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Rhodes, N.

Publications and source records attributed to Rhodes, N..

10 recordsLinked to original sources

OPM-MEG reveals protracted maturation of visual phase-amplitude coupling from early childhood to adulthood

Cross-frequency coupling describes interactions between neural ensembles operating at different frequency bands, and has been proposed to underlie coordination of brain activity over multiple temporal and spatial scales. Phase amplitude coupling (PAC) describes modulation of the amplitude of high-frequency oscillations by the phase of low frequency oscillations. MEG work in adults has demonstrated that alpha-gamma PAC may support visual perception. However, very little work has investigated visual PAC in children, or the development of this process between childhood and adulthood. Here we investigated the development of PAC in a sample of 101 individuals, comprising 50 children (aged 2-13 years) and 51 adults (21-34 years). Participants completed a passive visual stimulation paradigm while neural responses were recorded using a wearable whole-head OPM-MEG system. Sensor-level data were spatially resolved to visual cortex, and we quantified coupling between the phase of low-frequency oscillations (5-13 Hz) and the amplitude of broadband gamma oscillations (28-100 Hz) in each participant. In the adult data, we identified a cluster of phase-amplitude frequency pairs (phase: 7-11 Hz, amplitude: 52-66 Hz) in which there was strong evidence for an increase in PAC following stimulus presentation relative to baseline. Within this cluster, the magnitude of stimulus-induced PAC was positively correlated with age across all participants. Meanwhile, we did not see credible evidence for visual PAC at any frequency pair(s) within the child group. These results suggest that, alongside well-documented developmental changes in band-specific oscillatory power and connectivity, visual PAC represents a distinct functional process which matures with age.

neuroscience↗

Charting developmental trajectories of dynamic brain networks during emotional face processing

Emotional face processing is a critical component in the development of social cognition through childhood. The neural mechanisms supporting this development can be understood by tracking age-related changes in brain activity. Prior work in this area with MEG relies on static, bandlimited, or region-specific measures, which do not capture the dynamic, distributed nature of brain activity. Here we used Dynamic Network Modes (DyNeMo) to analyze MEG data from a large cohort of typically developing individuals (N=224, ages 5-40) during an emotional faces vigilance task. DyNeMo is a data-driven, generative modelling approach which captures functional networks as a set of whole-brain spatiospectral "modes" whose relative mixture (i.e., activation levels) can change dynamically in response to stimuli. We inferred six modes from the MEG data and characterized developmental trajectories in task-related activation and mode connectivity. Across modes we observed distinct developmental trajectories in both measures. With respect to mode activation, a visual mode and a frontotemporal mode (whose labels reflect their respective spatial profiles) increased nonlinearly with age; meanwhile, activation in temporal and sensorimotor modes decreased linearly with age. Meanwhile, connectivity broadly increased with age in all modes, but with different degrees of nonlinearity. These results suggest developmental dissociations between different modes (e.g., visual versus sensorimotor), as well as within individual modes (task-related mode activation versus connectivity). These results provide a comprehensive and complex picture of functional network development underlying emotional face processing. Significance StatementBrain networks supporting social cognition undergo profound changes from childhood through adolescence to adulthood. However, current understanding of how these networks develop has been limited by conventional analyses of brain imaging data, which typically provide a static picture of brain activity. Here we leveraged a cutting-edge, data-driven modeling approach (DyNeMo) to characterize age-related changes in distributed and dynamic networks supporting emotional face processing, in a large cohort of children and young adults (N=224). We inferred six functional networks whose activation levels changed rapidly in response to emotional faces. Network activation and connectivity exhibited profound and distinct non-linear changes with age, indicating that emotional face processing is supported by complex interactions among multiple dynamic networks, each with different maturational trajectories.

neuroscience↗

Source Reconstruction Without an MRI using Optically Pumped Magnetometer based Magnetoencephalography

