A Leak-Free Head-Out Plethysmography System to Accurately Assess Lung Function in Mice

Mice are a valuable model for elegant studies of complex, systems-dependent diseases, including pulmonary diseases. Current tools to assess lung function in mice are either terminal or lack accuracy. We set out to develop a low-cost, accurate, head-out variable-pressure plethysmography system to allow for repeated, non-terminal measurements of lung function in mice. Current head-out plethysmography systems are limited by air leaks that prevent accurate measures of volume and flow. We designed an inflatable cuff that encompasses the mouse’s neck preventing air leak. We wrote corresponding software to collect and analyze the data, remove movement artifacts, and automatically calibrate each dataset. This software calculates inspiratory/expiratory volume, inspiratory/expiratory time, breaths per minute, enhanced pause, mid-expiratory flow, and end-inspiratory pause. To validate the use, we established our plethysmography system accurately measured tidal breathing, the bronchoconstrictive response to methacholine, sex and age associated changes in breathing, and breathing changes associated with house dust mite sensitization. Our estimates of volume, flow, and timing of breaths are in line with published estimates, we observed dose-dependent decreases in volume and flow in response to methacholine (P < 0.05), increased lung volume and decreased breathing rate with aging (P < 0.05), and that house dust mite sensitization decreased tidal volume and flow (P <0.05) while exacerbating the methacholine induced increases in inspiratory and expiratory time (P < 0.05). We describe an accurate, sensitive, low-cost, head-out plethysmography system that allows for longitudinal studies of pulmonary disease in mice.New & NoteworthyWe describe a variable-pressure head-out plethysmography system that can be used to assess lung function in mice. A balloon cuff that inflates around the mouse’s neck prevents air leak, allowing for accurate measurements of lung volume and air flow. Custom software facilitates system calibration, removes movement artifacts, and eases data analysis. The system was validated by measuring tidal breathing, responses to methacholine, and changes associated with house dust mite sensitization, sex, and aging.Contributions to StudyStephanie Bruggink: development of head-out plethysmography chamber, measurement of breathing, data analysis, prepared manuscriptKyle Kentch: development of head-out plethysmography chamber, programmed software to collect and analyze data, prepared manuscriptJason Kronenfeld: development of tools to analyze data, analysis of dataBenjamin Renquist: development of head-out plethysmography chamber, statistical analysis, prepared manuscript

Magnetic field compensation coil design for magnetoencephalography

While optically pumped magnetometers (OPMs) can be attached to the head of a person and allow for highly sensitive recordings of the human magnetoencephalogram (MEG), they are mostly limited to an operational range of approximately 5 nT. Consequently, even inside a magnetically shielded room (MSR), movements in the remnant magnetic field disable the OPMs. Active suppression of the remnant field utilizing compensation coils is therefore essential. We propose 8 compensation coils on 5 sides of a cube with a side length of approximately 2 m which were optimized for operation inside an MSR. Compared to previously built bi-planar compensation coils, the coils proposed in this report are more complex in geometry and achieved smaller errors for simulated compensation fields. The proposed coils will allow for larger head movements or smaller movement artifacts in future MEG experiments compared to existing coils.

Pitfalls in EEG Analysis in Patients With Nonconvulsive Status Epilepticus: A Preliminary Study

Objective: Electroencephalography (EEG) interpretations through visual (by human raters) and automated (by computer technology) analysis were still not reliable for the diagnosis of nonconvulsive status epilepticus (NCSE). This study aimed to identify typical pitfalls in the EEG analysis and make suggestions as to how those pitfalls might be avoided. Methods: We analyzed the EEG recordings of individuals who had clinically confirmed or suspected NCSE. Epileptiform EEG activity during seizures (ictal discharges) was visually analyzed by 2 independent raters. We investigated whether unreliable EEG visual interpretations quantified by low interrater agreement can be predicted by the characteristics of ictal discharges and individuals’ clinical data. In addition, the EEG recordings were automatically analyzed by in-house algorithms. To further explore the causes of unreliable EEG interpretations, 2 epileptologists analyzed EEG patterns most likely misinterpreted as ictal discharges based on the differences between the EEG interpretations through the visual and automated analysis. Results: Short ictal discharges with a gradual onset (developing over 3 s in length) were liable to be misinterpreted. An extra 2 min of ictal discharges contributed to an increase in the kappa statistics of >0.1. Other problems were the misinterpretation of abnormal background activity (slow-wave activities, other abnormal brain activity, and the ictal-like movement artifacts), continuous interictal discharges, and continuous short ictal discharges. Conclusion: A longer duration criterion for NCSE-EEGs than 10 s that is commonly used in NCSE working criteria is recommended. Using knowledge of historical EEGs, individualized algorithms, and context-dependent alarm thresholds may also avoid the pitfalls.

