F H Lopes da Silva

Publications (186)445.68 Total impact

• Article: Slow brain oscillations of sleep, resting state, and vigilance.

  E J W Van Someren, Y D Van Der Werf, P R Roelfsema, H D Mansvelder, F H Lopes da Silva
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  ABSTRACT: The most important quest of cognitive neuroscience may be to unravel the mechanisms by which the brain selects, links, consolidates, and integrates new information into its neuronal network, while preventing saturation to occur. During the past decade, neuroscientists working within several disciplines have observed an important involvement of the specific types of brain oscillations that occur during sleep--the cortical slow oscillations; during the resting state--the fMRI resting state networks including the default-mode network (DMN); and during task performance--the performance modulations that link as well to modulations in electroencephalography or magnetoencephalography frequency content. Understanding the role of these slow oscillations thus appears to be essential for our fundamental understanding of brain function. Brain activity is characterized by oscillations occurring in spike frequency, field potentials or blood oxygen level-dependent functional magnetic resonance imaging signals. Environmental stimuli, reaching the brain through our senses, activate or inactivate neuronal populations and modulate ongoing activity. The effect they sort is to a large extent determined by the momentary state of the slow endogenous oscillations of the brain. In the absence of sensory input, as is the case during rest or sleep, brain activity does not cease. Rather, its oscillations continue and change with respect to their dominant frequencies and coupling topography. This chapter briefly introduces the topics that will be addressed in this dedicated volume of Progress in Brain Research on slow oscillations and sets the stage for excellent papers discussing their molecular, cellular, network physiological and cognitive performance aspects. Getting to know about slow oscillations is essential for our understanding of plasticity, memory, brain structure from synapse to DMN, cognition, consciousness, and ultimately for our understanding of the mechanisms and functions of sleep and vigilance.
  Progress in brain research 01/2011; 193:3-15. · 3.04 Impact Factor
• Article: Spatio‐temporal dynamics of theta oscillations in hippocampal–entorhinal slices

  N.L.M. Cappaert, F.H. Lopes da Silva, W.J. Wadman
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  ABSTRACT: Theta oscillations (4–12 Hz) are associated with learning and memory and are found in the hippocampus and the entorhinal cortex (EC). The spatio-temporal organization of rhythmic activity in the hippocampal–EC complex was investigated in vitro. The voltage sensitive absorption dye NK3630 was used to record the changes in aggregated membrane voltage simultaneously from the neuronal networks involved. Oscillatory activity at 7.0 Hz (range, 5.8–8.2) was induced in the slice with the muscarinic agonist carbachol (75–100 μM) in the presence of bicuculline (5 μM). Time relations between all recording sites were analyzed using cross-correlation functions which revealed systematic phase shifts in the theta oscillation recorded from the different entorhinal and hippocampal subregions. These phase shifts could be interpreted as propagation delays. The oscillation propagates over the slice in a characteristic spatio-temporal sequence, where the entorhinal cortex leads, followed by the subiculum and then the dentate gyrus (DG), to finally reach the CA3 and the CA1 area. The delay from dentate gyrus to the CA3 area was 12.4 ± 1.1 ms (mean ± s.e.m.) and from the CA3 to the CA1 region it was 10.9 ± 1.9 ms. The propagation delays between the hippocampal subregions resemble the latencies of electrically evoked responses in the same subregions. Removing the entorhinal cortex from the slice changed the spatiotemporal pattern into a more clustered pattern with higher local synchrony. We conclude that in the slice, carbachol-induced theta oscillations are initiated in the entorhinal cortex. The EC could serve to control the information flow through the neuronal network in the subregions of the hippocampus by synchronizing and/or entraining their responses to external inputs. © 2009 Wiley-Liss, Inc.
  Hippocampus 10/2009; 19(11):1065 - 1077. · 5.18 Impact Factor
• Article: Interactions between different EEG frequency bands and their effect on alpha-fMRI correlations.

