Monocyte chemoattractant protein (MCP)-1 is expressed by astrocytes in diverse inflammatory states and is a key regulator of monocyte recruitment to the central nervous system (CNS). In the current study, we addressed mechanisms by which transcription of the human MCP-1 gene (hMCP-1) was terminated, after induction by interferon (IFN)-gamma. Our results demonstrated that IFN-gamma-induced transcription of hMCP-1 was followed by a refractory state, during which hMCP-1 was resistant to restimulation by either IFN-gamma or heterologous activators such as TNF-alpha. This refractory state affected the hMCP-1 gene selectively, as other IFN-gamma-inducible genes remained responsive to restimulation. The IFN-gamma-induced hMCP-1 refractory state was governed at the transcriptional level and was sensitive to protein synthesis inhibitors, suggesting a requirement for newly expressed components. A minimal 213 base pair hMCP-1 regulatory element directed both IFN-gamma-mediated transcription and the subsequent refractory state. We previously demonstrated that IFN-gamma treatment resulted in coordinate protein occupancy in vivo of two hMCP-1 promoter elements, a gamma-activated site (GAS) and a GC-rich element. During the refractory state, IFN-gamma treatment failed to induce protection of either the hMCP-1 GAS element or the GC box. These results furnish insight into the expression of hMCP-1 during CNS inflammation and provide the first delineation of an IFN-gamma-induced transcriptional refractory state.

The posterior STS (pSTS) is an important brain region for perceptual analysis of social cognitive cues. This study seeks to characterize the pattern of network connectivity emerging from the pSTS in three core social perception localizers: biological motion perception, gaze recognition, and the interpretation of moving geometric shapes as animate. We identified brain regions associated with all three of these localizers and computed the functional connectivity pattern between them and the pSTS using a partial correlations metric that characterizes network connectivity. We find a core pattern of cortical connectivity that supports the hypothesis that the pSTS serves as a hub of the social brain network. The right pSTS was the most highly connected of the brain regions measured, with many long-range connections to pFC. Unlike other highly connected regions, connectivity to the pSTS was distinctly lateralized. We conclude that the functional importance of right pSTS is revealed when considering its role in the large-scale network of brain regions involved in various aspects of social cognition.

This study explored the modulatory effects of high-frequency transcranial random noise stimulation (tRNS) on visual sensitivity during a temporal attention task. We measured sensitivity to different onset asynchronies during a temporal order judgment task as a function of active stimulation relative to sham. While completing the task, participants were stimulated bilaterally for 20 min over either the TPJ or the human middle temporal area. We hypothesized that tRNS over the TPJ, which is critical to the temporal attention network, would selectively increase cortical excitability and induce cognitive training-like effects on performance, perhaps more so in the left visual field [Matthews, N., & Welch, L. Left visual field attentional advantage in judging simultaneity and temporal order. Journal of Vision, 15, 1-13, 2015; Romanska, A., Rezlescu, C., Susilo, T., Duchaine, B., & Banissy, M. J. High-frequency transcranial random noise stimulation enhances perception of facial identity. Cerebral Cortex, 25, 4334-4340, 2015]. In Experiment 1, we measured the performance of participants who judged the order of Gabors temporally imbedded in flickering discs, presented with onset asynchronies ranging from -75 msec (left disc first) to +75 msec (right disc first). In Experiment 2, we measured whether each participant's temporal sensitivity increased with stimulation by using temporal offsets that the participant initially perceived as simultaneous. We found that parietal cortex stimulation temporarily increased sensitivity on the temporal order judgment task, especially in the left visual field. Stimulation over human middle temporal area did not alter cortical excitability in a way that affected performance. The effects were cumulative across blocks of trials for tRNS over parietal cortex but dissipated when stimulation ended. We conclude that single-session tRNS can induce temporary improvements in behavioral sensitivity and that this shows promising insight into the relationship between cortical stimulation and neural plasticity.