Biology subjects

Chung, S. W.

Publications and source records attributed to Chung, S. W..

18 recordsLinked to original sources

bioRxiv2026

Blood-brain barrier-traversing multivalent TGFβ trap for anti-cancer immunomodulation of gliomas

Clinical studies have revealed that glioblastoma (GBM) is refractory to immunotherapy, such as immune checkpoint inhibitors (ICIs), due to the immunosuppressive tumor microenvironment (TME) primarily intensified by intratumoral upregulation of transforming growth factor-{beta} (TGF{beta}). Primary GBM tumor bulks are surgically removed in clinic, but invasive tumor cells infiltrated into surrounding normal brain tissue cannot be eradicated by systemic therapy due to the integral blood-brain barrier (BBB), leading to near-inevitable tumor recurrence. To address these translational challenges, we have engineered a TGF{beta}-inhibiting protein nanocage comprising human heavy-chain ferritin protein and TGF{beta} receptor II ectodomain that enables BBB penetration and multivalent TGF{beta} entrapment, respectively. We demonstrate that the nanocage platform, denoted T{beta}R2-HFt, following systemic administration, traverses the BBB, and extensively modulates immunosuppressive TME, both stromal and immune components, thereby potentiating the therapeutic efficacy of a clinically used ICI in multiple mouse glioma models. Notably, a majority of the glioma-bearing animals that received surgical tumor resection, followed by treatment with T{beta}R2-HFt and the ICI, survived the tumor and resisted tumor rechallenge, providing a potential means to control GBM in a durable manner.

bioengineering↗

bioRxiv2026

An immune-stimulating antibody conjugate spatiotemporally targeting CD47 and TLR9 elicits macrophage-dependent tumor clearance and durable anti-cancer adaptive immunity

Cluster of differentiation 47 (CD47) blockade promotes tumor cell phagocytosis; however, transitioning this initial innate immune event into durable anti-cancer adaptive immunity and tumor control remains a critical challenge. To address this translational gap, we have engineered aCD47 - CpG, a novel immune-stimulating antibody conjugate (ISAC) coupling a CD47-blocking antibody (aCD47) to a Toll-like receptor 9 agonist, unmethylated CpG, to enable synchronized deployment of co-stimulatory signals during tumor engulfment. This ISAC, aCD47-CpG, but not the parent aCD47, reprograms macrophages toward an anti-tumor M1-like phenotype, enhances antigen cross-presentation, and promotes robust CD8+ T cell priming. We found that systemically administered aCD47-CpG drove macrophage-dependent tumor suppression in a human lymphoma xenograft model. In parallel, the treatment in immunocompetent syngeneic models of lymphoma and highly immunosuppressive triple-negative breast cancer resulted in profound tumor regression, metastasis inhibition, and durable anti-cancer immune memory. These effects were accompanied by remodeling of the immunosuppressive tumor microenvironment toward an immune-permissive state, characterized by M2-to-M1 macrophage repolarization, intratumoral infiltration of cytotoxic and memory T cells, and depletion of regulatory T cells. This spatiotemporally coordinated immunotherapy platform offers a promising strategy to bridge innate and adaptive immunity, thereby advancing the translational potential of CD47-targeted cancer therapies.

cancer biology↗

bioRxiv2025

Atelocollagen exhibits superior performance compared to growth factors in upregulating proteins associated with tendon healing

