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Manz, S.

Publications and source records attributed to Manz, S..

2 recordsLinked to original sources

Transcranial direct current stimulation over the frontal eye field has no effect on visual search performance

Top-down attention for the goal-directed (de-)prioritization of information is fundamental for successful everyday-life behavior and poses tremendous problems when negatively impacted by disease. Attention-targeting enhancement and rehabilitation attempts using non-invasive brain stimulation techniques like transcranial direct current stimulation (tDCS) are therefore of major importance. tDCS-driven excitation of the left frontal eye field (FEF; a key region within fronto-parietal attention networks) has recently been suggested to improve attention-guided visual search with stronger effects for lower baseline performers. Here, we report two preregistered tDCS experiments that tested 1) whether the previously observed visual search improvement could be boosted through stimulation over the allegedly more dominant right FEF and 2) whether tDCS-related visual search improvements might depend on search field size. To this end, in experiments one and two, N=29 and N=31 healthy participants performed a visual search task, in which they searched for an upside-down T amongst upright Ts and Ls within small or large search fields, before and during the application of anodal (excitatory) or sham (control) tDCS over the right or left FEF, respectively. In contrast to previous studies, in both experiments (i.e., independent of stimulation site and search field size) we found neither tDCS-specific (anodal > sham) visual search improvements, nor stimulation-specific baseline dependencies (larger improvements for lower baseline performers were observed in both tDCS conditions, suggesting rather stimulation-unspecific effects like regression to the mean). Together, our results provide evidence against reliable top-down attention-guided visual search improvements through FEF tDCS.

neuroscience↗

Intestinal Epithelial PTPN2 Limits Pathobiont Colonization by Immune-Directed Antimicrobial Responses

Background and AimsLoss of activity of the inflammatory bowel disease (IBD) susceptibility gene, protein tyrosine phosphatase non-receptor type 2 (PTPN2), is associated with altered microbiome composition in both human subjects and mice. Further, expansion of the bacterial pathobiont, adherent- invasive E. coli (AIEC), is strongly linked to IBD pathogenesis. The mechanism by which intestinal epithelial cells (IEC) maintain equilibrium between commensal microbiota and immune cells to restrict invading pathobionts is poorly understood. Here, we investigated the role of IEC-specific PTPN2 in regulating AIEC colonization. MethodsTamoxifen-inducible, intestinal epithelial cell-specific Ptpn2 knockout mice (Ptpn2{Delta}IEC) and control Ptpn2fl/fl mice were infected with either non-invasive E. coli K12, or fluorescent-tagged mAIEC (mAIECred) for four consecutive days or administered PBS. Subsequently, bacterial colonization in mouse tissues was quantified. mRNA and protein expression were assayed in intestinal epithelial cells (IECs) or whole tissue lysates by PCR and Western blot. Tissue cytokine expression was determined by ELISA. Intestinal barrier function was determined by in vivo administration of 4 kDa FITC-dextran (FD4) or 70kDa Rhodamine-B dextran (RD70) fluorescent probes. Confocal microscopy was used to determine the localization of tight-junction proteins. ResultsPtpn2{Delta}IEC mice exhibited increased mAIECred - but not K12 - bacterial load in the distal colon compared to infected Ptpn2fl/fl mice. The higher susceptibility to mAIECred infection was associated with altered levels of antimicrobial peptide (AMPs). Ileal RNA expression of the alpha-defensin AMPs, Defa5 and Defa6, as well as MMP7, was significantly lower in Ptpn2{Delta}IEC vs. Ptpn2fl/fl mice, after mAIECred but not K12 infection. Further, we observed increased tight junction-regulated permeability determined by elevated in vivo FD4 but not RD70 permeability in Ptpn2{Delta}IEC-K12 mice compared to their respective controls. This effect was further exacerbated in Ptpn2{Delta}IEC mAIEC-infected mice. Further, Ptpn2{Delta}IEC mice displayed lower IL-22, IL-6, IL-17A cytokine expression post mAIEC infection compared to Ptpn2fl/fl controls. Recombinant IL-22 reversed the FD4 permeability defect and reduced bacterial burden in Ptpn2{Delta}IEC mice post mAIEC challenge. ConclusionOur findings highlight that intestinal epithelial PTPN2 is crucial for mucosal immunity and gut homeostasis by promoting anti-bacterial defense mechanisms involving coordinated epithelial-immune responses to restrict pathobiont colonization.

immunology↗