Source modelling in magnetoencephalography (MEG) maps the spatial origins of electrophysiological signals in the brain. Typically, this requires an anatomical MRI scan of the subjects head, from which a model of the neuromagnetic field (the forward model) is derived. Wearable MEG - based on optically pumped magnetometers (OPMs) - enables MEG measurement from participants who struggle to cope with conventional scanning environments (e.g. children), enabling study of novel cohorts. However, its value is limited if an MRI scan is still required for source modelling. Here we describe a method of warping template MRIs to 3D structured-light scans of the head, to generate "pseudo-MRIs". We apply our method using data from 20 participants during a sensory task, measuring induced (beta band) responses and whole-brain functional connectivity. Results show that the group average locations of peak task-induced beta modulation were separated by 2.75 mm, when comparing real- and pseudo-MRI approaches. Group averaged time-frequency spectra were also highly correlated (Pearson correlation 0.99) as were functional connectome matrices (0.87), and global connectivity (0.98). In sum, our results demonstrate that source-localized OPM-MEG data, modelled with and without an individual MRI scan can be similar. This will be useful for future studies where MRI data capture is challenging.

neuroscience↗

Measuring the neurodevelopmental trajectory of excitatory-inhibitory balance via visual gamma oscillations

Disruption of the balance between excitatory and inhibitory neurotransmission (E-I balance) underlies theories of many neurodevelopmental disorders, however, its study is typically restricted to adults, animal models and the lab-bench. Neurophysiological oscillations in the gamma frequency band relate closely to E-I balance, and a new technology - OPM-MEG - offers the possibility to measure such signals across the lifespan. We used OPM-MEG to measure gamma oscillations induced by visual stimulation in >100 participants, aged 2-34 years. We demonstrate a significantly changing spectrum with age, with low amplitude broadband gamma oscillations in children and high amplitude band limited oscillations dominating in adults. We used a canonical cortical microcircuit to model these gamma signals, revealing significant age-related shifts in E-I balance in superficial pyramidal neurons in visual cortex. Our findings detail the first MEG metrics of gamma oscillations and their underlying generators from toddlerhood, providing a benchmark against which future studies can contextualise.

neuroscience↗

The development of aperiodic and periodic resting-state power between early childhood and adulthood: new insights from optically pumped magnetometers

Neurophysiological signals, comprised of both periodic (e.g., oscillatory) and aperiodic (e.g., non-oscillatory) activity, undergo complex developmental changes between childhood and adulthood. With much of the existing literature primarily focused on the periodic features of brain function, our understanding of aperiodic signals is still in its infancy. Here, we are the first to examine age-related changes in periodic (peak frequency and power) and aperiodic (slope and offset) activity using optically pumped magnetometers (OPMs), a new, wearable magnetoencephalography (MEG) technology that is particularly well-suited for studying development. We examined age-related changes in these spectral features in a sample (N=65) of toddlers (1-3 years), children (4-5 years), young adults (20-26 years), and adults (27-38 years). Consistent with the extant literature, we found significant age-related decreases in the aperiodic slope and offset, and changes in peak frequency and power that were frequency-specific; we are the first to show that the effect sizes of these changes also varied across brain regions. This work not only adds to the growing body of work highlighting the advantages of using OPMs, especially for studying development, but also contributes novel information regarding the variation of neurophysiological changes with age across the brain.

neuroscience↗

A Novel, Robust, and Portable Platform for Magnetoencephalography using Optically Pumped Magnetometers