  J C de Munck, S I Gonçalves, R Mammoliti, R M Heethaar, F H Lopes da Silva
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  ABSTRACT: In EEG/fMRI correlation studies it is common to consider the fMRI BOLD as filtered version of the EEG alpha power. Here the question is addressed whether other EEG frequency components may affect the correlation between alpha and BOLD. This was done comparing the statistical parametric maps (SPMs) of three different filter models wherein either the free or the standard hemodynamic response functions (HRF) were used in combination with the full spectral bandwidth of the EEG. EEG and fMRI were co-registered in a 30 min resting state condition in 15 healthy young subjects. Power variations in the delta, theta, alpha, beta and gamma bands were extracted from the EEG and used as regressors in a general linear model. Statistical parametric maps (SPMs) were computed using three different filter models, wherein either the free or the standard hemodynamic response functions (HRF) were used in combination with the full spectral bandwidth of the EEG. Results show that the SPMs of different EEG frequency bands, when significant, are very similar to that of the alpha rhythm. This is true in particular for the beta band, despite the fact that the alpha harmonics were discarded. It is shown that inclusion of EEG frequency bands as confounder in the fMRI-alpha correlation model has a large effect on the resulting SPM, in particular when for each frequency band the HRF is extracted from the data. We conclude that power fluctuations of different EEG frequency bands are mutually highly correlated, and that a multi frequency model is required to extract the SPM of the frequency of interest from EEG/fMRI data. When no constraints are put on the shapes of the HRFs of the nuisance frequencies, the correlation model looses so much statistical power that no correlations can be detected.
  NeuroImage 05/2009; 47(1):69-76. · 5.89 Impact Factor
• Article: Spatio-temporal dynamics of theta oscillations in hippocampal-entorhinal slices.

  N L M Cappaert, F H Lopes da Silva, W J Wadman
  [show abstract] [hide abstract]
  ABSTRACT: Theta oscillations (4-12 Hz) are associated with learning and memory and are found in the hippocampus and the entorhinal cortex (EC). The spatio-temporal organization of rhythmic activity in the hippocampal-EC complex was investigated in vitro. The voltage sensitive absorption dye NK3630 was used to record the changes in aggregated membrane voltage simultaneously from the neuronal networks involved. Oscillatory activity at 7.0 Hz (range, 5.8-8.2) was induced in the slice with the muscarinic agonist carbachol (75-100 microM) in the presence of bicuculline (5 microM). Time relations between all recording sites were analyzed using cross-correlation functions which revealed systematic phase shifts in the theta oscillation recorded from the different entorhinal and hippocampal subregions. These phase shifts could be interpreted as propagation delays. The oscillation propagates over the slice in a characteristic spatio-temporal sequence, where the entorhinal cortex leads, followed by the subiculum and then the dentate gyrus (DG), to finally reach the CA3 and the CA1 area. The delay from dentate gyrus to the CA3 area was 12.4 +/- 1.1 ms (mean +/- s.e.m.) and from the CA3 to the CA1 region it was 10.9 +/- 1.9 ms. The propagation delays between the hippocampal subregions resemble the latencies of electrically evoked responses in the same subregions. Removing the entorhinal cortex from the slice changed the spatiotemporal pattern into a more clustered pattern with higher local synchrony. We conclude that in the slice, carbachol-induced theta oscillations are initiated in the entorhinal cortex. The EC could serve to control the information flow through the neuronal network in the subregions of the hippocampus by synchronizing and/or entraining their responses to external inputs.
  Hippocampus 04/2009; 19(11):1065-77. · 5.18 Impact Factor
• Article: A Data and Model-Driven Approach to Explore Inter-Subject Variability of Resting-State Brain Activity Using EEG-fMRI

  S.I. Goncalves, F. Bijma, P.W.J. Pouwels, M. Jonker, J.P.A. Kuijer, R.M. Heethaar, F.H. Lopes da Silva, J.C. de Munck
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  ABSTRACT: In this paper, we investigate the origin of the large inter-subject-variability of EEG-fMRI correlation patterns. For that purpose, a simplified representation of the fMRI signal is obtained by using a hierarchical clustering algorithm detecting spatial patterns of mutually correlated voxels. The general-linear model is subsequently used to determine which of the identified patterns correlates significantly to the spontaneous variations of the alpha rhythm. This strategy provides insight in the nature of resting state fMRI and reduces the number of statistical tests in the GLM correlation analysis. For all 16 subjects except one, the clustering of BOLD signal yielded very consistent regions which included areas belonging to the ldquodefault moderdquo network as well as the neuronal networks involved in the generation of the alpha and mu rhythms. These BOLD clusters showed much less inter-subject variability than the alpha-BOLD statistical parametric maps obtained on a voxel-by-voxel basis. It is shown that hierarchical clustering is applicable to whole head fMRI and that it is very appropriate to obtain data reduction thereby facilitating the comparison of the results of individual subjects. The very consistent results of BOLD clustering over subjects suggests that the large inter-subject variability observed in the alpha-BOLD statistical parametric maps is related to the individual variations in the EEG.
  IEEE Journal of Selected Topics in Signal Processing 01/2009; · 2.88 Impact Factor
• Article: A study of the brain's resting state based on alpha band power, heart rate and fMRI.

