Tailor-Made Surgery Based on Functional Networks for Intractable Epilepsy.

Normal and pathological networks related to seizure propagation have got attention to elucide complex seizure semiology and contribute to diagnosis and surgical monitoring in epilepsy treatment. Since focal and generalized epileptogenic syndromes abnormalities might involve multiple foci and large-scale networks, we applied electrophysiolpgy (cortco-cortico evoked potential; CCEP), and tractography to make detailed diagnosis for complex syndrome. All 14 epilepsy patients with no or little abnormality on images investigations underwent subdural grid implantation for epilepsy diagnosis. To perform quick network analysis, we recorded and analyzed high gamma activity (HGA) of epileptogenic activity and CCEPs to identify pathological activity distribution and network connectivity. [Results] Pathological CCEPs showed two negative deflections consisting of early (>40 ms) and late (>150 ms) components in electrically stable circumstance at bed side and early CCEPs appeared in 57% of the patients. On the basis of the CCEP findings, tractography detected anatomical connections. Early components of pathological CCEPs diminished after complete disconnection of tractoography-based fibers between the foci in seven of eight cases. One case with residual pathological CCEPs showed poorer outcome. Thirteen (92.8%) patients with or without CCEPs who underwent network surgery had favorable prognosis except for a case with wide traumatic epilepsy. Intraoperative CCEP measurements and HGA mapping enabled visualization of pathological networks and clinical impotence as a biomarker to improve functional prognosis. HGA/CCEP recording should shed light on pathological and complex propagation for epilepsy surgery.

Multispectrum Indocyanine Green Videography for Visualizing Brain Vascular Pathology.

OBJECTIVE: Currently, neurosurgical vascular surgery frequently uses indocyanine green (ICG)-videography (VG) to evaluate the blood flow in brain vessels. Although ICG-VG delineates intravascular ICG fluorescence as a high-intensity signal in gray-scale with dark background, it is hard to identify anatomical structures, including vasculature or surgical devices simultaneously. This report developed combination of a near-infrared (NIR) camera with particular sensitivity and an optical filter to observe the blood-flow conditions and anatomical structures. METHODS: To overcome the specific issues of ICG-VG, we applied a high-sensitivity camera with a 980-nm NIR component to delineate anatomical and fluorescence images, detecting signals between 830 and 1000 nm simultaneously during operation. We used a diluted ICG phantom to evaluate fluorescence signal changes by changing wavelength of the emission light. For clinical use, we used a high-sensitivity NIR camera with a high-pass filter on a surgical microscope. The new NIR system detected signals between 770 and 1000 nm, and the lighting system illuminated objects mainly at 980-nm wavelength. Both images with the blood flow and anatomical structures were projected to the smart glasses in real time. RESULTS: In the phantom experiment, we found that the emission light with wide band widths (575-800 nm) evoked various intensities of ICG fluorescence. This new NIR system allowed us to observe ICG fluorescence and anatomical structures without image fusion or time-delay. The both information of anatomy and fluorescence was projected on wearable smart glasses. Furthermore, the new NIR system detected ICG-fluorescence signals for a longer duration than the original camera, which allowed us to achieve careful and detailed observation of more vasculature and fine vessels. CONCLUSIONS: This study proposes a new NIR system and emphasizes simultaneous observation of anatomy and fluorescence signals during operation. It paves the way for further possibilities in the development of optical systems. To understand the natural phenomena and combination of different scientific and clinical fields, it might be important to understand and combine not only fluorescence, but also natural science, optics, and background pathology. This simple system would be available for neuroendoscope and robotic surgery.

Real-time spectrum quantification of tumor-related fluorescence during neurosurgery: A preliminary report.

