Investigating the post-stimulus undershoot of the BOLD signal – A simultaneous fMRI and fNIRS study

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Validating an image-based fNIRS approach with fMRI and a working memory task

In the current study, we extend a previous methodological pipeline by adding a novel image reconstruction approach to move functional near-infrared (fNIRS) signals from channel-space on the surface of the head to voxel-space within the brain volume. We validate this methodology by comparing voxel-wise fNIRS results to functional magnetic resonance imaging (fMRI) results from a visual working memory (VWM) task using two approaches. In the first approach, significant voxel-wise correlations were observed between fNIRS and fMRI measures for all experimental conditions across brain regions in the fronto-parieto-temporal cortices. In the second approach, we conducted separate multi-factorial ANOVAs on fNIRS and fMRI measures and then examined the correspondence between main and interaction effects within common regions of interest. Both fMRI and fNIRS showed similar trends in activation within the VWM network when the number of items held in working memory increases. These results validate the image-based fNIRS approach

Study of the Hemodynamic Response to Interictal Epileptiform Discharges in Human Epilepsy Using Functional Near Infrared Spectroscopy

RÉSUMÉ L'imagerie spectroscopique proche infrarouge fonctionnelle (ISPIf) s'est imposée comme technique d’imagerie neuronale prometteuse. Cette dernière permet une surveillance non invasive de l'évolution chronique de l'activité hémodynamique corticale. Durant la dernière décennie, ISPIf combiné avec l'électroencéphalographie (EEG) a été appliqué dans le contexte de l'épilepsie humaine, et a permi d’explorer le lien entre l’activité neurale et hémodynamique. Cependant, la plupart des travaux antérieurs sont uniquement axés sur l'étude des crises d'épilepsie qui sont aléatoires et se produisent rarement pendant un test de l’EEG-ISPIf. Cette thèse cherche à évaluer la capacité de l'EEG-ISPIf à observer les changements hémodynamiques associés aux décharges épileptiformes intercritiques (DEIs), et à déterminer si ces DEIs peuvent également être utilisés pour extraire de l'information additionnelle servant à la localisation du site d’un foyer épileptique. En se basant sur des données multimodales EEG-ISPIf recueillies sur un grand échantillon de patients (40), combiné à l'utilisation d'un modèle linéaire généralisé (MLG), une première étude a permis la quantification préliminaire de la sensibilité et la spécificité de la technique en utilisant la détection des zones cérébrales activées par des DEIs pour la localisation de la région du foyer épileptique. Dans un sous-groupe de 29 patients atteints au niveau de la région néocorticale, lorsque mesuré durant des évènements de DEIs, des diminutions de la concentration d’hémoglobine désoxygénée (HbR) (chez 62% des sujets) et des augmentations de la concentration de l’hémoglobine oxygénée (HbO) (chez 38% des sujets) ont été observées. De plus, cette variation en HbR et HbO était significativement plus forte dans la région du foyer épileptique (qui donc pourrait conduire à une localisation du foyer épileptique) dans 28% / 21% des patients. Ces estimations modestes de la sensibilité et de la spécificité suggèrent que l'utilisation d'une fonction de réponse hémodynamique (FRH) canonique n’est pas optimale dans l’analyse des DEIs par MLG classique. Par conséquent, une seconde approche a été explorée dans le cadre d’une deuxième étude par modélisation des variations spécifiques à chaque patient dans la construction de la réponse hémodynamique associée aux DEIs. Un terme quadratique a également été ajouté au modèle pour tenir compte de la non-linéarité de la réponse associée à une fréquence plus élevée d’évènements lors de l'enregistrement. Ces nouveaux modèles ont d'abord été validés numériquement par simulations, avant d’être appliqués à l'analyse de données de cinq patients sélectionnés. Lorsque comparée à la FRH canonique, l'utilisation de la FRH spécifique au patient dans l'analyse MLG a non seulement amélioré considérablement les scores statistiques et les étendues 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

Brain Cortical Mapping by Simultaneous Recording of Functional Near Infrared Spectroscopy and Electroencephalograms from the Whole Brain During Right Median Nerve Stimulation

To investigate relationships between hemodynamic responses and neural activities in the somatosensory cortices, hemodynamic responses by near infrared spectroscopy (NIRS) and electroencephalograms (EEGs) were recorded simultaneously while subjects received electrical stimulation in the right median nerve. The statistical significance of the hemodynamic responses was evaluated by a general linear model (GLM) with the boxcar design matrix convoluted with Gaussian function. The resulting NIRS and EEGs data were stereotaxically superimposed on the reconstructed brain of each subject. The NIRS data indicated that changes in oxy-hemoglobin concentration increased at the contralateral primary somatosensory (SI) area; responses then spread to the more posterior and ipsilateral somatosensory areas. The EEG data indicated that positive somatosensory evoked potentials peaking at 22 ms latency (P22) were recorded from the contralateral SI area. Comparison of these two sets of data indicated that the distance between the dipoles of P22 and NIRS channels with maximum hemodynamic responses was less than 10 mm, and that the two topographical maps of hemodynamic responses and current source density of P22 were significantly correlated. Furthermore, when onset of the boxcar function was delayed 5–15 s (onset delay), hemodynamic responses in the bilateral parietal association cortices posterior to the SI were more strongly correlated to electrical stimulation. This suggests that GLM analysis with onset delay could reveal the temporal ordering of neural activation in the hierarchical somatosensory pathway, consistent with the neurophysiological data. The present results suggest that simultaneous NIRS and EEG recording is useful for correlating hemodynamic responses to neural activity