Ictal and interictal electric source imaging in pre-surgical evaluation: a prospective study.

BACKGROUND AND PURPOSE: Accurate localization of the epileptic focus is essential for surgical treatment of patients with drug-resistant epilepsy. Electric source imaging (ESI) is increasingly used in pre-surgical evaluation. However, most previous studies have analysed interictal (II) discharges. Prospective studies comparing the feasibility and accuracy of II and ictal (IC) ESI are lacking. METHODS: We prospectively analysed long-term video-electroencephalography recordings (LTM) of patients admitted for pre-surgical evaluation. We performed ESI of II and IC signals using two methods, i.e. equivalent current dipole (ECD) and a distributed source model (DSM). LTM recordings employed the standard 25-electrode array (including inferior temporal electrodes). An age-matched template head model was used for source analysis. Results were compared with intracranial recordings, conventional neuroimaging methods [magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT)] and outcome at 1 year after surgery. RESULTS: A total of 87 consecutive patients were analysed. ECD gave a significantly higher proportion of patients with localized focal abnormalities (94%) compared with MRI (70%), PET (66%) and SPECT (64%). Agreement between the ESI methods and intracranial recording was moderate to substantial (k = 0.56-0.79). A total of 54 patients were operated (47 patients more than 1 year ago) and 62% of them became seizure-free. The localization accuracy of II-ESI was 51% for DSM and 57% for ECD, and that for IC-ESI was 51% for DSM and 62% for ECD. The differences between the ESI methods were not significant. Differences in localization accuracy between ESI and MRI (55%), PET (33%) and SPECT (40%) were not significant. CONCLUSIONS: The II-ESI and IC-ESI of LTM data have high feasibility and their localization accuracy is similar to that of conventional neuroimaging methods.

Influences of skull segmentation inaccuracies on EEG source analysis.

The low-conducting human skull is known to have an especially large influence on electroencephalography (EEG) source analysis. Because of difficulties segmenting the complex skull geometry out of magnetic resonance images, volume conductor models for EEG source analysis might contain inaccuracies and simplifications regarding the geometry of the skull. The computer simulation study presented here investigated the influences of a variety of skull geometry deficiencies on EEG forward simulations and source reconstruction from EEG data. Reference EEG data was simulated in a detailed and anatomically plausible reference model. Test models were derived from the reference model representing a variety of skull geometry inaccuracies and simplifications. These included erroneous skull holes, local errors in skull thickness, modeling cavities as bone, downward extension of the model and simplifying the inferior skull or the inferior skull and scalp as layers of constant thickness. The reference EEG data was compared to forward simulations in the test models, and source reconstruction in the test models was performed on the simulated reference data. The finite element method with high-resolution meshes was employed for all forward simulations. It was found that large skull geometry inaccuracies close to the source space, for example, when cutting the model directly below the skull, led to errors of 20mm and more for extended source space regions. Local defects, for example, erroneous skull holes, caused non-negligible errors only in the vicinity of the defect. The study design allowed a comparison of influence size, and guidelines for modeling the skull geometry were concluded.

Combined spike-related functional MRI and multiple source analysis in the non-invasive spike localization of benign rolandic epilepsy.

OBJECTIVE: To localize the irritative zone in children by combined spike-related fMRI and EEG multiple source analysis (MSA) in children with benign rolandic epilepsy. METHODS: Interictal spikes were averaged and localized using MSA, and source locations were displayed in the anatomical 3D-MRI in 11 patients (5-12 yrs, median 10). Interictal spikes were additionally recorded during the fMRI acquisition (EEG-fMRI), and the fMRI sequences were correlated off-line with the EEG spikes. RESULTS: MSA revealed an initial central dipole in all patients, including the face or hand area. A second dipolar source was mostly consistent with propagated activity. BOLD activations from EEG-fMRI, consistent with the locations of the initial dipoles, were found in four patients. We found additional large areas of BOLD activations in 3 of these subjects extending into the sylvian fissure and the insula. These were identified as propagated activity by MSA using the short time differences in the source waveforms. CONCLUSIONS: MSA provided reliable localization of the spike onset zone in all children with benign rolandic epilepsy. Using the combination of EEG-fMRI and MSA we were able to discriminate the spike onset zone from propagated epileptiform source activity, using the spatial resolution of the EEG-fMRI technique and the temporal resolution of the MSA. However, the sensitivity of the EEG-fMRI technique was low and further improvements of the technique are warranted. SIGNIFICANCE: This study shows that a combination of EEG-fMRI and MSA may be a powerful tool to describe the irritative zone of patients with idiopathic focal epilepsies. Clinical studies in patients with non-idiopathic focal epilepsies may clarify whether both techniques can be used as complementary clinical tools to localize the onset of interictal epileptic activity in focal epilepsies.

