Mapping Underlying Dynamic Effective Connectivity In Neural Systems Using The Deconvolved Neuronal Activity

ABSTRACTMAPPING UNDERLYING DYNAMIC EFFECTIVE CONNECTIVITY IN NEURAL SYSTEMS USING THE DECONVOLVED NEURONALACTIVITYSeo Hyon Baik, PhDUniversity of Pittsburgh, 2010Event-related functional magnetic resonance imaging (fMRI) has emerged as a tool for studying the functioning of the human brain. The study on fMRI supplies information on the underlying mechanism of the human brain, such as how a brain in good shape functions, how a brain affected by different diseases works, how a brain struggles to recover after damage and how different stimuli can modulate this recovery process.The variable of interest is the neuronal activities given a stimulus, however the signalbeing quantified by MRI scanner is the blood oxygenation level-dependent (BOLD) response which is the subordinate repercussion of the underlying neuronal activity such as local changes in blood flow, volume and oxygenation level that takes place within a few second of changes in neuronal activity. From this point of view, one may think that the neuronal-activity-based and BOLD-based studies would be dissimilar in yielding information on the underlying mechanism of the human brain. This dissertation is devoted primarily to estimating underlying neuronal activities given a stimuli. In particular, we develop a method of estimating intrinsic neuronal signals and haemodynamic responses under thefact that a BOLD response is expressed as a convolution of the underlying neuronal signaland the haemodynamic response function. We also present differences between the use of estimated neuronal signals and of observed BOLD responses in investigating causal relationships among heterogeneous brain regions using an ordinary vector autoregressive model

Multi-Scale Information, Network, Causality, and Dynamics: Mathematical Computation and Bayesian Inference to Cognitive Neuroscience and Aging

The human brain is estimated to contain 100 billion or so neurons and 10 thousand times as many connections. Neurons never function in isolation: each of them is connected to 10, 000 others and they interact extensively every millisecond. Brain cells are organized into neural circuits often in a dynamic way, processing specific types of information and providing th

Statistical approaches for resting state fMRI data analysis

This doctoral dissertation investigates the methodology to explore brain dynamics from resting state fMRI data. A standard resting state fMRI study gives rise to massive amounts of noisy data with a complicated spatio-temporal correlation structure. There are two main objectives in the analysis of these noisy data: establishing the link between neural activity and the measured signal, and determining distributed brain networks that correspond to brain function. These measures can then be used as indicators of psychological, cognitive or pathological states. Two main issues will be addressed: retrieving and interpreting the hemodynamic response function (HRF) at rest, and dealing with the redundancy inherent to fMRI data. Novel approaches are introduced, discussed and validated on simulated data and on real datasets, in health and disease, in order to track modulation of brain dynamics and HRF across different pathophysiological conditions

Paradigm free mapping: detection and characterization of single trial fMRI BOLD responses without prior stimulus information

The increased contrast to noise ratio available at Ultrahigh (7T) Magnetic Resonance Imaging (MRI) allows mapping in space and time the brain's response to single trial events with functional MRI (fMRI) based on the Blood Oxygenation Level Dependent (BOLD) contrast. This thesis primarily concerns with the development of techniques to detect and characterize single trial event-related BOLD responses without prior paradigm information, Paradigm Free Mapping, and assess variations in BOLD sensitivity across brain regions at high field fMRI. Based on a linear haemodynamic response model, Paradigm Free Mapping (PFM) techniques rely on the deconvolution of the neuronal-related signal driving the BOLD effect using regularized least squares estimators. The first approach, named PFM, builds on the ridge regression estimator and spatio-temporal t-statistics to detect statistically significant changes in the deconvolved fMRI signal. The second method, Sparse PFM, benefits from subset selection features of the LASSO and Dantzig Selector estimators that automatically detect the single trial BOLD responses by promoting a sparse deconvolution of the signal. The third technique, Multicomponent PFM, exploits further the benefits of sparse estimation to decompose the fMRI signal into a haemodynamical component and a baseline component using the morphological component analysis algorithm. These techniques were evaluated in simulations and experimental fMRI datasets, and the results were compared with well-established fMRI analysis methods. In particular, the methods developed here enabled the detection of single trial BOLD responses to visually-cued and self-paced finger tapping responses without prior information of the events. The potential application of Sparse PFM to identify interictal discharges in idiopathic generalized epilepsy was also investigated. Furthermore, Multicomponent PFM allowed us to extract cardiac and respiratory fluctuations of the signal without the need of physiological monitoring. To sum up, this work demonstrates the feasibility to do single trial fMRI analysis without prior stimulus or physiological information using PFM techniques

