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BackgroundConscious perception is thought to involve the large-scale, coordinated activation of distant brain regions, a process termed ignition in the Global Workspace Theory and integration in Integrated Information Theory, which are two of the major theories of consciousness.MethodsHere, we provide evidence for this process in humans by combining a magnetically-induced phosphene perception task with electroencephalography. Functional cortical networks were identified and characterized using graph theory to quantify the impact of conscious perception on local (segregation) and distant (integration) processing.ResultsConscious phosphene perception activated frequency-specific networks, each associated with a specific spatial scale of information processing. Integration increased within an alpha-band functional network, while segregation occurred in the beta band.ConclusionsThese results bring novel evidence for the functional role of distinct brain oscillations and confirm the key role of integration processes for conscious perception in humans.

International audience; We assessed the effects of power-line frequency (60 Hz in North America) magnetic fields (MF) in humans using simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Twenty-five participants were enrolled in a pseudo-double-blind experiment involving "real" or "sham" exposure to sinusoidal 60 Hz MF exposures delivered using the gradient coil of an MRI scanner following two conditions: (i) 10 s exposures at 3 mT (10 repetitions); (ii) 2 s exposures at 7.6 mT (100 repetitions). Occipital EEG spectral power was computed in the alpha range (8-12 Hz, reportedly the most sensitive to MF exposure in the literature) with/without exposure. Brain functional activation was studied using fMRI blood oxygen level-dependent (BOLD, inversely correlated with EEG alpha power) maps. No significant effects were detected on occipital EEG alpha power during or post-exposure for any exposure condition. Consistent with EEG results, no effects were observed on fMRI BOLD maps in any brain region. Our results suggest that acute exposure (2-10 s) to 60 Hz MF from 3 to 7.6 mT (30,000 to 76,000 times higher than average public exposure levels for 60 Hz MF) does not induce detectable changes in EEG or BOLD signals. Combined with previous findings in which effects were observed on the BOLD signal after 1 h exposure to 3 mT, 60 Hz MF, this suggests that MF exposure in the low mT range (

The effect of time-varying electrical currents (AC) on neuronal activity is currently the focus of intense translational and multidisciplinary research efforts. Thanks to a broad range of neuromodulation modalities, it is indeed possible to induce, more or less invasively, electrical currents in brain tissue. On the non-invasive side, transcranial alternating stimulation (tACS), or transcranial magnetic stimulation (TMS) have demonstrated their potential for the symptomatic treatment of neurological disorders. In the domain of more invasive stimulation techniques, deep brain stimulation (DBS), or cortical stimulation (electrical motor cortex stimulation, EMCS) have proven extremely successful therapies for Parkinson's Disease (PD) or pain management, and are used in tens of thousands of patients worldwide (over 100,000 patients for DBS only). The underlying mechanisms are increasingly understood, even if they remain wrapped in some mystery that refrains the outstanding potential of brain stimulation for treating neurological disorders. However, the basic idea is simple: information processing by the brain is achieved, at least partially, by neuronal electrical oscillations in various frequency ranges, produced by a variety of neuronal networks distributed throughout the brain. Efforts to link the spatiotemporal structure of these neuronal oscillations with brain function and behavior have provided an enormous amount of data that is shaping our understanding of brain function (see Buzsaki and Draguhn, 2004 for a review on the functional significance of brain oscillations). By inducing currents in brain tissue, it is possible to modulate the membrane potential of neurons, thereby resulting in detectable changes in neuronal activity, and to impact associated function of neuronal networks. The most widespread neurostimulation therapy today is DBS, clinically used to treat symptoms in neurological disorders such as in PD (see Modolo and Beuter, 2009 for a review). More than 25 years after its discovery, the technology of DBS has not changed much: high-frequency (>130 Hz) electrical stimulation using biphasic pulses, which are defined by their pulse width and amplitude. One minor recent innovation is the use of current-controlled DBS devices, which keep the stimulation steady at all times to avoid fluctuations in the stimulation signal being delivered and potential associated side effects (Bronstein et al., 2014). Given the tremendous progress of electronics over the last 25 years, and the advance in our qualitative and quantitative understanding of brain function, it is somewhat surprising that more personalized, sophisticated devices have not surfaced yet. Of course, using more advanced neuromodulation technologies would be meaningless if current technology was sufficient. With only 5–10% of patients eligible for DBS, a 1–3% rate of complications during surgery, batteries to replace every 4 years on average (under general anesthesia), stimulation parameters needing manual adjustments, and a complete absence of brain activity monitoring, there is however a consensus on the facts that current technology is not sufficient, and that the next generation of neuromodulation devices has to be pushed forward. Perhaps the most important aspect of all is the ability of novel neuromodulation devices to deliver stimuli with the right timing: with DBS, no matter what the ongoing brain activity is, the same stimulation pattern is continuously repeated. Why is that a limit, and why is it of fundamental importance to improve DBS drastically?

