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Zivanovic, M.

Publications and source records attributed to Zivanovic, M..

6 recordsLinked to original sources

Nanoscale Material Size Shapes Distinct Immune Transcriptional States Under Physiological Flow

Nanoplastics interact continuously with circulating immune cells, yet how particle size and exposure complexity shape immune transcriptional organization under physiological flow conditions remains poorly understood. Here, controlled microfluidic exposure was combined with single-cell RNA sequencing to investigate the effects of size-defined polystyrene nanoplastics (PSNPs; 40 nm, 200 nm, and 40 + 200 nm) on primary human peripheral blood mononuclear cells (PBMCs) under dynamic flow conditions. Across immune populations, PSNP exposure induced a conserved ribosome-associated and RNA-regulatory transcriptional program, indicating a shared intracellular adaptive response. Monocytes displayed the strongest transcriptional remodeling, characterized by coordinated modulation of ribosome-associated, metabolic, and inflammatory signaling pathways in a size-dependent manner. Exposure to 40 nm PSNPs negatively enriched (suppressed) mitochondrial metabolic pathways, whereas 200 nm PSNPs enriched inflammatory signaling programs. Combined exposure induced concurrent metabolic and inflammatory pathway engagement without evidence of major immune topology disruption or discrete inflammatory state transitions. In contrast, adaptive immune cells exhibited comparatively modest and lineage-preserving transcriptional modulation. Together, these findings demonstrate that nanoplastic size and exposure complexity shape coordinated immunometabolic adaptation in human immune cells under physiologically relevant flow conditions and establish a framework for studying dynamic material-immune interactions at single-cell resolution.

bioinformatics↗

Baseline cognitive abilities shape the effects of tDCS, tACS, and otDCS on object-location memory

Transcranial electrical stimulation (tES) can modulate neural dynamics, yet its effects on memory are heterogeneous. Individual differences in cognitive profiles, may well be one of the potential causes by setting boundary conditions on the extent and mode of the tES-induced modulation of network dynamics. In a sham-controlled, within-subject study (N = 42), we compared the effects of tDCS (1.5 mA), tACS ({+/-}1.0 mA at individual theta frequency, ITF), and otDCS (1.5 mA {+/-} 0.5 mA at ITF) over the left posterior parietal cortex on object-location (OL) associative memory, and examined whether six cognitive abilities (figural reasoning, semantic, visuospatial, processing speed, working memory, mnemonic binding) moderate stimulation outcomes. Associative memory recognition improved selectively under theta-otDCS, whereas tDCS and tACS showed no significant group-level effects. Yet all tES protocols exhibited considerable interindividual variability. Relative to cognitive abilities, processing speed moderated tES effects in line with neural efficiency predictions, yielding greater gains in cognitively faster individuals. In contrast, mnemonic binding and figural reasoning moderated benefits in a compensatory manner, with larger improvements in lower-ability individuals. Overall, the effects of tES on associative memory were specific to the tES protocol and outcome measure while being strongly shaped by cognitive profile via complementing magnification and compensation mechanisms.

neuroscience↗

Mechanistic Link between Executive Functions and Higher Cognition: Evidence from Psychometric Modeling and Brain Stimulation

Human cognitive abilities depend on flexible coordination across distributed cognitive control systems within the frontoparietal network, yet the causal architecture linking executive functions (EFs) to higher cognition remains debated. We combined psychometric modeling and neuromodulation to test causal contributions of EFs to distinct cognitive abilities. In a psychometric study, we modeled Unity-Diversity EF components (updating, inhibition, shifting) against four Cattell-Horn-Carroll (CHC) group factors. Fluid reasoning (Gf) was uniquely related to both Common EF and Updating-specific variance, whereas visual processing (Gv) and processing speed (Gs) were primarily linked to Common EF; crystallized ability (Gc) proved to be largely independent of EFs. To causally probe this architecture, in neuromodulatory study we applied anodal transcranial direct current stimulation (tDCS) over prefrontal and parietal hubs of the frontoparietal network. tDCS selectively enhanced working memory updating, with right-hemisphere stimulation improving Gv but reducing Gf performance. Mediation analyses revealed that working memory updating mediated tDCS effects on higher cognition, yet the direction of effects varied across hemispheres and ability domains, exposing indirect, updating-driven facilitative and compensatory mechanisms within the frontoparietal network. Together, these findings bridge psychometric and neuromodulatory approaches to advance mechanistic understanding of how EFs support higher cognition.