OBJECTIVES: The fluorescent dye, 5-aminolevulinic acid (5-ALA), is currently applied for fluorescence-guided resections of high-grade gliomas. Present limitations of this technique are qualitative and subjective analyses, which show little of the background structures. This paper describes the intraoperative quantitative analysis of fluorescence intensity, hot-spot enhancement by frame averaging, and observation of surrounding structures by using 1000-nm lighting in real time. PATIENTS AND METHODS: A sample of diluted protoporphyrin IX (PpIX) in a bottle and 37 samples from nine patients with brain lesions were involved in this study. In this preliminary study, we determined appropriate conditions for image averaging and filters and selected the most sensitive spectrometer. In addition, we utilized a 1000-nm lighting system to visualize surrounding structures with no interference from PpIX fluorescence. RESULTS: The novel system permitted the real-time quantitative analysis of PpIX fluorescence in operative fields by illuminating structures with 1000-nm-lighting. The real-time quantification provided subjective evaluations for surgical decision-making. We found good correlations between the fluorescence and PpIX contents in brain tissue. Furthermore, 1000-nm lighting visualized the anatomical structures and PpIX fluorescence simultaneously. CONCLUSION: The combination of spectroscopy and a 1000-nm lighting system could enable surgeons to create a spectrogram of targets of interest while observing background structures. The spectrometer that we selected is highly sensitive to PpIX fluorescence and enables us to perform intraoperative real-time tissue mapping. By using a real-time system, we can perform quantitative and objective evaluations to achieve maximal tumor resection.

Advanced dynamic statistical parametric mapping with MEG in localizing epileptogenicity of the bottom of sulcus dysplasia.

OBJECTIVE: To investigate whether advanced dynamic statistical parametric mapping (AdSPM) using magnetoencephalography (MEG) can better localize focal cortical dysplasia at bottom of sulcus (FCDB). METHODS: We analyzed 15 children with diagnosis of FCDB in surgical specimen and 3 T MRI by using MEG. Using AdSPM, we analyzed a ±50 ms epoch relative to each single moving dipole (SMD) and applied summation technique to estimate the source activity. The most active area in AdSPM was defined as the location of AdSPM spike source. We compared spatial congruence between MRI-visible FCDB and (1) dipole cluster in SMD method; and (2) AdSPM spike source. RESULTS: AdSPM localized FCDB in 12 (80%) of 15 children whereas dipole cluster localized six (40%). AdSPM spike source was concordant within seizure onset zone in nine (82%) of 11 children with intracranial video EEG. Eleven children with resective surgery achieved seizure freedom with follow-up period of 1.9 ±â€¯1.5 years. Ten (91%) of them had an AdSPM spike source in the resection area. CONCLUSION: AdSPM can noninvasively and neurophysiologically localize epileptogenic FCDB, whether it overlaps with the dipole cluster or not. SIGNIFICANCE: This is the first study to localize epileptogenic FCDB using MEG.

Disconnection of the pathological connectome for multifocal epilepsy surgery.

OBJECTIVERecent neuroimaging studies suggest that intractable epilepsy involves pathological functional networks as well as strong epileptogenic foci. Combining cortico-cortical evoked potential (CCEP) recording and tractography is a useful strategy for mapping functional connectivity in normal and pathological networks. In this study, the authors sought to demonstrate the efficacy of preoperative combined CCEP recording, high gamma activity (HGA) mapping, and tractography for surgical planning, and of intraoperative CCEP measures for confirmation of selective pathological network disconnection.METHODSThe authors treated 4 cases of intractable epilepsy. Diffusion tensor imaging-based tractography data were acquired before the first surgery for subdural grid implantation. HGA and CCEP investigations were done after the first surgery, before the second surgery was performed to resect epileptogenic foci, with continuous CCEP monitoring during resection.RESULTSAll 4 patients in this report had measurable pathological CCEPs. The mean negative peak-1 latency of normal CCEPs related to language functions was 22.2 ± 3.5 msec, whereas pathological CCEP latencies varied between 18.1 and 22.4 msec. Pathological CCEPs diminished after complete disconnection in all cases. At last follow-up, all of the patients were in long-term postoperative seizure-free status, although 1 patient still suffered from visual aura every other month.CONCLUSIONSCombined CCEP measurement, HGA mapping, and tractography greatly facilitated targeted disconnection of pathological networks in this study. Although CCEP recording requires technical expertise, it allows for assessment of pathological network involvement in intractable epilepsy and may improve seizure outcome.

