The effect of propofol on effective brain networks.

OBJECTIVE: We compared the effective networks derived from Single Pulse Electrical Stimulation (SPES) in intracranial electrocorticography (ECoG) of awake epilepsy patients and while under general propofol-anesthesia to investigate the effect of propofol on these brain networks. METHODS: We included nine patients who underwent ECoG for epilepsy surgery evaluation. We performed SPES when the patient was awake (SPES-clinical) and repeated this under propofol-anesthesia during the surgery in which the ECoG grids were removed (SPES-propofol). We detected the cortico-cortical evoked potentials (CCEPs) with an automatic detector. We constructed two effective networks derived from SPES-clinical and SPES-propofol. We compared three network measures (indegree, outdegree and betweenness centrality), the N1-peak-latency and amplitude of CCEPs between the two effective networks. RESULTS: Fewer CCEPs were observed during SPES-propofol (median: 6.0, range: 0-29) compared to SPES-clinical (median: 10.0, range: 0-36). We found a significant correlation for the indegree, outdegree and betweenness centrality between SPES-clinical and SPES-propofol (respectively rs = 0.77, rs = 0.70, rs = 0.55, p < 0.001). The median N1-peak-latency increased from 22.0 ms during SPES-clinical to 26.4 ms during SPES-propofol. CONCLUSIONS: Our findings suggest that the number of effective network connections decreases, but network measures are only marginally affected. SIGNIFICANCE: The primary network topology is preserved under propofol.

Evoked versus spontaneous high frequency oscillations in the chronic electrocorticogram in focal epilepsy.

OBJECTIVE: Spontaneous high frequency oscillations (HFOs; ripples 80-250Hz, fast ripples (FRs) 250-500Hz) are biomarkers for epileptogenic tissue in focal epilepsy. Single pulse electrical stimulation (SPES) can evoke HFOs. We hypothesized that stimulation distinguishes pathological from physiological ripples and compared the occurrence of evoked and spontaneous HFOs within the seizure onset zone (SOZ) and eloquent functional areas. METHODS: Ten patients underwent SPES during 2048Hz electrocorticography (ECoG). Evoked HFOs in time-frequency plots and spontaneous HFOs were visually analyzed. We compared electrodes with evoked and spontaneous HFOs for: percentages in the SOZ, sensitivity and specificity for the SOZ, percentages in functional areas outside the SOZ. RESULTS: Two patients without spontaneous FRs showed evoked FRs in the SOZ. Percentages of evoked and spontaneous HFOs in the SOZ were similar (ripples 32:33%, p=0.77; FRs 43:48%, p=0.63), but evoked HFOs had generally a lower specificity (ripples 45:69%, p=0.02; FRs 83:92%, p=0.04) and higher sensitivity (ripples 85:70%, p=0.27; FRs 52:37%, p=0.05). More electrodes with evoked than spontaneous ripples were found in functional (54:30%, p=0.03) and 'silent' areas (57:27%, p=0.01) outside the SOZ. CONCLUSIONS: SPES can elicit SOZ-specific FRs in patients without spontaneous FRs, but activates ripples in all areas. SIGNIFICANCE: SPES is an alternative for waiting for spontaneous HFOs, but does not warrant exclusively pathological ripples.

High frequency oscillations and high frequency functional network characteristics in the intraoperative electrocorticogram in epilepsy.

OBJECTIVE: High frequency oscillations (HFOs; > 80 Hz), especially fast ripples (FRs, 250-500 Hz), are novel biomarkers for epileptogenic tissue. The pathophysiology suggests enhanced functional connectivity within FR generating tissue. Our aim was to determine the relation between brain areas showing FRs and 'baseline' functional connectivity within EEG networks, especially in the high frequency bands. METHODS: We marked FRs, ripples (80-250 Hz) and spikes in the electrocorticogram of 14 patients with refractory temporal lobe epilepsy. We assessed 'baseline' functional connectivity in epochs free of epileptiform events within these recordings, using the phase lag index. We computed the Eigenvector Centrality (EC) per channel in the FR and gamma band network. We compared EC between channels that did or did not show events at other moments in time. RESULTS: FR-band EC was higher in channels with than without spikes. Gamma-band EC was lower in channels with ripples and FRs. CONCLUSIONS: We confirmed previous findings of functional isolation in the gamma-band and found a first proof of functional integration in the FR-band network of channels covering presumed epileptogenic tissue. SIGNIFICANCE: 'Baseline' high-frequency network parameters might help intra-operative recognition of epileptogenic tissue without the need for waiting for events. These findings can increase our understanding of the 'architecture' of epileptogenic networks and help unravel the pathophysiology of HFOs.