International audience; Several aspects of the human nervous system and associated motor and cognitive processes have been reported to be modulated by extremely low-frequency (ELF, < 300 Hz) time-varying Magnetic Fields (MF). Due do their worldwide prevalence; power-line frequencies (60 Hz in North America) are of particular interest. Despite intense research efforts over the last few decades, the potential effects of 60 Hz MF still need to be elucidated, and the underlying mechanisms to be understood. In this study, we have used functional Magnetic Resonance Imaging (fMRI) to characterize potential changes in functional brain activation following human exposure to a 60 Hz MF through motor and cognitive tasks. First, pilot results acquired in a first set of subjects (N=9) were used to demonstrate the technical feasibility of using fMRI to detect subtle changes in functional brain activation with 60 Hz MF exposure at 1800 μT. Second, a full study involving a larger cohort of subjects tested brain activation during 1) a finger tapping task (N=20), and 2) a mental rotation task (N=21); before and after a one-hour, 60 Hz, 3000 μT MF exposure. The results indicate significant changes in task-induced functional brain activation as a consequence of MF exposure. However, no impact on task performance was found. These results illustrate the potential of using fMRI to identify MF-induced changes in functional brain activation, suggesting that a one-hour 60 Hz, 3000 μT MF exposure can modulate activity in specific brain regions after the end of the exposure period (i.e., residual effects). We discuss the possibility that MF exposure at 60 Hz, 3000 μT may be capable of modulating cortical excitability via a modulation of synaptic plasticity processes.

International audience; Background To the knowledge of the authors, urinary osmolarity is the only tool currently available to assess kidney corticomedullary gradient (CMG). Comparisons between CMG and urinary osmolarity and the use of modalities such as sodium MRI to evaluate renal disease in humans are lacking. Purpose To investigate the ability of sodium MRI to measure CMG dynamics compared with urinary osmolarity after water load in healthy volunteers and CMG in participants with kidney disease. Materials and Methods A prospective study was conducted from July 2020 to January 2021 in fasting healthy volunteers undergoing water load and participants with chronic kidney disease (CKD) from cardiorenal syndrome included in a clinical trial. In both groups, CMG was estimated by measuring the medulla-to-cortex signal ratio from sodium MRI at 3.0 T. A custom-built two-loop (diameter, 18 cm) butterfly radiofrequency surface coil, tuned for sodium frequency (33.786 MHz), was used to acquire renal sodium images. Two independent observers measured all sodium MRI cortical and medullary values for each region of interest to compute the intraclass correlation coefficient. Pearson correlation was performed between urinary osmolarity and CMG. Results Five participants with CKD (mean age, 77 years ± 12 [standard deviation]; all men) and 10 healthy volunteers (mean age, 42 years ± 15; six men, four women) were evaluated. A reduction was observed between baseline and peak urinary dilution time for both mean medulla-to-cortex ratios (1.55 ± 0.11 to 1.31 ± 0.09, respectively; P < .001) and mean urinary osmolarity (756 mOsm/L ± 157 to 73 mOsm/L ± 14, respectively; P < .001) in healthy volunteers. Medulla-to-cortex and corresponding urinary osmolarity were correlated in both groups (r2 = 0.22; P < .001). Kidney sodium tissue content was successfully acquired in all five participants with CKD. The intraclass correlation coefficient measurement was 0.99 (P < .001). Conclusion Functional sodium MRI accurately depicted corticomedullary gradient (CMG) dynamic changes in healthy volunteers and demonstrated feasibility of CMG measurement in participants with reduced kidney function. Clinical trial registration no. NCT04170855. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Laustsen and Bøgh in this issue.

