Biomedical subjects

Eliane Kobayashi

Publications and source records attributed to Eliane Kobayashi.

At least 19 recordsLinked to original sources

PubMed2006

Using voxel-specific hemodynamic response function in EEG-fMRI data analysis: An estimation and detection model.

Research groups who study epileptic spikes with simultaneous EEG-fMRI have used mostly the general linear model (GLM). A shortcoming of the GLM is that the specification of a simple hemodynamic response function (HRF) may lead to biased results. Other methods, which predict the hemodynamic response from the measured data, have been termed "recognition models". The merit of recognition models lies in the power of estimating the region-specific or voxel-specific HRF. We propose an approach that merges these two models in a general framework: estimate the HRF on the training data sets, and applying the estimated HRF on the other part of the data sets. The merit of this framework is that it can utilize the advantages of both models. A comparison of performance is made between the GLM with three fixed HRFs and the new model with voxel-specific HRFs. The main results are as follows: (1) in 18 of the 21 patients, the new model has a higher adjusted coefficient of multiple determination than the GLM with fixed HRF; (2) in some subjects, with the new model, we found areas of activation that had not been detected with the three fixed HRFs at our threshold of significance. The results suggest that the new model can do better than the fixed HRF GLM for the analysis of epileptic activity with EEG-fMRI.

Electroencephalography↗

PubMed2006

Metabolic correlates of epileptic spikes in cerebral cavernous angiomas.

BACKGROUND: Cerebral cavernous angiomas (CCA) are frequently associated with focal intractable epilepsy. Epileptogenicity is usually attributed to hemosiderin deposits. Combined recording of electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) is a new method to investigate epileptic discharges. METHODS: We used EEG-fMRI to identify BOLD responses to interictal spikes in patients with CCA. Responses were analyzed in the lesional and perilesional area, and at distance. RESULTS: Eight patients were scanned, all with temporal lobe epilepsy and spikes. One patient had bilateral spikes, analyzed separately, and three studies with less than two spikes were excluded. All six studies analyzed showed BOLD responses. No response was found in the lesion itself or immediate periphery, and the raw fMRI signal showed signal loss in lesional and perilesional areas in all patients. Responses were close to the perilesional area in 2/6 studies. All patients showed responses at a distance from the lesions. CONCLUSIONS: Despite susceptibility artifacts caused by iron deposits, we demonstrated EEG-fMRI responses involving the perilesional areas in 33% of studies. We also demonstrated diffuse rather than focal responses, in accordance with previous studies in lesional and non-lesional temporal lobe epilepsy, confirming the frequent distant effect of epileptic spikes.

Adult↗

PubMed2006

THE SCN2A gene is not a likely candidate for familial mesial temporal lobe epilepsy.

A transgenic mouse model carrying a mutation in the Scn2a gene showed chronic focal seizures associated with extensive cell loss and gliosis in the hippocampus, a similar phenotype found in familial mesial temporal lobe epilepsy (FMTLE). Our objective was to test whether the human homolog of the Scn2a gene is responsible for hippocampal abnormalities in FMTLE by linkage analysis. We conclusively ruled out the SCN2A gene as candidate in FMTLE.

Epilepsy, Temporal Lobe↗

PubMed2006

Using voxel-specific hemodynamic response function in EEG-fMRI data analysis.

Most existing analytical techniques for EEG-fMRI data need specific assumptions about the hemodynamic response function (HRF). These assumptions may not be appropriate when the HRF varies from subject to subject or from region to region. In this article, we introduce a deconvolution method for EEG-fMRI activation detection, which can be implemented with voxel-specific HRFs. A comparison of performance is made between three fixed HRFs and the deconvolution method under the framework of the general linear model. The main results are as follows: (1) the volume of detected regions from the deconvolved HRFs is larger. (2) In some subjects, the deconvolution technique can find areas of activation that have not been detected with the three fixed HRFs at our threshold of significance. (3) Deconvolution obtained higher adjusted coefficients of multiple determination compared to those obtained with the three fixed HRFs. The results suggest that the fixed HRF methods may not be the most appropriate for the analysis of epileptic activity with EEG-fMRI, and the deconvolution method may be a better choice.

Brain↗

PubMed2006

Memory and language impairments and their relationships to hippocampal and perirhinal cortex damage in patients with medial temporal lobe epilepsy.

