Localization of epileptic foci using a large-area magnetometer and functional brain anatomy

We used a large-area, 7-channel, first-order superconducting quantum interference device (SQUID) gradiometer to preoperatively determine the sites of epileptic foci in 2 patients with intractable temporal lobe seizures. The equivalent dipoles for the epileptic spikes were located with respect to external landmarks of the skull and in relation to the generation sites of magnetic auditory evoked responses. It was also possible, for the first time, to determine the location of the equivalent source using simultaneously measured data from seven locations only. The sites of the equivalent dipoles, in the right temporal lobe, agreed with the electrocorticographic and depth electrode recordings made during the operation.     

Combined use of sphenoidal electrodes and the dipole localization method for the identification of the mesial temporal focus

We attempted to sub-classify four cases who show temporal spikes on standard scalp electroencephalogram (EEG), using sphenoidal electrodes and the dipole localization METHOD: In a case with mesial temporal epilepsy, spikes showed phase reversal in a sphenoidal electrode, and the spike dipoles were estimated to be in the mesial temporal lobe. In a case with lateral temporal epilepsy, spikes showed no phase reversal in a sphenoidal electrode, and the spike dipoles were estimated to be in the lateral temporal lobe. In two cases out of four, spikes showed phase reversal in sphenoidal electrodes, whilst the dipoles were estimated to be in the frontal lobe. Clinical features also suggested a diagnosis of frontal lobe epilepsy. In one of the two cases in which frontal lobe epilepsy was suspected, ictal dipoles as well as interictal spike dipoles indicated participation of the frontal lobe in the genesis of seizures. Nevertheless, only mesial temporal lobectomy was performed based on results obtained by invasive subdural electrodes. As a result, seizures were not controlled. Although sphenoidal electrodes were useful for differentiating between mesial and lateral temporal lobe foci, it is advisable to use them in combination with the dipole localization method to identify frontal lobe foci.     

Localization of magnetic interictal discharges in temporal lobe epilepsy

Three young adults with intractable complex partial seizures were studied by electroencephalography, magnetoencephalography, and electrocorticography. Interictal electroencephalographic (EEG) spikes for each patient were grouped according to their morphological characteristics and distribution across channels. Mapping of simultaneously recorded magnetoencephalographic signals produced dipolar patterns from which the three-dimensional locations of equivalent current dipoles were calculated, whereas the mapping of EEG spikes showed single regions of electronegativity. The magnetic spikes were localized to the anterotemporal lobe, and the EEG spikes were localized somewhat anterior or posterior to the magnetic spikes. The magnetoencephalographic findings corresponded well with intraoperative electrocorticographic and depth-electrode findings of discharging areas located over the lateral temporal lobe and on the basal and mesial surfaces of the temporal cortex.     

Neuromagnetic recordings in temporal lobe epilepsy.

The introduction of whole-head magnetoencephalography (MEG) systems facilitating simultaneous recording from the entire brain surface has established MEG as a clinically feasible method for the evaluation of patients with temporal lobe epilepsy (TLE). In mesial TLE, two types of MEG spike dipoles could be identified: an anterior vertical and an anterior horizontal dipole. Dipole orientations can be used to attribute spike activity to temporal lobe subcompartments. Whereas the anterior vertical dipole is compatible with epileptic activity in the mediobasal temporal lobe, the anterior horizontal dipole can be explained by epileptic activity of the temporal tip cortex. In nonlesional TLE, medial and lateral vertical dipoles were found which could distinguish between medial and lateral temporal seizure onset zones as evidenced from invasive recordings. In lesional TLE, MEG could clarify the spatial relationship of the structural lesion to the irritative zone. Evaluation of patients with persistent seizures after epilepsy surgery may represent another clinical important application of MEG because magnetic fields are less influenced than electric fields by the prior operation. Simultaneous MEG and invasive EEG recordings indicate that epileptic activity restricted to mesial temporal structures cannot reliably be detected on MEG and that an extended cortical area of at least 6 to 8 cm2 involving also the basal temporal lobe is necessary to produce a reproducible MEG signal. In lateral neocortical TLE MEG seems to be more sensitive than scalp-EEG which further underlines the potential role of MEG for the study of nonlesional TLE. Whole-head MEG therefore can be regarded as a valuable and clinically relevant noninvasive method for the evaluation of patients with TLE.     