Clinical Impact and Implication of Real-Time Oscillation Analysis for Language Mapping.

BACKGROUND: We developed a functional brain analysis system that enabled us to perform real-time task-related electrocorticography (ECoG) and evaluated its potential in clinical practice. We hypothesized that high gamma activity (HGA) mapping would provide better spatial and temporal resolution with high signal-to-noise ratios. METHODS: Seven awake craniotomy patients were evaluated. ECoG was recorded during language tasks using subdural grids, and HGA (60-170 Hz) maps were obtained in real time. The patients also underwent electrocortical stimulation (ECS) mapping to validate the suspected functional locations on HGA mapping. The results were compared and calculated to assess the sensitivity and specificity of HGA mapping. For reference, bedside HGA-ECS mapping was performed in 5 epilepsy patients. RESULTS: HGA mapping demonstrated functional brain areas in real time and was comparable with ECS mapping. Sensitivity and specificity for the language area were 90.1% ± 11.2% and 90.0% ± 4.2%, respectively. Most HGA-positive areas were consistent with ECS-positive regions in both groups, and there were no statistical between-group differences. CONCLUSIONS: Although this study included a small number of subjects, it showed real-time HGA mapping with the same setting and tasks under different conditions. This study demonstrates the clinical feasibility of real-time HGA mapping. Real-time HGA mapping enabled simple and rapid detection of language functional areas in awake craniotomy. The mapping results were highly accurate, although the mapping environment was noisy. Further studies of HGA mapping may provide the potential to elaborate complex brain functions and networks.

Passive language mapping combining real-time oscillation analysis with cortico-cortical evoked potentials for awake craniotomy.

OBJECTIVE Electrocortical stimulation (ECS) is the gold standard for functional brain mapping; however, precise functional mapping is still difficult in patients with language deficits. High gamma activity (HGA) between 80 and 140 Hz on electrocorticography is assumed to reflect localized cortical processing, whereas the cortico-cortical evoked potential (CCEP) can reflect bidirectional responses evoked by monophasic pulse stimuli to the language cortices when there is no patient cooperation. The authors propose the use of "passive" mapping by combining HGA mapping and CCEP recording without active tasks during conscious resections of brain tumors. METHODS Five patients, each with an intraaxial tumor in their dominant hemisphere, underwent conscious resection of their lesion with passive mapping. The authors performed functional localization for the receptive language area, using real-time HGA mapping, by listening passively to linguistic sounds. Furthermore, single electrical pulses were delivered to the identified receptive temporal language area to detect CCEPs in the frontal lobe. All mapping results were validated by ECS, and the sensitivity and specificity were evaluated. RESULTS Linguistic HGA mapping quickly identified the language area in the temporal lobe. Electrical stimulation by linguistic HGA mapping to the identified temporal receptive language area evoked CCEPs on the frontal lobe. The combination of linguistic HGA and frontal CCEPs needed no patient cooperation or effort. In this small case series, the sensitivity and specificity were 93.8% and 89%, respectively. CONCLUSIONS The described technique allows for simple and quick functional brain mapping with higher sensitivity and specificity than ECS mapping. The authors believe that this could improve the reliability of functional brain mapping and facilitate rational and objective operations. Passive mapping also sheds light on the underlying physiological mechanisms of language in the human brain.

The presence of short and sharp MEG spikes implies focal cortical dysplasia.