Chronic medial temporal lobe epilepsy (MTLE) is associated with memory loss due to damage in the hippocampal system. To investigate the relationship between volume of medial temporal lobe structures and performance on neuropsychological tests, we studied 39 consecutive patients with MTLE and unilateral hippocampal atrophy (HA) determined by volumetric magnetic resonance imaging (MRI). Structures of interest comprised hippocampus, amygdala, and entorhinal, perirhinal, parahippocampal, and temporopolar cortices. The findings indicated that (1) performance was significantly worse in the group with left HA as compared with the group with right HA on general memory, verbal memory, delayed recall, and verbal fluency tests and the Boston Naming Test (BNT), and (2) the volume of the left hippocampus and also the degree of asymmetry of perirhinal cortex volume were significant and independent predictors of performance on general memory, verbal memory, and verbal fluency tests and the BNT in patients with MTLE.

Adolescent↗

PubMed2006

EEG-fMRI of epileptic spikes: concordance with EEG source localization and intracranial EEG.

Simultaneous EEG and fMRI recordings permit the non-invasive investigation of the generators of spontaneous brain activity such as epileptic spikes. Despite a growing interest in this technique, the precise relationship between its results and the actual regions of activated cortex is not clear. In this study, we have quantified for the first time the concordance between EEG-fMRI results and stereotaxic EEG (SEEG) recordings in 5 patients with partial epilepsy. We also compared fMRI and SEEG with other non-invasive maps based on scalp EEG alone. We found that SEEG measures largely validated the results of EEG and fMRI. Indeed, when there is an intracranial electrode in the vicinity of an EEG or fMRI peak (in the range 20-40 mm), then it usually includes one active contact. This was the case for both increases ('activations') and decreases ('deactivations') of the fMRI signal: in our patients, fMRI signal decrease could be as important in understanding the complete picture of activity as increase of fMRI signal. The concordance between EEG and fMRI was not as good as the concordance between either of these non-invasive techniques and SEEG. This shows that the two techniques can show different regions of activity: they are complementary for the localization of the areas involved in the generation of epileptic spikes. Moreover, we found that the sign of the fMRI response correlated with the low frequency content of the SEEG epileptic transients, this latter being a reflection of the slow waves. Thus, we observed a higher proportion of energy in the low frequencies for the SEEG recorded in regions with fMRI signal increase compared to the regions with fMRI signal decrease. This could reflect an increase of metabolism linked to the presence of slow waves, which suggests that fMRI is a new source of information on the mechanisms of spike generation.

Brain Mapping↗

PubMed2006

Negative BOLD responses to epileptic spikes.

Simultaneous electroencephalogram/functional magnetic resonance imaging (EEG-fMRI) during interictal epileptiform discharges can result in positive (activation) and negative (deactivation) changes in the blood oxygenation level-dependent (BOLD) signal. Activation probably reflects increased neuronal activity and energy demand, but deactivation is more difficult to explain. Our objective was to evaluate the occurrence and significance of deactivations related to epileptiform discharges in epilepsy. We reviewed all EEG-fMRI studies from our database, identified those with robust responses (P = 0.01, with > or =5 contiguous voxels with a |t| > 3.1, including > or =1 voxel at |t| > 5.0), and divided them into three groups: activation (A = 8), deactivation (D = 9), and both responses (AD = 43). We correlated responses with discharge type and location and evaluated their spatial relationship with regions involved in the "default" brain state (Raichle et al. [2001]: Proc Natl Acad Sci 98:676-682]. Deactivations were seen in 52/60 studies (AD + D): 26 related to focal discharges, 12 bilateral, and 14 generalized. Deactivations were usually distant from anatomical areas related to the discharges and more frequently related to polyspike- and spike-and-slow waves than to spikes. The "default" pattern occurred in 10/43 AD studies, often associated with bursts of generalized discharges. In conclusion, deactivations are frequent, mostly with concomitant activation, for focal and generalized discharges. Discharges followed by a slow wave are more likely to result in deactivation, suggesting neuronal inhibition as the underlying phenomenon. Involvement of the "default" areas, related to bursts of generalized discharges, provides evidence of a subclinical effect of the discharges, temporarily suspending normal brain function in the resting state.

Electroencephalography↗

PubMed2006

Combining EEG and fMRI: a multimodal tool for epilepsy research.