  J C de Munck, S I Gonçalves, Th J C Faes, J P A Kuijer, P J W Pouwels, R M Heethaar, F H Lopes da Silva
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  ABSTRACT: Considering that there are several theoretical reasons why fMRI data is correlated to variations in heart rate, these correlations are explored using experimental resting state data. In particular, the possibility is discussed that the "default network", being a brain area that deactivates during non-specific general tasks, is a hemodynamic effect caused by heart rate variations. Of fifteen healthy controls ECG, EEG and fMRI were co-registered. Slice time dependent heart rate regressors were derived from the ECG data and correlated to fMRI using a linear correlation analysis where the impulse response is estimated from the data. It was found that in most subjects substantial correlations between heart rate variations and fMRI exist, both within the brain and at the ventricles. The brain areas with high correlation to heart rate are different from the "default network" and the response functions deviate from the canonical hemodynamic response function. Furthermore, a general negative correlation was found between heart beat intervals (reverse of heart rate) and alpha power. We interpret this finding by assuming that subject's state varies between drowsiness and wakefulness. Finally, given this large correlation, we re-examined the contribution of heart rate variations to earlier reported fMRI/alpha band correlations, by adding heart rate regressors as confounders. It was found that inclusion of these confounders most often had a negligible effect. From its strong correlation to alpha power, we conclude that the heart rate variations contain important physiological information about subject's resting state. However, it does not provide a full explanation of the behaviour of the "default network". Its application as confounder in fMRI experiments is a relatively small computational effort, but may have a substantial impact in paradigms where heart rate is controlled by the stimulus.
  NeuroImage 09/2008; 42(1):112-21. · 5.89 Impact Factor
• Article: Global dynamical analysis of the EEG in Alzheimer's disease: frequency-specific changes of functional interactions.

  B Jelles, Ph Scheltens, W M van der Flier, E J Jonkman, F H Lopes da Silva, C J Stam
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  ABSTRACT: EEG coherence is decreased in Alzheimer's disease (AD), suggesting decreased interaction between brain areas. Nonlinear EEG analysis in AD points to decreased complexity of brain dynamics, implicating increased interaction. To clarify these apparently paradoxical findings from linear and nonlinear analysis, we calculated global coherence and global correlation dimension (D2), a nonlinear measure, in the EEG of patients with probable AD and controls. Our hypothesis is that these measures are related to each other when calculated in a comparable way. From 15 patients with probable AD (mean age 63.1 years; SD 6.3) and 21 age-matched controls with subjective memory complaints (mean age 62.8; SD 12.0), band filtered EEG data were analysed in six frequency bands. For each frequency band average coherence and multichannel D2 were determined. ANOVA for repeated measures showed for D2 an interaction between band and group, but not for coherence. In the beta band and upper alpha band, D2 was higher in patients with probable AD compared to controls, while global coherence tended to be lower in these frequency bands in patients with probable AD. In the frequency range from theta to beta, coherence and D2 were inversely correlated without group differences. When calculated in comparable ways, global correlation dimension and coherence are related measures. In AD, these measures change especially in the higher frequency ranges, both pointing to decreased functional cortical connectivity. Both global coherence and global correlation dimension seem to measure global connectivity, but nonlinear measures may be more sensitive. In AD, connectivity measures are not equally impaired in all frequency ranges, possibly reflecting differentiated affection of the dynamical processes responsible for the different frequency bands.
  Clinical Neurophysiology 05/2008; 119(4):837-41. · 3.41 Impact Factor
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  Available from: Jan A Gorter

  Article: Gene expression profile analysis of epilepsy-associated gangliogliomas.