PURPOSE: This study focused on the characteristic needle-like epileptic spikes of short duration and steep shape seen on magnetoencephalography (MEG) in patients diagnosed with focal cortical dysplasia (FCD) morphologically. We aimed to validate the analysis of MEG spike morphology as a noninvasive method of identifying the presence and location of FCD. METHODS: MEG was collected by 204-channel helmet-shaped gradiometers. We analyzed MEG spike sources for 282 patients with symptomatic localization-related epilepsy. MEG showed clustered equivalent current dipoles when superimposed on their three-dimensional-magnetic resonance images (MRI) in 85 patients. Fifty-seven patients were excluded from our study, because they had destructive brain lesions or an insufficient number of spikes for statistical analysis. Twenty-eight patients (18 males, 10 females; aged 1-34 years) were finally matched to our inclusion criteria, and were categorized into three groups: FCD (7 patients), non-FCD (10 patients), and non-lesion (11 patients), based on the MRI findings. We measured the duration, amplitude, and tilt manually for at least 15 spikes per patient, and compared the three groups using a one-way analysis of variance, followed by the Tukey test when statistically significant (p < 0.05). In 17 patients with visible MRI lesions, we investigated the correlation between the depth of the lesion and the tilt using the Pearson product moment correlation. RESULTS: The average spike duration was significantly shorter in the FCD and non-lesion groups than in the non-FCD group (p < 0.05). The average amplitude was not significantly different between the three groups. The average spike tilt was significantly steeper in the FCD group than in the non-FCD group (p = 0.0058). There was no significant difference between FCD and non-lesion patients in both duration and tilt. Our additional study revealed a significant negative correlation between the depth of the lesion and the average tilt (p = 0.0009). SIGNIFICANCE: MEG epileptiform discharges of short duration and steep tilt characterize FCD, especially when located at the superficial neocortical gyrus. We speculate that this particular spike morphology results from the intrinsic epileptogenicity of FCD. Morphological analysis of MEG spikes can evaluate the etiology of epileptogenic lesions and detect a strong, localized epileptogenic focus such as that typically observed in FCD.

Advantageous information provided by magnetoencephalography for patients with neocortical epilepsy.

PURPOSE: We evaluated whether magnetoencephalography (MEG), in addition to surgery, was valuable for the diagnosis and management of epileptic syndromes in patients with neocortical epilepsy (NE). METHODS: We studied MEG in 73 patients (29 females; aged 1-26years; mean 10.3years) for the clinical diagnosis of epilepsy and for preoperative evaluation. MEG data were recorded by 204-channel whole head gradiometers with a 600Hz sampling rate. MEG spike sources were localized on magnetic resonance images (MRI) using a single dipole model to project equivalent current dipoles. RESULTS: MEG localized an epileptic focus with single clustered dipoles in 24 (33%) of 73 NE patients: 16 (25%) of 64 symptomatic localization-related epilepsy (SLRE) patients and eight (89%) of nine idiopathic localization-related epilepsy (ILRE) patients. MEG provided advantageous information in 12 (50%) of 24 patients with clustered dipoles and confirmed the diagnosis in the remaining 12 (50%). Furthermore, the use of MEG resulted in changes to surgical treatments in nine (38%) patients and in medical management in eight (33%). MEG confirmed the diagnosis in eight (16%) of 49 patients with scattered dipoles. MRI identified a single lesion (28 patients, 38%), multiple lesions (5, 7%), and no lesion (40, 55%). MRI provided confirming information in 19 of 28 patients with a single lesion and 18 of them required surgical resections. MRI did not provide any supportive information in 54 (74%) patients with a single (9), multiple (5) and no lesion (40). CONCLUSION: Our study shows that MEG provides fundamental information to aid the choice of diagnostic and therapeutic procedures including changes in medication in addition to surgical treatments for NE.

Magnetoencephalographic analysis of paroxysmal fast activity in patients with epileptic spasms.

PURPOSE: This study sought to demonstrate the origin and propagation of paroxysmal fast activity (PFA) in patients with epileptic spasms (ESs), using time-frequency analyses of magnetoencephalogram (MEG) PFA recordings. METHODS: A 204-channel helmet-shaped MEG, with a 600Hz sampling rate, was used to examine PFA in 3 children with ESs. We analyzed MEG recordings of PFA by short-time Fourier transform and the aberrant area or high-power spectrum was superimposed onto reconstructed three-dimensional magnetic resonance images as moving images. One ictal discharge was collected. One child and one adult with PFA due to Lennox-Gastaut syndrome were also examined for comparison. RESULTS: All four PFAs in Patient 1 and five PFAs in Patient 3 were generated from one hemisphere. In Patient 2, four of seven PFAs were generated from one hemisphere and the remaining three were generated from both hemispheres. In Patient 3, one ictal MEG showed ictal discharges that were generated from the same area as the PFA, although the electroencephalogram showed no discharge. In Patients with Lennox-Gastaut syndrome, all 10 PFAs were generated from bilateral hemispheres simultaneously. CONCLUSION: Short-time Fourier transform analyses of MEG PFA can show the origin and form of propagation of PFA. These results suggest that ESs are representative of focal seizures and the mechanism of PFA is different between ESs and Lennox-Gastaut syndrome.

