15 research outputs found
Physiological Gaussian Process Priors for the Hemodynamics in fMRI Analysis
Background: Inference from fMRI data faces the challenge that the hemodynamic
system that relates neural activity to the observed BOLD fMRI signal is
unknown.
New Method: We propose a new Bayesian model for task fMRI data with the
following features: (i) joint estimation of brain activity and the underlying
hemodynamics, (ii) the hemodynamics is modeled nonparametrically with a
Gaussian process (GP) prior guided by physiological information and (iii) the
predicted BOLD is not necessarily generated by a linear time-invariant (LTI)
system. We place a GP prior directly on the predicted BOLD response, rather
than on the hemodynamic response function as in previous literature. This
allows us to incorporate physiological information via the GP prior mean in a
flexible way, and simultaneously gives us the nonparametric flexibility of the
GP.
Results: Results on simulated data show that the proposed model is able to
discriminate between active and non-active voxels also when the GP prior
deviates from the true hemodynamics. Our model finds time varying dynamics when
applied to real fMRI data.
Comparison with Existing Method(s): The proposed model is better at detecting
activity in simulated data than standard models, without inflating the false
positive rate. When applied to real fMRI data, our GP model in several cases
finds brain activity where previously proposed LTI models does not.
Conclusions: We have proposed a new non-linear model for the hemodynamics in
task fMRI, that is able to detect active voxels, and gives the opportunity to
ask new kinds of questions related to hemodynamics.Comment: 18 pages, 14 figure
Mapping the Effect of Interictal Epileptic Activity Density During Wakefulness on Brain Functioning in Focal Childhood Epilepsies With Centrotemporal Spikes
Childhood epilepsy with centrotemporal spikes (CECTS) is the most common type of \u201cself-limited focal epilepsies.\u201d In its typical presentation, CECTS is a condition reflecting non-lesional cortical hyperexcitability of rolandic regions. The benign evolution of this disorder is challenged by the frequent observation of associated neuropsychological deficits and behavioral impairment. The abundance (or frequency) of interictal centrotemporal spikes (CTS) in CECTS is considered a risk factor for deficits in cognition. Herein, we captured the hemodynamic changes triggered by the CTS density measure (i.e., the number of CTS for time bin) obtained in a cohort of CECTS, studied by means of video electroencephalophy/functional MRI during quite wakefulness. We aim to demonstrate a direct influence of the diurnal CTS frequency on epileptogenic and cognitive networks of children with CECTS. A total number of 8,950 CTS (range between 27 and 801) were recorded in 23 CECTS (21 male), with a mean number of 255 CTS/patient and a mean density of CTS/30 s equal to 10,866 \ub1 11.46. Two independent general linear model models were created for each patient based on the effect of interest: \u201cindividual CTS\u201d in model 1 and \u201cCTS density\u201d in model 2. Hemodynamic correlates of CTS density revealed the involvement of a widespread cortical\u2013subcortical network encompassing the sensory-motor cortex, the Broca's area, the premotor cortex, the thalamus, the putamen, and red nucleus, while in the CTS event-related model, changes were limited to blood\u2013oxygen-level-dependent (BOLD) signal increases in the sensory-motor cortices. A linear relationship was observed between the CTS density hemodynamic changes and both disease duration (positive correlation) and age (negative correlation) within the language network and the bilateral insular cortices. Our results strongly support the critical role of the CTS frequency, even during wakefulness, to interfere with the normal functioning of language brain networks
Examining the relationship between home literacy environment and neural correlates of phonological processing in beginning readers with and without a familial risk for dyslexia: an fMRI study