Severe COVID-19 infection results in significant immune dysregulation resulting from excessive recruitment and activation of neutrophils. The aim of this study was to confirm feasibility, initial safety and detect signal of efficacy of a non-propriety device delivered using an intermittent extra-corporeal system (LMOD) allowing leucocytes modulation in the setting of Severe COVID-19 infection. Twelve patients were recruited. Inclusion criteria were > 18 years age, confirmed COVID-19, acute respiratory distress syndrome requiring mechanical support and hypotension requiring vasopressor support. Primary end point was vasopressor requirements (expressed as epinephrine dose equivalents) and principle secondary endpoints related to safety, ability to deliver the therapy and markers of inflammation assessed over five days after treatment initiation. LMOD treatment appeared safe, defined by hemodynamic stability and no evidence of white cell number depletion from blood. We demonstrated a significant decrease in vasopressor doses (−37%, p = 0.02) in patients receiving LMOD therapy (despite these patients having to tolerate an additional extracorporeal intermittent therapy). Vasopressor requirements unchanged/increasing in control group (+ 10%, p = 0.48). Although much about the use of this therapy in the setting of severe COVID-19 infection remains to be defined (e.g. optimal dose and duration), this preliminary study supports the further evaluation of this novel extracorporeal approach.

The effects of time-varying magnetic fields (MF) on humans have been actively investigated for the past three decades. One important unanswered question is the potential for MF exposure to have acute effects on human biology. Different strategies have been used to tackle this question using various physiological, neurophysiological and behavioral indicators. For example, researchers investigating electroencephalography (EEG) have reported that extremely low frequency (ELF

International audience; Let’s imagine the cruise control of your car locked at 120 km/h on any road in any condition (city, country, highway, sunny or rainy weather), or your car air conditioner set on maximum cold in any temperature condition (even during a snowy winter): would you find it efficient? That would probably not be the most optimal strategy for a proper and comfortable driving experience. As surprising as this may seem, this is a pretty accurate illustration of howdeep brain stimulation is used today to treat Parkinson’s disease motor symptoms and other neurological disorders such as essential tremor, obsessive-compulsive disorder, or epilepsy.

Background: International agencies such as the International Commission on Non-Ionizing Radiation Protection (ICNIRP) and the International Committee on Electromagnetic Safety (ICES) of the Institute of Electrical and Electronics Engineers (IEEE) need further data to set international guidelines to protect workers and the public from potential adverse effects to Extremely Low-Frequency Magnetic Fields (ELF-MF). Interestingly, electromagnetic induction has been hypothesized to impact human vestibular function (i.e. through induced electric fields). To date, a theoretical 4 T/s vestibular threshold was proposed to modulate postural control, but data is lacking above this limit. Objectives: This research aimed to investigate the impact of full head homogeneous ELF-MF stimulations above the 4 T/s threshold on human postural control. Methods: Postural control of twenty healthy participants was analyzed while full head homogeneous ELF-MF stimulations (20 Hz, 60 Hz, and 90 Hz) up to 40 T/s were applied. Velocity, main direction and spatial dispersion of sway were used to investigate postural modulations. Results: Despite a conclusive positive control effect, no significant effects of ELF-MF exposures on velocity, spatial dispersion, and direction of the postural sway were found for our 3 frequency conditions. Conclusions: The homogeneous full head MF stimulations oriented vertically and delivered at high frequencies induced E-fields having a weaker impact than anticipated, possibly because they impacted only a small portion of the vestibular system. This resulted in an absence of effect on postural control outcomes.

