Biology subjects

Wang, J. B.

Publications and source records attributed to Wang, J. B..

7 recordsLinked to original sources

bioRxiv2025

A Practical Preprocessing Pipeline for Concurrent TMS-iEEG: Critical Steps and Methodological Considerations

Transcranial magnetic stimulation combined with intracranial EEG (TMS-iEEG) has emerged as a powerful approach for probing the causal organization and dynamics of the human brain. Despite its promise, the presence of TMS-induced artifacts poses significant challenges for accurately characterizing and interpreting evoked neural responses. In this study, we present a practical preprocessing pipeline for single pulse TMS-iEEG data, incorporating key steps of re-referencing, filtering, artifact interpolation, and detrending. Using both real and simulated data, we systematically evaluated the effects of each step and compared alternative methodological choices. Our results demonstrate that this pipeline effectively attenuated various types of artifacts and noise, yielding cleaner signals for the subsequent analysis of intracranial TMS-evoked potentials (iTEPs). Moreover, we showed that methodological choices can substantially influence iTEPs outcomes. In particular, referencing methods might strongly affect iTEP morphology and amplitude, underscoring the importance of tailoring the referencing strategy to specific signal characteristics and research objectives. For filtering, we recommend a segment-based strategy, i.e., applying filters to data segments excluding the artifact window, to minimize distortion from abrupt TMS-related transients. Overall, this work represents an important step toward establishing a general preprocessing framework for TMS-iEEG data. We hope it encourages broader adoption and methodological development in concurrent TMS-iEEG research, ultimately advancing our understanding of brain organization and TMS mechanisms. HighlightsO_LIWe presented a practical preprocessing pipeline for single pulse TMS-iEEG data, incorporating key steps of re-referencing, filtering, artifact interpolation, and detrending. C_LIO_LIThe pipeline effectively attenuates multiple types of artifacts and noise, enabling accurate characterization of evoked neural responses. C_LIO_LIMethodological alternatives for each preprocessing step were evaluated using real and/or simulated datasets. C_LIO_LIRe-referencing substantially affects the morphology and amplitude of intracranial TMS-evoked potentials and requires careful consideration. C_LIO_LIA segment-based filtering strategy is recommended to better minimize distortion from TMS-related artifacts. C_LI

neuroscience↗

bioRxiv2025

Replication-Deficient Whole-Virus Vaccines Against Cytomegalovirus Induce Protective Immunity in a Guinea Pig Congenital Infection Model

Vaccines are needed to prevent congenital cytomegalovirus (CMV) infections. This study used the guinea pig cytomegalovirus (GPCMV) model to examine replication-deficient whole-virus vaccines against maternal viremia and congenital infection. Two recombinant GPCMVs, GP51-DD and GP52-DD, were engineered with destabilization domains fused to essential viral late proteins GP51 and GP52. These viruses, predicted to replicate in the presence of the synthetic ligand Shield-1 but not in its absence, were evaluated for Shield-1-dependence in vitro and for safety, immunogenicity, and efficacy in a pregnancy/challenge model. GP52-DD was profoundly Shield-1-dependent, producing no detectable infectious progeny in its absence. In contrast, the replication of GP51-DD was delayed in the absence of Shield-1, but the virus reached similar peak titers with or without the compound. GPCMV-seronegative guinea pigs received two subcutaneous injections of placebo (sham-immunized), GP51-DD, GP52-DD, or wild-type GPCMV (WT-GPCMV). DNAemia post-vaccination was detected in only one of 14 dams in each of the GP51-DD- and GP52-DD-immunized groups compared to 10/10 control animals immunized with WT-GPCMV, confirming the recombinant viruses were attenuated. GPCMV-specific antibody responses were similar in all three vaccinated groups. When immunized dams were bred and challenged with virulent GPCMV, DNAemia was detected in all sham-immunized controls and in 44% of GP52-DD-immunized dams (at significantly reduced levels) but was absent in dams immunized with GP51-DD or WT-GPCMV. Notably, immunization with GP52-DD, GP51-DD, or WT-GPCMV significantly reduced congenital GPCMV transmission (protective efficacies of 89%, 94%, and 100%, respectively). Thus, the replication-deficient GP52-DD vaccine was attenuated and protected against intrauterine GPCMV transmission. ImportanceCongenital cytomegalovirus (CMV) infections could be prevented by a vaccine, but most of the vaccine designs that have advanced to clinical trials have been subunit vaccines. These viral envelope glycoprotein-targeting designs have not yielded an effective vaccine that provides durable immunity. A vaccine that confers immune responses to a broader repertoire of viral immunogens, such as vaccines based on the whole virus, could enhance protection. However, there are concerns about the safety of live attenuated CMV vaccines. Using the guinea pig/guinea pig cytomegalovirus model of congenital infection, this study demonstrates that two replication-deficient whole virus vaccines are attenuated in animals while also being highly immunogenic, providing protective immunity against maternal viremia and fetal infection at levels similar to that conferred by a wild-type virus.