Magnetoencephalography (MEG) measures brain function via assessment of magnetic fields generated by neural currents. Conventional MEG uses superconducting sensors, which place significant limitations on performance, practicality, and deployment; however, the field has been revolutionised in recent years by the introduction of optically-pumped-magnetometers (OPMs). OPMs enable measurement of the MEG signal without cryogenics, and consequently the conception of OPM-MEG systems which ostensibly allow increased sensitivity and resolution, lifespan compliance, free subject movement, and lower cost. However, OPM-MEG remains in its infancy with limitations on both sensor and system design. Here, we report a new OPM-MEG design with miniaturised and integrated electronic control, a high level of portability, and improved sensor dynamic range (arguably the biggest limitation of existing instrumentation). We show that this system produces equivalent measures when compared to an established instrument; specifically, when measuring task-induced beta-band, gamma-band and evoked neuro-electrical responses, source localisations from the two systems were highly comparable and temporal correlation was >0.7 at the individual level and >0.9 for groups. Using an electromagnetic phantom, we demonstrate improved dynamic range by running the system in background fields up to 8 nT. We show that the system is effective in gathering data during free movement (including a sitting-to-standing paradigm) and that it is compatible with simultaneous electroencephalography (EEG - the clinical standard). Finally, we demonstrate portability by moving the system between two laboratories. Overall, our new system is shown to be a significant step forward for OPM-MEG technology and offers an attractive platform for next generation functional medical imaging.

neuroscience↗

The neurodevelopmental trajectory of beta band oscillations: an OPM-MEG study

Neural oscillations mediate the coordination of activity within and between brain networks, supporting cognition and behaviour. How these processes develop throughout childhood is not only an important neuroscientific question but could also shed light on the mechanisms underlying neurological and psychiatric disorders. However, measuring the neurodevelopmental trajectory of oscillations has been hampered by confounds from instrumentation. In this paper, we investigate the suitability of a disruptive new imaging platform - Optically Pumped Magnetometer-based magnetoencephalography (OPM-MEG) - to study oscillations during brain development. We show how a unique 192-channel OPM-MEG device, which is adaptable to head size and robust to participant movement, can be used to collect high-fidelity electrophysiological data in individuals aged between 2 and 34 years. Data were collected during a somatosensory task, and we measured both stimulus-induced modulation of beta oscillations in sensory cortex, and whole-brain connectivity, showing that both modulate significantly with age. Moreover, we show that pan-spectral bursts of electrophysiological activity drive task-induced beta modulation, and that their probability of occurrence and spectral content change with age. Our results offer new insights into the developmental trajectory of beta oscillations and provide clear evidence that OPM-MEG is an ideal platform for studying electrophysiology in neurodevelopment.

neuroscience↗

Naturalistic hyperscanning with wearable magnetoencephalography

The evolution of human cognitive function is reliant on complex social interactions which form the behavioural foundation of who we are. These social capacities are subject to dramatic change in disease and injury; yet their supporting neural substrates remain poorly understood. Hyperscanning employs functional neuroimaging to simultaneously assess brain activity in two individuals and offers the best means to understand the neural basis of social interaction. However, present technologies are limited, either by poor performance (low spatial/temporal precision) or unnatural scanning environment (claustrophobic scanners, with interactions via video). Here, we solve this problem by developing a new form of hyperscanning using wearable magnetoencephalography (MEG). This approach exploits quantum sensors for MEG signal detection, in combination with high-fidelity magnetic field control - afforded by a novel "matrix coil" system - to enable simultaneous scanning of two freely moving participants. We demonstrate our approach in a somatosensory task and an interactive ball game. Despite large and unpredictable subject motion, sensorimotor brain activity was delineated clearly in space and time, and correlation of the envelope of neuronal oscillations between people was demonstrated. In sum, unlike existing modalities, wearable-MEG combines high fidelity data acquisition and a naturalistic setting, which will facilitate a new generation of hyperscanning.

neuroscience↗

Urinary Metabolomics from a Dose-Fractionated Polymyxin B Rat Model of Acute Kidney Injury