Paradigm free mapping: detection and characterization of single trial fMRI BOLD responses without prior stimulus information

The increased contrast to noise ratio available at Ultrahigh (7T) Magnetic Resonance Imaging (MRI) allows mapping in space and time the brain's response to single trial events with functional MRI (fMRI) based on the Blood Oxygenation Level Dependent (BOLD) contrast. This thesis primarily concerns with the development of techniques to detect and characterize single trial event-related BOLD responses without prior paradigm information, Paradigm Free Mapping, and assess variations in BOLD sensitivity across brain regions at high field fMRI. Based on a linear haemodynamic response model, Paradigm Free Mapping (PFM) techniques rely on the deconvolution of the neuronal-related signal driving the BOLD effect using regularized least squares estimators. The first approach, named PFM, builds on the ridge regression estimator and spatio-temporal t-statistics to detect statistically significant changes in the deconvolved fMRI signal. The second method, Sparse PFM, benefits from subset selection features of the LASSO and Dantzig Selector estimators that automatically detect the single trial BOLD responses by promoting a sparse deconvolution of the signal. The third technique, Multicomponent PFM, exploits further the benefits of sparse estimation to decompose the fMRI signal into a haemodynamical component and a baseline component using the morphological component analysis algorithm. These techniques were evaluated in simulations and experimental fMRI datasets, and the results were compared with well-established fMRI analysis methods. In particular, the methods developed here enabled the detection of single trial BOLD responses to visually-cued and self-paced finger tapping responses without prior information of the events. The potential application of Sparse PFM to identify interictal discharges in idiopathic generalized epilepsy was also investigated. Furthermore, Multicomponent PFM allowed us to extract cardiac and respiratory fluctuations of the signal without the need of physiological monitoring. To sum up, this work demonstrates the feasibility to do single trial fMRI analysis without prior stimulus or physiological information using PFM techniques

Initial-Dip Existence and Estimation in Relation to DPF and Data Drift

Early de-oxygenation (initial dip) is an indicator of the primal cortical activity source in functional neuro-imaging. In this study, initial dip's existence and its estimation in relation to the differential pathlength factor (DPF) and data drift were investigated in detail. An efficient algorithm for estimation of drift in fNIRS data is proposed. The results favor the shifting of the fNIRS signal to a transformed coordinate system to infer correct information. Additionally, in this study, the effect of the DPF on initial dip was comprehensively analyzed. Four different cases of initial dip existence were treated, and the resultant characteristics of the hemodynamic response function (HRF) for DPF variation corresponding to particular near-infrared (NIR) wavelengths were summarized. A unique neuro-activation model and its iterative optimization solution that can estimate drift in fNIRS data and determine the best possible fit of HRF with free parameters were developed and herein proposed. The results were verified on simulated data sets. The algorithm is applied to free available datasets in addition to six healthy subjects those were experimented using fNIRS and observations and analysis regarding shape of HRF were summarized as well. A comparison with standard GLM is also discussed and effects of activity strength parameters have also been analyzed

Apport de nouvelles techniques dans l’évaluation de patients candidats à une chirurgie d’épilepsie : résonance magnétique à haut champ, spectroscopie proche infrarouge et magnétoencéphalographie