From EEG source localization to source imaging.

A new functional imaging technique, "FOCUS", has been developed to transform the traditional scalp EEG into an image of source activities. The image is based on multiple spatio-temporal dipole models and consists of gross spatial patterns and source waveforms reflecting the estimated activities of the different brain regions. The application of the 'FOCUS' technique to the EEG in temporal lobe epilepsy revealed the presence of different activities at the basal and lateral aspects of the temporal lobe. The source waveforms showed propagation patterns consistent with subdural recordings which were not recognizable in the scalp EEG.

The time course of brain activations during response inhibition: evidence from event-related potentials in a go/no go task.

The cortical organization of executive control was investigated using event-related potentials (ERPs). ERPs were collected while subjects performed a go/no go task that required response inhibition. First, around 260 ms after stimulus onset, an effect of response inhibition on ERPs was observed over inferior prefrontal areas. Generators in these regions were confirmed by source analysis. Later, between 300-600 ms after stimulus onset, a left lateralized fronto-central ERP effect was found which differed in topography from a non-specific effect of task difficulty. Source analysis indicated that generators in anterior cingulate and left premotor areas also contributed to this effect. Orchestrated activation of prefrontal areas and the anterior cingulate subserves executive function whereas relatively late activity of the left premotor cortex is involved in motor control.

Fast temporal interactions in human auditory cortex.

The temporal resolution of the human primary auditory cortex (AC) was studied using middle-latency evoked fields. Paired sounds with either the same or different spectral characteristics were presented with gaps between the sounds of 1, 4, 8 and 14 ms. Spatio-temporal modelling showed (1) that the response to the second sound was recognizable with gaps of 1 ms and rapidly increased in amplitude with increasing gap durations, (2) an enhanced N40m amplitude at gaps > 4 ms, (3) delayed N19m-P30m latencies when the stimuli were different. The median psychoacoustical thresholds were 1.6 ms for the same stimuli and 2.5 ms for different stimuli, confirming the electrophysiological evidence for rapid pattern-specific temporal processing in human primary auditory cortex.

Is frontal lobe involved in the generation of auditory evoked P50?

This study examined the functional substrate of P50 suppression. Auditory evoked potentials (AEPs) and magnetic fields (AEFs) were recorded from healthy subjects simultaneously and analyzed using spatio-temporal source analysis. The resulting equivalent dipole model for the AEP consisted of one source in the auditory cortex (AC) of each hemisphere and an radially oriented medial frontal source, both with maximum AEP activity around 50 ms. The frontal source was functionally separated from the AC sources since it peaked significantly later and showed significantly larger P50 amplitude suppression. P30m showed neither suppression nor substantial frontal activity. In sum, this study relates P50 suppression to reduction of AC source activity and is the first to yield direct evidence for frontal involvement in P50 suppression.

Magnetic source imaging of tactile input shows task-independent attention effects in SII.

We investigated whether attention to different stimulus attributes (location, intensity) has different effects on the activity of the secondary (SII) somatosensory cortex. Tactile stimuli were applied to the left index finger and somatosensory evoked fields (SEFs) were recorded using a whole-head magnetoencephalography (MEG) system. Two oddball paradigms with stimuli varying in location or intensity were performed in an ignore and an attend condition. Brain sources were estimated by magnetic source imaging. No attention effect was observed for the primary SI area. However, attention enhanced SII activity bilaterally from 55 to 130 ms by 52% in the spatial and 64% in the intensity discrimination task. SII attentional enhancement was very similar in both paradigms and occurred both for deviants and standards.