neuroscience↗

EEG Microstates Reveal Differential Network Dynamics under Constant Current and Oscillatory Brain Stimulation

BackgroundEEG microstates are brief, quasi-stable scalp topographies that index large-scale network dynamics and may sensitively capture the net effects of transcranial electrical stimulation (tES). ObjectiveTo evaluate differential effects of three types of tES - tDCS, tACS and oscillatory tDCS - (otDCS), on canonical EEG microstates (A-D) in healthy adults. MethodsIn a randomized, sham-controlled, crossover study, 42 participants completed four sessions (tDCS, tACS, otDCS, sham). Stimulation (20 min) used a P3-cheek montage: tDCS +1.5 mA; tACS at individualized theta frequency (ITF, 4-8 Hz), {+/-}1 mA; otDCS anodal with {+/-}0.5 mA oscillation around +1.5 mA at ITF. A five-minute resting EEG (eyes closed then eyes open) was recorded pre- and post-intervention. Microstates were extracted (A-D), back-fitted, and assessed on duration, occurrence, contribution, and mean GFP using linear mixed-effects models with sham and pre/post adjustments. ResultsFour canonical microstates explained ~80% variance with stable topographies across conditions. Modulation patterns were modality-specific. MS A (sensory/arousal) increased across all active protocols, strongest after otDCS. MS B (visual-autobiographical) was consistently suppressed, again most following otDCS. MS C (self-referential) decreased selectively after oscillatory stimulation (tACS, otDCS) only. MS D (executive/attention) diverged by waveform: enhanced by tACS and otDCS but reduced by tDCS. Across outcomes, otDCS produced the largest and most widespread effects, overlapping features of both tDCS (tonic/stabilizing) and tACS (oscillatory/entraining) influences. ConclusionsResting-state EEG microstates provide a sensitive systems-level assay of tES aftereffects. Constant and oscillatory current waveforms reorganize network states in dissociable ways, with otDCS exerting the most robust, comprehensive modulation. These findings support microstates as practical biomarkers for differentiating, optimizing, and monitoring neuromodulation strategies.

neuroscience↗

Negative affective traits moderate transcranial direct current stimulation (tDCS) effects on memory

BackgroundThe cognitive effects of transcranial direct current stimulation (tDCS) show substantial inter-individual variability, emphasizing the need to identify moderators of responsiveness, with negative affectivity as a potential factor influencing both cognitive performance and tDCS outcomes. Here we examine if and how negative affectivity (depressiveness, anxiety, and stress level), conceptualized as both transient states and stable traits, moderates the effects of tDCS on working memory (WM) and associative memory (AM). MethodsWe pooled data from six sham-controlled experiments involving 144 healthy young adults (351 tDCS sessions) using within-subject crossover designs. Participants completed WM and AM tasks following active anodal tDCS or sham, as well as Depression, Anxiety, and Stress Scale (DASS-21) before each session. ResultsTrait-level, but not state-level, negative affectivity moderated WM. Individuals with higher levels of depression, anxiety, or stress demonstrated greater tDCS-induced WM gains. tDCS-induced AM benefits were consistent and unaffected by affective traits or states. ConclusionNegative affectivity may shape individual susceptibility to tDCS, increasing the potential for stimulation-induced improvement on tasks requiring significant executive control.

neuroscience↗

Extraction of individual associative memory related dominant theta frequency for personalized transcranial brain stimulation

Non-invasive brain stimulation (NIBS) has gained increased interest in research and therapy of associative memory (AM) and its impairments. However, the one-size-fits-all approach yields inconsistent findings, thus putting forward the need for the development of personalized frequency-modulated NIBS protocols to increase the focality and the effectiveness of the interventions. There have been only a few attempts to deliver theta frequency-personalized tES. The current study explores the feasibility of determining dominant individual theta-band frequency (ITF) based on AM task evoked EEG activity. In a sample of 42 healthy young adults, we extracted the frequencies (2-15 Hz, in 0.5 Hz steps) with the highest event-related spectral perturbation from the EEG recorded during successful encoding in the AM task. The developed method for extraction of the dominant theta-band frequency based on the AM-evoked EEG changes is able to reliably determine the AM-related ITF and can be used for personalization of the oscillatory NIBS techniques.

neuroscience↗