prosodic prominence and prosodic boundary.

The influence of information structure on the depth of semantic processing: how focus and pitch accent determine the size of the N400 effect.

To highlight relevant information in dialogues, both wh-question context and pitch accent in answers can be used, such that focused information gains more attention and is processed more elaborately. To evaluate the relative influence of context and pitch accent on the depth of semantic processing, we measured event-related potentials (ERPs) to auditorily presented wh-question-answer pairs. A semantically incongruent word in the answer occurred either in focus or in non-focus position as determined by the context, and this word was either accented or unaccented. Semantic incongruency elicited different N400 effects in different conditions. The largest N400 effect was found when the question-marked focus was accented, while the other three conditions elicited smaller N400 effects. The results suggest that context and accentuation interact. Thus accented focused words were processed more deeply compared to conditions where focus and accentuation mismatched, or when the new information had no marking. In addition, there seems to be sex differences in the depth of semantic processing. For males, a significant N400 effect was observed only when the question-marked focus was accented, reduced N400 effects were found in the other dialogues. In contrast, females produced similar N400 effects in all the conditions. These results suggest that regardless of external cues, females tend to engage in more elaborate semantic processing compared to males.

Event-related potential correlates of the expectancy violation effect during emotional prosody processing.

The present study investigated the expectancy violation effects evoked by deviation in sentential emotional prosody (EP), and their association with the deviation patterns. Event-related potentials (ERPs) were recorded for mismatching EPs with different patterns of deviation and for matching control EPs while subjects performed emotional congruousness judgment in Experiment 1 and visual probe detection tasks in Experiment 2. In the control experiment, EPs and acoustically matched non-emotional materials were presented and ERPs were recorded while participants judged the sound intensity congruousness. It was found that an early negativity, whose peak latency varied with deviation pattern, was elicited by mismatching EPs relative to matching ones, irrespective of task-relevance. A late positivity was specifically induced by mismatching EPs, and was modulated by both deviation pattern and task-relevance. Moreover, these effects cannot be simply attributed to the change in non-emotional acoustic properties. These findings suggest that the brain detects the EP deviation rapidly, and then integrates it with context for comprehension, during which the emotionality plays a role of speeding up the perception and enhancing vigilance.

Processing melodic contour and speech intonation in congenital amusics with Mandarin Chinese.

Congenital amusia is a disorder in the perception and production of musical pitch. It has been suggested that early exposure to a tonal language may compensate for the pitch disorder (Peretz, 2008). If so, it is reasonable to expect that there would be different characterizations of pitch perception in music and speech in congenital amusics who speak a tonal language, such as Mandarin. In this study, a group of 11 adults with amusia whose first language was Mandarin were tested with melodic contour and speech intonation discrimination and identification tasks. The participants with amusia were impaired in discriminating and identifying melodic contour. These abnormalities were also detected in identifying both speech and non-linguistic analogue derived patterns for the Mandarin intonation tasks. In addition, there was an overall trend for the participants with amusia to show deficits with respect to controls in the intonation discrimination tasks for both speech and non-linguistic analogues. These findings suggest that the amusics' melodic pitch deficits may extend to the perception of speech, and could potentially result in some language deficits in those who speak a tonal language.