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ABSTRACT: In order to analyze where epileptic spikes are generated, we assessed the level of concordance between EEG source localization using distributed source models and simultaneous EEG-fMRI which measures the hemodynamic correlates of EEG activity. Data to be compared were first estimated on the same cortical surface and two comparison strategies were used: (1) MEM-concordance: a comparison between EEG sources localized with the Maximum Entropy on the Mean (MEM) method and fMRI clusters showing a significant hemodynamic response. Minimal geodesic distances between local extrema and overlap measurements between spatial extents of EEG sources and fMRI clusters were used to quantify MEM-concordance. (2) fMRI-relevance: estimation of the fMRI-relevance index alpha quantifying if sources located in an fMRI cluster could explain some scalp EEG data, when this fMRI cluster was used to constrain the EEG inverse problem. Combining MEM-concordance and fMRI-relevance (alpha) indexes, each fMRI cluster showing a significant hemodynamic response (p<0.05 corrected) was classified according to its concordance with EEG data. Nine patients with focal epilepsy who underwent EEG-fMRI examination followed by EEG recording outside the scanner were selected for this study. Among the 62 fMRI clusters analyzed (7 patients), 15 (24%) found in 6 patients were highly concordant with EEG according to both MEM-concordance and fMRI-relevance. EEG concordance was found for 5 clusters (8%) according to alpha only, suggesting sources missed by the MEM. No concordance with EEG was found for 30 clusters (48%) and for 10 clusters (16%) alpha was significantly negative, suggesting EEG-fMRI discordance. We proposed two complementary strategies to assess and classify EEG-fMRI concordance. We showed that for most patients, part of the hemodynamic response to spikes was highly concordant with EEG sources, whereas other fMRI clusters in response to the same spikes were found distant or discordant with EEG sources.
NeuroImage 02/2008; 39(2):755-74. · 5.89 Impact Factor
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ABSTRACT: To determine the blood oxygen level-dependent (BOLD) responses to epileptic discharges in the thalamus and cerebral cortex in patients with partial epilepsy.
Among 64 tested patients, 40 had EEG spikes during scanning and were divided in two groups: unilateral or bilateral independent spikes (29 patients) and bilaterally synchronous spikes (11 patients). Each spike topography was analyzed separately, yielding 40 studies in the first group and 17 in the second.
Forty-five percent of focal spike studies showed significant BOLD responses. Cortical activation (positive BOLD) represented the dominant response and had a better correlation with spike location than cortical deactivation (negative BOLD). In the second group, all patients had significant BOLD responses; they were more widespread compared to the first group, and deactivated areas were as important as activated regions. A thalamic response was seen in 12.5% of studies in the first group and 55% in the second.
The thalamus is involved in partial epilepsy during interictal discharges. This involvement and also cortical deactivation are more commonly seen with bilateral spikes than focal discharges.
These findings show evidence for a role for the thalamus and a more important role for inhibition in secondary bilateral synchrony.
Clinical Neurophysiology 02/2006; 117(1):177-91. · 3.41 Impact Factor
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ABSTRACT: Polymicrogyria (PMG) is a widespread cortical malformation frequently associated with seizures and EEG spikes. Its epileptogenicity is poorly understood. Nine patients with simultaneous EEG and fMRI were studied to assess the blood oxygenation level-dependent response to spikes. Sixteen of 18 studies showed responses, with maximum activation involving the lesion in 61.5%, but often limited to a small fraction of that lesion, suggesting intrinsic epileptogenicity in small areas of the PMG cortex.
Neurology 05/2005; 64(7):1263-6. · 8.31 Impact Factor
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NeuroImage 01/2005; 24(4):1099-1112. · 5.89 Impact Factor
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ABSTRACT: The objectives of this study were to evaluate the haemodynamic response of the cerebral cortex and thalamus during generalized spike and wave or polyspike and wave (GSW) bursts in patients with idiopathic generalized epilepsy (IGE). The haemodynamic response is measured by fMRI [blood oxygenation level-dependent (BOLD) effect]. We used combined EEG-functional MRI, a method that allows the unambiguous measurement of the BOLD effect during bursts, compared with measurements during the inter-burst interval. Fifteen patients with IGE had GSW bursts during scanning and technically acceptable studies. fMRI cortical changes as a result of GSW activity were present in 14 patients (93%). Changes in the form of activation (increased BOLD) or deactivation (decreased BOLD) occurred symmetrically in the cortex of both hemispheres, involved anterior as much as posterior head regions, but were variable across patients. Bilateral thalamic changes were also found in 12 patients (80%). Activation predominated over deactivation in the thalamus, whereas the opposite was seen in the cerebral cortex. These results bring a new light to the pathophysiolocal mechanisms generating GSW. The spatial distribution of BOLD responses to GSW was unexpected: it involved as many posterior as anterior head regions, contrary to the usual fronto-central predominance seen in EEG. The presence of a thalamic BOLD response in most patients provided, for the first time in a group of human patients, confirmation of the evidence of thalamic involvement seen in animal models. The possible mechanisms underlying these phenomena are discussed.