PurposeWe aimed to compare the effects of atelocollagen (AC) and individual growth factors on the expression of key molecular markers associated with tendon healing. MethodsC2C12 myoblasts were cultured in Dulbeccos Modified Eagle Medium (DMEM) containing 5% fetal bovine serum (FBS) and treated with 1 nM or 10 nM of Atelocollagen (AC), bone morphogenetic protein-2 (BMP-2), transforming growth factor-beta 1 (TGF-{beta}1), insulin-like growth factor-1 (IGF-1), or vascular endothelial growth factor (VEGF) for 5 days. After 5 days of treatment, cells were harvested from the culture medium, and Western blot analysis was performed to quantify the expression of phosphorylated extracellular signal-regulated kinase (p-ERK), Collagen type I (Col I), Collagen type III (Col III), and Tenascin C (TnC). Additionally, immunofluorescence staining was conducted to qualitatively assess cytoskeletal organization and cell adhesion, which are key factors in tendon healing. ResultsIn the AC-treated groups, the expression levels of p-ERK, Col I/Col III, and TnC were significantly higher compared to the groups treated with individual growth factors (BMP-2, IGF, VEGF, and TGF-{beta}1) (p < 0.05). These changes were dose-dependent, as there was no significant difference in protein expression between AC and the growth factors at 1 nM, whereas at 10 nM, AC treatment resulted in a significant increase (p < 0.05). In the cell proliferation assay, C2C12 myoblasts treated with AC at 10 nM exhibited significantly higher proliferation rates compared to those treated with individual growth factors (p < 0.05). Additionally, immunofluorescence analysis revealed greater cytoskeletal alignment in AC-treated cells, suggesting enhanced cell adhesion, structural organization, and mechanical stability. ConclusionsAC significantly upregulated key molecular markers involved in cell proliferation, extracellular matrix remodeling, and tendon structural integrity more effectively than individual growth factors. The increased expression of these genes in myoblasts suggests ACs potential role in promoting tendon healing. Clinical relevanceThrough the modulation of key molecular pathways critical to tendon healing, AC presents strong potential as an effective biological augmentation strategy for improving tendon-to-bone interface healing after surgical repair.

cell biology↗

bioRxiv2025

Optical Brain Pulse Monitoring for Detection of Large Vessel Occlusion Stroke in a Sheep Model

Early stroke detection and treatment are critical for improving patient outcomes. Optical brain pulse monitoring (OBPM) uses red and infrared light to capture brain pulse waveforms reflecting arteriole-to-venous pressure levels driving microvascular blood flow. This study assessed OBPMs potential to detect middle cerebral artery occlusion (MCAo) and reperfusion in a clinically relevant sheep model. Stroke was induced in 11 Merino wethers via 4-hour occlusion of the right MCA, followed by 6 hours of reperfusion. OBPM recordings were taken at baseline, MCAo, early and late reperfusion. The OBPM brain pulse waveform classes were classified based on the presence of arterial or central venous circulation wave features. Magnetic resonance imaging assessed infarct volume at 2 hours post-reperfusion. Invasive brain tissue oxygen and intracranial pressures were also monitored. The OBPM brain pulse waveform classes changed during MCAo and reperfusion (p <0.0001). MCAo was associated brain pulses with venous circulation features (p = 0.0007). Reperfusion was associated with the return of arterial circulation features (p = 0.001). Early reperfusion was also associated with an increase in the brain pulse amplitude (p < 0.05) and the respiratory wave amplitude (p < 0.05). OBPM may aid in early stroke detection and reperfusion assessment following intervention.

physiology↗

bioRxiv2024

Neural differences in conflict monitoring and stimulus expectancy processes in experienced meditators are likely driven by enhanced attention

ObjectivesMindfulness meditation has been linked to enhanced attention and executive function, likely resulting from practice-related effects on neural activity patterns. In this study, we used an event-related potential (ERP) paradigm to examine brain responses related to conflict monitoring and attention in experienced mindfulness meditators to better understand key factors driving meditation-related effects. MethodsWe measured electroencephalography-derived N2 and P3 ERPs reflecting conflict monitoring and attention processes from 35 meditators and 29 non-meditators across both an easy and a hard Go/Nogo task (50% Nogo and 25% Nogo stimuli, respectively). ResultsMeditators displayed distinct neural activity patterns compared to non-meditators, with enhanced N2 responses in fronto-midline electrodes following hard Nogo trials (pFDR = 0.011, np2 = 0.111). The fronto-midline N2 ERP was also larger following Nogo trials than Go trials, in the harder task condition, and was related to correct responses. Meditators also exhibited a more frontally distributed P3 ERP in the easy task compared to the hard task, while non-meditators showed a more frontally distributed P3 ERP in the hard task (pFDR = 0.015, np2 = 0.079). ConclusionsMindfulness meditation was associated with distinct topographical patterns of neural activity in the attention task, without corresponding increases in global neural activity amplitudes. These meditation-related effects appear to be driven by attention-specific mechanisms, despite the examined neural activity being associated with conflict monitoring and stimulus expectancy. Our findings suggest that the cognitive benefits of meditation may only emerge in tasks that actively engage targeted cognitive processes, such as sustained attention.