L'épilepsie constitue le désordre neurologique le plus fréquent après les maladies cérébrovasculaires. Bien que le contrôle des crises se fasse généralement au moyen d'anticonvulsivants, environ 30 % des patients y sont réfractaires. Pour ceux-ci, la chirurgie de l'épilepsie s'avère une option intéressante, surtout si l’imagerie par résonance magnétique (IRM) cérébrale révèle une lésion épileptogène bien délimitée. Malheureusement, près du quart des épilepsies partielles réfractaires sont dites « non lésionnelles ». Chez ces patients avec une IRM négative, la délimitation de la zone épileptogène doit alors reposer sur la mise en commun des données cliniques, électrophysiologiques (EEG de surface ou intracrânien) et fonctionnelles (tomographie à émission monophotonique ou de positrons). La faible résolution spatiale et/ou temporelle de ces outils de localisation se traduit par un taux de succès chirurgical décevant. Dans le cadre de cette thèse, nous avons exploré le potentiel de trois nouvelles techniques pouvant améliorer la localisation du foyer épileptique chez les patients avec épilepsie focale réfractaire considérés candidats potentiels à une chirurgie d’épilepsie : l’IRM à haut champ, la spectroscopie proche infrarouge (SPIR) et la magnétoencéphalographie (MEG). Dans une première étude, nous avons évalué si l’IRM de haut champ à 3 Tesla (T), présentant théoriquement un rapport signal sur bruit plus élevé que l’IRM conventionnelle à 1,5 T, pouvait permettre la détection des lésions épileptogènes subtiles qui auraient été manquées par cette dernière. Malheureusement, l’IRM 3 T n’a permis de détecter qu’un faible nombre de lésions épileptogènes supplémentaires (5,6 %) d’où la nécessité d’explorer d’autres techniques. Dans les seconde et troisième études, nous avons examiné le potentiel de la SPIR pour localiser le foyer épileptique en analysant le comportement hémodynamique au cours de crises temporales et frontales. Ces études ont montré que les crises sont associées à une augmentation significative de l’hémoglobine oxygénée (HbO) et l’hémoglobine totale au niveau de la région épileptique. Bien qu’une activation contralatérale en image miroir puisse être observée sur la majorité des crises, la latéralisation du foyer était possible dans la plupart des cas. Une augmentation surprenante de l’hémoglobine désoxygénée a parfois pu être observée suggérant qu’une hypoxie puisse survenir même lors de courtes crises focales. Dans la quatrième et dernière étude, nous avons évalué l’apport de la MEG dans l’évaluation des patients avec épilepsie focale réfractaire considérés candidats potentiels à une chirurgie. Il s’est avéré que les localisations de sources des pointes épileptiques interictales par la MEG ont eu un impact majeur sur le plan de traitement chez plus des deux tiers des sujets ainsi que sur le devenir postchirurgical au niveau du contrôle des crises.Epilepsy is the most common chronic neurological disorder after stroke. The major form of treatment is long-term drug therapy to which approximately 30% of patients are unfortunately refractory to. Brain surgery is recommended when medication fails, especially if magnetic resonance imaging (MRI) can identify a well-defined epileptogenic lesion. Unfortunately, close to a quarter of patients have nonlesional refractory focal epilepsy. For these MRI-negative cases, identification of the epileptogenic zone rely heavily on remaining tools: clinical history, video-electroencephalography (EEG) monitoring, ictal single-photon emission computed tomography (SPECT), and a positron emission tomography (PET). Unfortunately, the limited spatial and/or temporal resolution of these localization techniques translates into poor surgical outcome rates. In this thesis, we explore three relatively novel techniques to improve the localization of the epileptic focus for patients with drug-resistant focal epilepsy who are potential candidates for epilepsy surgery: high-field 3 Tesla (T) MRI, near-infrared spectroscopy (NIRS) and magnetoencephalography (MEG). In the first study, we evaluated if high-field 3T MRI, providing a higher signal to noise ratio, could help detect subtle epileptogenic lesions missed by conventional 1.5T MRIs. Unfortunately, we show that the former was able to detect an epileptogenic lesion in only 5.6% of cases of 1.5T MRI-negative epileptic patients, emphasizing the need for additional techniques. In the second and third studies, we evaluated the potential of NIRS in localizing the epileptic focus by analyzing the hemodynamic behavior of temporal and frontal lobe seizures respectively. We show that focal seizures are associated with significant increases in oxygenated haemoglobin (HbO) and total haemoglobin (HbT) over the epileptic area. While a contralateral mirror-like activation was seen in the majority of seizures, lateralization of the epileptic focus was possible most of the time. In addition, an unexpected increase in deoxygenated haemoglobin (HbR) was noted in some seizures, suggesting possible hypoxia even during relatively brief focal seizures. In the fourth and last study, the utility of MEG in the evaluation of nonlesional drug-refractory focal epileptic patients was studied. It was found that MEG source localization of interictal epileptic spikes had an impact both on patient management for over two thirds of patients and their surgical outcome

