BrainWave: A Matlab Toolbox for Beamformer Source Analysis of MEG Data

BrainWave is an easy-to-use Matlab toolbox for the analysis of magnetoencephalography data. It provides a graphical user interface for performing minimum-variance beamforming analysis with rapid and interactive visualization of evoked and induced brain activity. This article provides an overview of the main features of BrainWave with a step-by-step demonstration of how to proceed from raw experimental data to group source images and time series analyses. This includes data selection and pre-processing, magnetic resonance image co-registration and normalization procedures, and the generation of volumetric (whole-brain) or cortical surface based source images, and corresponding source time series as virtual sensor waveforms and their time-frequency representations. We illustrate these steps using example data from a recently published study on response inhibition (Isabella et al., 2015) using the sustained attention to response task paradigm in 12 healthy adult participants. In this task participants were required to press a button with their right index finger to a rapidly presented series of numerical digits and withhold their response to an infrequently presented target digit. This paradigm elicited movement-locked brain responses, as well as task-related modulation of brain rhythmic activity in different frequency bands (e.g., theta, beta, and gamma), and is used to illustrate two different types of source reconstruction implemented in the BrainWave toolbox: (1) event-related beamforming of averaged brain responses and (2) beamformer analysis of modulation of rhythmic brain activity using the synthetic aperture magnetometry algorithm. We also demonstrate the ability to generate group contrast images between different response types, using the example of frontal theta activation patterns during error responses (failure to withhold on target trials). BrainWave is free academic software available for download at http://cheynelab.utoronto.ca/brainwave along with supporting software and documentation. The development of the BrainWave toolbox was supported by grants from the Canadian Institutes of Health Research, the National Research and Engineering Research Council of Canada, and the Ontario Brain Institute

MEG event-related desynchronization and synchronization deficits during basic somatosensory processing in individuals with ADHD

<p>Abstract</p> <p>Background</p> <p>Attention-Deficit/Hyperactivity Disorder (ADHD) is a prevalent, complex disorder which is characterized by symptoms of inattention, hyperactivity, and impulsivity. Convergent evidence from neurobiological studies of ADHD identifies dysfunction in fronto-striatal-cerebellar circuitry as the source of behavioural deficits. Recent studies have shown that regions governing basic sensory processing, such as the somatosensory cortex, show abnormalities in those with ADHD suggesting that these processes may also be compromised.</p> <p>Methods</p> <p>We used event-related magnetoencephalography (MEG) to examine patterns of cortical rhythms in the primary (SI) and secondary (SII) somatosensory cortices in response to median nerve stimulation, in 9 adults with ADHD and 10 healthy controls. Stimuli were brief (0.2 ms) non-painful electrical pulses presented to the median nerve in two counterbalanced conditions: unpredictable and predictable stimulus presentation. We measured changes in strength, synchronicity, and frequency of cortical rhythms.</p> <p>Results</p> <p>Healthy comparison group showed strong event-related desynchrony and synchrony in SI and SII. By contrast, those with ADHD showed significantly weaker event-related desynchrony and event-related synchrony in the alpha (8–12 Hz) and beta (15–30 Hz) bands, respectively. This was most striking during random presentation of median nerve stimulation. Adults with ADHD showed significantly shorter duration of beta rebound in both SI and SII except for when the onset of the stimulus event could be predicted. In this case, the rhythmicity of SI (but not SII) in the ADHD group did not differ from that of controls.</p> <p>Conclusion</p> <p>Our findings suggest that somatosensory processing is altered in individuals with ADHD. MEG constitutes a promising approach to profiling patterns of neural activity during the processing of sensory input (e.g., detection of a tactile stimulus, stimulus predictability) and facilitating our understanding of how basic sensory processing may underlie and/or be influenced by more complex neural networks involved in higher order processing.</p

Complexity-dependent modulations of beta oscillations for verbal and nonverbal movements

Purpose The planning and execution of motor behaviors require coordination of neurons that are established through synchronization of neural activity. Movements are typically preceded by event-related desynchronization (ERD) in the beta range (15–30 Hz) primarily localized in the motor cortex, while movement onset is associated with event-related synchronization (ERS). It is hypothesized that ERD is important for movement preparation and execution, and ERS serves to inhibit movement and update the motor plan. The primary objective of this study was to determine to what extent movement-related oscillatory brain patterns (ERD and ERS) during verbal and nonverbal tasks may be affected differentially by variations in task complexity. Method Seventeen right-handed adult participants (nine women, eight men; Mage = 25.8 years, SD = 5.13) completed a sequential button press and verbal task. The final analyses included data for 15 participants for the nonverbal task and 13 for the verbal task. Both tasks consisted of two complexity levels: simple and complex sequences. Magnetoencephalography was used to record modulations in beta band brain oscillations during task performance. Results Both the verbal and button press tasks were characterized by significant premovement ERD and postmovement ERS. However, only simple sequences showed a distinct transient synchronization during the premovement phase of the task. Differences between the two tasks were reflected in both latency and peak amplitude of ERD and ERS, as well as in lateralization of oscillations. Conclusions Both verbal and nonverbal movements showed a significant desynchronization of beta oscillations during the movement preparation and holding phase and a resynchronization upon movement termination. Importantly, the premovement phase for simple but not complex tasks was characterized by a transient partial synchronization. In addition, the data revealed significant differences between the two tasks in terms of lateralization of oscillatory modulations. Our findings suggest that, while data from the general motor control research can inform our understanding of speech motor control, significant differences exist between the two motor systems that caution against overgeneralization of underlying neural control processes