neuroscience↗

bioRxiv2024

Intracortical injection of immune checkpoint inhibitor promotes monocyte/macrophage infiltration and restores microglial function and neuronal activity in an AD mouse model

Alzheimer's disease (AD) involves complex neuroimmune interactions. However, the role of immune checkpoint pathways in regulating the glial and neuronal functions of the AD brain remains unclear. This study aims to investigate how the brain-specific modulation of the PD-1/PD-L1 axis affects glial and neuronal function in an AD mouse model, which is characterized by the significant upregulation of microglial PD-1 and astrocytic PD-L1. A single intracortical administration of anti-PD-L1 antibody reshaped the glial microenvironment, which was accompanied by the restoration of impaired microglial process convergence. Astrocyte-specific Pd-l1 knockdown using the pSico system validated the essential role of astrocytic PD-L1 in enhancing microglial responses. Notably, the blockade of the PD-1/PD-L1 signaling pathway increased the microglial P2RY12 expression, a key marker of microglial homeostasis, which likely contributed to the restoration of neuronal hyperactivity. Collectively, these findings confirmed the potential of targeting the astrocyte-microglia PD-1/PD-L1 axis to mitigate AD pathology.

neuroscience↗

bioRxiv2023

TMS-EEG shows mindfulness meditation is associated with an altered excitation/inhibition balance in the dorsolateral prefrontal cortex

ObjectiveMindfulness meditation is associated with functional brain changes in regions subserving higher order cognitive processes such as attention. However, no research to date has causally probed these areas in meditators using combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG). This study aimed to investigate whether cortical reactivity to TMS differs in a community sample of experienced mindfulness meditators when compared to matched controls MethodsTMS was applied to the left and right dorsolateral prefrontal cortices (DLPFC) of 19 controls and 15 meditators while brain responses were measured using EEG. TMS-evoked potentials (P60 and N100) were analysed, and exploratory analyses using the whole EEG scalp field were performed to test whether TMS-evoked global neural response strength or the distribution of neural activity differed between groups. ResultsMeditators were found to have statistically larger P60/N100 ratios in response to left and right hemisphere DLPFC stimulation compared to controls (pFDR = 0.004, BF10 > 39). No differences were observed in P60 or N100 amplitudes when examined in isolation. We also found preliminary evidence for differences in the distribution of neural activity 269-332ms post stimulation. ConclusionThese findings demonstrate differences in cortical reactivity to TMS in meditators. Differences in the distribution of neural activity approximately 300ms following stimulation suggest differences in cortico-subcortical reverberation in meditators that may be indicative of greater inhibitory activity in frontal regions. This research contributes to our current understanding of the neurophysiology of mindfulness and highlights opportunities for further exploration into the mechanisms underpinning the benefits of mindfulness meditation.

neuroscience↗

bioRxiv2023

Exploring the Dose-Dependency of After-Effects: A Computational Model for Theta-Burst Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) is a non-invasive neurostimulation and neuromodulation technique that is widely applied in brain research and clinical applications. However, the optimal parameters of neuromodulating TMS protocols describing the specific rhythms, such as number of pulses, frequency, and stimulation strength, are widely unknown. Improving previous rather limited and ad-hoc models, we aimed to investigate the dose-dependency of theta-burst stimulation (TBS) protocols with a more elaborate but still parsimonious quantitative model representing the non-linearities of the mechanisms of synaptic plasticity and metaplasticity during repetitive magnetic stimulation. Our model, which considers the interaction between facilitatory and inhibitory processes, successfully reproduced results from TBS experiments and provide testable predictions for prolonged TBS protocols. Moreover, we suggested that the activation of kinases and phosphatases could be potential candidates for later TMS modelling research. Although this model still simplifies the complex dynamics of cellular and molecular processes, it offers a starting basis for future studies to incorporate more intricate mechanisms. By further refining our understanding of the underlying mechanisms and improving the accuracy of prediction models, we can advance the efficacy and clinical application of TBS protocols in various neurological and psychiatric conditions.