Tests of EEG localization accuracy using implanted sources in the human brain

The accuracy with which electrical sources in the brain can be localized by using electroencephalograms measured on the scalp is not well known. In this study, tests of localization accuracy were performed by using implanted dipolar sources in the human brain. These dipoles are created by passing a weak (subthreshold) current through intracerebral electrodes implanted in the brains of epileptic patients for seizure monitoring. The locations of these dipoles are accurately known from roentgenographs. First, 16 electroencephalograms produced by these dipoles were recorded, then inverse solutions were calculated for the apparent sources of these electroencephalograms. Finally, the locations of the apparent sources were compared with the known locations of the implanted dipoles to determine localization error. The average localization error for a total of 28 dipoles in 3 subjects was 1.1 cm. These results indicate that good localization accuracy for focal sources in the brain can be provided by scalp electroencephalograms.     

Use of simultaneous depth and MEG recording may provide complementary information regarding the epileptogenic region

Simultaneous SEEG-MEG recording has the potential to define the epileptic spike source accurately. We present a case of a 55-year-old female with intractable left temporal lobe epilepsy in whom we evaluated the relationship between the amplitude recorded from SEEG electrodes, inserted in the lateral temporal region, and their distance from the MEG-modelled spike. We found a quadratic fall-off relationship between the amplitude and distance. This result supports the concept that the MEG dipoles reflect the "centre" of spike locations and may provide comprehensive information for SEEG which records spike activities directly but is inherently limited in spatial sampling.     

Abstracts of the 5th joint meeting of the German, Austrian, and Swiss Sections of the International League Against Epilepsy, Basle, May 16-19, 2007