immunology↗

bioRxiv2024

Latitudinal clines in climate and sleep patterns shape disease outcomes in Drosophila melanogaster infected by Metarhizium anisopliae

Major latitudinal clines have been observed in Drosophila melanogaster, a human commensal that originated in tropical Africa and has spread world-wide to colonize temperate habitats. However, despite the significant impact of pathogens on species distribution, the influence of geographical factors on disease susceptibility remains poorly understood. This study investigated the effects of latitudinal clines and biomes on disease resistance using the common fly pathogen Metarhizium anisopliae and 43 global Drosophila melanogaster populations. The results showed that disease resistance was correlated with latitudinal gradients of sleep duration, temperature and humidity. While fungal diversity at tropical latitudes may drive enhanced defenses, the most disease-resistant males were also the most susceptible to desiccation, indicating potential trade-offs between abiotic stress resistance, necessary for survival in temperate habitats, and disease resistance. The study also found that sex, mating status, and sleep interacted with abiotic stresses to impact disease resistance, with longer-sleeping males and virgin flies surviving infections longer, and extra daytime sleep post-infection being protective, especially in the most resistant fly lines. These findings promote the idea that sleep and defense against disease are intertwined traits related to organismal fitness and subject to joint clinal evolution. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=161 SRC="FIGDIR/small/617675v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@10057bborg.highwire.dtl.DTLVardef@17fecdeorg.highwire.dtl.DTLVardef@19815daorg.highwire.dtl.DTLVardef@1c2ce4b_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

bioRxiv2024

Naturalistic acute pain states decoded from neural and facial dynamics

Pain is a complex experience that remains largely unexplored in naturalistic contexts, hindering our understanding of its neurobehavioral representation in ecologically valid settings. To address this, we employed a multimodal, data-driven approach integrating intracranial electroencephalography, pain self-reports, and facial expression quantification to characterize the neural and behavioral correlates of naturalistic acute pain in twelve epilepsy patients undergoing continuous monitoring with neural and audiovisual recordings. High self-reported pain states were associated with elevated blood pressure, increased pain medication use, and distinct facial muscle activations. Using machine learning, we successfully decoded individual participants high versus low self-reported pain states from distributed neural activity patterns (mean AUC = 0.70), involving mesolimbic regions, striatum, and temporoparietal cortex. High self-reported pain states exhibited increased low-frequency activity in temporoparietal areas and decreased high-frequency activity in mesolimbic regions (hippocampus, cingulate, and orbitofrontal cortex) compared to low pain states. This neural pain representation remained stable for hours and was modulated by pain onset and relief. Objective facial expression changes also classified self-reported pain states, with results concordant with electrophysiological predictions. Importantly, we identified transient periods of momentary pain as a distinct naturalistic acute pain measure, which could be reliably differentiated from affect-neutral periods using intracranial and facial features, albeit with neural and facial patterns distinct from self-reported pain. These findings reveal reliable neurobehavioral markers of naturalistic acute pain across contexts and timescales, underscoring the potential for developing personalized pain interventions in real-world settings.

neuroscience↗

bioRxiv2023

TMS provokes target-dependent intracranial rhythms across human cortical and subcortical sites