Developmental dyslexia is a language-based learning disability characterized by persistent difficulty in learning to read. While an understanding of genetic contributions is emerging, the ways the environment affects brain functioning in children with developmental dyslexia are poorly understood. A relationship between the home literacy environment (HLE) and neural correlates of reading has been identified in typically developing children, yet it remains unclear whether similar effects are observable in children with a genetic predisposition for dyslexia. Understanding environmental contributions is important given that we do not understand why some genetically at-risk children do not develop dyslexia. Here we investigate for the first time the relationship between HLE and the neural correlates of phonological processing in beginning readers with (FHD+, n=29) and without (FHDâ, n=21) a family history of developmental dyslexia. We controlled for socio-economic status to isolate the neurobiological mechanism by which HLE affects reading development. Group differences revealed stronger correlation of HLE with brain activation in the left inferior/middle frontal and right fusiform gyri in FHDâ compared to FHD+ children, suggesting greater impact of HLE on manipulation of phonological codes and recruitment of orthographic representations in typically developing children. In contrast, activation in the right precentral gyrus showed a significantly stronger correlation with HLE in FHD+ compared to FHDâ children, suggesting emerging compensatory networks in genetically at-risk children. Overall, our results suggest that genetic predisposition for dyslexia alters contributions of HLE to early reading skills before formal reading instruction, which has important implications for educational practice and intervention models
Deconvolution of hemodynamic response from fMRI data
Tato prĂĄce pojednĂĄvĂĄ o variabilitÄ HRF, kterĂĄ mĆŻĆŸe mĂt v urÄitĂœch pĆĂpadech zĂĄsadnĂ vliv na vĂœsledky detekce neuronĂĄlnĂ aktivace pomocĂ fMRI. Jsou popsĂĄny tĆi metody â kumulace, regresnĂ dekonvoluce a metoda bikonjugovanĂœch gradientĆŻ - kterĂ© umoĆŸnĂ odhadnout tvar HRF. V rĂĄmci simulacĂ byla vybrĂĄna jako nejrobustÄjĆĄĂ regresnĂ metoda, kterĂĄ pro dekonvoluÄnĂ odhad o dĂ©lce 30 s vyuĆŸĂvĂĄ kĆivky B-spline 4. ĆĂĄdu. DekonvoluÄnĂ odhady byly vyuĆŸity jako modely HRF pro klasickou analĂœzu dat fMRI, konkrĂ©tnÄ vizuĂĄlnĂ oddball pradigma, obecnĂœm lineĂĄrnĂm modelem. Bylo pozororovĂĄno rozĆĄĂĆenĂ lokalizovanĂœch oblastĂ a vĂœsledky byly po odbornĂ© konzultaci s vÄdeckĂœmi pracovnĂky neurologickĂ© kliniky vyhodnoceny jako relevantnĂ. TakĂ© bylo vytvoĆeno v Matlabu programovĂ© prostĆedĂ, kterĂ© umoĆŸnuje pohodlnÄ pozorovat variabilitu HRF mezi jednotlivĂœmi oblastmi mozku.This paper deals with the variability of HRF, which may have crucial impact on outcomes of fMRI neuronal activation detection in some cases. There are three methods described - averaging, regression deconvolution and biconjugate gradient method - which provide HRF shape estimation. In frame of simulations regression method, which uses B-spline curves of 4-th order for window length of 30 s, was chosen as the most robust method. Deconvolution estimates was used as HRF models for classic analyse of fMRI data, concretely visual oddball paradigm, via general linear model. Enlargement of localizated areas was observed and after expert consultation with scientific employees from neurology clinic, outcomes was evaluated as relevant. Furthermore Matlab application, which provides confortable observation of HRF variability among brain areas, was made.
Multimodale Bildgebung in der prÀchirurgischenEpilepsiediagnostik bei Kindern und Jugendlichen
Kinder mit einer Epilepsie, die nicht auf Medikamente ansprechen, können durch einen operativen Eingriff geheilt werden. In der prÀchirurgischen Diagnostik dieser Kinder ist es notwendig die epileptogene Zone eindeutig zu bestimmen: dazu bedarf es Hypothesen. Verschiedene Verfahren (Elektroenzephalographie, Magnetresonanztomographie, Positron-Emissions-Tomographie, Single-Photon-Emissionscom-putertomographie) werden aktuell angewandt. Doch keine der genannten Methoden kann die epileptogene Zone mit der erforderlichen Sicherheit eingrenzen, jede hat Limitationen, so dass es auf die Zusammenschau der Verfahren ankommt.
Deshalb wurde in dieser Studie erstmalig bei Kindern mit symptomatischen und kryptogenen fokalen Epilepsien die Kombination aus der simultanen Ableitung von Elektroenzephalographie und der Aufzeichnung von funktioneller Magnetresonanztomographie in Kombination mit einer Quellenanlyse untersucht.
Die Kombination von Elektroenzephalographie und funktioneller Magnetresonanztomographie ist eine nicht invasive Methode, die hÀmodynamische VerÀnderungen im gesamten Gehirn wÀhrend interiktaler epileptischer AktivitÀt detektieren kann. Dabei werden bei 540 Magnetresonanz-Aufnahmen mit schnellen Sequenzen die Unterschiede dargestellt, die einerseits zwischen den Aufnahmen bestehen, bei denen eine interiktale epileptische AktivitÀt im Elektroenzephalogramm zu sehen war und andererseits zwischen den Aufnahmen, bei denen dies nicht der Fall war.
