Analysis of Dynamic Brain Imaging Data

Modern imaging techniques for probing brain function, including functional Magnetic Resonance Imaging, intrinsic and extrinsic contrast optical imaging, and magnetoencephalography, generate large data sets with complex content. In this paper we develop appropriate techniques of analysis and visualization of such imaging data, in order to separate the signal from the noise, as well as to characterize the signal. The techniques developed fall into the general category of multivariate time series analysis, and in particular we extensively use the multitaper framework of spectral analysis. We develop specific protocols for the analysis of fMRI, optical imaging and MEG data, and illustrate the techniques by applications to real data sets generated by these imaging modalities. In general, the analysis protocols involve two distinct stages: `noise' characterization and suppression, and `signal' characterization and visualization. An important general conclusion of our study is the utility of a frequency-based representation, with short, moving analysis windows to account for non-stationarity in the data. Of particular note are (a) the development of a decomposition technique (`space-frequency singular value decomposition') that is shown to be a useful means of characterizing the image data, and (b) the development of an algorithm, based on multitaper methods, for the removal of approximately periodic physiological artifacts arising from cardiac and respiratory sources.Comment: 40 pages; 26 figures with subparts including 3 figures as .gif files. Originally submitted to the neuro-sys archive which was never publicly announced (was 9804003

Regional coherence evaluation in mild cognitive impairment and Alzheimer's disease based on adaptively extracted magnetoencephalogram rhythms

This study assesses the connectivity alterations caused by Alzheimer's disease (AD) and mild cognitive impairment (MCI) in magnetoencephalogram (MEG) background activity. Moreover, a novel methodology to adaptively extract brain rhythms from the MEG is introduced. This methodology relies on the ability of empirical mode decomposition to isolate local signal oscillations and constrained blind source separation to extract the activity that jointly represents a subset of channels. Inter-regional MEG connectivity was analysed for 36 AD, 18 MCI and 26 control subjects in δ, θ, α and β bands over left and right central, anterior, lateral and posterior regions with magnitude squared coherence—c(f). For the sake of comparison, c(f) was calculated from the original MEG channels and from the adaptively extracted rhythms. The results indicated that AD and MCI cause slight alterations in the MEG connectivity. Computed from the extracted rhythms, c(f) distinguished AD and MCI subjects from controls with 69.4% and 77.3% accuracies, respectively, in a full leave-one-out cross-validation evaluation. These values were higher than those obtained without the proposed extraction methodology

Maturation trajectories of cortical resting-state networks depend on the mediating frequency band

The functional significance of resting state networks and their abnormal manifestations in psychiatric disorders are firmly established, as is the importance of the cortical rhythms in mediating these networks. Resting state networks are known to undergo substantial reorganization from childhood to adulthood, but whether distinct cortical rhythms, which are generated by separable neural mechanisms and are often manifested abnormally in psychiatric conditions, mediate maturation differentially, remains unknown. Using magnetoencephalography (MEG) to map frequency band specific maturation of resting state networks from age 7 to 29 in 162 participants (31 independent), we found significant changes with age in networks mediated by the beta (13–30 Hz) and gamma (31–80 Hz) bands. More specifically, gamma band mediated networks followed an expected asymptotic trajectory, but beta band mediated networks followed a linear trajectory. Network integration increased with age in gamma band mediated networks, while local segregation increased with age in beta band mediated networks. Spatially, the hubs that changed in importance with age in the beta band mediated networks had relatively little overlap with those that showed the greatest changes in the gamma band mediated networks. These findings are relevant for our understanding of the neural mechanisms of cortical maturation, in both typical and atypical development.This work was supported by grants from the Nancy Lurie Marks Family Foundation (TK, SK, MGK), Autism Speaks (TK), The Simons Foundation (SFARI 239395, TK), The National Institute of Child Health and Development (R01HD073254, TK), National Institute for Biomedical Imaging and Bioengineering (P41EB015896, 5R01EB009048, MSH), and the Cognitive Rhythms Collaborative: A Discovery Network (NFS 1042134, MSH). (Nancy Lurie Marks Family Foundation; Autism Speaks; SFARI 239395 - Simons Foundation; R01HD073254 - National Institute of Child Health and Development; P41EB015896 - National Institute for Biomedical Imaging and Bioengineering; 5R01EB009048 - National Institute for Biomedical Imaging and Bioengineering; NFS 1042134 - Cognitive Rhythms Collaborative: A Discovery Network

