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The posterior superior temporal gyrus (pSTG) has been implicated in the integration of auditory feedback and motor system for controlling vocal production. However, the question as to whether and how the pSTG is causally involved in vocal feedback control is currently unclear. To this end, the present study selectively stimulated the left or right pSTG with continuous theta burst stimulation (c-TBS) in healthy participants, then used event-related potentials to investigate neurobehavioral changes in response to altered auditory feedback during vocal pitch regulation. The results showed that, compared to control (vertex) stimulation, c-TBS over the right pSTG led to smaller vocal compensations for pitch perturbations accompanied by smaller cortical N1 and larger P2 responses. Enhanced P2 responses received contributions from the right-lateralized temporal and parietal regions as well as the insula, and were significantly correlated with suppressed vocal compensations. Surprisingly, these effects were not found when comparing c-TBS over the left pSTG with control stimulation. Our findings provide evidence, for the first time, that supports a causal relationship between right, but not left, pSTG and auditory-motor integration for vocal pitch regulation. This lends support to a right-lateralized contribution of the pSTG in not only the bottom-up detection of vocal feedback errors but also the involvement of driving motor commands for error correction in a top-down manner.

The supplementary motor area (SMA) has been implicated in the feedforward control of speech production. Whether this region is involved in speech motor control through auditory feedback, however, remains uncertain. The present event-related potential (ERP) study examined the role of the left SMA in vocal pitch regulation in a causal manner by combining auditory feedback manipulations and neuronavigated continuous theta bust stimulation (c-TBS). After receiving c-TBS over the left SMA or the control site (vertex), twenty young adults vocalized the vowel sound /u/ while hearing their voice unexpectedly pitch-shifted -50 or -200 cents. Compared to the control stimulation, c-TBS over the left SMA led to decreased vocal compensations for pitch perturbations of -50 and -200 cents. A significant decrease of N1 and P2 responses to -200 cents perturbations was also found when comparing active and control stimulation. Major neural generators of decreased P2 responses included the right-lateralized superior and middle temporal gyrus and angular gyrus. Notably, a significant correlation was found between active-control differences in the vocal compensation and P2 responses for the -200 cents perturbations. These findings provide neurobehavioral evidence for a causal link between the left SMA and auditory-motor integration for vocal pitch regulation, suggesting that the left SMA receives auditory feedback information and mediates vocal compensations for feedback errors in a bottom-up manner.

Sedum sarmentosum (Sedi Herba) has traditionally been used to treat jaundice and various types of liver disease. This study aimed to clarify the anti-cholestatic efficacy and the mechanism of S. sarmentosum ethyl acetate extract (SDEAE), as well as to screen the potential compounds with FXR activation. SDEAE effectively ameliorated ANIT-induced cholestasis in rats, as evidenced by the ameliorative histopathology of the liver and the significant decrease in biochemical markers (ALT, AST, ALP, GGT, TBIL, DBIL and TBA). The analysis of bile acid profile by LC–MS indicated that SDEAE decreased the toxic bile acid levels (TCA, TMCA and CA). Western blotting indicated that SDEAE activated FXR-associated pathway, thereby upregulating FXR, SHP, BSEP and UGT2B4 expression, and downregulating CYP7A1 and NTCP expression. Twenty-three compounds (7 nor-sesquiterpenoids, 13 flavonoids, 1 lignin, 1 sterol and 1 anthraquinone) were isolated and identified from SDEAE by comparing NMR data with the literature. The HPLC profiles of SDEAE and isolated compounds were also compared. High-content analysis showed that eight compounds (6, 7, 8, 11, 12, 13, 14 and 23) could activate FXR and compound 8 exhibited the most potent activity (p