neuroscience↗

bioRxiv2023

Effect of hexanal treatment on fruit qualities and antioxidant activities on 'Umran' Indian jujube fruit during cold storage

Umran Indian jujube is a widely grown cultivar due to its marketable quality and productivity, resulting in excellent market value. Despite its high quality, the products short shelf life poses a challenge for transportation, even within the domestic market. Hexanal with three concentrations (0.15%, 0.20%, and 0.25%) was applied to the fruit of Umran Indian jujube at both pit hardening and color break stages. Harvested fruits were stored for 28 days in a cold chamber of 7.5{+/-}1{degrees}C and 90-95% RH. The changes in fruit qualities were assessed with physicochemical characteristics, bioactive compounds, and enzymatic antioxidant activities every seven days. Fruits treated with hexanal of 0.20% reduced fruit weight loss and spoilage and maintained fruit firmness, soluble solids content, carotenoid content, and antioxidant activity. The activities of cell wall degrading enzymes investigated were suppressed. Of the antioxidant activities, superoxide dismutase and peroxidase were positively activated. Therefore, these results indicated that pre-harvest application of hexanal 0.20% improved physiochemical characteristics, maintained bioactive compounds, antioxidant enzyme activities, and extended the shelf life of Indian jujube fruits up to 21 days during cold storage.

plant biology↗

bioRxiv2023

Spatial and compositional variations in fruit characteristics of papaya (Carica papaya cv. Tainung No. 2) during ripening

Papaya fruit (Carica papaya) has different degrees of ripening within a fruit, affecting its commercial market value. The fruit characteristics of Tainung No. 2 papaya was investigated at the stem-end, middle, and calyx-end parts at three ripening stages and categorized based on fruit skin coloration: unripe at ca. 16 weeks after anthesis (WAA), half-ripe at ca. 18 WAA, and full-ripe at ca. 20 WAA. The fruits maintained an elliptical shape during ripening with 2.36 of the ratios of the length to the width. The peel and pulp color changed from green to white to yellow during ripening, regardless of the fruit three parts. In the pulp, soluble solid content increased to about 320% and firmness decreased to about 99% during ripening but did not differ among fruit three parts. Individual nutrient contents, including primary and secondary metabolites, and minerals, changed dynamically between the ripening stages and fruit parts. Total carbohydrates and proteins, N, and K, were more accumulated at the stem-end during ripening, meanwhile fructose, glucose, Mg, and Mn were at the calyx-end. In the principal component analysis, ripening stages and fruit parts were distinctly determined by the first and second principal components, respectively. These results provide fundamental information for improving ripening during papaya cultivation.

plant biology↗

bioRxiv2022

Single cell profiling reveals strain-specific differences in myeloid inflammatory potential in the rat liver

Liver transplantation is currently the only treatment for end-stage liver disease and acute liver failure. Liver transplant rejection is among the most lethal complications of transplantation, and therapeutic development is limited by our lack of a comprehensive understanding of the cellular landscape of the liver. The laboratory rat (Rattus norvegicus), ideal in size as a model for surgical procedures, is a strong platform to study liver biology in the context of liver transplantation. Liver allograft rejection is known to be strain-specific in the rat model, although the transplantation is accepted without rejection in some strains, it leads to acute rejection in others. To shed light on the cellular landscape of the rat liver and build a foundation for strain comparison, we present a comprehensive single-cell transcriptomics map of the healthy rat liver of Lewis and Dark Agouti strains. Using a novel computational pipeline we developed to guide the detailed annotation of our rat liver atlas, we discovered that hepatic myeloid cells have strong Lewis and Dark Agouti strain-specific differences focused on inflammatory signaling pathways. We experimentally validated these strain-specific differences in myeloid inflammatory potential in vitro using intracellular cytokine staining. Our work provides the first examination of the multi-strain healthy rat liver by single cell transcriptomics and uncovers key insights into strain-specific differences in this valuable model animal. SummaryThe laboratory rat (Rattus norvegicus) is a standard model animal for orthotopic liver transplantation. Transplanting a liver from a Dark agouti (DA) to a Lewis (LEW) strain rat leads to transplant rejection and the reverse procedure leads to tolerance. Understanding this strain difference may help explain the cellular drivers of liver allograft rejection post-transplant. This study uses single-cell transcriptomics to better understand the complex cellular composition of the rat liver and unravels cellular and molecular sources of inter-strain hepatic variation. We generated single-cell transcriptomic maps of the livers of healthy DA and LEW rat strains and developed a novel, factor analysis-based bioinformatics pipeline to study data covariates, such as strain and batch. Using this approach, we discovered variations within hepatocyte and myeloid populations that explain how the states of these cells differ between strains in the healthy rat, which may explain why these strains respond differently to liver transplants.