In frĂŒheren Studien bei Kindern mit verschiedenen Epilepsieformen zeigte sich je-doch, dass die Ergebnisse selten lokalisiert, sondern meist ausgedehnt zur Darstel-lung kamen. Daher untersuchten wir, ob eine Kombination mit einer Quellenanalyse, die auf verteilten Quellen basiert, diese ausgedehnten Aktivierungsareale zeitlich differenzieren kann.
Wir wĂ€hlten von 26 Patienten, die an einem epilepsiechirurgischen Programm teil-nahmen, sechs Patienten aus, die einen klaren erwarteten epileptogenen Fokus durch Ăbereinstimmung von Positron-Emissions-Tomographie, iktaler Single-Photon-Emissionscomputertomographie und Video-Elektroenzephalographie zeigten. Bei allen Patienten fanden wir eine signifikante SignalĂ€nderung in der Elektroenzephalographie und funktioneller Magnetresonanztomographie sowie eine Ăbereinstimmung mit der erwarteten epileptogenen Zone bei fĂŒnf Patienten. Bei fĂŒnf Patienten sahen wir zusĂ€tzlich ausgedehnte Aktivierungsareale. Die Quel-lenanalyse zeigte, dass der Beginn der interiktalen epileptischen AktivitĂ€t bei allen Patienten in der erwarteten epileptogenen Zone lag und bei fĂŒnf Patienten eine Verlagerung in nahe Gehirnregionen erfolgte. Diese Ausbreitungen der Quellen korrespondierten mit Arealen der SignalĂ€nderungen im funktionellen MRT.
Die Kombination von Elektroenzephalographie und funktioneller Magnetresonanztomographie ist eine Methode, die signifikante Aktivierungen im Bereich der epileptogenen Zone zeigen kann, jedoch sind diese Aktivierungen meist darĂŒber hinaus ausgebreitet, so dass es zusĂ€tzlicher Methoden bedarf, diese ausgedehnten Bereiche zu erklĂ€ren. Die Quellenanalyse, die auf verteilte Quellen basiert, ist in der Lage, die Ergebnisse der funktionellen Magnetresonanztomographie durch die hohe zeitliche Auflösung zu interpretieren und fĂŒr die prĂ€chirurgische Diagnostik zu verbessern
Study of the Hemodynamic Response to Interictal Epileptiform Discharges in Human Epilepsy Using Functional Near Infrared Spectroscopy
RĂSUMĂ
L'imagerie spectroscopique proche infrarouge fonctionnelle (ISPIf) s'est imposĂ©e comme technique dâimagerie neuronale prometteuse. Cette derniĂšre permet une surveillance non invasive de l'Ă©volution chronique de l'activitĂ© hĂ©modynamique corticale. Durant la derniĂšre dĂ©cennie, ISPIf combinĂ© avec l'Ă©lectroencĂ©phalographie (EEG) a Ă©tĂ© appliquĂ© dans le contexte de l'Ă©pilepsie humaine, et a permi dâexplorer le lien entre lâactivitĂ© neurale et hĂ©modynamique. Cependant, la plupart des travaux antĂ©rieurs sont uniquement axĂ©s sur l'Ă©tude des crises d'Ă©pilepsie qui sont alĂ©atoires et se produisent rarement pendant un test de lâEEG-ISPIf. Cette thĂšse cherche Ă Ă©valuer la capacitĂ© de l'EEG-ISPIf Ă observer les changements hĂ©modynamiques associĂ©s aux dĂ©charges Ă©pileptiformes intercritiques (DEIs), et Ă dĂ©terminer si ces DEIs peuvent Ă©galement ĂȘtre utilisĂ©s pour extraire de l'information additionnelle servant Ă la localisation du site dâun foyer Ă©pileptique.