Brain 06/2004; 127(Pt 5):1127-44. · 9.46 Impact Factor
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ABSTRACT: Three types of commercially available headnet electrode arrays, designed for use in EEG, and conventional EEG Ag/AgCl cup electrodes were tested on human subjects, and a realistic, saline-filled head-shaped tank was prepared with vegetable skin to simulate human skin in order to determine the optimum electrode system for electrical impedance tomography (EIT) of the human head. Impedance changes during EIT acquisition were produced in healthy volunteers during a finger-thumb apposition task and in tanks by the insertion of a Perspex rod. Signal-to-baseline noise, measured from raw EIT data, was 2.3 +/- 0.3 and 2.3 +/- 0.2 for the human and tank data, respectively. In both the human and tank experiments, a commercial hydrogel elasticated electrode headnet produced the least amount of baseline noise, and was the only headnet in the human data with noise levels acceptable for EIT imaging. Image quality measured in the tank was similar for most of the headnets tested, except that the EEG electrodes produced a higher positional error and electrodes in a geodesic elasticated net produced images with worse subjective image quality. Overall, the hydrogel elasticated headnet was judged to be the most suitable for human neuroimaging with EIT.
Physiological Measurement 06/2003; 24(2):527-44. · 1.68 Impact Factor
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ABSTRACT: A system based on the detection of K-shell x-ray fluorescence (XRF) has been used to investigate whether a correlation exists between the concentration of iron in the skin and the concentration of iron in the liver, as the degree of iron loading increases. The motivation behind this work is to develop a non-invasive method of determining the extent of the body's iron stores via measurements on the skin, in order to monitor the efficacy of chelation therapy administered to patients with beta-thalassaemia. Sprague-Dawley rats were iron loaded via injections of iron dextran and subsequently treated with the iron chelator CP94. The non-haem iron concentrations of the liver, heart and spleen were determined using bathophenanthroline sulphonate as the chromogen reagent. Samples of abdominal skin were taken and the iron concentrations determined using XRF. A strong correlation between the skin iron concentration and the liver iron concentration has been demonstrated (R2 = 0.86). Similar correlations exist for the heart and the spleen. These results show that this method holds great potential as a tool in the diagnosis and treatment of hereditary haemochromatosis and beta-thalassaemia.
Physics in Medicine and Biology 06/2000; 45(5):1387-96. · 2.83 Impact Factor
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ABSTRACT: Electrical impedance tomography (EIT) is a recently developed technique which enables the internal conductivity of an object to be imaged using rings of external electrodes. In a recent study, EIT during cortical evoked responses showed encouraging changes in the raw impedance measurements, but reconstructed images were noisy. A simplified reconstruction algorithm was used which modelled the head as a homogeneous sphere. In the current study, the development and validation of an improved reconstruction algorithm are described in which realistic geometry and conductivity distributions have been incorporated using the finite element method. Data from computer simulations and spherical or head-shaped saline-filled tank phantoms, in which the skull was represented by a concentric shell of plaster of Paris or a real human skull, have been reconstructed into images. There were significant improvements in image quality as a result of the incorporation of accurate geometry and extracerebral layers in the reconstruction algorithm. Image quality, assessed by blinded subjective expert observers, also improved significantly when data from the previous evoked response study were reanalysed with the new algorithm. In preliminary images collected during epileptic seizures, the new algorithm generated EIT conductivity changes which were consistent with the electrographic ictal activity. Incorporation of realistic geometry and conductivity into the reconstruction algorithm significantly improves the quality of EIT images and lends encouragement to the belief that EIT may provide a low-cost, portable functional neuroimaging system in the foreseeable future.