Laajat aivoverkot ja MEG: koodikirjasto ja sovellus mittausaineistoon

Research has shown that functional connectivity is a powerful tool in the study of the complex processes of the human brain. Functional connectivity is generally defined as the synchronisation of anatomically distant areas and it can be inspected for example through coherent oscillations. Magnetoencephalography (MEG) is well suited for functional connectivity studies as it has a good time resolution that allows us to observe the changes in magnetic field in real time. Dynamic Imaging of Coherent Sources (DICS) uses spatial filters to estimate the oscillatory activity in the human brain. In my master's thesis, I introduce a python-based pipeline and code library that estimates functional connectivity from MEG data using DICS. I will then demonstrate the application with a real MEG dataset. This pipeline also implements the use of canonical coherence, which provides a fast and stable way of calculating coherence between a large number of signal sources. The pipeline presented here consists of seven steps: First the data is preprocessed and the cross-spectral density (CSD) matrices are computed. Then the source space is computed and used with the CSD matrices to compute both oscillatory power and connectivity. These results are then analysed at the group-level and visualised. The results show that the pipeline is easy to apply to a real world dataset. Selection of the parameters in different steps should be made based on the dataset at hand and the results should be interpreted carefully. Further research on the stability of this pipeline is suggested.Toiminnallisten kytkösten tarkastelu on osoittautunut tehokkaaksi apuvälineeksi aivojen monimutkaisten toimintojen tutkimisessa. Neurotieteessä toiminnallinen kytkeytyvyys määritellään yleensä aivojen rakenteellisesti etäisten rakenteiden tahdistumisena. Toiminnallista kytkeytyvyyttä voidaan tarkastella esimerkiksi koherenssin avulla. Magnetoenkefalografia (MEG) on osoittautunut hyvän aikaresoluutionsa takia sopivaksi menetelmäksi tarkastella toiminnallisia kytköksiä. Keilanmuodostusmenetelmä koherenttien lähteiden dynaaminen kuvaaminen (Dynamic Imaging of Coherent Sources, DICS) käyttää spatiaalisuodattimia tarkastellakseen aivoissa tapahtuvia värähtelyitä. Tässä diplomityössä esittelen python-ohjelmointikielellä toteutetun koodikirjaston, joka DICS-menetelmän avulla arvioi aivojen värähtelyjen tehoa ja koherenssia ja näin toiminnallista kytkeytyvyyttä. Tämän kirjaston DICS-menetelmässä koherenssi kahden lähteen välillä lasketaan kanonisella koherenssilla, joka on nopea ja vakaa tapa laskea koherenssi suurelle määrälle lähdepisteitä. Koodikirjaston vaiheita on seitsemän: Data esikäsitellään ja siitä lasketaan ristispektritiheysmatriisi (CSD-matriisi). Lähdepisteet määritellään ja niitä käytetään CSD-matriisien kanssa värähtelyn tehon ja yhteyksien laskemiseen. Tämän jälkeen tuloksia käsitellään ryhmätasolla ja näytetään kuvina. Tulokset osoittavat, että koodikirjaston soveltaminen mittausaineistoon on helppoa. Eri vaiheissa tarvittavat parametrit on valittava aineiston ominaisuuksien perusteella ja tuloksia on tarkasteltava varoen. Lisätutkimusta suositellaan menetelmän vakauden varmistamiseksi

Influence of the head model on EEG and MEG source connectivity analysis

The results of brain connectivity analysis using reconstructed source time courses derived from EEG and MEG data depend on a number of algorithmic choices. While previous studies have investigated the influence of the choice of source estimation method or connectivity measure, the effects of the head modeling errors or simplifications have not been studied sufficiently. In the present simulation study, we investigated the influence of particular properties of the head model on the reconstructed source time courses as well as on source connectivity analysis in EEG and MEG. Therefore, we constructed a realistic head model and applied the finite element method to solve the EEG and MEG forward problem. We considered the distinction between white and gray matter, the distinction between compact and spongy bone, the inclusion of a cerebrospinal fluid (CSF) compartment, and the reduction to a simple 3-layer model comprising only skin, skull, and brain. Source time courses were reconstructed using a beamforming approach and the source connectivity was estimated by the imaginary coherence (ICoh) and the generalized partial directed coherence (GPDC). Our results show that in both EEG and MEG, neglecting the white and gray matter distinction or the CSF causes considerable errors in reconstructed source time courses and connectivity analysis, while the distinction between spongy and compact bone is just of minor relevance, provided that an adequate skull conductivity value is used. Large inverse and connectivity errors are found in the same regions that show large topography errors in the forward solution. Moreover, we demonstrate that the very conservative ICoh is relatively safe from the crosstalk effects caused by imperfect head models, as opposed to the GPDC