Rationale & Objective Current hemodialysis (HD) treatments have limited ability to clear larger-molecular-weight uremic toxins. Retention is associated with increased symptom burden, low health-related quality of life (HRQoL), and high mortality. Improved clearance, using novel medium cut-off dialyzers, termed expanded HD (HDx), may be associated with improved subjective experience. We have previously developed a dynamic patient-reported outcome measure (PROM) instrument to allow iterative recording to better appreciate the overall burden of disease and assess the impact of therapy changes. Study Design Single-center interventional pilot study. Setting & Participants 28 patients established on maintenance HD, London, Ontario, Canada. Intervention Initial study consisting of 2-week observation (baseline-conventional high-flux HD) followed by 12 weeks of HDx. HRQoL was assessed using the dynamic PROM instrument thrice weekly (enabled in a dedicated app as the London Evaluation of Illness [LEVIL]). Extension phase; 2-week baseline with 24 weeks of HDx and 8-week washout. Outcomes Principal aim was to establish whether HDx therapy was associated with improved HRQoL, evidence of dose-dependant response, and whether effects were durable over time, using LEVIL. Results Patients with lower LEVIL scores (, Graphical abstract

Background: Preclinical data suggest sodium deposited (without water) in tissues may lead to aberrant remodeling and systemic inflammation, independently of fluid overload in patients with heart failure (HF). Tissue salt storage can be measured noninvasively and quantitatively with 23 Na-magnetic resonance imaging. We aimed to investigate the possibility that patients with HF complicated by renal dysfunction are subject to higher tissue sodium concentration exposure than patients with chronic kidney disease alone. Methods: We conducted an exploratory study including 18 patients with HF, 34 hemodialysis patients (with no meaningful renal clearance of sodium), and 31 patients with chronic kidney disease, with glomerular filtration rate matched to the patients with HF. Every patient underwent 23 Na-magnetic resonance imaging of the calf, to quantify tissue sodium and allow comparison among the 3 patient groups. Results: There were no differences in age, sex, and body mass index between groups. Median (interquartile range) skin sodium content in HF (31 [23–37] mmol/L) was very high and indistinguishable from skin sodium content in hemodialysis patients (30 [22–35] mmol/L), P =0.6. Patients with HF exhibited significantly higher skin sodium content than matched estimated glomerular filtration rate chronic kidney disease patients (22 [19–26] mmol/L), P =0.005. Median muscle sodium content in patients with HF was significantly higher than in patients with chronic kidney disease, P =0.002. There was no relationship with estimated glomerular filtration rate in patients with HF. We report a significant correlation between skin sodium and urinary sodium ( P =0.04) but no correlation with muscle sodium. Patients who were assessed as being volume depleted (sodium excretion fraction 1% ( P =0.03). Conclusions: We have demonstrated that patients with HF characteristically have very high levels of skin sodium storage, comparable to well-characterized extreme levels seen in patients with end-stage kidney disease requiring hemodialysis. 23 Na-magnetic resonance imaging may allow precision medicine in the management of this challenging group of patients with HF. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03004547.