Brain-stem auditory-evoked potentials in post-comatose patients after severe closed head trauma.

Brain-stem auditory-evoked potentials (BAEPs) were recorded in 35 post-comatose patients after severe closed head trauma. Compared to the normal BAEPs obtained from 30 normal controls, significant individual abnormality could be detected in only 2 patients. This abnormality consisted of lateral asymmetry, but not prolonged interpeak latencies or abnormal amplitude ratios. Further, no differences were found between groups as regards interpeak latencies. A significant reduction of BAEP amplitudes was seen in the patient group, being most pronounced in the 13 patients with hearing loss. It is concluded that the BAEP does not sufficiently reveal brain-stem lesions expected to persist after severe closed head trauma, presumably because the structures generating waves IV and V are not permanently affected. The amplitude reductions observed may be explained by the diffuse cochlear damage known to occur concurrently with head trauma.

Common spatial subspace decomposition applied to analysis of brain responses under multiple task conditions: a simulation study.

A method, called common spatial subspace decomposition, is presented which can extract signal components specific to one condition from multiple magnetoencephalography/electroencephalography data sets of multiple task conditions. Signal matrices or covariance matrices are decomposed using spatial factors common to multiple conditions. The spatial factors and corresponding spatial filters are then dissociated into specific and common parts, according to the common spatial subspace which exists among the data sets. Finally, the specific signal components are extracted using the corresponding spatial filters and spatial factors. The relationship between this decomposition and spatio-temporal source models is described in this paper. Computer simulations suggest that this method can facilitate the analysis of brain responses under multiple task conditions and merits further application.

Stability of high-frequency (600 Hz) components in human somatosensory evoked potentials under variation of stimulus rate--evidence for a thalamic origin.

The generators of spike-like high-frequency (600 Hz) wavelets superimposed on the primary cortical response (N20) in human median nerve somatosensory evoked potentials (SEP) have been localized anatomically both close to the primary somatosensory hand cortex and in deep axon segments of thalamo-cortical projection neurons. Here, N20 and 600 Hz burst components were functionally dissociated by varying the stimulus rate (1.5, 3, 6, 9 Hz). The N20 source amplitudes were significantly reduced at the higher stimulus rates. In contrast, the source amplitudes of the 600 Hz oscillations remained stable across all stimulus rates. This reflects different source origins, confirming a postsynaptic intracortical generation of the N20 component and provides further evidence for a presynaptic origin of the 600 Hz activity like repetitive neuronal population spikes conducted in deep and superficial segments of thalamo-cortical projection fibers.

The correction of ocular artifacts: a topographic perspective.

OBJECTIVE: To evaluate the scalp topography of the potentials related to saccades and blinks. METHODS: The scalp topographies of the potentials associated with saccades and blinks were recorded in 60 subjects. The topographies were analyzed using both source components and attenuation factors, with each factor representing the fraction of the potential recorded in peri-ocular electrodes that contributes to the EEG recorded from a particular scalp location. RESULTS: Blinks and upward saccades generated potentials with very different topographies. Left and right saccades and up and down saccades generated equal but inverted fields except at peri-ocular locations where subtle inequalities occurred. The potentials associated with lateral saccades were consistently larger in female subjects than in male subjects. CONCLUSIONS: The differences in the scalp topographies between blinks and vertical saccades can be explained by the different ways in which they are generated. Blink potentials are caused by the eyelids sliding down over the positively charged cornea, whereas saccade potentials are caused by changes in the orientation of the corneoretinal dipole. Any compensation procedure for ocular artifacts must take into account the topographic differences between blinks and upward saccades.

Deconvolution of 40 Hz steady-state fields reveals two overlapping source activities of the human auditory cortex.