Bagshaw, A.P. and Liston, A.D. and Bayford, R.H. and Tizzard, A. and Gibson, A.P. and Tidswell, A.T. and Sparkes, M.K. and Dehghani, H. and Binnie, C.D. and Holder, D.S. (2003) Electrical impedance tomography of human brain function using reconstruction algorithms based on the finite element method. NeuroImage, 20 (2). pp. 752-764. ISSN 10538119.
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Phsyiological Measurement. 24(2).
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ABSTRACT: Electrical impedance tomography (EIT) is a recently developed technique which enables the internal conductivity of an object to be imaged using rings of external electrodes. In a recent study, EIT during cortical evoked responses showed encouraging changes in the raw impedance measurements, but reconstructed images were noisy. A simplified reconstruction algorithm was used which modelled the head as a homogeneous sphere. In the current study, the development and validation of an improved reconstruction algorithm are described in which realistic geometry and conductivity distributions have been incorporated using the finite element method. Data from computer simulations and spherical or head-shaped saline-filled tank phantoms, in which the skull was represented by a concentric shell of plaster of Paris or a real human skull, have been reconstructed into images. There were significant improvements in image quality as a result of the incorporation of accurate geometry and extracerebral layers in the reconstruction algorithm. Image quality, assessed by blinded subjective expert observers, also improved significantly when data from the previous evoked response study were reanalysed with the new algorithm. In preliminary images collected during epileptic seizures, the new algorithm generated EIT conductivity changes which were consistent with the electrographic ictal activity. Incorporation of realistic geometry and conductivity into the reconstruction algorithm significantly improves the quality of EIT images and lends encouragement to the belief that EIT may provide a low-cost, portable functional neuroimaging system in the foreseeable future
Neuroimage. 20(2).
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ABSTRACT: PURPOSE: Simultaneous EEG and functional MRI (fMRI) allows measuring metabolic changes related to interictal spikes. Our objective was to investigate blood oxygenation level-dependent (BOLD) responses to temporal lobe (TL) spikes by using EEG-fMRI recording. METHODS: We studied 35 patients who had a diagnosis of temporal lobe epilepsy (TLE) and active TL spiking on routine scalp EEG recording. Two-hour sessions of continuous EEG-fMRI were recorded, and spikes were identified after offline artifact removal and used as events in the fMRI analysis. Each type of spike was analyzed separately, as one EEG-fMRI study. We determined significant (p < 0.05) positive (activation) and negative (deactivation) BOLD responses for each study. RESULTS: Twenty-seven patients had spikes during scanning (19 unilateral and eight bilateral). From a total of 35 fMRI studies, 29 (83%) showed BOLD responses: 14 had both activations and deactivations; 12, activations only; and three, deactivations only. Six (17%) showed no responses. Nineteen studies had mainly neocortical TL activation: Sixteen (84%) of 19 concordant with spikes, 12 of 16 with concomitant activation of the contralateral TL, and 16 of 19 with additional extratemporal activation; few showed exclusively mesial TL activation. Seventeen studies showed deactivation, either extratemporal plus temporal (n = 8) or exclusively extratemporal (n = 9). CONCLUSIONS: BOLD responses to TL spikes occurred in 83% of studies, predominated in the spiking temporal lobe, and manifested as activation or deactivation. Responses often involved the contralateral homologous cortex at the time of unilateral spikes and were frequently observed in extratemporal regions, suggesting that TL epileptic spikes can affect neuronal activity at a distance through synaptic connections.
Epilepsia. 47(2):343-54.
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ABSTRACT: This study examined BOLD changes prior to interictal discharges in the EEG of patients with epilepsy. From a database of 143 EEG-fMRI studies, we selected the 16 data sets that showed both strong fMRI activation in the original analysis and only a single spike type in the EEG. Scans were then analyzed using seven model HRFs, peaking 3 or 1 s before the event, or 1, 3, 5, 7, or 9 s after it. An HRF was calculated using a deconvolution method for all activations seen in each analysis. The results showed that seven data sets had HRFs that peaked 1 s after the event or earlier, indicating a BOLD change starting prior to the spike seen on the scalp EEG. This is surprising since the BOLD change is expected to result from the spike. For most of the data sets with early peaking HRFs, the maximum activation in all of the statistical maps was when the model HRF peaked 1 s after the event, suggesting that the early activation was at least as important as any later activation. We suggest that this early activity is the result of neuronal changes occurring several seconds prior to a surface EEG event, but that these changes are not visible on the scalp. This is the first report of a BOLD response occurring several seconds prior to an interictal event seen on the scalp and could have important implications for our understanding of the generation of epileptic discharges.