Presidential Symposium ¹ E. Pataraia
¹ University Hospital of Neurology (Vienna, A) Goals, methodology: Epilepsy surgery is defined as any neurosurgical intervention with the primary goal to relieve intractable epilepsy. On the other hand essential brain regions like primary motor and sensory cortex as well as brain areas supporting language and memory functions have to be spared to avoid neurological deficits caused by the operation. Thus, the exact localization of the epileptogenic zone and of essential brain regions is crucial for the successful surgical treatment of seizures that can only be accomplished during a thorough presurgical work‐up. A new noninvasive brain mapping procedure magnetoencephalography (MEG) was employed during the presurgical evaluation for localization of the epileptogenic zones and for the determination of hemispheric dominance and intrahemispheric localization of linguistic functions in patients with drug‐resistant focal epilepsies. Results: The role of MEG for the localization of the epileptogenic zone in the noninvasive evaluation of patients with focal drug‐resistant epilepsies: We evaluated the sensitivity and selectivity of interictal MEG versus prolonged ictal and interictal scalp video‐ EEG in order to identify patient groups that would benefit from preoperative MEG testing. One hundred thirteen consecutive patients with medically refractory epilepsy who underwent surgery were included. The epileptogenic region predicted by interictal and ictal Video‐EEG (V‐EEG) and MEG was defined in relation to the resected area as perfectly overlapping with the resected area, partially overlapping, or nonoverlapping. Using MEG, we were able to localize the resected region in a greater proportion of patients (72.3%) than with noninvasive V‐EEG (40%). MEG contributed to the localization of the resected region in 58.8% of the patients with a non‐localizing V‐EEG study and 72.8% of the patients for whom V‐EEG only partially identified the resected zone. Overall, MEG and V‐EEG results were equivalent in 32.3% of the cases, and additional localization information was obtained using MEG in 40% of the patients. MEG was most useful for presurgical planning in patients who had either partially or nonlocalizing V‐EEG results. Functional organization of interictal spike complex in medial temporal lobe epilepsies: Thirty patients with mesial temporal lobe epilepsy (MTLE) using combined MEG and EEG recordings were icluded. Spikes could be recorded in 14 patients (47%) during the 2‐ to 3‐h MEG/EEG recording session. The MEG and EEG spikes were subjected to separate dipole analyses and the spike dipole localizations were superimposed on MRI scans. All spike dipoles could be localized to the temporal lobe with a clear preponderance in the medial region. Based on dipole orientations in MEG, patients could be classified into two groups: patients with anterior medial vertical (AMV) dipoles, suggesting epileptic activity in the mediobasal temporal lobe and patients with anterior medial horizontal (AMH) dipoles, indicating involvement of the temporal pole and the anterior parts of the lateral temporal lobe. Whereas patients with AMV dipoles had strictly unitemporal interictal and ictal EEG changes during prolonged video‐EEG monitoring, 50% of patients with AMH dipoles showed evidence of bitemporal affection on interictal and ictal EEG. Nine patients underwent epilepsy surgery so far: all five patients with AMV dipoles became completely seizure‐free postoperatively (Class Ia) and two out of four patients with AMH dipoles experienced persistent auras (Class Ib). Plasticity of the brain mechanisms for receptive language in patients with mesial temporal lobe epilepsy and structural lesions: We examined brain activation profiles for receptive language function in patients with left hemisphere space occupying lesions and patients with left temporal lobe epilepsy due to mesial temporal sclerosis (MTS) to assess whether cross‐ and intrahemispheric plasticity for language varied as a function of lesion type or location. We evaluated 44 patients: 21 patients with MTS and 23 lesional patients. All patients underwent preoperative language mapping while performing a word recognition task. The location of the activity sources was subsequently determined by co‐registering them with MRIs. The number of clustered, contiguous activity sources located in temporal and inferior parietal regions (excluding sources in somatosensory cortices) was then assessed. Hemispheric lateralization of language‐specific magnetic activity was determined as left hemispheric, right hemispheric and bilateral according to relation of the acceptable late activity sources in left and right hemispheres. Patients were classified into two groups based on the location of the cluster(s) of language‐specific activity sources within the dominant hemisphere: typical localization of receptive language‐specific cortex (if the cluster of activity sources fell within the cortical region that is commonly identified as Wernicke's area) and atypical localization of receptive language‐specific cortex (if the cluster of activity sources did not overlap with Wernicke's area). A higher incidence of atypical language lateralization was noted among patients with MTS compared with lesional patients (43% vs. 13%). The majority of MTS patients with early seizure onset (before 5 years of age) showed atypical language lateralization. In contrast, the precise location of receptive language‐specific cortex within the dominant hemisphere was found to be outside of Wernicke's area in 30% of lesional patients and only 14% of MTS patients. There is an increased probability of a partial or total displacement of key components of the brain mechanisms responsible for receptive language function to the nondominant hemisphere in MTS patients. Early onset of seizures was strongly associated with atypical language lateralization. Lesions in the dominant hemisphere tend to result in an intrahemispheric reorganization of linguistic function. Organization of receptive language‐specific cortex before and after left temporal lobectomy: In the present study we documented the reorganization of brain areas mediating receptive language function in patients with left temporal lobe epilepsy after a standard anterior temporal lobe resection. We evaluated which patients were most likely to show a change in the lateralization and localization of the mechanisms supporting receptive language and if such changes were associated with neuropsychological function. The results of preoperative Wada‐testing and pre‐ and post‐operative neuropsychological testing and MEG language mapping were compared. Patients with atypical (bilateral) hemispheric dominance pre‐operatively were significantly more likely than patients with (typical) left‐hemisphere dominance to show evidence of increased right hemisphere participation in language functions after surgery. Patients with left hemispheric dominance preoperatively were more likely to show intra‐hemispheric changes involving a slight inferior shift of the putative location of Wernicke's area. Patients with bilateral representation tended to perform worse on neuropsychological test measures obtained both pre‐ and postoperatively. Interhemispheric functional reorganization of language‐specific areas may occur in patients undergoing left anterior temporal lobectomy. Intrahemispheric reorganization may take place even when the resection does not directly impinge upon Wernicke's area. Conclusions: Combined MEG/EEG dipole modeling can identify subcompartments of the temporal lobe involved in epileptic activity and may be helpful to differentiate between subtypes of mesial temporal lobe epilepsy noninvasively. MEG is most useful for presurgical planning in patients who have either partially or nonlocalizing V‐EEG results in the noninvasive evaluation phase. We predict the replacement of the more invasive procedure with MEG in the near future for temporal lobe epilepsies, subsequent to the optimization of the conditions under which preoperative MEG is performed. MEG can be especially helpful in the localization of language‐critical cortex in sites other than those expected within the dominant hemisphere. Our findings also suggest that not only structural elements, but also functional factors have an effect on receptive language organization in the brain. Factors influencing atypical language lateralization have theoretical importance for understanding the organization and reorganization of higher cognitive functions, as well as practical implications, especially in brain surgery and neurological rehabilitation. MEG is a useful method in clinical practice, as it has the capacity to provide reliable images of the working brain of individual subjects, and it is capable of capturing relevant aspects of brain activation by reflecting the actual participation of a particular area in the function under investigation. Finally, it is capable of capturing both the spatial as well as the temporal features of that activation.     