Steady-state auditory evoked fields were recorded from 15 subjects using a whole head MEG system. Stimuli were 800 ms trains of binaural clicks with constant stimulus onset asynchrony (SOA). Seven different SOA settings (19, 21, 23, 25, 27, 29 and 31 ms) were used to give click rates near 40 Hz. Transient responses to each click were reconstructed using a new algorithm that deconvoluted the averaged responses to the different trains. Spatio-temporal multiple dipole modelling in relation to 3D MRI scans revealed two overlapping source components in both the left and right auditory cortex. The primary sources in the medial part of Heschl's gyrus exhibited a N19-P30-N40 m pattern. The secondary, weaker sources at more lateral sites on Heschl's gyrus showed a N24-P36-N46 m pattern. When applied to transient middle latency auditory evoked fields (MAEFs) recorded at SOAs of 95-135 ms, the primary sources imaged activities similar to the deconvoluted steady-state responses, but the secondary source activities were inconsistent. Linear summation of the deconvoluted source waveforms accounted for more than 96% of the steady-state variance. This indicates that the primary activity of the auditory cortex remains constant up to high stimulation rates and is not specifically enhanced around 40 Hz.

Eyeblinks evoke potentials in the occipital brain region.

The subjects performed voluntary eyeblinks under illuminated and dark laboratory conditions. 32-channel EEG recordings were averaged in relation to the eyeblinks and a brain electric source analysis (BESA) was performed. Two dipoles located near the eyeballs and a third dipole in the occipital region of the brain were found to explain the scalp potentials. The frontally located potentials described electromechanical potentials associated with lid movements and simultaneous eye movements. The occipitally located dipole explained a visually evoked potential with a first peak at about 180 ms after the maximum of the frontal blink potential. The visually evoked potential was observed only under illumination and was probably caused by changes in luminance during the eyeblinks.

Somatotopic source arrangement of 600 Hz oscillatory magnetic fields at the human primary somatosensory hand cortex.

Based on low-noise superconducting quantum interference devices (SQUIDs) magnetoencephalography allows the non-invasive detection of low-amplitude high-frequency brain responses evoked about 20 ms after electric hand nerve stimulation. The main spectral energy of these brief oscillatory bursts (near 600 Hz) is in the range typical for rapidly repeated action potentials. Here, the magnetic fields of median and ulnar nerve evoked 600 Hz bursts are shown to exhibit a somatotopic arrangement at the primary somatosensory hand cortex closely resembling that of the concomitant postsynaptic primary cortical response (¿N20m'). Two possible burst generators are discussed: (1) repetitive spike volleys conducted along the terminal segments of somatotopically arranged thalamocortical axons, and (2) early intracortical spike activity in nerve-specific subterritories of the 3b hand area.

Sustained attention modulates the immediate effect of de-afferentation on the cortical representation of the digits: source localization of somatosensory evoked potentials in humans.

Long-term cortical reorganization of the somatotopic arrangement of the digits after alterations of the peripheral input is well established. Studies on the immediate effects of manipulating peripheral input have shown conflicting results indicating that additional factors might modulate cortical reorganization. We present a source localization study using somatosensory evoked potentials (SEP) following electric stimulation of digits one and five before and during anaesthesia of digits two, three and four in 10 normal volunteers. When attention was directed to a stimulus at the dorsal hand, the 3D-distance between digits one and five decreased during as compared to before anaesthesia. In contrast, this distance enlarged when subjects were not attending a particular stimulus. In this condition most subjects focused their attention on the clear sensation of the de-afferented hand region. These results indicate that attention modulates the effect of immediate cortical reorganization of the hand area during partial deafferentation. As an hypothesis: it may be speculated that the sensation of the de-afferentation results in increased synchronized activity of the de-afferented somatosensory cortex and, thus, to its enlarged representation. Conversely, if attention is directed to a different hand region, the representations of the neighboring digits may expand into the de-afferented cortex.

The time course and location of cerebral evoked activity associated with the processing of colour stimuli in man.

