Sulaj, A. | bioRxiv Science

bioRxiv2026

Neural correlates of location-response compatibility in an immersive virtual-reality Attention Network Test: a multiverse electroencephalography analysis

Immersive virtual reality (VR) can preserve the logic of laboratory attention tasks while altering the perceptual-action context in which attentional control is expressed. In this study, we examined the neural underpinnings of location-response compatibility in a VR adaptation of the Attention Network Test-Revised (ANT-VR), using a restricted preprocessing multiverse to account for uncertainty arising from defensible EEG analysis choices. Forty-four young adults contributed complete ANT-VR behavioural data. Target-locked EEG analyses were conducted across 192 preprocessing branches, with branch-level participant contributions varying after quality check and trial-count filtering. The contrast compared location-response incompatible with compatible trials and was balanced within participants across cue-target interval, cue condition, flanker congruency, and, for spatial-cue trials, conditions in which spatial cues were valid or invalid for subsequent targets. Across the multiverse, the N2pc-window posterior-lateralisation contrast could be defined in all branches and showed high directional stability: the median incompatible-minus-compatible effect was 0.30 uV [IQR: 0.22 to 0.41], with positive effects in 192/192 branches, nominal evidence in 79/192 branches, and Holm-corrected evidence in 42/192 branches. Comparison across ERP measures indicated that this pattern was more consistent for N2pc-window posterior lateralisation than for P1, posterior N1, frontocentral N2, P3, or response-referenced C3/C4 measures. Comparison across C3/C4 reference frames further constrained the interpretation: target-location-referenced C3/C4 showed the strongest effect, whereas response-referenced C3/C4 was weaker. Behavioural analyses showed no reliable compatibility differences. These findings suggest that location-response compatibility in immersive ANT-VR modulates target-locked lateralised neural activity associated with spatial selection and target-location coding, rather than producing broad sensory, conflict-related, P3-related, or specifically response-referenced modulation.

neuroscience↗

bioRxiv2021

Reversal of the renal hyperglycemic memory by targeting sustained tubular p21 expression

A major therapeutic obstacle in diabetes mellitus is the metabolic or hyperglycemic memory: the persistence of impaired organ function despite improvement of blood glucose. Therapies reversing the hyperglycemic memory and thus improving already established organ-dysfunction are lacking, but urgently needed considering the increasing prevalence of diabetes mellitus worldwide. Here we show that glucose-mediated changes in gene expression largely persist in diabetic kidney disease (DKD) despite reversing hyperglycemia. The senescence-associated cyclin-dependent kinase inhibitor p21 (Cdkn1a) was the top hit among genes persistently induced by hyperglycemia and was associated with sustained induction of the p53-p21 pathway. Persistent p21 induction was confirmed in various animal models, in several independent human samples and in in vitro models. Tubular p21 expression and urinary p21-levels were associated with DKD severity and remained elevated despite improved blood glucose levels in humans, suggesting that p21 may be a biomarker indicating persistent ("memorized") kidney damage. Glucose-mediated p21 induction and tubular senescence were enhanced in mice with reduced levels of the disease resolving protease activated protein C (aPC). Mechanistically, glucose-induced and sustained tubular p21 expression is linked with demethylation of its promoter and reduced DNMT1 expression. aPC reverses already established p21 expression independent of its anticoagulant function through receptor signaling. Accordingly, new pharmacological approaches specifically mimicking aPC signaling (3K3A-aPC, parmodulin-2) enabled the reversal of glucose-mediated sustained tubular p21 expression, tubular senescence, and DKD. Thus, p21-dependent tubular senescence contributes to the hyperglycemic memory but can be therapeutically targeted. Single sentence summaryaPC signaling targets persistent p21 expression and tubular senescence and reverses the hyperglycemic memory in diabetic kidney disease.

molecular biology↗