Sequential Monte Carlo methods: applications to disease surveillance and fMRI data

We present contributions to epidemic tracking and analysis of fMRI data using sequential Monte Carlo methods within a state-space modeling framework. Using a model for tracking and prediction of a disease outbreak via a syndromic surveillance system, we compare the performance of several particle filtering algorithms in terms of their abilities to efficiently estimate disease states and unknown fixed parameters governing disease transmission. In this context, we demonstrate that basic particle filters may fail due to degeneracy when estimating fixed parameters, and we suggest the use of an algorithm developed by Liu and West (2001), which incorporates a kernel density approximation to the filtered distribution of the fixed parameters to allow for their regeneration. In addition, we show that seemingly uninformative uniform priors on fixed parameters can affect posterior inferences, and we suggest the use of priors bounded only by the support of the parameter. We demonstrate the negative impact of using multinomial resampling and suggest the use of either stratified or residual resampling within the particle filter. We also run a particle MCMC algorithm and show that the performance of the Liu and West (2001) particle filter is competitive with particle MCMC in this particular syndromic surveillance model setting. Finally, the improved performance of the Liu and West (2001) particle filter enables us to relax prior assumptions on model parameters, yet still provide reasonable estimates for model parameters and disease states.We also analyze real and simulated fMRI data using a state-space formulation of a regression model with autocorrelated error structure. We demonstrate via simulation that analyzing autocorrelated fMRI data using a model with independent error structure can inflate the false positive rate of concluding significant neural activity, and we compare methods of accounting for autocorrelation in fMRI data by examining ROC curves. In addition, we show that comparing models with different autocorrelated error structures on the basis of the independence of fitted model residuals can produce misleading results. Using data collected from an fMRI experiment featuring an episodic word recognition task, we estimate parameters in dynamic regression models using maximum likelihood and identify clusters of low and high activation in specific brain regions. We compare alternative models for fMRI time series from these brain regions by approximating the marginal likelihood of the data using particle learning. Our results suggest that a regression model with a dynamic intercept is the preferred model for most fMRI time series in the episodic word recognition experiment within the brain regions we considered, while a model with a dynamic slope is preferred for a small percentage of voxels in these brain regions

Issues in the processing and analysis of functional NIRS imaging and a contrast with fMRI findings in a study of sensorimotor deactivation and connectivity

Includes abstract.~Includes bibliographical references.The first part of this thesis examines issues in the processing and analysis of continuous wave functional linear infrared spectroscopy (fNIRS) of the brain usung the DYNOT system. In the second part, the same sensorimotor experiment is carried out using functional magnetic resonance imaging (fMRI) and near infrared spectroscopy in eleven of the same subjects, to establish whether similar results can be obtained at the group level with each modality. Various techniques for motion artefact removal in fNIRS are compared. Imaging channels with negligible distance between source and detector are used to detect subject motion, and in data sets containing deliberate motion artefacts, independent component analysis and multiple-channel regression are found to improve the signal-to-noise ratio