Zivkovic, L. | Search bioRxiv

bioRxiv2026

Differentiating filter-induced oscillations from physiological stimulation-evoked potentials in intracranial recordings

IntroductionStimulation-evoked potentials (SEPs), recorded both during and after deep brain stimulation (DBS) surgery, have shown promise for guiding DBS targeting and programming. However, filtering protocols applied to stimulation trains produce an artifact we call a filter-induced oscillation (FIO) which closely mimics physiological SEPs. Hence, we outline the mechanistic origins of this distortion and describe a means of differentiating it from valid SEP activity. MethodsWe recorded in 18 patients undergoing DBS surgery targeting the subthalamic nucleus or globus pallidus internus. We stimulated target nuclei with cathode-first (CF) and anode-first (AF) pulses to record native SEPs, and in white matter tracts (null condition). Recordings were subsequently filtered to illustrate FIO. Next, we filtered harmonic frequencies of an artificial stimulation train to demonstrate FIO origins. Finally, FIO was deliberately generated in white matter recordings with a notch filter, and its behaviour contrasted with SEPs during AF and CF stimulation. ResultsFiltering stimulation trains produced FIOs that depended on filter order and corner frequency. We also showed that FIO emerges from filter-induced attenuations of harmonic frequencies which compose stimulation trains, producing oscillations of like frequency around pulses. Finally, FIOs reverse in polarity depending on AF or CF stimulation, whereas SEPs do not. ConclusionsGiven the potential for widespread adoption of SEPs in DBS targeting and programming, safe analytical protocols are imperative to avoid the induction of processing-related artifacts which can be misinterpreted as biological signals. Here we establish the necessary theory for identifying FIOs and tuning analytical pipelines to avoid their generation.

neuroscience↗

bioRxiv2021

CCL2/CCR2 inhibition in atherosclerosis: a meta-analysis of preclinical studies

RationaleThe CC-chemokine ligand-2 (CCL2)/ CC-chemokine receptor-2 (CCR2) axis governs monocyte recruitment to atherosclerotic lesions. Coherent evidence from experimental studies employing genetic deletion of CCL2 or CCR2 and human epidemiological studies support a causal involvement of the CCL2/CCR2 axis in atherosclerosis. Still, preclinical studies testing pharmacological inhibition of CCL2 or CCR2 in atheroprone mice apply widely different approaches and report inconsistent results, thus halting clinical translation. ObjectiveTo systematically review and meta-analyze preclinical studies pharmacologically targeting the CCL2/CCR2 axis in atherosclerosis in an effort to inform the design of future trials. Methods and ResultsWe identified 14 studies testing CCL2/CCR2 inhibition using 11 different pharmacological agents in mouse models of atherosclerosis. In meta-analyses, blockade of CCL2 or CCR2 attenuated atherosclerotic lesion size in the aortic root or arch (g=-0.75 [-1.17 to -0.32], p=6x10-4; N=171/171 mice in experimental/control group), the carotid (g=-2.39 [-4.23 to -0.55], p=0.01; N=24/25) and the femoral artery (g=-2.38 [-3.50 to -1.26], p=3x10-5; N=10/10). Furthermore, CCL2/CCR2 inhibition reduced intralesional macrophage accumulation and increased smooth muscle cell content and collagen deposition, consistent with a plaque-stabilizing effect. While there was heterogeneity across studies, the effects of CCL2/CCR2 inhibition on lesion size correlated with reductions in plaque macrophage accumulation, in accord with a prominent role of CCL2/CCR2 signaling in monocyte recruitment. Subgroup analyses revealed similar efficacy of both CCL2- and CCR2-inhibiting approaches across different atherosclerosis models in reducing lesion size and intralesional macrophage accumulation, but stronger atheroprotective effects in carotid and femoral arteries, as compared to the aorta. ConclusionsPharmacological targeting of CCL2 or CCR2 lowers atherosclerotic lesion burden and confers plaque stability in mice across different vascular territories, drug candidates, and models of atherosclerosis. Our findings in conjunction with recent human data highlight the translational potential of targeting the CCL2/CCR2 axis in atherosclerosis and can inform future clinical trials. Subject codesatherosclerosis, inflammation, vascular biology, translational studies

immunology↗