genomics↗

bioRxiv2022

Meditators probably show increased behaviour-monitoring related neural activity

ObjectivesMindfulness meditation is associated with better attention function. Performance monitoring and error-processing are important aspects of attention. We investigated whether experienced meditators showed different neural activity related to performance monitoring and error-processing. Previous research has produced inconsistent results. This study used more rigorous analyses and a larger sample to resolve the inconsistencies. MethodsWe used electroencephalography (EEG) to measure the error-related negativity (ERN) and error positivity (Pe) following correct and incorrect responses to a Go/Nogo task from 27 experienced meditators and 27 non-meditators. ResultsNo differences were found in the ERN (all p > 0.05). Meditators showed larger global field potentials (GFP) in the Pe after both correct responses and errors, indicating stronger neural responses (p = 0.0190, FDR-p = 0.152, np2 = 0.0951, BFincl = 2.691). This effect did not pass multiple comparison controls. However, single electrode analysis of the Pe did pass multiple comparison controls (p = 0.002, FDR-p = 0.016, np2 = 0.133, BFincl = 220.659). Meditators also showed a significantly larger Pe GFP for errors only, which would have passed multiple comparison controls, but was not a primary analysis (p = 0.0028, np2 = 0.1493, BF10 = 9.999). ConclusionsMeditation may strengthen neural responses related to performance monitoring (measured by the Pe), but not specifically to error monitoring (although measurements of the Pe after errors may be more sensitive to group differences). However, only the single electrode analysis passed multiple comparison controls, while analysis including all electrodes did not, so this conclusion remains tentative.

neuroscience↗

bioRxiv2022

Selective Control of Parasitic Nematodes Using Bioactivated Nematicides

Parasitic nematodes are a major threat to global food security, particularly as the world amasses 10 billion people amidst limited arable land. Most traditional nematicides have been banned due to poor nematode-selectivity, leaving farmers with inadequate controls. Here, we use the model nematode Caenorhabditis elegans to identify a family of selective imidazothiazole nematicides, called selectivins, that undergo cytochrome p450-dependent bioactivation exclusively in nematodes. At low parts-per-million concentrations, selectivins perform comparably well with commercial nematicides to control root infection by Meloidogyne incognita - the worlds most destructive plant-parasitic nematode. Tests against a wide range of phylogenetically diverse non-target systems demonstrate that selectivins are more nematode-selective than nearly all marketed nematicides. Thus, selectivins are first-in-class bioactivated nematode controls that provide efficacy as well as much-needed nematode selectivity.

pharmacology and toxicology↗

bioRxiv2021

Keratin 19 interacts with GSK3β to regulate its nuclear accumulation and degradation of cyclin D3