Background: Moderate therapeutic hypothermia (TH) is a well-recognized cardio-protective strategy. The instillation of fluid into the peritoneum provides an opportunity to deliver moderate hypothermia as primary prevention against cardiovascular events. We aimed to to investigate both cardiac perfusion consequences (overall blood flow and detailed assessment of perfusion heterogeneity) and subsequently simulate the associated arrhythmic risk for patients undergoing peritoneal dialysis (PD) induced TH.Methods: Patients underwent high resolution myocardial perfusion scanning using high resolution 256 slice CT scanning, at rest and with adenosine stress. The first visit using the patient's usual PD regimen, on the second visit the same regime was utilized but with cooled peritoneal dialysate at 32°C. Myocardial blood flow (MBF) was quantified from generated perfusion maps, reconstructed in 3D. MBF heterogeneity was assessed by fractal dimension (FD) measurement on the 3D left ventricular reconstruction. Arrhythmogenicity was quantified from a sophisticated computational simulation using a multi-scale human 3D ventricle wedge electrophysiological computational model.Results: We studied 7 PD patients, mean age of 60 ± 7 and mean vintage dialysis of 23.6 ± 17.6 months. There were no significant different in overall segmental MBF between normothermic condition (NT) and TH. MBF heterogeneity was significantly decreased (−14%, p = 0.03) at rest and after stress (−14%, p = 0.03) when cooling was applied. Computational simulation showed that TH allowed a normalization of action potential, QT duration and T wave.Conclusion: TH-PD results in moderate hypothermia leading to a reduction in perfusion heterogeneity and simulated risk of non-terminating malignant ventricular arrhythmias.

It is well known that applying transcranial alternating current stimulation (tACS) to the scalp can generate artefactual visual perceptions of flashing or shimmering light known as phosphenes. The thresholds for generating these phosphenes have been used by international standards bodies to provide conservative estimates of the field strength required to interfere with human neural functioning and set safety limits accordingly. However, the precise relationship between electric currents and phosphene perception thresholds remains uncertain. The present study used tACS to systematically investigate the effects of the location and the frequency of stimulation on phosphene perception thresholds. These thresholds were obtained from 24 participants using a within-subject design as a function of scalp stimulation sites (FPz-Cz versus Oz-Cz) and stimulation frequency (2-30 Hz in steps of 2 Hz). Phosphene perception thresholds were consistently lower for FPz-Cz stimulation, and regardless of tACS location were lowest for 16 Hz stimulation. Threshold variation between participants was very small, which is meaningful when setting standards based on phosphenes. Bioelectromagnetics. 2019;40:365-374. © 2019 Bioelectromagnetics Society.

Context The recent discovery of the existence of a human genitourinary microbiome has led to the investigation of its role in mediating the pathogenesis of genitourinary malignancies, including bladder, kidney, and prostate cancers. Furthermore, although it is largely recognized that members of the gastrointestinal microbiota are actively involved in drug metabolism, new studies demonstrate additional roles and the potential necessity of the gastrointestinal microbiota in dictating cancer treatment response. Objective To summarize the current evidence of a mechanistic role for the genitourinary and gastrointestinal microbiome in genitourinary cancer initiation and treatment response. Evidence acquisition We conducted a literature search up to October 2018. Search terms included microbiome, microbiota, urinary microbiome, bladder cancer, urothelial carcinoma, renal cell carcinoma, kidney cancer, testicular cancer, and prostate cancer. Evidence synthesis There is preliminary evidence to implicate the members of the genitourinary microbiota as causative factors or cofactors in genitourinary malignancy. Likewise, the current evidence for gastrointestinal microbes in dictating cancer treatment response is mainly correlative; however, we provide examples where therapeutic agents used for the treatment of genitourinary cancers are affected by the human-associated microbiota, or vice versa. Clinical trials, such as fecal microbiota transplant to increase the efficacy of immunotherapy, are currently underway. Conclusions The role of the microbiome in genitourinary cancer is an emerging field that merits further studies. Translating microbiome research into clinical action will require incorporation of microbiome surveillance into ongoing and future clinical trials as well as expansion of studies to include metagenomic sequencing and metabolomics. Patient summary This review covers recent evidence that microbial populations that reside in the genitourinary tract—and were previously not known to exist—may influence the development of genitourinary malignancies including bladder, kidney, and prostate cancers. Furthermore, microbial populations that exist at sites outside of the genitourinary tract, such as those that reside in our gut, may influence cancer development and/or treatment response.

International audience; No abstract available

International audience; No abstract available