Auditory training changes temporal lobe connectivity in Wernicke's aphasia: a randomised trial

Introduction Aphasia is one of the most disabling sequelae after stroke, occurring in 25%–40% of stroke survivors. However, there remains a lack of good evidence for the efficacy or mechanisms of speech comprehension rehabilitation. Trial Design This within-subjects trial tested two concurrent interventions in 20 patients with chronic aphasia with speech comprehension impairment following left hemisphere stroke: (1) phonological training using ‘Earobics’ software and (2) a pharmacological intervention using donepezil, an acetylcholinesterase inhibitor. Donepezil was tested in a double-blind, placebo-controlled, cross-over design using block randomisation with bias minimisation. Methods The primary outcome measure was speech comprehension score on the comprehensive aphasia test. Magnetoencephalography (MEG) with an established index of auditory perception, the mismatch negativity response, tested whether the therapies altered effective connectivity at the lower (primary) or higher (secondary) level of the auditory network. Results Phonological training improved speech comprehension abilities and was particularly effective for patients with severe deficits. No major adverse effects of donepezil were observed, but it had an unpredicted negative effect on speech comprehension. The MEG analysis demonstrated that phonological training increased synaptic gain in the left superior temporal gyrus (STG). Patients with more severe speech comprehension impairments also showed strengthening of bidirectional connections between the left and right STG. Conclusions Phonological training resulted in a small but significant improvement in speech comprehension, whereas donepezil had a negative effect. The connectivity results indicated that training reshaped higher order phonological representations in the left STG and (in more severe patients) induced stronger interhemispheric transfer of information between higher levels of auditory cortex

The IAS-MEEG Package: A Flexible Inverse Source Reconstruction Platform for Reconstruction and Visualization of Brain Activity from M/EEG Data

We present a standalone Matlab software platform complete with visualization for the reconstruction of the neural activity in the brain from MEG or EEG data. The underlying inversion combines hierarchical Bayesian models and Krylov subspace iterative least squares solvers. The Bayesian framework of the underlying inversion algorithm allows to account for anatomical information and possible a priori belief about the focality of the reconstruction. The computational efficiency makes the software suitable for the reconstruction of lengthy time series on standard computing equipment. The algorithm requires minimal user provided input parameters, although the user can express the desired focality and accuracy of the solution. The code has been designed so as to favor the parallelization performed automatically by Matlab, according to the resources of the host computer. We demonstrate the flexibility of the platform by reconstructing activity patterns with supports of different sizes from MEG and EEG data. Moreover, we show that the software reconstructs well activity patches located either in the subcortical brain structures or on the cortex. The inverse solver and visualization modules can be used either individually or in combination. We also provide a version of the inverse solver that can be used within Brainstorm toolbox. All the software is available online by Github, including the Brainstorm plugin, with accompanying documentation and test data

Using optically-pumped magnetometers to measure magnetoencephalographic signals in the human cerebellum

KEY POINTS: The application of conventional cryogenic magnetoencephalography (MEG) to the study of cerebellar functions is highly limited because typical cryogenic sensor arrays are far away from the cerebellum and naturalistic movement is not allowed in the recording. A new generation of MEG using optically pumped magnetometers (OPMs) that can be worn on the head during movement has opened up an opportunity to image the cerebellar electrophysiological activity non-invasively. We use OPMs to record human cerebellar MEG signals elicited by air-puff stimulation to the eye. We demonstrate robust responses in the cerebellum. OPMs pave the way for studying the neurophysiology of the human cerebellum. ABSTRACT: We test the feasibility of an optically pumped magnetometer-based magnetoencephalographic (OP-MEG) system for the measurement of human cerebellar activity. This is to our knowledge the first study investigating the human cerebellar electrophysiology using optically pumped magnetometers. As a proof of principle, we use an air-puff stimulus to the eyeball in order to elicit cerebellar activity that is well characterized in non-human models. In three subjects, we observe an evoked component at approx. 50 ms post-stimulus, followed by a second component at approx. 85-115 ms post-stimulus. Source inversion localizes both components in the cerebellum, while control experiments exclude potential sources elsewhere. We also assess the induced oscillations, with time-frequency decompositions, and identify additional sources in the occipital lobe, a region expected to be active in our paradigm, and in the neck muscles. Neither of these contributes to the stimulus-evoked responses at 50-115 ms. We conclude that OP-MEG technology offers a promising way to advance the understanding of the information processing mechanisms in the human cerebellum

Probabilistic algorithms for MEG/EEG source reconstruction using temporal basis functions learned from data.