  E Aronica, K Boer, A Becker, S Redeker, W G M Spliet, P C van Rijen, F Wittink, T Breit, W J Wadman, F H Lopes da Silva, D Troost, J A Gorter
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  ABSTRACT: Gangliogliomas (GG) constitute the most frequent tumor entity in young patients undergoing surgery for intractable epilepsy. The histological composition of GG, with the presence of dysplastic neurons, corroborates their maldevelopmental origin. However, their histogenesis, the pathogenetic relationship with other developmental lesions, and the molecular alterations underlying the epileptogenicity of these tumors remain largely unknown. We performed gene expression analysis using the Affymetrix Gene Chip System (U133 plus 2.0 array). We used GENMAPP and the Gene Ontology database to identify global trends in gene expression data. Our analysis has identified various interesting genes and processes that are differentially expressed in GG when compared with normal tissue. The immune and inflammatory responses were the most prominent processes expressed in GG. Several genes involved in the complement pathway displayed a high level of expression compared with control expression levels. Higher expression was also observed for genes involved in cell adhesion, extracellular matrix and proliferation processes. We observed differential expression of genes as cyclin D1 and cyclin-dependent kinases, essential for neuronal cell cycle regulation and differentiation. Synaptic transmission, including GABA receptor signaling was an under-expressed process compared with control tissue. These data provide some suggestions for the molecular pathogenesis of GG. Furthermore, they indicate possible targets that may be investigated in order to dissect the mechanisms of epileptogenesis and possibly counteract the epileptogenic process in these developmental lesions.
  Neuroscience 02/2008; 151(1):272-92. · 3.38 Impact Factor
• Article: Complement activation in experimental and human temporal lobe epilepsy.

  E Aronica, K Boer, E A van Vliet, S Redeker, J C Baayen, W G M Spliet, P C van Rijen, D Troost, F H Lopes da Silva, W J Wadman, J A Gorter
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  ABSTRACT: We investigated the involvement of the complement cascade during epileptogenesis in a rat model of temporal lobe epilepsy (TLE), and in the chronic epileptic phase in both experimental as well as human TLE. Previous rat gene expression analysis using microarrays indicated prominent activation of the classical complement pathway which peaked at 1 week after SE in CA3 and entorhinal cortex. Increased expression of C1q, C3 and C4 was confirmed in CA3 tissue using quantitative PCR at 1 day, 1 week and 3-4 months after status epilepticus (SE). Upregulation of C1q and C3d protein expression was confirmed mainly to be present in microglia and in a few hippocampal neurons. In human TLE with hippocampal sclerosis, astroglial, microglial and neuronal (5/8 cases) expression of C1q, C3c and C3d was observed particularly within regions where neuronal cell loss occurs. The membrane attack protein complex (C5b-C9) was predominantly detected in activated microglial cells. The persistence of complement activation could contribute to a sustained inflammatory response and could destabilize neuronal networks involved.
  Neurobiology of Disease 07/2007; 26(3):497-511. · 5.40 Impact Factor
• Article: The hemodynamic response of the alpha rhythm: an EEG/fMRI study.

  J C de Munck, S I Gonçalves, L Huijboom, J P A Kuijer, P J W Pouwels, R M Heethaar, F H Lopes da Silva
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  ABSTRACT: EEG was recorded during fMRI scanning of 16 normal controls in resting condition with eyes closed. Time variations of the occipital alpha band amplitudes were correlated to the fMRI signal variations to obtain insight into the hemodynamic correlates of the EEG alpha activity. Contrary to earlier studies, no a priori assumptions were made on the expected shape of the alpha band response function (ARF). The ARF of different brain regions and subjects were explored and compared. It was found that: (1) the ARF of the thalamus is mainly positive. (2) The ARFs at the occipital and left and right parietal points are similar in amplitude and timing. (3) The peak time of the thalamus is a few seconds earlier than that of occipital and parietal cortex. (4) No systematic BOLD activity was found preceding the alpha band activity, although in the two subjects with the strongest alpha band power such correlation was present. (5) There is a strong and immediate positive correlation at the eyeball, and a strong negative correlation at the back of the eye. Furthermore, it was found that in one subject the cortical ARF was positive, contrary to the other subjects. Finally, a cluster analysis of the observed ARF, in combination with a Modulated Sine Model (MSM) fit to the estimated ARF, revealed that within the cortex the ARF peak time shows a spatial pattern that may be interpreted as a traveling wave. The spatial pattern of alpha band response function represents the combined effect of local differences in electrical alpha band activity and local differences in the hemodynamic response function (HRF) onto these electrical activities. To disentangle the contributions of both factors, more advanced integration of EEG inverse modeling and hemodynamic response modeling is required in future studies.
  NeuroImage 05/2007; 35(3):1142-51. · 5.89 Impact Factor
• Conference Proceeding: Signal processing aspects of simultaneously recorded EEG, PULSE and fMRI