Neuroimage. 35(4):1450-8.
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ABSTRACT: To investigate the coupling between the hemodynamic and metabolic changes following functional brain activation as well as interictal epileptiform discharges (IEDs), blood oxygenation level dependent (BOLD), perfusion and oxygen consumption responses to a unilateral distal motor task and interictal epileptiform discharges (IEDs) were examined via continuous EEG-fMRI. Seven epilepsy patients performed a periodic (1 Hz) right-hand pinch grip using approximately 8% of their maximum voluntary contraction, a paradigm previously shown to produce contralateral MI neuronal excitation and ipsilateral MI neuronal inhibition. A multi-slice interleaved pulsed arterial spin labeling and T(2)*-weighted gradient echo sequence was employed to quantify cerebral blood flow (CBF) and BOLD changes. EEG was recorded throughout the imaging session and reviewed to identify the IEDs. During the motor task, BOLD, CBF and cerebral metabolic rate of oxygen consumption (CMR(O(2))) signals increased in the contra- and decreased in the ipsilateral primary motor cortex. The relative changes in CMR(O(2)) and CBF were linearly related, with a slope of 0.46 +/- 0.05. The ratio of contra- to ipsilateral CBF changes was smaller in the present group of epilepsy patients than in the healthy subjects examined previously. IEDs produced both increases and decreases in BOLD and CBF signals. In the two case studies for which the estimation criteria were met, the coupling ratio between IED-induced CMR(O(2)) and CBF changes was estimated at 0.48 +/- 0.17. These findings provide evidence for a preserved coupling between hemodynamic and metabolic changes in response to both functional activation and, for the two case studies available, in response to interictal epileptiform activity.
Neuroimage. 28(1):205-15.
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ABSTRACT: EEG-fMRI and EEG dipole source localisation are two non-invasive imaging methods that can be applied to the study of the haemodynamic and electrical consequences of epileptic discharges. Using them in combination has the potential to allow imaging with the spatial resolution of fMRI and the temporal resolution of EEG. However, although considerable data are available concerning their concordance in studies involving event-related potentials (ERPs), less is known about how well they agree in epilepsy. To this end, 17 patients were selected from a database of 57 who had undergone an EEG-fMRI scanning session followed by a separate EEG session outside of the scanner. Spatiotemporal dipole modelling was compared with the peak and closest EEG-fMRI activations and deactivations. On average, the dipoles were 58.5 mm from the voxel with the highest positive t value and 32.5 mm from the nearest activated voxel. For deactivations, the corresponding values were 60.8 and 34.0 mm. These values are considerably higher than is generally observed with ERPs, probably as a result of the relatively widespread field, which can lead to artificially deep dipoles, and the occurrence of EEG-fMRI responses remote from the presumed focus of the epileptic activity. The results suggest that EEG and MEG inverse solutions for equivalent current dipole approaches should not be strongly constrained by EEG-fMRI results in epilepsy, and that the use of distributed source modelling will be a more appropriate way of combining EEG-fMRI results with source localisation techniques.
Neuroimage. 30(2):417-25.
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ABSTRACT: Combined EEG-fMRI has recently been used to explore the BOLD responses to interictal epileptiform discharges. This study examines whether misspecification of the form of the haemodynamic response function (HRF) results in significant fMRI responses being missed in the statistical analysis. EEG-fMRI data from 31 patients with focal epilepsy were analysed with four HRFs peaking from 3 to 9 sec after each interictal event, in addition to a standard HRF that peaked after 5.4 sec. In four patients, fMRI responses were correlated with gadolinium-enhanced MR angiograms and with EEG data from intracranial electrodes. In an attempt to understand the absence of BOLD responses in a significant group of patients, the degree of signal loss occurring as a result of magnetic field inhomogeneities was compared with the detected fMRI responses in ten patients with temporal lobe spikes. Using multiple HRFs resulted in an increased percentage of data sets with significant fMRI activations, from 45% when using the standard HRF alone, to 62.5%. The standard HRF was good at detecting positive BOLD responses, but less appropriate for negative BOLD responses, the majority of which were more accurately modelled by an HRF that peaked later than the standard. Co-registration of statistical maps with gadolinium-enhanced MRIs suggested that the detected fMRI responses were not in general related to large veins. Signal loss in the temporal lobes seemed to be an important factor in 7 of 12 patients who did not show fMRI activations with any of the HRFs.
Hum Brain Mapp. 22(3):179-92.
