Glioblastoma multiforme (GBM) shows a high influx of tumor-associated macrophages (TAMs). The CCR2/CCL2 pathway is considered a relevant signal for the recruitment of TAMs and has been suggested as a therapeutic target in malignant gliomas. We found that TAMs of human GBM specimens and of a syngeneic glioma model express CCR2 to varying extents. Using a Ccr2-deficient strain for glioma inoculation revealed a 30% reduction of TAMs intratumorally. This diminished immune cell infiltration occurred with augmented tumor volumes likely based on increased cell proliferation. Remaining TAMs in Ccr2-/- mice showed comparable surface marker expression patterns in comparison to wildtype mice, but expression levels of inflammatory transcription factors (Stat3, Irf7, Cox2) and cytokines (Ifnβ, Il1β, Il12α) were considerably affected. Furthermore, we demonstrated an impact on blood vessel integrity, while vascularization of tumors appeared similar between mouse strains. The higher stability and attenuated leakiness of the tumor vasculature imply improved sustenance of glioma tissue in Ccr2-/- mice. Additionally, despite TAMs residing in the perivascular niche in Ccr2-/- mice, their pro-angiogenic activity was reduced by the downregulation of Vegf. In conclusion, lacking CCR2 solely on tumor microenvironmental cells leads to enhanced tumor progression, whereby high numbers of TAMs infiltrate gliomas independently of the CCR2/CCL2 signal.

The present study aimed to examine EEG correlates of cognitive load in a task, in which multiple stimulus-response mappings have to be maintained in working memory (WM) combined with selective inhibition of irrelevant stimulus-response mappings on every trial. Twenty-four healthy younger adults had to perform choice reaction tasks differed in the number of S-R mappings and motor response requirements. Performance was lower in the high load than in the low load condition. Performance decline at higher WM loads was accompanied by an increase of EEG power in delta, theta, and beta frequency bands and by a reduction in alpha band. The effect on alpha was generalized across all the electrodes. Correlations between EEG and performance were observed in the high load condition but not in the low load condition. Theta activity negatively correlated with reaction time, whereas positive correlations between beta activity and reaction time were found. The two frequency bands negatively correlated with each other at all electrodes. The results suggest that changes in alpha and theta power may be considered as the most sensitive indicators of cognitive load. The alpha reduction may be related to activation of widespread cortical areas which were recruited for performance of complex WM tasks. The beta increase, especially in the beta-2 range, may partly be associated with activation of motor cortex due to difficulties in preparation and execution of motor responses. Theta increases may be considered as an index of facilitation of information processing in WM and improvements in higher-order executive control, which in turn facilitates motor processes.

Counting objects, especially moving ones, is an important capacity that has been intensively explored in experimental psychology and related disciplines. The common approach is to trace the three counting principles (estimating, subitizing, serial counting) back to functional constructs like the Approximate Number System and the Object Tracking System. While usually attempts are made to explain these competing models by computational processes at the neural level, their first-person dimensions have been hardly investigated so far. However, explanatory gaps in both psychological and philosophical terms may suggest a methodologically complementary approach that systematically incorporates introspective data. For example, the mental-action debate raises the question of whether mental activity plays only a marginal role in otherwise automatic cognitive processes or if it can be developed in such a way that it can count as genuine mental action. To address this question not only theoretically, we conducted an exploratory study with a moving-dots task and analyze the self-report data qualitatively and quantitatively on different levels. Building on this, a multi-layered, consciousness-immanent model of counting is presented, which integrates the various counting principles and concretizes mental agency as developing from pre-reflective to increasingly conscious mental activity.