Neurobiological underpinnings of cyberbullying: A pilot functional magnetic resonance imaging study

There is a dearth of research that has investigated the neural correlates of cyberbullying, using task‐based functional magnetic resonance imaging (fMRI) and, specifically, in a real‐time context such as observing cyberbullying scenarios. This article presents pilot data from a novel protocol designed to undertake such research with the overall aim being to elucidate the neurobiological underpinnings of cyberbullying via task‐based fMRI (tb‐fMRI)) in passive cyberbystanders. Young adults (N = 32, 18 to 25 years old) viewed six negative (cyberbullying) and six neutral stimuli from the Cyberbullying Picture Series (CyPicS) while undergoing tb‐fMRI. Our results revealed 12 clusters of significantly greater blood‐oxygenation‐level‐dependent (BOLD) responses (family wise error corrected p _FWE < .05) in participants when viewing cyberbullying stimuli compared to neutral stimuli, across a distributed network of regions including left and right middle temporal gyrus, default mode network hubs, left and right posterior cerebellum/vermis, and putamen. Further analysis also revealed greater BOLD response in females compared to males, as well as in those with no prior experience of cyberbullying compared to those with prior experience (despite gender), when viewing the cyberbullying stimuli compared to the neutral stimuli. These results bring us closer to understanding the neurobiological underpinnings that may be associated with cybervictim/bully status and outcomes.     

Tractostorm 2: Optimizing tractography dissection reproducibility with segmentation protocol dissemination

The segmentation of brain structures is a key component of many neuroimaging studies. Consistent anatomical definitions are crucial to ensure consensus on the position and shape of brain structures, but segmentations are prone to variation in their interpretation and execution. White‐matter (WM) pathways are global structures of the brain defined by local landmarks, which leads to anatomical definitions being difficult to convey, learn, or teach. Moreover, the complex shape of WM pathways and their representation using tractography (streamlines) make the design and evaluation of dissection protocols difficult and time‐consuming. The first iteration of Tractostorm quantified the variability of a pyramidal tract dissection protocol and compared results between experts in neuroanatomy and nonexperts. Despite virtual dissection being used for decades, in‐depth investigations of how learning or practicing such protocols impact dissection results are nonexistent. To begin to fill the gap, we evaluate an online educational tractography course and investigate the impact learning and practicing a dissection protocol has on interrater (groupwise) reproducibility. To generate the required data to quantify reproducibility across raters and time, 20 independent raters performed dissections of three bundles of interest on five Human Connectome Project subjects, each with four timepoints. Our investigation shows that the dissection protocol in conjunction with an online course achieves a high level of reproducibility (between 0.85 and 0.90 for the voxel‐based Dice score) for the three bundles of interest and remains stable over time (repetition of the protocol). Suggesting that once raters are familiar with the software and tasks at hand, their interpretation and execution at the group level do not drastically vary. When compared to previous work that used a different method of communication for the protocol, our results show that incorporating a virtual educational session increased reproducibility. Insights from this work may be used to improve the future design of WM pathway dissection protocols and to further inform neuroanatomical definitions.     

A bioreactor for studying negative pressure wound therapy on skin grafts

Negative pressure wound therapy (NPWT) has become the prevailing standard of care for treating complex soft tissue wounds and is now being considered for use in alternative applications including improving skin graft take. While it is generally agreed that negative pressure leads to improved wound healing, universal consensus on its optimal application is not supported in the literature. We describe the design and validation of a bioreactor to determine the prospective benefits of NPWT on skin grafts and engineered skin substitutes (ESS). Clinically relevant pressures were applied, and the native human skin was able to withstand greater negative pressures than the engineered substitutes. Both skin types were cultured under static, flow‐only, and −75 mm Hg conditions for 3 days. While it remained intact, there was damage to the epidermal‐dermal junction in the ESS after application of negative pressure. The normal skin remained viable under all culture conditions. The engineered skin underwent apoptosis in the flow‐only group; however, the application of negative pressure reduced apoptosis. Vascular endothelial growth factor levels were significantly higher in the normal flow‐only group, 152.0 ± 75.1 pg/mg protein, than the other culture conditions, 81.6 ± 35.5 pg/mg for the static and 103.6 ± pg/mg for the negative pressure conditions. The engineered skin had a similar trend but the differences were not significant. This bioreactor design can be used to evaluate the impacts of NPWT on the anatomy and physiology of skin to improve outcomes in wounds after grafting with normal or engineered skin.     

Fluctuations in EEG band power at subject‐specific timescales over minutes to days explain changes in seizure evolutions

Epilepsy is recognised as a dynamic disease, where both seizure susceptibility and seizure characteristics themselves change over time. Specifically, we recently quantified the variable electrographic spatio‐temporal seizure evolutions that exist within individual patients. This variability appears to follow subject‐specific circadian, or longer, timescale modulations. It is therefore important to know whether continuously recorded interictaliEEG features can capture signatures of these modulations over different timescales. In this study, we analyse continuous intracranial electroencephalographic (iEEG) recordings from video‐telemetry units and find fluctuations in iEEG band power over timescales ranging from minutes up to 12 days. As expected and in agreement with previous studies, we find that all subjects show a circadian fluctuation in their iEEG band power. We additionally detect other fluctuations of similar magnitude on subject‐specific timescales. Importantly, we find that a combination of these fluctuations on different timescales can explain changes in seizure evolutions in most subjects above chance level. These results suggest that subject‐specific fluctuations in iEEG band power over timescales of minutes to days may serve as markers of seizure modulating processes. We hope that future study can link these detected fluctuations to their biological driver(s). There is a critical need to better understand seizure modulating processes, as this will enable the development of novel treatment strategies that could minimise the seizure spread, duration or severity and therefore the clinical impact of seizures.     

Long-term male-specific chronic pain via telomere- and p53‑mediated spinal cord cellular senescence

Mice with experimental nerve damage can display long‑lasting neuropathic pain behavior. We show here that 4 months and later after nerve injury, male but not female mice displayed telomere length (TL) reduction and p53‑mediated cellular senescence in the spinal cord, resulting in maintenance of pain and associated with decreased lifespan. Nerve injury increased the number of p53‑positive spinal cord neurons, astrocytes, and microglia, but only in microglia was the increase male‑specific, matching a robust sex specificity of TL reduction in this cell type, which has been previously implicated in male‑specific pain processing. Pain hypersensitivity was reversed by repeated intrathecal administration of a p53‑specific senolytic peptide, only in male mice and only many months after injury. Analysis of UK Biobank data revealed sex-specific relevance of this pathway in humans, featuring male‑specific genetic association of the human p53 locus (TP53) with chronic pain and a male-specific effect of chronic pain on mortality. Our findings demonstrate the existence of a biological mechanism maintaining pain behavior, at least in males, occurring much later than the time span of virtually all extant preclinical studies.