Single Pulse Electrical Stimulation to identify epileptogenic cortex: Clinical information obtained from early evoked responses.

OBJECTIVE: Single Pulse Electrical Stimulation (SPES) probes epileptogenic cortex during electrocorticography. Two SPES responses are described: pathological delayed responses (DR, >100 ms) associated with the seizure onset zone (SOZ) and physiological early responses (ER, <100 ms) that map cortical connectivity. We analyzed properties of ERs, including frequencies >80 Hz, in the SOZ and seizure propagation areas. METHODS: We used data from 12 refractory epilepsy patients. SPES consisted of 10 pulses of 1 ms, 4-8 mA and 5s interval on adjacent electrodes pairs. Data were available at 2048 samples/s for six and 512 samples/s (22 bits) for eight patients and analyzed in the time-frequency (TF) and time-domain (TD). RESULTS: Electrodes with ERs were stronger associated with SOZ than non-SOZ electrodes. ERs with frequency content >80 Hz exist and are specific for SOZ channels. ERs evoked by stimulation of seizure onset electrodes were associated with electrodes involved in seizure propagation. CONCLUSION: Analysis of ERs can reveal aspects of pathology, manifested by association with seizure propagation and areas with high ER numbers that coincide with the SOZ. SIGNIFICANCE: Not only DRs, but also ERs could have clinical value for mapping epileptogenic cortex and help to unravel aspects of the epileptic network.

High frequency oscillations in intra-operative electrocorticography before and after epilepsy surgery.

OBJECTIVE: Removal of brain tissue showing high frequency oscillations (HFOs; ripples: 80-250Hz and fast ripples: 250-500Hz) in preresection electrocorticography (preECoG) in epilepsy patients seems a predictor of good surgical outcome. We analyzed occurrence and localization of HFOs in intra-operative preECoG and postresection electrocorticography (postECoG). METHODS: HFOs were automatically detected in one-minute epochs of intra-operative ECoG sampled at 2048Hz of fourteen patients. Ripple, fast ripple, spike, ripples on a spike (RoS) and not on a spike (RnoS) rates were analyzed in pre- and postECoG for resected and nonresected electrodes. RESULTS: Ripple, spike and fast ripple rates decreased after resection. RnoS decreased less than RoS (74% vs. 83%; p=0.01). Most fast ripples in preECoG were located in resected tissue. PostECoG fast ripples occurred in one patient with poor outcome. Patients with good outcome had relatively high postECoG RnoS rates, specifically in the sensorimotor cortex. CONCLUSIONS: Our observations show that fast ripples in intra-operative ECoG, compared to ripples, may be a better biomarker for epileptogenicity. Further studies have to determine the relation between resection of epileptogenic tissue and physiological ripples generated by the sensorimotor cortex. SIGNIFICANCE: Fast ripples in intra-operative ECoG can help identify the epileptogenic zone, while ripples might also be physiological.

The contribution of posterior circulation to memory function during the intracarotid amobarbital procedure.

The purpose of this study was to evaluate the contribution of posterior circulation to memory function by comparing memory scores between patients with and without a foetal-type posterior cerebral artery (FTP) during the intracarotid amobarbital procedure (IAP) in epilepsy patients. Patients undergoing bilateral IAP between January 2004 and January 2010 were retrospectively included. Pre-test angiograms were assessed for the presence of a FTP. Memory function scores (% correct) after right and left injections were obtained. Functional significance of FTP was affirmed by relative occipital versus parietal EEG slow-wave increase during IAP. Memory and EEG scores were compared between patients with and without FTP (Mann-Whitney U test). A total of 106 patients were included, 73 with posterior cerebral arteries (PCA) without FTP ('non-FTP'), 28 patients with unilateral FTP and 5 with a bilateral FTP. Memory scores were lower when amytal was injected to the hemisphere contralateral to the presumed seizure focus (on the right decreasing from 98.3 to 59.1, and on the left decreasing from 89.1 to 72.4; p < 0.001). When IAP was performed on the side of FTP memory scores were significantly lower (70.8) compared to non-FTP (82.0; p = 0.02). Relative occipital EEG changes were 0.44 for FTP cases and 0.36 for non-FTP patients (p = 0.01). A relationship between vasculature and brain function was demonstrated by lower memory scores and more slow-wave activity on occipital EEG during IAP in patients with foetal-type PCA compared to patients with non-FTP. This suggests an important contribution of brain areas supplied by the PCA to memory function.