Transcranial magnetic stimulation (TMS) is increasingly deployed in the treatment of neuropsychiatric illness, under the presumption that stimulation of specific cortical targets can alter ongoing neural activity and cause circuit-level changes in brain function. While the electrophysiological effects of TMS have been extensively studied with scalp electroencephalography (EEG), this approach is most useful for evaluating low-frequency neural activity at the cortical surface. As such, little is known about how TMS perturbs rhythmic activity among deeper structures - such as the hippocampus and amygdala - and whether stimulation can alter higher-frequency oscillations. Recent work has established that TMS can be safely used in patients with intracranial electrodes (iEEG), allowing for direct neural recordings at sufficient spatiotemporal resolution to examine localized oscillatory responses across the frequency spectrum. To that end, we recruited 17 neurosurgical patients with indwelling electrodes and recorded neural activity while patients underwent repeated trials of single-pulse TMS at several cortical sites. Stimulation to the dorsolateral prefrontal cortex (DLPFC) drove widespread low-frequency increases (3-8Hz) in frontolimbic cortices, as well as high-frequency decreases (30-110Hz) in frontotemporal areas, including the hippocampus. Stimulation to parietal cortex specifically provoked low-frequency responses in the medial temporal lobe. While most low-frequency activity was consistent with brief evoked responses, anterior frontal regions exhibited induced theta oscillations following DLPFC stimulation. Taken together, we established that non-invasive stimulation can (1) provoke a mixture of low-frequency evoked power and induced theta oscillations and (2) suppress high-frequency activity in deeper brain structures not directly accessed by stimulation itself.

neuroscience↗

bioRxiv2022

Effects of transcranial magnetic stimulation on the human brain recorded with intracranial electrocorticography: First-in-human study

Transcranial magnetic stimulation (TMS) is increasingly used as a noninvasive technique for neuromodulation in research and clinical applications, yet its mechanisms are not well understood. Here, we present the first in-human study evaluating the effects of TMS using intracranial electrocorticography (iEEG) in neurosurgical patients. We first evaluated safety in a gel-based phantom. We then performed TMS-iEEG in 20 neurosurgical participants with no adverse events. Next, we evaluated brain-wide intracranial responses to single pulses of TMS to the dorsolateral prefrontal cortex (dlPFC) (N=10, 1414 electrodes). We demonstrate that TMS preferentially induces neuronal responses locally within the dlPFC at sites with higher electric field strength. Evoked responses were also noted downstream in the anterior cingulate and anterior insular cortex, regions functionally connected to the dlPFC. These findings support the safety and promise of TMS-iEEG in humans to examine local and network-level effects of TMS with higher spatiotemporal resolution than currently available methods.

neuroscience↗

bioRxiv2018

Polymeric perfluoropentane nanoemulsions are a versatile platform for ultrasonic drug uncaging

Catheter-based intra-arterial drug therapies have proven effective for a range of oncologic, neurologic, and cardiovascular applications. However, these procedures are limited by their invasiveness, as well as the relatively broad drug spatial distribution that is achievable with selective arterial catheterization. The ideal technique for local pharmacotherapy would be noninvasive and would flexibly deliver a given drug to any region of the body. Combining polymeric perfluorocarbon nanoemulsions with existent clinical focused ultrasound systems could in principle enable noninvasive targeted drug delivery, but it has not been clear whether these nanoparticles could provide the necessary drug loading, stability, and generalizability across a range of drugs to meet these needs, beyond a few niche applications. Here, we directly address all of those challenges and fully develop polymeric perfluorocarbon nanoemulsions into a generalized platform for ultrasound-targeted drug delivery with high potential for clinical translation. We demonstrate that a wide variety of drugs may be effectively uncaged with ultrasound using these nanoparticles, with drug loading increasing with hydrophobicity. We also set the stage for clinical translation by delineating production protocols that hew to clinical standards and yield stable and optimized ultrasound-activated drug-loaded nanoemulsions. Finally, as a new potential clinical application for these nanoemulsions, we exhibit their in vivo efficacy and performance for cardiovascular applications, by achieving local vasodilation in the highest flow vessel of the body, the aorta. This work establishes the power of polymeric perfluorocarbon nanoemulsions as a clinically-translatable platform for effective noninvasive ultrasonic drug uncaging for myriad targets in the brain and body.

bioengineering↗