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

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

Dissecting the structural and chemical determinants of the "open-to-closed" motion in the mannosyltransferase PimA from Mycobacteria

The phosphatidyl-myo-inositol mannosyltransferase A (PimA) is an essential peripheral membrane glycosyltransferase that initiates the biosynthetic pathway of phosphatidyl-myo-inositol mannosides (PIMs), key structural elements and virulence factors of Mycobacterium tuberculosis. PimA undergoes functionally important conformational changes, including (i) α-helix-To-β-strand and β-strand-To-α-helix transitions and (ii) an "open-To-closed"motion between the two Rossmann-fold domains, a conformational change that is necessary to generate a catalytically competent active site. In previous work, we established that GDP-Man and GDP stabilize the enzyme and facilitate the switch to a more compact active state. To determine the structural contribution of the mannose ring in such an activation mechanism, we analyzed a series of chemical derivatives, including mannose phosphate (Man-P) and mannose pyrophosphate-ribose (Man-PP-RIB), and additional GDP derivatives, such as pyrophosphate ribose (PP-RIB) and GMP, by the combined use of X-ray crystallography, limited proteolysis, circular dichroism, isothermal titration calorimetry, and small angle X-ray scattering methods. Although the β-phosphate is present, we found that the mannose ring, covalently attached to neither phosphate (Man-P) nor PP-RIB (Man-PP-RIB), does promote the switch to the active compact form of the enzyme. Therefore, the nucleotide moiety of GDP-Man, and not the sugar ring, facilitates the "open-To-closed"motion, with the β-phosphate group providing the high-Affinity binding to PimA. Altogether, the experimental data contribute to a better understanding of the structural determinants involved in the "open-To-closed"motion not only observed in PimA but also visualized and/or predicted in other glycosyltransfeases. In addition, the experimental data might prove to be useful for the discovery and/or development of PimA and/or glycosyltransferase inhibitors

Movement-related neuromagnetic fields in preschool age children

We examined sensorimotor brain activity associated with voluntary movements in preschool children using a customized pediatric magnetoencephalographic system. A videogame-like task was used to generate self-initiated right or left index finger movements in 17 healthy right-handed subjects (8 females, ages 3.2-4.8 years). We successfully identified spatiotemporal patterns of movement-related brain activity in 15/17 children using beamformer source analysis and surrogate MRI spatial normalization. Readiness fields in the contralateral sensorimotor cortex began ?0.5 s prior to movement onset (motor field, MF), followed by transient movement-evoked fields (MEFs), similar to that observed during self-paced movements in adults, but slightly delayed and with inverted source polarities. We also observed modulation of mu (8-12 Hz) and beta (15-30 Hz) oscillations in sensorimotor cortex with movement, but with different timing and a stronger frequency band coupling compared to that observed in adults. Adult-like high-frequency (70-80 Hz) gamma bursts were detected at movement onset. All children showed activation of the right superior temporal gyrus that was independent of the side of movement, a response that has not been reported in adults. These results provide new insights into the development of movement-related brain function, for an age group in which no previous data exist. The results show that children under 5 years of age have markedly different patterns of movement-related brain activity in comparison to older children and adults, and indicate that significant maturational changes occur in the sensorimotor system between the preschool years and later childhood.18 page(s

Sensorimotor oscillations prior to speech onset reflect altered motor networks in adults who stutter

Adults who stutter (AWS) have demonstrated atypical coordination of motor and sensory regions during speech production. Yet little is known of the speech-motor network in AWS in the brief time window preceding audible speech onset. The purpose of the current study was to characterize neural oscillations in the speech-motor network during preparation for and execution of overt speech production in AWS using magnetoencephalography (MEG). Twelve AWS and twelve age-matched controls were presented with 220 words, each word embedded in a carrier phrase. Controls were presented with the same word list as their matched AWS participant. Neural oscillatory activity was localized using minimum-variance beamforming during two time periods of interest: speech preparation (prior to speech onset) and speech execution (following speech onset). Compared to controls, AWS showed stronger beta (15-25Hz) suppression in the speech preparation stage, followed by stronger beta synchronization in the bilateral mouth motor cortex. AWS also recruited the right mouth motor cortex significantly earlier in the speech preparation stage compared to controls. Exaggerated motor preparation is discussed in the context of reduced coordination in the speech-motor network of AWS. It is further proposed that exaggerated beta synchronization may reflect a more strongly inhibited motor system that requires a stronger beta suppression to disengage prior to speech initiation. These novel findings highlight critical differences in the speech-motor network of AWS that occur prior to speech onset and emphasize the need to investigate further the speech-motor assembly in the stuttering population