Area V4 has been located in man in the region of the fusiform gyrus on the inferior surface of the occipital lobe. Using multiple dipole source analysis on multichannel EEG recordings of visual evoked potentials to coloured 'Mondrian' stimuli in man, we have confirmed that activity is consistently seen in this area regardless of the retinal area stimulated and have obtained new information concerning its time course. Three different localized centres of activity follow the visual stimulus, with peak latencies of 90, 110 and 160 ms, and arising respectively in the region of visual areas V1, V2/V3 and V4. The time course and character of the V4 dipole activity to a colourless black-and-white Mondrian is indistinguishable from that to the coloured Mondrian, supporting the evidence that the cells of V4 are not exclusively concerned with colour processing.

Multiple source analysis of interictal spikes: goals, requirements, and clinical value.

When evaluating interictal spikes using dipole source analysis it is important to account for multiple sources and the overlapping background EEG. Analyses of spike peaks may be modeling only propagated sources. Careful filtering of averaged spike data and multiple source analysis can provide useful information about the onset of epileptiform activity. A forward high-pass filter can help to enhance the initial spike activity during onset over the propagated activity. These points are illustrated with examples of a temporal, a parietal, and a frontal averaged spike. Multiple source analysis was applied using a genetic algorithm and a sequential strategy, in one case including a model of background alpha activity. Multiple source analysis could model sources describing the onset activity that were distinct in location and orientation from the propagated activity. In all cases, the prominent peak on the scalp was dominated by the contribution of propagated sources. Clinical interpretation benefits from an approach that combines the temporal evolution of EEG scalp topography and multiple source activities with the information from localization and orientation of equivalent dipole sources to identify the cortical generators underlying the earliest phase of interictal spikes.

Preoperative localization of the central sulcus by dipole source analysis of early somatosensory evoked potentials and three-dimensional magnetic resonance imaging.

Surgery of lesions within or close to the central area of the brain always carries the risk of iatrogenic motor or sensory deficits. Functional localization by means of intraoperative direct stimulation of the motor area or by recording somatosensory evoked potentials (SSEP's) from the surface of the somatosensory cortex is believed to reduce the operative risk. The authors introduce the combination of dipole source analysis of scalp-recorded SSEP's with three-dimensional (3-D) magnetic resonance (MR) imaging as a tool for preoperative localization of the central sulcus. This provides information on both functional and structural localization for preoperative planning. Four repeated measurements of right and left median nerve SSEP's were obtained from 20 subjects. Dipole source analysis showed a retest reliability of the 3-D localization error of 2.9 +/- 2.0 mm. Compared to the MR evaluation, dipole source analysis was found to mark the central sulcus within 3 mm for 15 conditions (subjects x side of stimulation), while the 3-D MR measurement was accurate to within 6 mm for 10 conditions and 9 mm for 14 conditions. Dipole locations were confirmed in six patients who underwent surgery of the central region. With respect to this application, dipole source analysis combined with 3-D MR imaging appears to be a valuable tool for preoperative functional localization. The accuracy in localization will be further improved when realistic head models become available that can take into account individual head geometry. Further development of the proposed new method holds promise that evoked potentials and electroencephalography will gain greater use in presurgical functional localization.

Brain source imaging of focal and multifocal epileptiform EEG activity.

Brain electric source analysis (BESA) of the scalp EEG has been used to identify multiple equivalent current sources in the brain during during interictal spikes and seizure onset. To obviate the need for fitting dipole sources to every EEG segment, a new method has been developed on the basis of multiple fixed dipoles, each designed to emphasize functional imaging of particular cortical areas. "FOCUS" can quickly display EEG in various montages including new "sources montages" which provide a high sensitivity for source currents near each dipole while largely suppressing contributions from other brain areas. By comparing this "source EEG" to routine digital EEG in patients with complex partial epilepsy, we have observed that "FOCUS" can more readily determine whether an epileptiform discharge is consistent with a discrete or multifocal generator, characterize likely cerebral source(s), differentiate between spikes and seizures of mesio-basal versus lateral temporal or frontal origin, and estimate the presence and direction of propagation from source potential timing differences. Improved non-invasive EEG evaluations of partial epilepsy will undoubtedly result from this advance.