  J.C. de Munck, S.I. Goncalves, P.W.J. Pouwels, J.P.A. Kuijer, R.M. Heethaar, F.H. Lopes da Silva
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  ABSTRACT: Recording of EEG during fMRI scanning is a recent technique that provides new perspectives on the underlying generators of classical EEG phenomena appearing in spontaneous brain activity, such as the alpha rhythm, interictal spikes and sleep spindles. The theoretical principle, on which the method is based, is quite simple. By making a statistical comparison between fMRI scans in which the EEG-phenomenon is present and in which it is absent, and detecting the voxels in which this difference is significant, one can localize the brain regions involved in the generation of the EEG phenomenon under study. Furthermore, one can determine whether the phenomenon corresponds to an activation or a de-activation of the brain region. In practice, however, there are many bio-signal processing problems to be solved: the artifact removal in the EEG, the demodulation of the EEG, the extraction of an EEG reference from the multi-channels, the determination of a sensible correlation co-efficient (in which heart beat effects and breathing are eliminated) and its statistical significance. In this paper, several innovations concerning the signal processing of simultaneously recorded fMRI, PULSE and fMRI are presented and applied in a case study on the generators of the alpha-rhythm
  Biomedical Imaging: Nano to Macro, 2006. 3rd IEEE International Symposium on; 05/2006
• Article: Correlating the alpha rhythm to BOLD using simultaneous EEG/fMRI: inter-subject variability.

  S I Gonçalves, J C de Munck, P J W Pouwels, R Schoonhoven, J P A Kuijer, N M Maurits, J M Hoogduin, E J W Van Someren, R M Heethaar, F H Lopes da Silva
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  ABSTRACT: Simultaneous recording of electroencephalogram/functional magnetic resonance images (EEG/fMRI) was applied to identify blood oxygenation level-dependent (BOLD) changes associated with spontaneous variations of the alpha rhythm, which is considered the hallmark of the brain resting state. The analysis was focused on inter-subject variability associated with the resting state. Data from 7 normal subjects are presented. Confirming earlier findings, three subjects showed a negative correlation between the BOLD signal and the average power time series within the alpha band (8--12 Hz) in extensive areas of the occipital, parietal and frontal lobes. In small thalamic areas, the BOLD signal was positively correlated with the alpha power. For subjects 3 and 4, who displayed two different states during the data acquisition time, it was shown that the corresponding correlation patterns were different, thus demonstrating the state dependency of the results. In subject 5, the changes in BOLD were observed mainly in the frontal and temporal lobes. Subject 6 only showed positive correlations, thus contradicting the negative BOLD alpha power cortical correlations that were found in most subjects. Results suggest that the resting state varies over subjects and, sometimes, even within one subject. As the resting state plays an important role in many fMRI experiments, the inter-subject variability of this state should be addressed when comparing fMRI results from different subjects.
  NeuroImage 04/2006; 30(1):203-13. · 5.89 Impact Factor
• Article: Removal of epileptogenic sequences from video material: the role of color.