En se basant sur des donnĂ©es multimodales EEG-ISPIf recueillies sur un grand Ă©chantillon de patients (40), combinĂ© Ă l'utilisation d'un modĂšle linĂ©aire gĂ©nĂ©ralisĂ© (MLG), une premiĂšre Ă©tude a permis la quantification prĂ©liminaire de la sensibilitĂ© et la spĂ©cificitĂ© de la technique en utilisant la dĂ©tection des zones cĂ©rĂ©brales activĂ©es par des DEIs pour la localisation de la rĂ©gion du foyer Ă©pileptique. Dans un sous-groupe de 29 patients atteints au niveau de la rĂ©gion nĂ©ocorticale, lorsque mesurĂ© durant des Ă©vĂšnements de DEIs, des diminutions de la concentration dâhĂ©moglobine dĂ©soxygĂ©nĂ©e (HbR) (chez 62% des sujets) et des augmentations de la concentration de lâhĂ©moglobine oxygĂ©nĂ©e (HbO) (chez 38% des sujets) ont Ă©tĂ© observĂ©es. De plus, cette variation en HbR et HbO Ă©tait significativement plus forte dans la rĂ©gion du foyer Ă©pileptique (qui donc pourrait conduire Ă une localisation du foyer Ă©pileptique) dans 28% / 21% des patients. Ces estimations modestes de la sensibilitĂ© et de la spĂ©cificitĂ© suggĂšrent que l'utilisation d'une fonction de rĂ©ponse hĂ©modynamique (FRH) canonique nâest pas optimale dans lâanalyse des DEIs par MLG classique. Par consĂ©quent, une seconde approche a Ă©tĂ© explorĂ©e dans le cadre dâune deuxiĂšme Ă©tude par modĂ©lisation des variations spĂ©cifiques Ă chaque patient dans la construction de la rĂ©ponse hĂ©modynamique associĂ©e aux DEIs. Un terme quadratique a Ă©galement Ă©tĂ© ajoutĂ© au modĂšle pour tenir compte de la non-linĂ©aritĂ© de la rĂ©ponse associĂ©e Ă une frĂ©quence plus Ă©levĂ©e dâĂ©vĂšnements lors de l'enregistrement. Ces nouveaux modĂšles ont d'abord Ă©tĂ© validĂ©s numĂ©riquement par simulations, avant dâĂȘtre appliquĂ©s Ă l'analyse de donnĂ©es de cinq patients sĂ©lectionnĂ©s. Lorsque comparĂ©e Ă la FRH canonique, l'utilisation de la FRH spĂ©cifique au patient dans l'analyse MLG a non seulement amĂ©liorĂ© considĂ©rablement les scores statistiques et les Ă©tendues spatiales des----------ABSTRACT
Functional near-infrared spectroscopy (fNIRS) has emerged as a promising neuroimaging technique as it allows non-invasive and long-term monitoring of cortical hemodynamics. For the last decades, fNIRS combined with electroencephalography (EEG) has been applied in the context of human epilepsy, and has yielded good results. However, most previous work only focused on the study of epileptic seizures which are random and seldom occur during EEG-fNIRS testing. This thesis sought to evaluate the potential of EEG-fNIRS in observing the hemodynamic changes associated with interictal epileptiform discharges (IEDs), and to determine whether these IEDs can also be used to extract useful information in the localization of the epileptic focus site.
Based on the EEG-fNIRS data collected from a relatively large number of patients (40) and using a standard general linear model (GLM) approach, the first study of this thesis provided preliminary estimates of the sensitivity and the specificity of EEG-fNIRS in detecting brain areas activated by IEDs and in localizing the epileptic focus region. In the 29 patients with neocortical epilepsies, significant deoxygenated hemoglobin (HbR) concentration decreases and oxygenated hemoglobin (HbO) concentration increases corresponding to IEDs were observed in 62% and 38% of patients respectively. This HbR/HbO response was most significant in the epileptic focus region among all the activations, and thus could lead to successful identification of the epileptic focus site in 28%/21% of the patients. These modest estimates of the sensitivity and the specificity suggested that using a standard GLM with a canonical hemodynamic response function (HRF) might not be the optimal method in the analysis of IEDs. Therefore, the second study of this thesis made a first attempt to model the patient-specific variations in the shape of the hemodynamic response to IEDs. A quadratic term was also added to the model to account for the nonlinearity in the response when frequent IEDs were present in the recording. The new models were first validated through carefully designed simulations, and were then applied in the data analysis of five selected patients. Compared with the canonical HRF, including patient-specific HRFs in the GLM analysis not only significantly improved the statistical scores and the spatial extents of existing activations, but also was able to detect new brain regions activated by IEDs on all of the five patients. These improvements in activation detection also helped obtain more accurate focus localization results in some cases
Hemodynamic Response Function Modeling