Graph analysis of functional brain networks: practical issues in translational neuroscience

The brain can be regarded as a network: a connected system where nodes, or units, represent different specialized regions and links, or connections, represent communication pathways. From a functional perspective communication is coded by temporal dependence between the activities of different brain areas. In the last decade, the abstract representation of the brain as a graph has allowed to visualize functional brain networks and describe their non-trivial topological properties in a compact and objective way. Nowadays, the use of graph analysis in translational neuroscience has become essential to quantify brain dysfunctions in terms of aberrant reconfiguration of functional brain networks. Despite its evident impact, graph analysis of functional brain networks is not a simple toolbox that can be blindly applied to brain signals. On the one hand, it requires a know-how of all the methodological steps of the processing pipeline that manipulates the input brain signals and extract the functional network properties. On the other hand, a knowledge of the neural phenomenon under study is required to perform physiological-relevant analysis. The aim of this review is to provide practical indications to make sense of brain network analysis and contrast counterproductive attitudes

Advancing functional connectivity research from association to causation

Cognition and behavior emerge from brain network interactions, such that investigating causal interactions should be central to the study of brain function. Approaches that characterize statistical associations among neural time series-functional connectivity (FC) methods-are likely a good starting point for estimating brain network interactions. Yet only a subset of FC methods ('effective connectivity') is explicitly designed to infer causal interactions from statistical associations. Here we incorporate best practices from diverse areas of FC research to illustrate how FC methods can be refined to improve inferences about neural mechanisms, with properties of causal neural interactions as a common ontology to facilitate cumulative progress across FC approaches. We further demonstrate how the most common FC measures (correlation and coherence) reduce the set of likely causal models, facilitating causal inferences despite major limitations. Alternative FC measures are suggested to immediately start improving causal inferences beyond these common FC measures

Network perspectives on epilepsy using EEG/MEG source connectivity

The evolution of EEG/MEG source connectivity is both, a promising, and controversial advance in the characterization of epileptic brain activity. In this narrative review we elucidate the potential of this technology to provide an intuitive view of the epileptic network at its origin, the different brain regions involved in the epilepsy, without the limitation of electrodes at the scalp level. Several studies have confirmed the added value of using source connectivity to localize the seizure onset zone and irritative zone or to quantify the propagation of epileptic activity over time. It has been shown in pilot studies that source connectivity has the potential to obtain prognostic correlates, to assist in the diagnosis of the epilepsy type even in the absence of visually noticeable epileptic activity in the EEG/MEG, and to predict treatment outcome. Nevertheless, prospective validation studies in large and heterogeneous patient cohorts are still lacking and are needed to bring these techniques into clinical use. Moreover, the methodological approach is challenging, with several poorly examined parameters that most likely impact the resulting network patterns. These fundamental challenges affect all potential applications of EEG/MEG source connectivity analysis, be it in a resting, spiking, or ictal state, and also its application to cognitive activation of the eloquent area in presurgical evaluation. However, such method can allow unique insights into physiological and pathological brain functions and have great potential in (clinical) neuroscience

Harmoni: A method for eliminating spurious interactions due to the harmonic components in neuronal data

Cross-frequency synchronization (CFS) has been proposed as a mechanism for integrating spatially and spectrally distributed information in the brain. However, investigating CFS in Magneto- and Electroencephalography (MEG/EEG) is hampered by the presence of spurious neuronal interactions due to the non-sinusoidal waveshape of brain oscillations. Such waveshape gives rise to the presence of oscillatory harmonics mimicking genuine neuronal oscillations. Until recently, however, there has been no methodology for removing these harmonics from neuronal data. In order to address this long-standing challenge, we introduce a novel method (called HARMOnic miNImization - Harmoni) that removes the signal components which can be harmonics of a non-sinusoidal signal. Harmoni’s working principle is based on the presence of CFS between harmonic components and the fundamental component of a non-sinusoidal signal. We extensively tested Harmoni in realistic EEG simulations. The simulated couplings between the source signals represented genuine and spurious CFS and within-frequency phase synchronization. Using diverse evaluation criteria, including ROC analyses, we showed that the within- and cross-frequency spurious interactions are suppressed significantly, while the genuine activities are not affected. Additionally, we applied Harmoni to real resting-state EEG data revealing intricate remote connectivity patterns which are usually masked by the spurious connections. Given the ubiquity of non-sinusoidal neuronal oscillations in electrophysiological recordings, Harmoni is expected to facilitate novel insights into genuine neuronal interactions in various research fields, and can also serve as a steppingstone towards the development of further signal processing methods aiming at refining within- and cross-frequency synchronization in electrophysiological recordings