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Biomedical subjects

Jean Gotman

Publications and source records attributed to Jean Gotman.

At least 19 recordsLinked to original sources
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

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

Dipole localization using simulated intracerebral EEG.

OBJECTIVE: In the clinical interpretation of intracerebral EEGs, epileptic foci are commonly identified by visually analyzing the amplitude of the potentials. This is potentially misleading since electrodes record activity from several sources, but the nearest ones generate large amplitudes that can overpower distant sources. Our objective was to improve foci detection in intracerebral recordings by applying source localization methods. METHODS: Data were simulated by placing 3 sources in a semi-infinite medium near 3 intracerebral electrodes. Potentials were generated and contaminated with white and correlated noise. Two inverse problem algorithms, beamforming and RAP-MUSIC, were used to calculate equivalent dipoles. RESULTS: Simulations for each noise types showed that the two methods detected the source locations accurately, with RAP-MUSIC reporting lower orientation errors. With correlated noise, beamforming reconstructed original source waveforms poorly. A spatial resolution analysis was performed, in which beamforming adequately distinguished sources separated by 1.2 cm, whereas RAP-MUSIC separated sources as close as 0.4-0.6 cm. CONCLUSIONS: Both source localization methods proved useful in detecting the location of dipolar sources based on simulated intracerebral potentials. For all simulations, RAP-MUSIC was more accurate than beamforming. SIGNIFICANCE: It is possible to use source localization methods traditionally applied to scalp recordings for improving source detection from intracerebral recordings.

Algorithms↗
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

The role of periventricular nodular heterotopia in epileptogenesis.

A temporal resection in patients with periventricular nodular heterotopia (PNH) and intractable focal seizures yields poor results. To define the role of heterotopic grey matter tissue in epileptogenesis and to improve outcome, we performed stereoencephalography (SEEG) recordings in eight patients with uni- or bilateral PNH and intractable focal epilepsy. The SEEG studies aimed to evaluate the most epileptogenic areas and included the allo- and neocortex and at least one nodule of grey matter. Interictal spiking activity was found in ectopic grey matter in three patients, in the cortex overlying the nodules in five and in the mesial temporal structures in all. At least one heterotopion was involved at seizure onset in six patients, synchronous with the overlying neocortex or ipsilateral hippocampus. Two patients had their seizures originating in the mesial temporal structures only. Six patients had surgery and the resected areas included the seizure onset, with follow-up from 1 to 8 years. An amygdalo-hippocampectomy was performed in two (Engel class Id and III), an amygdalo-hippocampectomy plus removal of an adjacent heterotopion in two (class Ia), and a resection of two contiguous nodules plus a small rim of overlying occipital cortex in one patient (class Id). One patient with bilateral PNH had three adjacent nodules resected and an ipsilateral amygdalo-hippocampectomy resulting in a reduction of the number of seizures by 25-50%. The best predictor of surgical outcome is the presence of a focal epileptic generator; this generator may or may not include the PNH. Invasive recording is required in patients with PNH; it improves localization and is the key to better outcome.

Adolescent↗
PubMed2005

An automatic warning system for epileptic seizures recorded on intracerebral EEGs.

OBJECTIVE: A new clinical seizure waning system for intracerebral EEG is proposed. It is aimed at a better performance than existing systems and at user tuneability. METHODS: The system employs data filtering in multiple bands, spectral feature extraction, Bayes' theorem, and spatio-temporal analysis. The a priori information in Bayes' theorem was provided by 407 h of EEG from 19 patients having 152 seizures. RESULTS: The testing data (19 patients, 389 h, 100 seizures, independent of the training data) yielded a sensitivity of 89.4%, a false detection rate of 0.22/h, and median delay time of 17.1 s when tuning was used, and 86%, 0.47/h and 16.2 s without tuning. Missed seizures were of short duration or had subtle seizure activity. False detections were caused by technical artefacts, non-epileptic large amplitude rhythmic bursts or very low amplitude activity. It was established that performance could easily be tuned. Results were also compared to the clinical system of . CONCLUSIONS: The system offers a performance that is acceptable for clinical use. User tuneability allows for reduction in false detection with minimal loss to sensitivity. SIGNIFICANCE: Epilepsy monitoring generates large amounts of recordings and requires intense observation. Automatic seizure detection and warning systems reduce review time and facilitate observation. We propose a method with high sensitivity and few false alarms.

Acute Disease↗
PubMed2005

Statistical maps for EEG dipolar source localization.

We present a method that estimates three-dimensional statistical maps for electroencephalogram (EEG) source localization. The maps assess the likelihood that a point in the brain contains a dipolar source, under the hypothesis of one, two or three activated sources. This is achieved by examining all combinations of one to three dipoles on a coarse grid and attributing to each combination a score based on an F statistic. The probability density function of the statistic under the null hypothesis is estimated nonparametrically, using bootstrap resampling. A theoretical F distribution is then fitted to the empirical distribution in order to allow correction for multiple comparisons. The maps allow for the systematic exploration of the solution space for dipolar sources. They permit to test whether the data support a given solution. They do not rely on the assumption of uncorrelated source time courses. They can be compared to other statistical parametric maps such as those used in functional magnetic resonance imaging (fMRI). Results are presented for both simulated and real data. The maps were compared with LORETA and MUSIC results. For the real data consisting of an average of epileptic spikes, we observed good agreement between the EEG statistical maps, intracranial EEG recordings, and fMRI activations.