Functional Magnetic Resonance Imaging (fMRI) is a medical-imaging technique for studying brain function. It can be used to capture the response of the brain to various tasks. The response to a brief, intense period of neural stimulation is called the hemodynamic response function (HRF). Modeling HRF is essential to identifying the brain activation by exploring the relationship between the experimental stimulus and the response. In this dissertation, we discuss three research problems related to HRF estimation. First, when multiple types of stimuli are present, how can we capture the characteristic HRF for each stimulus? Second, is there any difference among the HRFs corresponding to multiple stimuli? Third, how can we improve the HRF estimator's efficiency? We propose a nonparametric method, transfer function estimate (TFE), to answer these three questions. Building on existing work, we extend the nonparametric approach to a multivariate form, which adapts to the multiple types of stimuli, and we develop hypothesis testing to identify the brain activation and to compare the HRFs under different stimuli. In order to improve estimation efficiency, we propose using weighted least square (WLS) in a multiple system of regression by spectral methods. The finite-sample performance of the TFE is illustrated through several simulation studies and real fRMI data sets. We also establish the asymptotic normality of the TFE, as well as the efficiency of the WLS estimator.Doctor of Philosoph
Apport de nouvelles techniques dans lâĂ©valuation de patients candidats Ă une chirurgie dâĂ©pilepsie : rĂ©sonance magnĂ©tique Ă haut champ, spectroscopie proche infrarouge et magnĂ©toencĂ©phalographie
L'Ă©pilepsie constitue le dĂ©sordre neurologique le plus frĂ©quent aprĂšs les maladies cĂ©rĂ©brovasculaires. Bien que le contrĂŽle des crises se fasse gĂ©nĂ©ralement au moyen d'anticonvulsivants, environ 30 % des patients y sont rĂ©fractaires. Pour ceux-ci, la chirurgie de l'Ă©pilepsie s'avĂšre une option intĂ©ressante, surtout si lâimagerie par rĂ©sonance magnĂ©tique (IRM) cĂ©rĂ©brale rĂ©vĂšle une lĂ©sion Ă©pileptogĂšne bien dĂ©limitĂ©e. Malheureusement, prĂšs du quart des Ă©pilepsies partielles rĂ©fractaires sont dites « non lĂ©sionnelles ». Chez ces patients avec une IRM nĂ©gative, la dĂ©limitation de la zone Ă©pileptogĂšne doit alors reposer sur la mise en commun des donnĂ©es cliniques, Ă©lectrophysiologiques (EEG de surface ou intracrĂąnien) et fonctionnelles (tomographie Ă Ă©mission monophotonique ou de positrons). La faible rĂ©solution spatiale et/ou temporelle de ces outils de localisation se traduit par un taux de succĂšs chirurgical dĂ©cevant. Dans le cadre de cette thĂšse, nous avons explorĂ© le potentiel de trois nouvelles techniques pouvant amĂ©liorer la localisation du foyer Ă©pileptique chez les patients avec Ă©pilepsie focale rĂ©fractaire considĂ©rĂ©s candidats potentiels Ă une chirurgie dâĂ©pilepsie : lâIRM Ă haut champ, la spectroscopie proche infrarouge (SPIR) et la magnĂ©toencĂ©phalographie (MEG).
Dans une premiĂšre Ă©tude, nous avons Ă©valuĂ© si lâIRM de haut champ Ă 3 Tesla (T), prĂ©sentant thĂ©oriquement un rapport signal sur bruit plus Ă©levĂ© que lâIRM conventionnelle Ă 1,5 T, pouvait permettre la dĂ©tection des lĂ©sions Ă©pileptogĂšnes subtiles qui auraient Ă©tĂ© manquĂ©es par cette derniĂšre. Malheureusement, lâIRM 3 T nâa permis de dĂ©tecter quâun faible nombre de lĂ©sions Ă©pileptogĂšnes supplĂ©mentaires (5,6 %) dâoĂč la nĂ©cessitĂ© dâexplorer dâautres techniques.
Dans les seconde et troisiĂšme Ă©tudes, nous avons examinĂ© le potentiel de la SPIR pour localiser le foyer Ă©pileptique en analysant le comportement hĂ©modynamique au cours de crises temporales et frontales. Ces Ă©tudes ont montrĂ© que les crises sont associĂ©es Ă une augmentation significative de lâhĂ©moglobine oxygĂ©nĂ©e (HbO) et lâhĂ©moglobine totale au niveau de la rĂ©gion Ă©pileptique. Bien quâune activation contralatĂ©rale en image miroir puisse ĂȘtre observĂ©e sur la majoritĂ© des crises, la latĂ©ralisation du foyer Ă©tait possible dans la plupart des cas. Une augmentation surprenante de lâhĂ©moglobine dĂ©soxygĂ©nĂ©e a parfois pu ĂȘtre observĂ©e suggĂ©rant quâune hypoxie puisse survenir mĂȘme lors de courtes crises focales.
Dans la quatriĂšme et derniĂšre Ă©tude, nous avons Ă©valuĂ© lâapport de la MEG dans lâĂ©valuation des patients avec Ă©pilepsie focale rĂ©fractaire considĂ©rĂ©s candidats potentiels Ă une chirurgie. Il sâest avĂ©rĂ© que les localisations de sources des pointes Ă©pileptiques 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 contrĂŽle 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