  J Parra, S N Kalitzin, H Stroink, E Dekker, C de Wit, F H Lopes da Silva
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  ABSTRACT: After Pokémon viewing triggered an epidemic of seizures in Japan, many efforts have been made to design safety guidelines and systems to protect subjects with photosensitivity. The authors developed a new method based upon nonlinear diffusion techniques capable of filtering the epileptogenic content of a video sequence related to color without altering its spatial and luminance content. The authors showed to 25 photosensitive patients (18 women, mean age: 22 years) the original Pokémon sequence and a modified one in an ABBA protocol using two television (TV) sets (100 and 50 Hz). Twenty-three patients had a photoparoxysmal response (PPR) according to Waltz classification with at least one of the scenes. The modified sequence triggered fewer and less severe PPRs than the original version in both TVs (p < 0.001). Original sequences elicited generalized PPRs in 56.5% of the trials for the 50 Hz TV and in 41.3% for the 100 Hz TV, whereas modified sequences elicited these responses in only 8.7% (50 Hz) and 4.3% (100 Hz TV) of the trials (p < 0.001). Sensitivity to the modified version on the 50 Hz TV correlated with pattern sensitivity (p < 0.05). Specific manipulations of the color modulation-depth could be enough to decrease dramatically the risk of triggering seizures in susceptible subjects exposed to provocative visual scenes. This new method can be implemented in protective devices able to filter out the epileptogenic video sequences in which color plays a fundamental role while leaving intact the spatial content, frequency, and average luminance.
  Neurology 04/2005; 64(5):787-91. · 8.31 Impact Factor
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  Available from: utl.pt

  Article: Dynamics of non-convulsive epileptic phenomena modeled by a bistable neuronal network.

  P Suffczynski, S Kalitzin, F H Lopes Da Silva
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  ABSTRACT: It is currently believed that the mechanisms underlying spindle oscillations are related to those that generate spike and wave (SW) discharges. The mechanisms of transition between these two types of activity, however, are not well understood. In order to provide more insight into the dynamics of the neuronal networks leading to seizure generation in a rat experimental model of absence epilepsy we developed a computational model of thalamo-cortical circuits based on relevant (patho)physiological data. The model is constructed at the macroscopic level since this approach allows to investigate dynamical properties of the system and the role played by different mechanisms in the process of seizure generation, both at short and long time scales. The main results are the following: (i) SW discharges represent dynamical bifurcations that occur in a bistable neuronal network; (ii) the durations of paroxysmal and normal epochs have exponential distributions, indicating that transitions between these two stable states occur randomly over time with constant probabilities; (iii) the probabilistic nature of the onset of paroxysmal activity implies that it is not possible to predict its occurrence; (iv) the bistable nature of the dynamical system allows that an ictal state may be aborted by a single counter-stimulus.
  Neuroscience 02/2004; 126(2):467-84. · 3.38 Impact Factor
• Article: Spike cluster analysis in neocortical localization related epilepsy yields clinically significant equivalent source localization results in magnetoencephalogram (MEG).

  D Van 't Ent, I Manshanden, P Ossenblok, D N Velis, J C de Munck, J P A Verbunt, F H Lopes da Silva
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  ABSTRACT: In magnetoencephalogram (MEG) recordings of patients with epilepsy several types of sharp transients with different spatiotemporal distributions are commonly present. Our objective was to develop a computer based method to identify and classify groups of epileptiform spikes, as well as other transients, in order to improve the characterization of irritative areas in the brain of epileptic patients. MEG data centered on selected spikes were stored in signal matrices of C channels by T time samples. The matrices were normalized and euclidean distances between spike representations in vector space R(CxT) were input to a Ward's hierarchical clustering algorithm. The method was applied to MEG data from 4 patients with localization-related epilepsy. For each patient, distinct spike subpopulations were found with clearly different topographical field maps. Inverse computations to selected spike subaverages yielded source solutions in agreement with seizure classification and location of structural lesions, if present, on magnetic resonance images. With the proposed method a reliable categorization of epileptiform spikes is obtained, that can be applied in an automatic way. Computation of subaverages of similar spikes enhances the signal-to-noise ratio of spike field maps and allows for more accurate reconstruction of sources generating the epileptiform discharges.
  Clinical Neurophysiology 11/2003; 114(10):1948-62. · 3.41 Impact Factor
• Article: In vivo measurement of the brain and skull resistivities using an EIT-based method and the combined analysis of SEF/SEP data.