Cyclin D3 regulates the G1/S transition and is frequently overexpressed in several cancer types including breast cancer, where it promotes tumor progression. Here, we show that a cytoskeletal protein keratin 19 (K19) physically interacts with a serine/threonine kinase GSK3{beta} and prevents GSK3{beta}-dependent degradation of cyclin D3. The absence of K19 allowed active GSK3{beta} to accumulate in the nucleus and degrade cyclin D3. Specifically, the head domain of K19 was required to sustain inhibitory phosphorylation of GSK3{beta} Ser9, prevent nuclear accumulation of GSK3{beta}, and maintain cyclin D3 levels and cell proliferation. K19 was found to interact with GSK3{beta} and K19-GSK3{beta} interaction was mapped out to require Ser10 and Ser35 residues on the head domain of K19. Unlike wildtype K19, S10A and S35A mutants failed to maintain total and nuclear cyclin D3 levels and induce cell proliferation. Finally, we show that the K19-GSK3{beta}-cyclin D3 pathway affected sensitivity of cells towards inhibitors to cyclin dependent kinase 4 and 6 (CDK4/6). Overall, these findings establish a role for K19 in the regulation of GSK3{beta}-cyclin D3 pathway and demonstrate a potential strategy for overcoming resistance to CDK4/6 inhibitors.

cancer biology↗

bioRxiv2021

An mRNA vaccine against SARS-CoV-2: Lyophilized, liposome-based vaccine candidate EG-COVID induces high levels of virus neutralizing antibodies

In addition to the traditional method of vaccine development, the mRNA coronavirus vaccine, which is attractive as a challenging vaccination, recently opened a new era in vaccinology. Here we describe the EG-COVID which is a novel liposome-based mRNA candidate vaccine that encodes the spike (S) protein of SARS-CoV-2 with 2P-3Q substitution in European variant. We developed the mRNA vaccine platform that can be lyophilized using liposome-based technology. Intramuscular injection of the EG-COVID elicited robust humoral and cellular immune response to SARS-CoV-2. Furthermore, sera obtained from mice successfully inhibited SARS-CoV-2 viral infection into Vero cells. We developed EG-COVID and found it to be effective based on in vitro data, and we plan to initiate a clinical trial soon. Since EG-COVID is a lyophilized mRNA vaccine that is convenient for transportation and storage, accessibility to vaccines will be significantly improved.

molecular biology↗

bioRxiv2019

Mindfulness meditators show enhanced working memory performance concurrent with different brain region engagement patterns during recall

Mindfulness meditation has been shown to improve working memory (WM). However, the altered brain activity underpinning these improvements is underexplored. In non-meditating individuals, modulation of theta and alpha oscillations and 1/f aperiodic activity during WM has been found to be related to WM performance. Resting theta and alpha oscillations have been found to differ in meditators, but WM related oscillation changes and 1/f aperiodic activity have not yet been examined. Additionally, WM event-related-potentials (ERPs) are modulated by attention, which is also enhanced by meditation, so these neural measures are candidates for exploring neural activity underpinning WM improvement in meditators. We recorded EEG from 29 controls and 29 meditators during a modified Sternberg WM task and compared theta, alpha, and 1/f aperiodic activity during the WM delay, and ERPs time-locked to the WM probe. Meditators responded more accurately (p = 0.008, Cohens d = 0.688). Meditators also showed different ERP distributions with earlier left-temporal activation and more frontal distribution of activity (FDR-p = 0.0186, {eta}2 = 0.0903), as well as a reduction in overall neural response strength (FDR-p = 0.0098, {eta}2 = 0.1251). While a higher proportion of meditators showed theta oscillations during the WM delay, no other differences in theta, alpha or 1/f aperiodic activity were present. These results suggest that increased WM performance in meditators might not be the result of higher amplitudes of typical WM activity, but instead due to an alternative neural strategy during WM decision making, which may allow more accurate responses with less neural activation.\n\nHighlights- Long term mindfulness meditators showed improved working memory (WM) accuracy\n- This was concurrent with earlier left temporal activation following probe stimuli\n- As well as a more frontal distribution and reduced overall neural response strength\n- No oscillation differences were present in the working memory delay period\n- Improved WM from altered neural strategy rather than increased neural activity

neuroscience↗

bioRxiv2017

Impact of different intensities of intermittent theta burst stimulation on the cortical properties during TMS-EEG and working memory performance