Adaptive single-channel EEG artifact removal with applications to clinical monitoring

Objective: Electroencephalography (EEG) has become very common in clinical practice due to its relatively low cost, ease of installation, non-invasiveness, and good temporal resolution. Portable EEG devices are increasingly popular in clinical monitoring applications such as sleep scoring or anesthesia monitoring. In these situations, for reasons of speed and simplicity only few electrodes are used and contamination of the EEG signal by artifacts is inevitable. Visual inspection and manual removal of artifacts is often not possible, especially in real-time applications. Our goal is to develop a flexible technique to remove EEG artifacts in these contexts with minimal supervision. Methods: We propose here a new wavelet-based method which allows to remove artifacts from single-channel EEGs. The method is based on a datadriven renormalization of the wavelet components and is capable of adaptively attenuate artifacts of different nature. We benchmark our method against alternative artifact removal techniques. Results: We assessed the performance of the proposed method on publicly available datasets comprising ocular, muscular, and movement artifacts. The proposed method shows superior performances on different kinds of artifacts and signal-to-noise levels. Finally, we present an application of our method to the monitoring of general anesthesia. Conclusions: We show that our method can successfully attenuate various types of artifacts in single-channel EEG. Significance: Thanks to its data-driven approach and low computational cost, the proposed method provides a valuable tool to remove artifacts in real-time EEG applications with few electrodes, such as monitoring in special care units.

On-scalp magnetoencephalography for childhood epilepsies

Magnetoencephalography (MEG) is an established method to investigate epilepsy. Current MEG systems house hundreds of cryogenic sensors in a rigid, one-size-fits-all helmet, which results in several limitations, particularly in children. On-scalp MEG based on optically-pumped magnetometers (OPMs) may alleviate these limitations.We report on five children (5–11 years old) with self-limited focal (n=3) or structural (n=2) epilepsy who underwent cryogenic (102 magnetometers) and on-scalp (32 OPMs) MEG. We compared the two modalities for the detection and localization of interictal epileptiform discharges (IEDs).We identified IEDs in all children with comparable sensor topographies for both MEG devices. IED amplitudes were 2.3-4.8 times higher with on-scalp MEG and signal-to-noise ratio (SNR) was also 27-60% higher with on-scalp MEG in all but one patient with large head movement artifacts. The neural source of averaged IEDs was located at about 5 mm (n=3) or higher (8.3 mm, n=1; 15.6 mm, n=1) between on-scalp and cryogenic MEG.Despite limited number of sensors and scalp coverage, on-scalp MEG detects IEDs in epileptic children with higher SNR than cryogenic MEG. This technology, which is in constant development, should become a reference in the diagnostic workup of epilepsy and replace cryogenic MEG in the near future.

Software for Non-Parametric Image Registration of 2-Photon Imaging Data

Functional 2-photon microscopy is a key technology for imaging neuronal activity which can, however, contain non-rigid movement artifacts. Despite the established performance of variational optical flow (OF) estimation in different computer vision areas and the importance of movement correction for 2-photon applications, no OF-based method for 2-photon imaging is available. We developed the easy-to-use toolbox Flow-Registration that outperforms previous alignment tools and allows to align and reconstruct even low signal-to-noise 2-photon imaging data.

Internal Consistency of Sway Measures via Embedded Head-Mounted Accelerometers: Implications for Neuromotor Investigations

Accelerometers are being increasingly incorporated into neuroimaging devices to enable real-time filtering of movement artifacts. In this study, we evaluate the reliability of sway metrics derived from these accelerometers in a standard eyes-open balance assessment to determine their utility in multimodal study designs. Ten participants equipped with a head-mounted accelerometer performed an eyes-open standing condition on 7 consecutive days. Sway performance was quantified with 4 standard metrics: root-mean-square (RMS) acceleration, peak-to-peak (P2P) acceleration, jerk, and ellipse area. Intraclass correlation coefficients (ICC) quantified reliability. P2P in both the mediolateral (ICC = 0.65) and anteroposterior (ICC = 0.67) planes yielded the poorest reliability. Both ellipse area and RMS exhibited good reliability, ranging from 0.76 to 0.84 depending on the plane. Finally, jerk displayed the highest reliability with an ICC value of 0.95. Moderate to excellent reliability was observed in all sway metrics. These findings demonstrate that head-mounted accelerometers, commonly found in neuroimaging devices, can be used to reliably assess sway. These data validate the use of head-mounted accelerometers in the assessment of motor control alongside other measures of brain activity such as electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS).

Magnetic Field Compensation Coil Design for Magnetoencephalography

While optically pumped magnetometers (OPMs) can be attached to the head of a person and allow for highly sensitive recordings of the human magnetoencephalogram (MEG), they are mostly limited to an operational range of approximately ±5 nT. Consequently, even inside a magnetically shielded room (MSR), movements in the remnant magnetic field disable the OPMs. Active suppression of the remnant field utilizing compensation coils is therefore essential. We propose 8 compensation coils on 5 sides of a cube with a side length of approximately 2 m which were optimized for operation inside an MSR. Compared to previously built bi-planar compensation coils, the coils proposed in this report are more complex in geometry and achieved 10 times smaller errors for simulated compensation fields. The proposed coils will allow for larger head movements or smaller movement artifacts in future MEG experiments compared to existing coils.

Classroom Discourse and Multimodal Conversation Analysis

This chapter provides a background of classroom discourse research with particular focus on research into the interactional organization of classroom interaction. Walsh’s (200, 2011) modes are introduced as a key framework for this volume. Prior research on student participation is summarized here, including the concepts of (un)willingness to participate and classroom interactional competence. Finally, multimodal conversation analysis, the methodological framework for this volume, is presented, including brief summaries of research on gaze, gesture, body movement, artifacts, and complex multimodal Gestalts. Notes on transcription practices are presented here, as well as descriptions of the data corpora drawn upon for this study.