Interictal magnetoencephalography and the irritative zone in the electrocorticogram.

Magnetoencephalography (MEG) is considered a useful tool for planning electrode placement for chronic intracranial subdural electrocorticography (ECoG) in candidates for epilepsy surgery or even as a substitute for ECoG. MEG recordings are usually interictal and therefore, at best, reflect the interictal ECoG. To estimate the clinical value of MEG, it is important to know how well interictal MEG reflects interictal activity in the ECoG. From 1998 to 2008, 38 candidates for ECoG underwent a 151-channel MEG recording and 3D magnetic resonance imaging as a part of their presurgical evaluation. Interictal MEG spikes were identified, clustered, averaged and modelled using the multiple signal classification algorithm and co-registered to magnetic resonance imaging. ECoG was continuously recorded with electrode grids and strips for approximately 1 week. In a representative sample of awake interictal ECoG, interictal spikes were identified and averaged. The different spikes were characterized and quantified using a combined amplitude and synchronous surface-area measure. The ECoG spikes were ranked according to this measure and plotted on the magnetic resonance imaging surface rendering. Interictal spikes in MEG and ECoG were allocated to a predefined anatomical brain region and an association analysis was performed. All interictal MEG spikes were associated with an interictal ECoG spike. Overall, 56% of all interictal ECoG spikes had an interictal MEG counterpart. The association between the two was >or=90% in the interhemispheric and frontal orbital region, approximately 75% in the superior frontal, central and lateral temporal regions, but only approximately 25% in the mesial temporal region. MEG is a reliable indicator of the presence of interictal ECoG spikes and can be used to plan intracranial electrode placements. However, a substantial number of interictal ECoG spikes are not detected by MEG, and therefore MEG cannot be considered a substitute for ECoG.

Reduction of the Ballistocardiogram Artifact in Simultaneous EEG-fMRI using ICA.

The recording of EEG signals during fMRI scanning is now technically feasible and safe. However, artifacts relating to pulsatile blood flow (the ballistocardiogram) may still be prominently present in EEG data recorded in the MRI magnet. The application of Independent Component Analysis (ICA) in order to reduce these artifacts off-line was investigated in three different types of EEG, one normal Visually Evoked Potential (VEP), one normal ongoing EEG in a normal subject and the EEG of an epilepsy patient showing abnormal transients in the EEG. Results show that ICA is effective in reducing these pulsation artifacts, but that remaining signal quality may be affected.

Measurement of the conductivity of skull, temporarily removed during epilepsy surgery.

The conductivity of the human skull plays an important role in source localization of brain activity, because it is low as compared to other tissues in the head. The value usually taken for the conductivity of skull is questionable. In a carefully chosen procedure, in which sterility, a stable temperature, and relative humidity were guaranteed, we measured the (lumped, homogeneous) conductivity of the skull in five patients undergoing epilepsy surgery, using an extended four-point method. Twenty-eight current configurations were used, in each of which the potential due to an applied current was measured. A finite difference model, incorporating the geometry of the skull and the electrode locations, derived from CT data, was used to mimic the measurements. The conductivity values found were ranging from 32 mS/m to 80 mS/m, which is much higher than the values reported in other studies. Causes for these higher conductivity values are discussed.

Magnetic source imaging contributes to the presurgical identification of sensorimotor cortex in patients with frontal lobe epilepsy.

OBJECTIVE: One of the primary goals of preoperative evaluation of patients considered to be candidates for epilepsy surgery is the delineation of eloquent cortex adjacent to the area of resection. The aim of this study is the functional localization of the sensorimotor cortex in relation to an epileptogenic frontal lobe lesion, thus enabling a more complete resection in these patients while minimizing the risk of postoperative neurological deficits. METHODS: Participating in this study were patients with epilepsy, diagnosed as being related to a left or right frontal lobe lesion. Magnetoencephalographic responses evoked by electrical stimulation of the left and right hand median nerve were localized using single time-point equivalent dipole (ED) modeling, taking into account the realistic shape of the head. Instead of relying on the primary component (N/P 20) of the somatosensory evoked magnetic fields (SEFs) in this study ED fits were obtained for each time-point of the somatosensory evoked responses. On a cortical rendering, the reconstructed dipoles were depicted relative to the anatomy obtained from 3D-magnetic resonance imaging. RESULTS: The results of single time-point ED analysis including all the components of the responses indicated that the sources underlying the SEFs are located at the borders of the central sulcus (CS). The opposite direction of the sources underlying, respectively, the primary and subsequent late component of the SEFs indicated distinct sources located at the opposite banks of the CS. These sources, therefore, might correspond to the sensory hand projection area and the primary motor area of the sensorimotor cortex. It appeared that the location of the EDs obtained for the SEFs of 4 of the 7 patients studied were asymmetric for the left and right hemisphere, probably because of a displacement of the sensorimotor areas relative to the CS. The systematic assessment of the dipole fits compared to brain anatomy confirmed that volume conduction changes due to the lesion were not responsible for these observed deviations, thus leaving as explanation space-occupying and neurophysiological changes due to the lesion.