  S Gonçalves, J C de Munck, J P A Verbunt, R M Heethaar, F H Lopes da Silva
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  ABSTRACT: Results of "in vivo" measurements of the skull and brain resistivities are presented for six subjects. Results are obtained using two different methods, based on spherical head models. The first method uses the principles of electrical impedance tomography (EIT) to estimate the equivalent electrical resistivities of brain (rhobrain), skull (rhoskull) and skin (rhoskin) according to. The second one estimates the same parameters through a combined analysis of the evoked somatosensory cortical response, recorded simultaneously using magnetoencephalography (MEG) and electroencephalography (EEG). The EIT results, obtained with the same relative skull thickness (0.05) for all subjects, show a wide variation of the ratio rhoskull/rhobrain among subjects (average = 72, SD = 48%). However, the rhoskull/rhobrain ratios of the individual subjects are well reproduced by combined analysis of somatosensory evoked fields (SEF) and somatosensory evoked potentials (SEP). These preliminary results suggest that the rhoskull/rhobrain variations over subjects cannot be disregarded in the EEG inverse problem (IP) when a spherical model is used. The agreement between EIT and SEF/SEP points to the fact that whatever the source of variability, the proposed EIT-based method <Au: Addition of "method" O.K? appears to have the potential to reduce systematic errors in EEG IP associated to the misspecification of rhoskull/rhobrain, rhobrain, rhoskull and rhoskin.
  IEEE Transactions on Biomedical Engineering 09/2003; 50(9):1124-8. · 2.28 Impact Factor
• Article: Gamma-band phase clustering and photosensitivity: is there an underlying mechanism common to photosensitive epilepsy and visual perception?

  J Parra, S N Kalitzin, J Iriarte, W Blanes, D N Velis, F H Lopes da Silva
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  ABSTRACT: Photosensitive epilepsy (PSE) is the most common form of human reflex epilepsy, appearing in up to 10% of epileptic children. It also offers a highly reproducible model to investigate whether changes in neuronal activity preceding the transition to an epileptic photoparoxysmal response (PPR) may be detected. We studied 10 patients with idiopathic PSE (eight female, mean age 26 years, range 9-51 years) using magnetoencephalography. In addition, we also studied the responses of five normal controls (mean age 24 years, age range 9-35 years) and three non-photosensitive epileptic patients (mean age 10 years, range 8-11 years). Spectral analysis of the MEG signals recorded during intermittent photic stimulation revealed relevant information in the phase spectrum. To quantify this effect, we introduced a second order response feature of the stimulus-triggered visual response preceding the PPR: the phase clustering index, which measures how close the phases of successive periods are grouped for each frequency component for all periods of the stimuli applied. We recorded a total of 86 PPRs, including several absence seizures, in nine of the 10 patients. We found that an enhancement of phase synchrony in the gamma-band (30-120 Hz), harmonically related to the frequency of stimulation, preceded the stimulation trials that evolved into PPRs, and differed significantly from that encountered in trials not followed by PPR or in control subjects. This novel finding leads us to postulate that a pathological deviation of normally occurring synchronization of gamma oscillations, underlying perceptional processes, mediates the epileptic transition in PSE.
  Brain 06/2003; 126(Pt 5):1164-72. · 9.46 Impact Factor
• Article: Sequential changes in synaptic vesicle pools and endosome-like organelles during depolarization near the active zone of central nerve terminals.

  A G M Leenders, G Scholten, R P J de Lange, F H Lopes da Silva, W E J M Ghijsen
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  ABSTRACT: During periods of high-frequency stimulation the maintenance of synaptic transmission depends on a continued supply of synaptic vesicles. Local recycling in the terminals ensures synaptic vesicle replenishment, but the intermediate steps are still a matter of debate. We analyzed changes in synaptic vesicle pools and endosome-like organelles near the active zone in central nerve terminals during depolarization at the ultrastructural level by electron microscopy. A short, 100 ms, depolarization-induced recruitment of synaptic vesicles was observed from a reserve pool to a recruited pool, within 150 nm of the active zone, and the docked pool at the active zone was increased as well. Prolonged, 15 s or 3 min, depolarization decreased the total amount of synaptic vesicles, which was accompanied by a parallel increase in size and amount of endosome-like organelles. After a period of rest, the number of endosome-like organelles decreased and the amount of synaptic vesicles was restored to control level. The endocytotic nature of part of the endosome-like organelles after 15 s and 3 min depolarization was indicated by their labeling with extracellularly added horseradish peroxidase (HRP). In addition, a small number of synaptic vesicles entrapped HRP under these conditions. After repolarization, the number of HRP-loaded endosome-like structures decreased. Simultaneously, a strong increase in amount of HRP-loaded small vesicles did occur. These results indicate that during sub-second depolarization, synaptic vesicles were rapidly recruited from the reserve pool to replenish the releasable pool, whereas prolonged depolarization (s-min) induced local endocytosis in at least two ways, i.e. either directly as vesicles or via endosome-like organelles from which synaptic vesicles were reformed.
  Neuroscience 02/2002; 109(1):195-206. · 3.38 Impact Factor
• Article: Computational model of thalamo-cortical networks: dynamical control of alpha rhythms in relation to focal attention.