Patients with epilepsy often present in their electroencephalogram (EEG) short electrical potentials (spikes or spike-wave bursts) that are not accompanied by clinical manifestations but are of important diagnostic significance. They result from a population of abnormally hyperactive and hypersynchronous neurons. It is not easy to determine the location of the cerebral generators and the other brain regions that may be involved as a result of this abnormal activity. The possibility to combine EEG recording with functional MRI (fMRI) scanning opens the opportunity to uncover the regions of the brain showing changes in the fMRI signal in response to epileptic spikes seen in the EEG. These regions are presumably involved in the abnormal neuronal activity at the origin of epileptic discharges. This paper reviews the methodology involved in performing such studies, particularly the challenge of recording a good quality EEG inside the MR scanner while scanning is taking place, and the methods required for the statistical analysis of the combined EEG and fMRI time series. We review the results obtained in patients with different types of epileptic disorders and discuss the difficult theoretical problems raised by the interpretation of an increase (activation) and decrease (deactivation) in blood oxygen level dependent (BOLD) signal, both frequently seen in response to spikes.

Biomedical Research↗

PubMed2006

EEG-fMRI using z-shimming in patients with temporal lobe epilepsy.

PURPOSE: To use z-shimming, a technique that reduces signal loss due to susceptibility artifacts that can result in reduced or absent activation in electroencephalography (EEG) functional MRI (fMRI) sessions in patients with temporal lobe epilepsy (TLE), to determine whether it would result in an increased ability to detect significant regions of blood oxygenation level-dependent (BOLD) signal change. MATERIALS AND METHODS: Eight patients with TL EEG spikes underwent an EEG-fMRI scanning session using z-shimming. The signal intensities in the z-shimmed images were compared with those in the standard images. BOLD activation maps were created from the two sets of images using the timings of the spikes observed on the EEG. RESULTS: The mean signal increase in the TLs as a result of z-shimming was 45.9%+/-4.5%. The percentage of TL voxels above a brain intensity threshold rose from 66.1%+/-7.6% to 77.6%+/-5.7%. This appreciable increase in signal did not lead to any significant differences in the statistical maps created with the two sets of functional images. CONCLUSION: The results suggest that loss of signal is not the limiting factor for the detection of spike-related BOLD signal changes in patients with TLE activity.

Algorithms↗

PubMed2006

Temporal and extratemporal BOLD responses to temporal lobe interictal spikes.

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.

Adult↗

PubMed2005

Grey matter heterotopia: what EEG-fMRI can tell us about epileptogenicity of neuronal migration disorders.

Grey matter heterotopia are commonly associated with refractory epilepsy. Depth electrodes recordings have shown that epileptiform activity can be generated within these lesions, and also at a distance in the neocortex. Heterotopia seem to be part of a more complex circuitry involving also the surrounding and distant cerebral cortex. Blood oxygenation level-dependent (BOLD) changes to interictal spikes using continuous EEG and functional MRI (EEG-fMRI) can help to understand non-invasively the mechanisms of epileptogenicity in these patients. We studied 14 patients with epilepsy and heterotopia using simultaneous recording of EEG-fMRI. EEG was continuously acquired from inside the scanner during 2 h sessions. Epileptic spikes were visually identified in the filtered EEG and each type of spike determined one EEG-fMRI study. We looked at positive (activation) and negative (deactivation) changes in the BOLD signal. Eleven patients had nodular heterotopia and three band heterotopia. Four patients had more than one type of spikes, with a total of 26 EEG-fMRI studies. We excluded three with less than three spikes, and therefore a total of 23 studies (12 with nodular and 11 with band heterotopia) were analysed. Nodular heterotopia: Activation was present in nine studies, with involvement of the heterotopia or surrounding cortex in six, three of which had concomitant distant activation. Deactivation was also observed in nine studies, with involvement of the heterotopia and surrounding cortex in four, three of which had concomitant distant deactivation. Band heterotopia: Activation was present in all 11 studies, and always involved the heterotopia and surrounding cortex, 9 of which had concomitant distant activation. Deactivation was also observed in all 11 studies, with involvement of both the heterotopia and surrounding cortex, in addition to distant deactivation in 5 studies. EEG-fMRI studies reveal, non-invasively, metabolic responses in the heterotopia despite the fact that spikes are generated in the neocortex. The responses, activation or deactivation, had different correlation with the lesion and surrounding or distant cortex, activation reflecting intense neuronal activity, or excitation, and deactivation a possible distant (extra-lesional) inhibition. EEG-fMRI may become a useful tool to understand the epileptogenicity of such malformations.

Brain↗

PubMed2005

Correspondence between EEG-fMRI and EEG dipole localisation of interictal discharges in focal epilepsy.

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.

Data Interpretation, Statistical↗

PubMed2005

Hemodynamic and metabolic responses to activation, deactivation and epileptic discharges.

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.

Adult↗

PubMed2005

Hippocampal atrophy and neurocysticercosis calcifications.