The existence of two sources in rolandic epilepsy: confirmation with high resolution EEG, MEG and fMRI.

In benign rolandic epilepsy seizure semiology suggests that the epileptic focus resides in the lower sensorimotor cortex. Previous studies involving dipole modeling based on 32 channel EEG have confirmed this localization. These studies have also suggested that two distinct dipole sources are required to adequately describe the typical interictal spikes. Since in benign epilepsy invasive validation is prohibited, this study tries to further establish these results using a multi-modal approach, involving 32 channel EEG, high resolution 84 channel EEG, 151 channel MEG and fMRI. From one patient interictal spikes were recorded and analyzed using the MUSIC algorithm in a realistic volume conductor model. In an fMRI experiment the same patient performed voluntary tongue movements, thus mimicking a typical seizure. Results show that EEC, MEG and fMRI localization converge on the same area in the lower part of the sensorimotor cortex, and that high resolution EEG clearly reveals two distinct sources, one in the post- and one in the pre-central cortex.

A bidomain model based BEM-FEM coupling formulation for anisotropic cardiac tissue.

A hybrid boundary element method (BEM)/finite element method (FEM) approach is proposed in order to properly consider the anisotropic properties of the cardiac muscle in the magneto- and electrocardiographic forward problem. Within the anisotropic myocardium a bidomain model based FEM formulation is applied. In the surrounding isotropic volume conductor the BEM is adopted. Coupling is enabled by requesting continuity of the electric potential and the normal of the current density across the boundary of the heart. Here, the BEM part is coupled as an equivalent finite element to the finite element stiffness matrix, thus preserving in part its sparse property. First, continuous convergence of the coupling scheme is shown for a spherical model comparing the computed results to an analytic reference solution. Then, the method is extended to the depolarization phase in a fibrous model of a dog ventricle. A precomputed activation sequence obtained using a fine mesh of the heart was downsampled and used to calculate body surface potentials and extracorporal magnetic fields considering the anisotropic bidomain conductivities. Results are compared to those obtained by neglecting in part or totally (oblique or uniform dipole layer model) anisotropic properties. The relatively large errors computed indicate that the cardiac muscle is one of the major torso inhomogeneities.

The inverse problem in electroretinography: a study based on skin potentials and a realistic geometry model.

The problem of obtaining the retinal source distribution that generates the electroretinogram (ERG) from measured skin potentials is addressed. A realistic three-dimensional (3-D) volume conductor model of the head is constructed from magnetic resonance image (MRI) data sets. The skin potential distribution generated in this model by a dipole layer source at the retina is computed by using the boundary element method (BEM). The influence of the various compartments of the complete model on the results was investigated, and a simplified model was defined. An inverse procedure for estimating the source distribution at the retina from ERG's obtained from skin electrodes was developed. The procedure was tested on simulated potentials. A fair correspondence between the original and estimated source distribution was found. Furthermore, the ERG's measured at seven skin electrodes were used to estimate the source distribution at the retina. The ERG potential waveform at an additional skin electrode was computed from this source distribution and compared to the measured potential at this electrode. Again a fair correspondence was obtained. It is concluded that the methods may become a useful tool for clinical applications, i.e., for the assessment of localized defects in retinal function.

The uniform double layer model and myocardial infarction: forward solution consideration.