IntroductionIntermittent theta burst stimulation (iTBS) is a non-invasive brain stimulation technique capable of increasing cortical excitability beyond the stimulation period. Due to the rapid induction of modulatory effects compared to conventional repetitive transcranial magnetic stimulation (rTMS) paradigms, prefrontal application of iTBS is gaining popularity as a therapeutic tool for psychiatric disorders such as depression. In an attempt to increase efficacy, higher than conventional intensities are currently being applied. The assumption that this increases neuromodulatory effect is well established for the standard rTMS paradigms but may be mechanistically false for iTBS. This study examined the influence of intensity on the neurophysiological and behavioural effects of iTBS in the prefrontal cortex.\n\nMethods16 healthy participants received iTBS over prefrontal cortex (F1 electrode) at either 50, 75 or 100% resting motor threshold (rMT) in separate sessions. Single-pulse TMS and concurrent electroencephalography (EEG) was used to assess changes in cortical reactivity measured as TMS-evoked potentials (TEPs) and TMS-evoked oscillations. The n-back task (2-back and 3-back) were used to assess changes in working memory (accuracy and reaction time).\n\nResultsThe data can be summarised as an inverse U-shape relationship between intensity and iTBS plastic effects, where 75% iTBS resulted in the largest neurophysiological changes both in TMS-EEG and working memory. Even though 75% iTBS showed significantly decreased reaction time in the 3-back task, between condition comparisons revealed no significant differences.\n\nConclusionsThe assumption that higher intensity results in greater neuromodulatory effects is false, at least in healthy individuals, and should be carefully considered for clinical populations. Neurophysiological changes associated with working memory following iTBS suggest functional relevance. However, the effects of different intensities on behavioural performance remain elusive in the present healthy sample.\n\nHighlightsO_LIEffects of prefrontal iTBS at 50, 75 and 100% rMT were investigated\nC_LIO_LIInverse U-shape relationship between intensity and neurophysiological effects\nC_LIO_LIEffects on the behavioural performance remain elusive in healthy individuals\nC_LI\n\nDisclosures and conflict of interestsSWC was supported by a Monash Graduate Scholarship. NCR is supported by a NHMRC Early Career Fellowship (1072057). KEH is supported by a NHMRC Career Development Fellowship (1082894). PBF is supported by a NHMRC Practitioner Fellowship (1078567). PBF has received equipment for research from MagVenture A/S, Medtronic Ltd, Cervel Neurotech and Brainsway Ltd and funding for research from Neuronetics and Cervel Neurotech. He is on the scientific advisory board for Bionomics Ltd. There are no other conflicts.

neuroscience↗

bioRxiv2017

Demonstration of short-term plasticity in the dorsolateral prefrontal cortexwith theta burst stimulation: A TMS-EEG study

ObjectivesTo examine the effects of intermittent TBS (iTBS) and continuous TBS (cTBS) on cortical reactivity in the dorsolateral prefrontal cortex.\n\nMethods10 healthy participants were stimulated with either iTBS, cTBS or sham at F3 electrode. Single- and paired-pulse TMS and concurrent electroencephalography (EEG) were used to assess change in cortical reactivity and long-interval intracortical inhibition (LICI) via TMS-evoked potentials (TEPs) and TMS-evoked oscillations.\n\nResultsSignificant increases in N120 amplitudes (p < 0.01) were observed following iTBS over prefrontal cortex. Changes in TMS-evoked theta oscillations and LICI of theta oscillations were also observed following iTBS (increase) and cTBS (decrease). Change in LICI of theta oscillations correlated with change in N120 amplitude following TBS (r = -0.670, p = 0.001).\n\nConclusionsThis study provides preliminary evidence that TBS produces direct changes in cortical reactivity in the prefrontal cortex. Combining TBS with TMS-EEG may be a useful approach to optimise stimulation paradigms prior to the conduct of clinical trials.\n\nSignificanceTBS is able to modulate cortical reactivity and cortical inhibition in the prefrontal cortex.\n\nHighlightsO_LIEffects of iTBS and cTBS were studied in the DLPFC using TMS-EEG\nC_LIO_LIiTBS increased N120 amplitude, theta power and LICI of theta\nC_LIO_LIcTBS decreased theta power alone\nC_LI

neuroscience↗