State-space solutions to the dynamic magnetoencephalography inverse problem using high performance computing

Determining the magnitude and location of neural sources within the brain that are responsible for generating magnetoencephalography (MEG) signals measured on the surface of the head is a challenging problem in functional neuroimaging. The number of potential sources within the brain exceeds by an order of magnitude the number of recording sites. As a consequence, the estimates for the magnitude and location of the neural sources will be ill-conditioned because of the underdetermined nature of the problem. One well-known technique designed to address this imbalance is the minimum norm estimator (MNE). This approach imposes an $L^2$ regularization constraint that serves to stabilize and condition the source parameter estimates. However, these classes of regularizer are static in time and do not consider the temporal constraints inherent to the biophysics of the MEG experiment. In this paper we propose a dynamic state-space model that accounts for both spatial and temporal correlations within and across candidate intracortical sources. In our model, the observation model is derived from the steady-state solution to Maxwell's equations while the latent model representing neural dynamics is given by a random walk process.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS483 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Tracking dynamic interactions between structural and functional connectivity : a TMS/EEG-dMRI study

Transcranial magnetic stimulation (TMS) in combination with neuroimaging techniques allows to measure the effects of a direct perturbation of the brain. When coupled with high-density electroencephalography (TMS/hd-EEG), TMS pulses revealed electrophysiological signatures of different cortical modules in health and disease. However, the neural underpinnings of these signatures remain unclear. Here, by applying multimodal analyses of cortical response to TMS recordings and diffusion magnetic resonance imaging (dMRI) tractography, we investigated the relationship between functional and structural features of different cortical modules in a cohort of awake healthy volunteers. For each subject, we computed directed functional connectivity interactions between cortical areas from the source-reconstructed TMS/hd-EEG recordings and correlated them with the correspondent structural connectivity matrix extracted from dMRI tractography, in three different frequency bands (alpha, beta, gamma) and two sites of stimulation (left precuneus and left premotor). Each stimulated area appeared to mainly respond to TMS by being functionally elicited in specific frequency bands, that is, beta for precuneus and gamma for premotor. We also observed a temporary decrease in the whole-brain correlation between directed functional connectivity and structural connectivity after TMS in all frequency bands. Notably, when focusing on the stimulated areas only, we found that the structure-function correlation significantly increases over time in the premotor area controlateral to TMS. Our study points out the importance of taking into account the major role played by different cortical oscillations when investigating the mechanisms for integration and segregation of information in the human brain

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

Cooperation of different neuronal systems during hand sign recognition.

Hand signs with symbolic meaning can often be utilized more successfully than words to communicate an intention; however, the underlying brain mechanisms are undefined. The present study using magnetoencephalography (MEG) demonstrates that the primary visual, mirror neuron, social recognition and object recognition systems are involved in hand sign recognition. MEG detected well-orchestrated multiple brain regional electrical activity among these neuronal systems. During the assessment of the meaning of hand signs, the inferior parietal, superior temporal sulcus (STS) and inferior occipitotemporal regions were simultaneously activated. These three regions showed similar time courses in their electrical activity, suggesting that they work together during hand sign recognition by integrating information in the ventral and dorsal pathways through the STS. The results also demonstrated marked right hemispheric predominance, suggesting that hand expression is processed in a manner similar to that in which social signs, such as facial expressions, are processed

Multimodal imaging of human brain activity: rational, biophysical aspects and modes of integration

Until relatively recently the vast majority of imaging and electrophysiological studies of human brain activity have relied on single-modality measurements usually correlated with readily observable or experimentally modified behavioural or brain state patterns. Multi-modal imaging is the concept of bringing together observations or measurements from different instruments. We discuss the aims of multi-modal imaging and the ways in which it can be accomplished using representative applications. Given the importance of haemodynamic and electrophysiological signals in current multi-modal imaging applications, we also review some of the basic physiology relevant to understanding their relationship

Computerized Analysis of Magnetic Resonance Images to Study Cerebral Anatomy in Developing Neonates

The study of cerebral anatomy in developing neonates is of great importance for the understanding of brain development during the early period of life. This dissertation therefore focuses on three challenges in the modelling of cerebral anatomy in neonates during brain development. The methods that have been developed all use Magnetic Resonance Images (MRI) as source data. To facilitate study of vascular development in the neonatal period, a set of image analysis algorithms are developed to automatically extract and model cerebral vessel trees. The whole process consists of cerebral vessel tracking from automatically placed seed points, vessel tree generation, and vasculature registration and matching. These algorithms have been tested on clinical Time-of- Flight (TOF) MR angiographic datasets. To facilitate study of the neonatal cortex a complete cerebral cortex segmentation and reconstruction pipeline has been developed. Segmentation of the neonatal cortex is not effectively done by existing algorithms designed for the adult brain because the contrast between grey and white matter is reversed. This causes pixels containing tissue mixtures to be incorrectly labelled by conventional methods. The neonatal cortical segmentation method that has been developed is based on a novel expectation-maximization (EM) method with explicit correction for mislabelled partial volume voxels. Based on the resulting cortical segmentation, an implicit surface evolution technique is adopted for the reconstruction of the cortex in neonates. The performance of the method is investigated by performing a detailed landmark study. To facilitate study of cortical development, a cortical surface registration algorithm for aligning the cortical surface is developed. The method first inflates extracted cortical surfaces and then performs a non-rigid surface registration using free-form deformations (FFDs) to remove residual alignment. Validation experiments using data labelled by an expert observer demonstrate that the method can capture local changes and follow the growth of specific sulcus

Dynamic imaging of coherent sources reveals different network connectivity underlying the generation and perpetuation of epileptic seizures

The concept of focal epilepsies includes a seizure origin in brain regions with hyper synchronous activity (epileptogenic zone and seizure onset zone) and a complex epileptic network of different brain areas involved in the generation, propagation, and modulation of seizures. The purpose of this work was to study functional and effective connectivity between regions involved in networks of epileptic seizures. The beginning and middle part of focal seizures from ictal surface EEG data were analyzed using dynamic imaging of coherent sources (DICS), an inverse solution in the frequency domain which describes neuronal networks and coherences of oscillatory brain activities. The information flow (effective connectivity) between coherent sources was investigated using the renormalized partial directed coherence (RPDC) method. In 8/11 patients, the first and second source of epileptic activity as found by DICS were concordant with the operative resection site; these patients became seizure free after epilepsy surgery. In the remaining 3 patients, the results of DICS / RPDC calculations and the resection site were discordant; these patients had a poorer post-operative outcome. The first sources as found by DICS were located predominantly in cortical structures; subsequent sources included some subcortical structures: thalamus, Nucl. Subthalamicus and cerebellum. DICS seems to be a powerful tool to define the seizure onset zone and the epileptic networks involved. Seizure generation seems to be related to the propagation of epileptic activity from the primary source in the seizure onset zone, and maintenance of seizures is attributed to the perpetuation of epileptic activity between nodes in the epileptic network. Despite of these promising results, this proof of principle study needs further confirmation prior to the use of the described methods in the clinical praxis