OBJECTIVE: To determine the relationship between hippocampal atrophy (HA), neurocysticercosis calcifications (NC) and seizure semiology in patients with partial epilepsy. METHODS: We identified two groups of patients: mesial temporal lobe epilepsy (MTLE) and extra-temporal epilepsy (ETE) patients. Each group was subdivided according to CT findings: normal, NC in the temporal regions, and NC in extra-temporal regions. MRI was obtained in a 2-T scanner and hippocampal volumetry was performed using 3-mm coronal T1-IR images. Hippocampal volumes below 2 standard deviations from the mean of the control group determined the presence of HA. RESULTS: We studied 89 consecutive patients: 63 with MTLE and 26 with ETE. HA was found in 43/89 (49.5 %) patients, 42 of them with MTLE. There was no difference in frequency of HA in the comparison between patients with (25/50) and without NC (18/39) (chi(2), p=0.71). Furthermore, there was no relationship between localization of NC (temporal or extra-temporal) and seizure semiology (MTLE or ETE). CONCLUSIONS: HA was more frequent and more severe in patients with MTLE, with no differences regarding the presence and localization of NC. These findings further support the concept that NC on CT not necessarily indicate the etiology of epilepsy and may represent only a co-existent pathology.

Adolescent↗

PubMed2005

Familial temporal lobe epilepsy with auditory features.

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Adult↗

PubMed2005

Genetic focal epilepsies: state of the art and paths to the future.

The concept of genetic focal epilepsies is relatively new as compared to awareness of the importance of genetic factors in the generalized epilepsies. However, in the past decade, there has been increasing recognition of families with dominantly inherited partial epilepsies. Better definition of the phenotypes allows identification of distinct syndromes. The main familial focal epilepsies are autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE), familial mesial TLE (FMTLE), familial lateral TLE (FLTLE), and familial partial epilepsy with variable foci (FPEVF). The only genes identified so far are those for ADNFLE and FLTLE. In these disorders, functional studies are the next step and could provide advances leading to clarification of the pathophysiology as well as to new therapeutic strategies. At present, we can provide genetic counseling and a more accurate prognosis for most of the familial focal epilepsies. Greater awareness of the genetic basis in this group of disorders by the treating physicians is essential for identification of new families. This will allow further linkage studies, candidate gene screening, and identification of new genes, which will hopefully result in genetically based prevention and treatment.

Adolescent↗

PubMed2005

Tonic status epilepticus in patients with idiopathic generalized epilepsy.

RATIONALE: Tonic status epilepticus (TSE) in patients with idiopathic generalized epilepsy (IGE) is not well recognized. The objective of this study is to report episodes of TSE in patients with IGE. METHODS: We retrospectively reviewed the clinical and EEG evaluation of three IGE patients who presented TSE. RESULTS: The three patients had mainly clinical features of IGE, but had developed, in addition, focal discharges, diffuse EEG abnormalities and some focal or diffuse neuropsychological dysfunction. The tonic attacks eventually responded to treatment, but were not completely controlled in any of the patients. DISCUSSION: The continuum between IGE and secondary generalized epilepsy is demonstrated in these patients. Most of their clinical and EEG features are however, in keeping with an idiopathic generalized epileptic process with additional focal and diffuse components. Recognition of the significance of TSE in such patients has important therapeutic and prognostic implications. [Published with video sequences].

Adult↗

PubMed2004

Analysis of the EEG-fMRI response to prolonged bursts of interictal epileptiform activity.

The use of combined EEG-fMRI to study interictal epileptiform activity is increasing and has great potential as a clinical tool, but the haemodynamic response to epileptiform activity remains incompletely characterised. To this end, 19 data sets from 14 patients with prolonged bursts of focal or generalised interictal epileptiform activity lasting up to 15 s were analysed. To determine whether the inclusion of the durations of the epileptic events in the general linear model resulted in increased statistical significance of activated regions, statistical maps were generated with and without the event durations. The mean differences when including the durations were a 14.5% increase in peak t value and a 29.5% increase in volume of activation. This suggests that when analysing EEG-fMRI data from patients with prolonged bursts of interictal epileptiform activity, it is better to include the event durations. To determine whether the amplitudes and latencies of the measured responses were consistent with the general linear model, the haemodynamic response functions for bursts of different durations were calculated and compared with the model predictions. The measured amplitude of the response to the shortest duration events was consistently larger than predicted, which is consistent with studies in normal subjects. For the two data sets with the widest range of event durations, the measured amplitudes increased with the durations of the events without evidence of the plateau that was expected from the general linear model. There were no consistent differences between the measured and modelled latencies.

Adolescent↗