The applications of time-frequency analyses to ictal magnetoencephalography in neocortical epilepsy.

PURPOSE: Ictal magenetoencephalographic (MEG) discharges convey significant information about ictal onset and propagation, but there is no established method for analyzing ictal MEG. This study sought to clarify the usefulness of time-frequency analyses using short-time Fourier transform (STFT) for ictal onset and propagation of ictal MEG activity in patients with neocortical epilepsy. METHODS: Four ictal MEG discharges in two patients with perirolandic epilepsy and one with frontal lobe epilepsy (FLE) were evaluated by time-frequency analyses using STFT. Prominent oscillation bands were collected manually and the magnitudes of those specific bands were superimposed on individual 3D-magnetic resonance images. RESULTS: STFT showed specific rhythmic activities from alpha to beta bands at the magnetological onset in all four ictal MEG records. Those activities were located at the vicinity of interictal spike sources, as estimated by the single dipole method (SDM), and two of the four ictal rhythmic activities promptly propagated to ipsilateral or bilateral cerebral cortices. The patients with FLE and perirolandic epilepsy underwent frontal lobectomy and resection of primary motor area, respectively including the origin of high-magnitude areas of a specific band indicated by STFT, and have been seizure free after the surgery. CONCLUSIONS: STFT for ictal MEG discharges readily demonstrated the ictal onset and propagation. These data were important for decisions on surgical procedure and extent of resection. Ictal MEG analyses using STFT could provide a powerful tool for noninvasive evaluation of ictal onset zone.

Generalized spike-wave discharges involve a default mode network in patients with juvenile absence epilepsy: a MEG study.

This study uses magnetoencephalography (MEG) to examine whether cortical regions that constitute a default mode network are involved during generalized spike-wave discharges (GSWs) in patients with juvenile absence epilepsy (JAE). We studied five JAE patients for whom MEG was recorded using a 204-channel, whole-head gradiometer system. Dynamic statistical parametric mapping (dSPM) was done to estimate the cortical source distribution of GSW. The dSPM results showed strong medial prefrontal activation in all patients, with activation in the posterior cingulate and precuneus in three of five patients simultaneously or slightly after medial prefrontal activation. Furthermore, dSPM showed that the initial activation of a GSW appears in the focal cortical regions. Cortical regions that constitute a default mode network are strongly involved in the GSW process in some patients with JAE. Results also show that focal cortical activation appears at the onset of a GSW.

Comprehension of degraded speech sounds with m-sequence modulation: an fMRI study.

In a recent electroencephalography (EEG) study (Takeichi et al., 2007a), we developed a new technique for assessing speech comprehension using speech degraded by m-sequence modulation and found a correlation peak with a 400-ms delay. This peak depended on the comprehensibility of the modulated speech sounds. Here we report the results of a functional magnetic resonance imaging (fMRI) experiment comparable to our previous EEG experiment. We examined brain areas related to verbal comprehension of the modulated speech sound to examine which neural system processes this modulated speech. A non-integer, alternating-block factorial design was used with 23 Japanese-speaking participants, with time reversal and m-sequence modulation as factors. A main effect of time reversal was found in the left temporal cortex along the superior temporal sulcus (BA21 and BA39), left precentral gyrus (BA6) and right inferior temporal gyrus (BA21). A main effect of modulation was found in the left postcentral gyrus (BA43) and the right medial frontal gyri (BA6) as an increase by modulation and in the left temporal cortex (BA21, 39), parahippocampal gyrus (BA34), posterior cingulate (BA23), caudate and thalamus and right superior temporal gyrus (BA38) as a decrease by modulation. An interaction effect associated specifically with non-modulated speech was found in the left frontal gyrus (BA47), left occipital cortex in the cuneus (BA18), left precuneus (BA7, 31), right precuneus (BA31) and right thalamus (forward>reverse). The other interaction effect associated specifically with modulation of speech sound was found in the inferior frontal gyrus in the opercular area (BA44) (forward>reverse). Estimated scalp projection of the component correlation function (Cao et al., 2002) for the corresponding EEG data (Takeichi et al., 2007a, showed leftward dominance. Hence, activities in the superior temporal sulcus (BA21 and BA39), which are commonly observed for speech processing, as well as left precentral gyrus (BA6) and left inferior frontal gyrus in the opercular area (BA44) is suggested to contribute to the comprehension-related EEG signal.