We present two related probabilistic methods for neural source reconstruction from MEG/EEG data that reduce effects of interference, noise, and correlated sources. Both methods localize source activity using a linear mixture of temporal basis functions (TBFs) learned from the data. In contrast to existing methods that use predetermined TBFs, we compute TBFs from data using a graphical factor analysis based model [Nagarajan, S.S., Attias, H.T., Hild, K.E., Sekihara, K., 2007a. A probabilistic algorithm for robust interference suppression in bioelectromagnetic sensor data. Stat Med 26, 3886–3910], which separates evoked or event-related source activity from ongoing spontaneous background brain activity. Both algorithms compute an optimal weighting of these TBFs at each voxel to provide a spatiotemporal map of activity across the brain and a source image map from the likelihood of a dipole source at each voxel. We explicitly model, with two different robust parameterizations, the contribution from signals outside a voxel of interest. The two models differ in a trade-off of computational speed versus accuracy of learning the unknown interference contributions. Performance in simulations and real data, both with large noise and interference and/or correlated sources, demonstrates significant improvement over existing source localization methods

Brain Activity Mapping from MEG Data via a Hierarchical Bayesian Algorithm with Automatic Depth Weighting

A recently proposed iterated alternating sequential (IAS) MEG inverse solver algorithm, based on the coupling of a hierarchical Bayesian model with computationally efficient Krylov subspace linear solver, has been shown to perform well for both superficial and deep brain sources. However, a systematic study of its ability to correctly identify active brain regions is still missing. We propose novel statistical protocols to quantify the performance of MEG inverse solvers, focusing in particular on how their accuracy and precision at identifying active brain regions. We use these protocols for a systematic study of the performance of the IAS MEG inverse solver, comparing it with three standard inversion methods, wMNE, dSPM, and sLORETA. To avoid the bias of anecdotal tests towards a particular algorithm, the proposed protocols are Monte Carlo sampling based, generating an ensemble of activity patches in each brain region identified in a given atlas. The performance in correctly identifying the active areas is measured by how much, on average, the reconstructed activity is concentrated in the brain region of the simulated active patch. The analysis is based on Bayes factors, interpreting the estimated current activity as data for testing the hypothesis that the active brain region is correctly identified, versus the hypothesis of any erroneous attribution. The methodology allows the presence of a single or several simultaneous activity regions, without assuming that the number of active regions is known. The testing protocols suggest that the IAS solver performs well with both with cortical and subcortical activity estimation

Applying stochastic spike train theory for high-accuracy MEG/EEG

The accuracy of electroencephalography (EEG) and magnetoencephalography (MEG) is challenged by overlapping sources from within the brain. This lack of accuracy is a severe limitation to the possibilities and reliability of modern stimulation protocols in basic research and clinical diagnostics. As a solution, we here introduce a theory of stochastic neuronal spike timing probability densities for describing the large-scale spiking activity in neural networks, and a novel spike density component analysis (SCA) method for isolating specific neural sources. Three studies are conducted based on 564 cases of evoked responses to auditory stimuli from 94 human subjects each measured with 60 EEG electrodes and 306 MEG sensors. In the first study we show that the large-scale spike timing (but not non-encephalographic artifacts) in MEG/EEG waveforms can be modeled with Gaussian probability density functions with …Non peer reviewe

Particle filtering for EEG source localization and constrained state spaces

Particle Filters (PFs) have a unique ability to perform asymptotically optimal estimation for non-linear and non-Gaussian state-space models. However, the numerical nature of PFs cause them to have major weakness in two important areas: (1) handling constraints on the state, and (2) dealing with high-dimensional states. In the first area, handling constraints within the PF framework is crucial in dynamical systems, which are often required to satisfy constraints that arise from basic physical laws or other considerations. The current trend in constrained particle filtering is to enforce the constraints on all particles of the PF. We show that this approach leads to more stringent conditions on the posterior density that can cause incorrect state estimates. We subsequently describe a novel algorithm that restricts the mean estimate without restricting the posterior pdf, thus providing a more accurate state estimate. In the second area, we tackle the curse of dimensionality, which causes the PF to require an exponential increase in computational complexity as the dimension of the state increases. The application of interest is localization of the brain neural generators that create the Electroencephalogram (EEG) signal. Specifically, we describe a state-space model that tracks the position and moments of multiple dynamic dipoles and apply the marginalized PF, which alleviates the curse of dimensionality for tracking multiple dynamic dipoles. This modified framework allows us to consider dynamic dipoles, which were historically considered time-invariant