White matter microstructural differences underlying beta oscillations during speech in adults who stutter

The basal ganglia-thalamocortical (BGTC) loop may underlie speech deficits in developmental stuttering. In this study, we investigated the relationship between abnormal cortical neural oscillations and structural integrity alterations in adults who stutter (AWS) using a novel magnetoencephalography (MEG) guided tractography approach. Beta oscillations were analyzed using sensorimotor speech MEG, and white matter pathways were examined using tract-based spatial statistics (TBSS) and probabilistic tractography in 11 AWS and 11 fluent speakers. TBSS analysis revealed overlap between cortical regions of increased beta suppression localized to the mouth motor area and a reduced fractional anisotropy (FA) in the AWS group. MEG-guided tractography showed reduced FA within the BGTC loop from left putamen to subject-specific MEG peak. This is the first study to provide evidence that structural abnormalities may be associated with functional deficits in stuttering and reflect a network deficit within the BGTC loop that includes areas of the left ventral premotor cortex and putamen

The brain's response to pleasant touch: an EEG investigation of tactile caressing

Somatosensation as a proximal sense can have a strong impact on our attitude toward physical objects and other human beings. However, relatively little is known about how hedonic valence of touch is processed at the cortical level. Here we investigated the electrophysiological correlates of affective tactile sensation during caressing of the right forearm with pleasant and unpleasant textile fabrics. We show dissociation between more physically driven differential brain responses to the different fabrics in early somatosensory cortex - the well-known mu-suppression (10-20 Hz) - and a beta-band response (25-30 Hz) in presumably higher-order somatosensory areas in the right hemisphere that correlated well with the subjective valence of tactile caressing. Importantly, when using single trial classification techniques, beta-power significantly distinguished between pleasant and unpleasant stimulation on a single trial basis with high accuracy. Our results therefore suggest a dissociation of the sensory and affective aspects of touch in the somatosensory system and may provide features that may be used for single trial decoding of affective mental states from simple electroencephalographic measurements

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

A realist analysis of hospital patient safety in Wales:Applied learning for alternative contexts from a multisite case study

Background: Hospital patient safety is a major social problem. In the UK, policy responses focus on the introduction of improvement programmes that seek to implement evidence-based clinical practices using the Model for Improvement, Plan-Do-Study-Act cycle. Empirical evidence that the outcomes of such programmes vary across hospitals demonstrates that the context of their implementation matters. However, the relationships between features of context and the implementation of safety programmes are both undertheorised and poorly understood in empirical terms. Objectives: This study is designed to address gaps in conceptual, methodological and empirical knowledge about the influence of context on the local implementation of patient safety programmes. Design: We used concepts from critical realism and institutional analysis to conduct a qualitative comparative-intensive case study involving 21 hospitals across all seven Welsh health boards. We focused on the local implementation of three focal interventions from the 1000 Lives+ patient safety programme: Improving Leadership for Quality Improvement, Reducing Surgical Complications and Reducing Health-care Associated Infection. Our main sources of data were 160 semistructured interviews, observation and 1700 health policy and organisational documents. These data were analysed using the realist approaches of abstraction, abduction and retroduction. Setting: Welsh Government and NHS Wales. Participants: Interviews were conducted with 160 participants including government policy leads, health managers and professionals, partner agencies with strategic oversight of patient safety, advocacy groups and academics with expertise in patient safety. Main outcome measures: Identification of the contextual factors pertinent to the local implementation of the 1000 Lives+ patient safety programme in Welsh NHS hospitals. Results: An innovative conceptual framework harnessing realist social theory and institutional theory was produced to address challenges identified within previous applications of realist inquiry in patient safety research. This involved the development and use of an explanatory intervention–context–mechanism–agency–outcome (I-CMAO) configuration to illustrate the processes behind implementation of a change programme. Our findings, illustrated by multiple nested I-CMAO configurations, show how local implementation of patient safety interventions are impacted and modified by particular aspects of context: specifically, isomorphism, by which an intervention becomes adapted to the environment in which it is implemented; institutional logics, the beliefs and values underpinning the intervention and its source, and their perceived legitimacy among different groups of health-care professionals; and the relational structure and power dynamics of the functional group, that is, those tasked with implementing the initiative. This dynamic interplay shapes and guides actions leading to the normalisation or the rejection of the patient safety programme. Conclusions: Heightened awareness of the influence of context on the local implementation of patient safety programmes is required to inform the design of such interventions and to ensure their effective implementation and operationalisation in the day-to-day practice of health-care teams. Future work is required to elaborate our conceptual model and findings in similar settings where different interventions are introduced, and in different settings where similar innovations are implemented. Funding: The National Institute for Health Research Health Services and Delivery Research programme