MEG time-frequency analyses for pre- and post-surgical evaluation of patients with epileptic rhythmic fast activity.

PURPOSE: To evaluate the effectiveness of surgery for epilepsy, we analyzed rhythmic fast activity by magnetoencephalography (MEG) before and after surgery using time-frequency analysis. To assess reliability, the results obtained by pre-surgical MEG and intraoperative electrocorticography were compared. METHODS: Four children with symptomatic localization-related epilepsy caused by circumscribed cortical lesion were examined in the present study using 204-channel helmet-shaped MEG with a sampling rate of 600Hz. One patient had dysembryoplastic neuroepithelial tumor (DNT) and three patients had focal cortical dysplasia (FCD). Aberrant areas were superimposed, to reconstruct 3D MRI images, and illustrated as moving images. RESULTS: In three patients, short-time Fourier transform (STFT) analyses of MEG showed rhythmic activities just above the lesion with FCD and in the vicinity of DNT. In one patient with FCD in the medial temporal lobe, rhythmic activity appeared in the ipsilateral frontal lobe and temporal lateral aspect. These findings correlate well with the results obtained by intraoperative electrocorticography. After the surgery, three patients were relieved of their seizures, and the area of rhythmic MEG activity disappeared or become smaller. One patient had residual rhythmic MEG activity, and she suffered from seizure relapse. CONCLUSION: Time-frequency analyses using STFT successfully depicted MEG rhythmic fast activity, and would provide valuable information for pre- and post-surgical evaluations to define surgical strategies for patients with epilepsy.

The motor-evoked potential threshold evaluated by tractography and electrical stimulation.

OBJECT: To validate the corticospinal tract (CST) illustrated by diffusion tensor imaging, the authors used tractography-integrated neuronavigation and direct fiber stimulation with monopolar electric currents. METHODS: Forty patients with brain lesions adjacent to the CST were studied. During the operation, the motor responses (motor evoked potential [MEP]) elicited at the hand by the cortical stimulation to the hand motor area were continuously monitored, maintaining the consistent stimulus intensity (mean 15.1 +/- 2.21 mA). During lesion resection, direct fiber stimulation was applied to elicit MEP (referred to as fiber MEP) to identify the CST functionally. The threshold intensity for the fiber MEP was determined by searching for the best stimulus point and changing the stimulus intensity. The minimum distance between the resection border and illustrated CST was measured on postoperative isotropic images. RESULTS: Direct fiber stimulation demonstrated that tractography accurately reflected anatomical CST functioning. There were strong correlations between stimulus intensity for the fiber MEP and the distance between the CST and the stimulus points. The results indicate that the minimum stimulus intensity of 20, 15, 10, and 5 mA had stimulus points approximately 16, 13.2, 9.6, and 4.8 mm from the CST, respectively. The convergent calculation formulated 1.8 mA as the electrical threshold of the CST for the fiber MEP, which was much smaller than that of the hand motor area. CONCLUSIONS: The investigators found that diffusion tensor imaging-based tractography is a reliable way to map the white matter connections in the entire brain in clinical and basic neuroscience applications. By combining these techniques, investigating the cortical-subcortical connections in the human CNS could contribute to elucidating the neural networks of the human brain and shed light on higher brain functions.

Aberrant somatosensory-evoked responses imply GABAergic dysfunction in Angelman syndrome.