Enhanced late components of AEFs associated with the temporal lobe lesions

We recorded auditory evoked magnetic fields (AEFs) by presenting pure tone bursts once every 4000 ms in 11 patients with a brain lesion in or in the vicinity of the auditory cortex. AEFs on the damaged side revealed several enhanced deflections in late-latency AEFs (slow AEFs), peaking at approximately 320 (DI), 1030 (D2) and 1600 (D3) ms post-stimulus in eight patients. All the dipoles of slow AEFs were concentrated in the superior temporal regions which were not involved by brain lesions. D1, D2 and D3 dipoles were uniformly upward, downward and upward, respectively. The dipole moment varied from 12 to 122 nAm and had no consistent relationship with latency. This is the first report describing slow AEFs in cases with temporal lobe lesions.     

A temporal lobe factor in verb fluency

Verb fluency requires self-sustained verb retrieval. The brain correlates of this task are virtually unknown. We investigated the relations between verb and noun (semantic) fluency and regional brain perfusion in subjects with varying degrees of cognitive decline, ranging from very mild subjective impairment to Alzheimer's disease (AD). Data consisted of single-photon emission computed tomography (SPECT) data and temporally resolved verb and noun fluency scores from 93 participants. Impaired verb fluency was predicted by a temporal lobe hypoperfusion factor and low education, whereas high age and low perfusion in the parietotemporal-occipital region predicted impaired noun fluency. Analysis of perfusion within the temporal region indicated primary involvement of the temporal pole and medial temporal lobe in AD. This might reflect pathology of the anterior parahippocampal region, which appears early in neurodegenerative disease. Although temporal lobe structures have not usually been implicated in verb processing, early temporal pathology thus appears to contribute to impaired verb fluency in cognitive decline.     

Structural abnormalities in frontal, temporal, and limbic regions and interconnecting white matter tracts in schizophrenic patients with prominent negative symptoms

OBJECTIVE: Imaging studies of schizophrenia have repeatedly demonstrated global abnormalities of cerebral and ventricular volumes. However, pathological changes at more local levels of brain organization have not yet been so clearly characterized because of the few brain regions of interest heretofore included in morphometric analyses as well as heterogeneity of patient samples. METHOD: Dual echo magnetic resonance imaging (MRI) data were acquired at 1.5 T from 27 right-handed patients who met DSM-IV criteria for schizophrenia with enduring negative symptoms and from 27 healthy comparison subjects. Between-group differences in gray and white matter volume were estimated at each intracerebral voxel after registration of the images in standard space. The relationship between clinical symptom scores and brain structure was also examined within the patient group. Spatial statistics and permutation tests were used for inference. RESULTS: Significant deficits of gray matter volume in the patient group were found at three main locations: 1) the left superior temporal gyrus and insular cortex, 2) the left medial temporal lobe (including the parahippocampal gyrus and hippocampus), and 3) the anterior cingulate and medial frontal gyri. The volume of these three regions combined was 14% lower in the patients relative to the comparison subjects. White matter deficits were found in similar locations in the left temporal lobe and extended into the left frontal lobe. The patient group showed a relative excess of gray matter volume in the basal ganglia. Within the patient group, basal ganglia gray matter volume was positively correlated with positive symptom scores. CONCLUSIONS: Anatomical abnormalities in these schizophrenic patients with marked negative symptoms were most evident in left hemispheric neocortical and limbic regions and related white matter tracts. These data are compatible with models that depict schizophrenia as a supraregional disorder of multiple, distributed brain regions and the axonal connections between them.