  P Suffczynski, S Kalitzin, G Pfurtscheller, F H Lopes da Silva
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  ABSTRACT: EEG/MEG rhythmic activities such as alpha rhythms, of the visual or of the somato-sensory cortex, are commonly modulated as subjects perform certain tasks or react to specific stimuli. In general, these activities change depending on extrinsic or intrinsic events. A decrease of the amplitude of alpha rhythmic activity occurring after a given event, which manifests as a decrease of a spectral peak, is called event-related desynchronization (ERD), whereas the inverse is called event-related synchronization (ERS), since it is assumed that the power of a spectral peak is related to the degree of synchrony of the underlying oscillating neuronal populations. An intriguing observation in this respect [Pfurtscheller and Neuper, Neurosci. Lett. 174 (1994) 93-96] was that ERD of alpha rhythms recorded over the central areas was accompanied by ERS, within the same frequency band, recorded over neighboring areas. In case the event was a hand movement, ERD was recorded over the scalp overlying the hand cortical area, whereas ERS was concomitantly recorded over the midline, whereas if the movement was of the foot the opposite was found. We called this phenomenon 'focal ERD/surround ERS'. The question of how this phenomenon may be generated was approached by means of a computational model of thalamo-cortical networks, that incorporates basic properties of neurons and synaptic interactions. These simulation studies revealed that this antagonistic ERD/ERS phenomenon depends on the functional interaction between the populations of thalamo-cortical cells (TCR) and reticular nucleus cells (RE) and on how this interaction is modulated by cholinergic inputs. An essential feature of this interaction is the existence of cross-talk between different sectors of RE that correspond to distinct sensory modules (e.g. hand, foot). These observations led us to formulate the hypothesis that this basic neurophysiological mechanism can account for the general observation that enhanced attention given to a certain stimulus (the focus) is coupled to inhibition of attention to other stimuli (the surround).
  International Journal of Psychophysiology 01/2002; 43(1):25-40. · 2.14 Impact Factor
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  Available from: Jan A Gorter

  Article: Cystatin C, a cysteine protease inhibitor, is persistently up-regulated in neurons and glia in a rat model for mesial temporal lobe epilepsy.

  E Aronica, E A van Vliet, E Hendriksen, D Troost, F H Lopes da Silva, J A Gorter
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  ABSTRACT: Cystatin C (CSTC), a cysteine protease inhibitor, has been implicated in the processes of neuronal degeneration and repair of the nervous system. Using serial analysis of gene expression (SAGE), we recently identified CSTC as one of the genes that are overexpressed after electrically induced status epilepticus (SE). In the present study, Western blot analysis extended the SAGE results, showing increased CSTC protein in the hippocampus and entorhinal cortex. Immunocytochemistry revealed an increase in CSTC expression in glial cells, which was first apparent 24 h after onset of SE, and persisted for at least 3 months. Double immunolabelling confirmed that both reactive astrocytes, and activated microglia were CSTC immunopositive. Within the hippocampus, up-regulation was also observed in neuronal cells within one day after SE. Up-regulation was still present in hippocampal pyramidal cells and surviving interneurons of chronic epileptic rats (3-8 months post-SE). This study demonstrates that status epilepticus leads to a widespread and persistent up-regulation of CSTC in the hippocampus and entorhinal cortex, which may represent an intrinsic neuroprotective mechanism in the course of epileptogenesis that may counteract progression of the disease.
  European Journal of Neuroscience 12/2001; 14(9):1485-91. · 3.63 Impact Factor