The Uniform Double Layer (UDL) model of the cardiac generator is often used for forward simulation of body surface potentials (BSPs). The model also proved to be very useful for the inverse computation of heart activation. However, for the purposes of Myocardial Infarction (MI) modelling mostly the Multiple Dipole (MD) models are used. In our study, the ability of UDL model to represent the activation of the heart with an old MI was examined. The finite element model of the heart was used to simulate electrical activation of the heart with an old MI. Different locations of endocardial MI were used. For each of them three cases were considered according to the scale of the infarcted area: small and medium endocardial and large transmural. For the further computation of the electric field within the torso volume conductor two types of UDL representation of the cardiac generator were used. For the first UDL model, supposing the scared tissue to be unexcitable, an "infarcted" surface (different from the "healthy" surface) of activated myocardium was generated for each case of MI. Times when activation wavefront reached particular nodes on the surface served as an input for the forward computation of BSPs. To be able to understand the behaviour of the UDL, we also created the second UDL model, where the "infarcted activation sequence" was approximated on the original "healthy" heart surface. The BSPs were computed for each case of MI using both UDL cardiac generators. The boundary element method with the inhomogeneous volume conductor was used for computations. The BSPs generated by both models for the same case of MI were compared using the correlation coefficient. The results show, that it is possible to find an approximation of the "infarcted activation sequence" on the "healthy" heart generator surface in a way that BSPs generated by both models have a correlation coefficient higher than 0.96 for the entire period of depolarisation. Visualisation of the epicardial isochrones might help to understand the UDL model behaviour under the MI conditions. It would be useful for the correct interpretation of the results when using the UDL model for inverse solution. (Fig. 7, Ref. 5.)

Lead system transformation for pooling of body surface map data: a surface Laplacian approach.

In this paper, a method is described to transform Body Surface Map (BSM) data from one lead system to that of another. This enables pooling of BSM data between different centres. The transformation tool is based upon Laplacian interpolation. It is evaluated by inspecting transformations from lead systems having few leads to one having many leads.

Heart position and orientation in forward and inverse electrocardiography.

A study has been made of the influence of the position and orientation of the heart within the thorax on computed ECG waveforms (forward model) and on computed activation sequences (inverse model) in three normal cases. Results show that differences in heart position and orientation, associated with shifts relative to the precordium of the order of 0.5 cm, may result in amplitude differences or QRS waveforms of typically tenths or millivolts, which constitute part of the observed interindividual variability of the ECG. The inverse study shows that, in spite of similar errors in estimated heart position and orientation, stable solutions of the ventricular activation sequence can still be found. However, in the case where the heart is very close to precordial leads, the stability of the inverse solution is found to be intrinsically poor.

Implicit and explicit constraints in inverse electrocardiography.

This paper reviews the major distributed source models that have been postulated over the years to support the interpretation of observed body surface potentials: double-layer models, the source description in terms of epicardial (ie, pericardial) potentials, and its equivalent: the distributed monolayer. This includes a presentation and discussion of a source model that has been developed over the past decade: the uniform double-layer model. The properties of this model are contrasted to those of other distributed source models from the perspective of their inherent capacity for imposing the constraints that are essential for regularizing the involved inverse problem.

A realistic torso model for magnetocardiography.

This paper contains the description of an inhomogeneous, multi-compartmental volume conductor model which is in use in our group. Although initially developed for the study of the ECG, it has been found to serve equally well for simulating the magnetocardiogram (MCG), the forward problem, and as a basis for source analysis of the MCG, the inverse problem. For both problems some illustrative examples are included demonstrating the necessity of using an inhomogeneous volume conductor model of the torso, having realistic--preferably tailored--geometry. A simple inverse procedure, based on correlation techniques, is included for the solution of the problem of source localization when an accurate description of the inhomogeneous volume conductor is available.

The magnetocardiogram as derived from electrocardiographic data.

Magnetocardiographic signals, as present outside the thorax and generated by the depolarization process within the ventricles of the human heart, have been computed by using a model that incorporates the uniform double layer as the exclusive primary source. The volume conductor effects are treated by using an inhomogeneous, multicompartmental model of the thorax, based on "tailored" geometry derived from magnetic resonance imaging. The required activation function, specifying the timing of the ventricular depolarization process, was derived from an inverse procedure that uses as input data electric signals measured at the body surface. Next, the magnetic signals from the same subjects were measured. A close correspondence between computed and measured magnetic signals was observed (relative root mean square residual difference of 0.37). These results demonstrate that magnetocardiograms and electrocardiograms have a common basis and that it is unlikely that prominent sources exist that are electrically silent and yet active in the genesis of the magnetic fields associated with the depolarization process of the heart. Moreover, fresh support is implied for the usefulness of the classical uniform double layer as the electrical source model during ventricular depolarization. The contributions of the secondary sources have previously been found to be a major component of the electric signals; they are now also shown to be a major component of the magnetic signals.