Mismatch negativity (MMN) stands at the crossroads between explicit and implicit emotional processing.

The amygdala is known as a key brain region involved in the explicit and implicit processing of emotional faces, and plays a crucial role in salience detection. Not until recently was the mismatch negativity (MMN), a component of the event-related potentials to an odd stimulus in a sequence of stimuli, utilized as an index of preattentive salience detection of emotional voice processing. However, their relationship remains to be delineated. This study combined the fMRI scanning and event-related potential recording by examining amygdala reactivity in response to explicit and implicit (backward masked) perception of fearful and angry faces, along with recording MMN in response to the fearfully and angrily spoken syllables dada in healthy subjects who varied in trait anxiety (STAI-T). Results indicated that the amplitudes of fearful MMN were positively correlated with left amygdala reactivity to explicit perception of fear, but negatively correlated with right amygdala reactivity to implicit perception of fear. The fearful MMN predicted STAI-T along with left amygdala reactivity to explicit fear, whereas the association between fearful MMN and STAI-T was mediated by right amygdala reactivity to implicit fear. These findings suggest that amygdala reactivity in response to explicit and implicit threatening faces exhibits opposite associations with emotional MMN. In terms of emotional processing, MMN not only reflects preattentive saliency detection but also stands at the crossroads of explicit and implicit perception. Hum Brain Mapp 38:140-150, 2017. © 2016 Wiley Periodicals, Inc.

Differential Immunomodulatory Effects of Human Bone Marrow-Derived Mesenchymal Stromal Cells on Natural Killer Cells.

Mesenchymal stromal cells (MSCs) modulate immune responses through cell contact-dependent or paracrine mechanisms and are themselves known to have low immunogenicity. Given the increasing use of both natural killer (NK) cells and MSCs in cell-based therapies, we investigated the interaction between the two cell types using the NK cell lines, KHYG-1 and NK-92, and human bone marrow-derived MSCs. NK lines were cocultured with MSCs, either directly or in a transwell system, and the effects on proliferation, interferon-gamma (IFN-γ) production, and cytolytic activity of NK cells were analyzed. Cytotoxicity was measured in a 4 h chromium release assay. MSCs did not affect the proliferation of NK cell lines but reduced IFN-γ production by KHYG-1, but not NK-92, when cocultured directly at 10:1 NK:MSC ratio. MSCs suppressed K562 lysis by both KHYG-1 and NK-92 cells in contact-free transwell cocultures but only reduced cytotoxicity of KHYG-1 and not NK-92 cells when cells were in direct contact in coculture. Immunosuppressive effects of MSCs were mediated by indoleamine-2,3-dioxygenase (IDO) and prostaglandin E2 (PGE2) secreted by MSCs and were abrogated in the presence of IDO and PGE2 inhibitors. In the presence of MSCs, granule polarization was suppressed and induced respectively, in KHYG-1 and NK-92. Consistent with this, MSCs were susceptible to lysis by NK-92 but not KHYG-1. These studies indicate the differential crosstalk between MSCs and two highly cytotoxic NK lines and may be important when designing future cell therapy protocols with these two cell types.