BackgroundPolymyxin B remains an important antimicrobial against multi-drug resistant bacteria; however, kidney injury is often a treatment limiting event with kidney failure rates that range from 5-13%. MethodsSamples were obtained from a previously conducted study of male Sprague-Dawley rats that received dose fractionated polymyxin B (12 mg/kg/day subcutaneously) once daily (QD), twice daily (BID), and thrice daily (TID) for three days. In the original study, urinary biomarkers and kidney histopathology scores were determined. Urine was sampled daily and analyzed for urinary metabolites via 1H NMR analysis. Unsupervised Principal Components Analysis was applied for exploratory data analysis to identify trends and outliers in the spectral data. Then, supervised Orthogonal Partial Least Square Discriminant Analysis was applied to classify the samples collected in different days and identify metabolic differences during the treatment. Metabolomes were compared across study groups (i.e. those receiving QD, BID, TID, and control) using a mixed-effects models. Spearman correlation was performed for injury biomarkers and the metabolome. ResultsA total of 27 rats contributed 77 urinary samples; n=25 rats were included that were treated with Polymyxin B and n=2 received saline. Pre-dosing samples clustered well and were characterized by higher amounts of citrate, 2-oxoglutarate, and Hippurate. On day 1 post treatment, day 1 samples showed higher taurine; day 3 samples had higher lactate, acetate and creatine. Taurine was the only metabolite significantly increased in both BID and TID compared to QD group. Taurine on day 1 correlated with increasing histopathology scores (Spearmans rho = 0.4167, P=0.038) and KIM-1 (Spearmans rho =0.4052, P=0.036); whereas KIM-1 on day one and day 3 did not reach significance with histopathology (Spearmans rho = 0.3248, P=0.11 and Spearmans rho = 0.3739, P=0.066). ConclusionPolymyxin B causes increased amounts of urinary taurine on day 1 which then normalizes to baseline concentrations. Taurine may provide one of the earlier signals of acute kidney damage caused by polymyxin B.

pharmacology and toxicology↗

Urinary biomarker and histopathological evaluation of vancomycin and piperacillin-tazobactam nephrotoxicity in comparison with vancomycin in a rat model and a confirmatory cellular model

IntroductionVancomycin and piperacillin tazobactam (VAN+TZP) are two of the most commonly utilized antibiotics in the hospital setting and are reported in clinical studies to increase acute kidney injury (AKI). However, no clinical study has demonstrated that synergistic toxicity occurs, only that serum creatinine (SCr) increases with VAN+TZP. The purpose of this study was to assess biologic plausibility by quantifying kidney injury between VAN, TZP, and VAN+TZP treatments using a translational rat model of AKI and rat kidney epithelial cell studies.\n\nMethods(i) Male Sprague-Dawley rats (n=32) received either saline, VAN 150 mg/kg/day intravenously, TZP 1400 mg/kg/day via intraperitoneal injection, or VAN+TZP. Animals were placed in metabolic cages pre-study and on drug dosing days 1-3. Urinary biomarkers and histopathology were analyzed. (ii) Cellular injury of VAN+TZP was assessed in serum-deprived rat kidney cells (NRK-52E) using an alamarBlue(R) viability assay. Cells were incubated with antibiotics VAN, TZP, cefepime, and gentamicin alone or combined with the same drugs plus VAN 1 mg/mL.\n\nResultsIn the VAN-treated rats, urinary KIM-1 and clusterin were increased on days 1, 2, and 3 compared to controls (P<0.001). Elevations were seen only after 3 days of treatment with VAN+TZP (P<0.001 KIM-1, P<0.05 clusterin). Histopathology was only elevated in the VAN group when compared to TZP as a control (P=0.04). Results were consistent across biomarkers and histopathology suggesting that adding TZP did not worsen VAN induced AKI and may even be protective. In NRK-52E cells, VAN alone caused moderate cell death with high doses (IC5048.76 mg/mL). TZP alone did not cause cellular death under the same conditions. VAN+TZP was not different from VAN alone in NRK-52E cells (P>0.2).\n\nConclusionsVAN+TZP does not cause more kidney injury than VAN alone in a rat model of VIKI or in rat kidney epithelial cells.

pharmacology and toxicology↗