Brain↗
PubMed2005

Detection of rapid-eye movements in sleep studies.

One of the key features of rapid-eye movement (REM) sleep is the presence of bursts of REMs. Sleep studies routinely use REMs to classify sleep stages. Moreover, REM count or density has been used in studies involving learning and various psychiatric disorders. Most of these studies have been based on the visual identification of REMs, which is generally a very time-consuming task. This and the varying definitions of REMs across scorers have warranted the development of automatic REM detection methodologies. In this paper, we present a new detection scheme that combines many of the intrinsic properties of REMs and requires minimal parameter adjustments. In the proposed method, a single parameter can be used to control the REM detection sensitivity and specificity tradeoff. Manually scored training data are used to develop the method. We assess the performance of the method against manual scoring of individual REM events and present validation results using a separate data set. The ability of the method to discriminate fast horizontal ocular movement in REM sleep from other types of events is highlighted. A key advantage of the presented method is the minimal a priori information requirement. The results of training data (recordings from five subjects) show an overall sensitivity of 78.8% and specificity of 81.6%. The performance on the testing data (recording from five subjects different from the training data) showed overall sensitivity of 67.2% and specificity of 77.5%.

Adolescent↗
PubMed2005

Seizure anticipation: do mathematical measures correlate with video-EEG evaluation?

PURPOSE: Analysis of the EEG signal has recently shown evidence of dynamic changes preceding ictal onset in seizures selected from patients with clear epileptogenic foci. Most of the studies were conducted in highly selected EEG epochs and patients. In addition, these studies relied mostly on mathematical approaches and neglected clinical and visual EEG parameters. We therefore performed a systematic comparison of a nonlinear method (the similarity measure) with classic visual inspection of the EEG and the patient's clinical state. METHODS: We analyzed the dynamics of long epochs of intracranial EEG containing 129 electroclinical and 45 electrographic seizures in 13 successive unselected patients undergoing presurgical evaluation. RESULTS: (a) The similarity measure detected preictal dynamical changes of the EEG signal in two thirds of the seizures whether or not a clear focus was identified, and whether seizures were electroclinical or purely electrographic. The mean duration of preictal changes was 12 min. (b) The preictal changes were correlated with various visually detectable EEG changes in 78.9% of electroclinical seizures. (c) 81.5% of the preictal dynamic changes were correlated with changes of vigilance or behavior. (d) Fluctuations of the dynamics were not necessarily followed by seizures. CONCLUSIONS: Our results indicate that EEG dynamics frequently change before seizures. These preictal changes are most often associated with the EEG changes accompanying transitions between states of vigilance. The preictal dynamic changes may represent physiologic changes acting as facilitating factors or pathologic changes reflecting a network dysfunction.

Adolescent↗
PubMed2005

Dipole modeling of epileptic spikes can be accurate or misleading.

PURPOSE: We investigated the accuracy and potential for serious error when representing cortical generators of epileptic spikes with the common single-dipole model. Spike generators were realistically simulated with cortical areas of different extents. METHODS: The source was simulated by using a patch that comprised small triangles on the cortical surface, each triangle having an elementary dipole generator with a moment corresponding to real intracerebral fields of spikes. The source-patch covered various clinically important parts of the temporal and frontal lobes, with an area ranging from 6 to 120 cm2. The scalp field was computed for each source-patch by using a realistic head model and was fitted by the single-dipole model to determine the best-fit dipole and the intracerebral distribution of residual variance (RV). Dipole modeling also was performed for the simulated scalp field with additional real EEG background. RESULTS: The RV after fitting a dipole to the scalp field without noise was at most 1.34%. Scalp spikes arising from sources of 6 cm2 were of small amplitude, and the dipoles estimated for these spikes were inconsistent. Extension of the source area was associated with increase of scalp potential amplitude, only very small increase of RV, and increased consistency of the estimated dipoles. When the source was very large, the dipoles clustered at very misleading locations. CONCLUSIONS: Pitfalls in dipole source localization are caused by the procedure of fitting the simplistic dipole model to real cortical sources with spatial extent and complex configuration.

Action Potentials↗
PubMed2005

Removing eye-movement artifacts from the EEG during the intracarotid amobarbital procedure.

PURPOSE: The EEG is often recorded during the intracarotid amobarbital procedure (IAP) to help in the assessment of the spatial extent and the duration of the effect of the drug. In scalp recordings, the EEG is always heavily contaminated with eye movement artifacts as the patient actively performs visual tasks. METHODS: Independent component analysis (ICA) is a new technique for blind source separation. In this study, we separated the EEG data recorded during the IAP into independent components using ICA. The EEG signal was reconstructed by excluding the components related to eye movement and eye blinks. RESULTS: EEGs from 10 IAP tests were analyzed. The experimental results indicate that ICA is very efficient at subtracting eye-movement artifacts, while retaining the EEG slow waves and making their interpretation easier. CONCLUSIONS: ICA appears to be a generally applicable and effective method for removing ocular artifacts from EEG recordings during IAP, although slow waves and ocular artifacts share similar frequency distributions.

Algorithms↗
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↗
PubMed2004

EEG-fMRI of focal epileptic spikes: analysis with multiple haemodynamic functions and comparison with gadolinium-enhanced MR angiograms.

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.

Artifacts↗