A role for gamma-aminobutyric acid (GABA)ergic inhibition in cortical sensory processing is one of the principle concerns of brain research. Angelman syndrome (AS) is thought to be one of the few neurodevelopmental disorders with GABAergic-related genetic involvement. AS results from a functional deficit of the imprinted UBE3A gene, located at 15q11-q13, resulting mainly from a 4-Mb deletion that includes GABA(A) receptor subunit genes. These genes are believed to affect the GABAergic system and modulate the clinical severity of AS. To understand the underlying cortical dysfunction, we have investigated the primary somatosensory-evoked responses in AS patients. Subjects included eleven AS patients with a 15q11-q13 deletion (AS Del), two AS patients without a 15q11-q13 deletion, but with a UBE3A mutation (AS non-Del), six epilepsy patients (non-AS) and eleven normal control subjects. Somatosensory-evoked fields (SEFs) in response to median nerve stimulation were measured by magnetoencephalography. The N1m peak latency in AS Del patients was significantly longer (34.6+/-4.8 ms) than in non-AS patients (19.5+/-1.2 ms, P<0.001) or normal control subjects (18.4+/-1.8 ms, P<0.001). The next component, P1m, was prolonged and ambiguous and was only detected in patients taking clonazepam. In contrast, SEF waveforms of AS non-Del patients were similar to those of control individuals, rather than to AS Del patients. Thus, GABAergic dysfunction in AS Del patients is likely due to hemizygosity of GABA(A) receptor subunit genes, suggesting that GABAergic inhibition plays an important role in synchronous activity of human sensory systems.

Magnetoencephalographic studies of focal epileptic activity in three patients with epilepsy suggestive of Lennox-Gastaut syndrome.

PURPOSE: To determine the electromagnetic sources of localized epileptic activities using magnetoencephalography (MEG) in three adult patients with epilepsy suggestive of Lennox-Gastaut syndrome (LGS). METHODS: MEG and simultaneous electroencephalography (EEG) were recorded from three adult patients using a 204-channel, whole-head MEG system. Equivalent current dipoles (ECDs) were calculated for epileptic spikes on MEG according to the single dipole model. RESULTS: In two patients, MEG showed epileptiform discharges restricted to the unilateral temporal area, corresponding to the EEG spikes. The ECDs calculated from these MEG spikes were clustered in the unilateral temporal lobe. In our third patient, MEG spikes appeared in the right centroparietal area; ECDs were located to the right parietal lobe. CONCLUSIONS: The sources of epileptiform discharges that were detected in a restricted area were localized to specific parts of the brain cortex. Despite certain limitations (small number of patients; atypical late-onset epilepsy in one) our study suggests that MEG may prove to be a useful tool for investigating electromagnetic features of localized epileptic discharges in patients with LGS. Based on these preliminary results, further studies performed in patients with typical LGS features are justified.

Expressive and receptive language areas determined by a non-invasive reliable method using functional magnetic resonance imaging and magnetoencephalography.

OBJECTIVE: It is known that functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) are sensitive to the frontal and temporal language function, respectively. Therefore, we established combined use of fMRI and MEG to make reliable identification of the global language dominance in pathological brain conditions. METHODS: We investigated 117 patients with brain lesions whose language dominance was successfully confirmed by the Wada test. All patients were asked to generate verbs related to acoustically presented nouns (verb generation) for fMRI and to read three-letter words for fMRI and MEG. RESULTS: fMRI typically showed prominent activations in the inferior and middle frontal gyri, whereas calculated dipoles on MEG typically clustered in the superior temporal region and the fusiform gyrus of the dominant hemisphere. A total of 87 patients were further analyzed using useful data from both the combined method and the Wada test. Remarkably, we observed a 100% match of the combined method results with the results of the Wada test, including two patients who showed expressive and receptive language areas dissociated into bilateral hemispheres. CONCLUSION: The results demonstrate that this non-invasive and repeatable method is not only highly reliable in determining language dominance, but can also locate the expressive and receptive language areas separately. The method may be a potent alternative to invasive procedures of the Wada test and useful in treating patients with brain lesions.

Functional identification of the primary motor area by corticospinal tractography.

OBJECTIVE: For quick and stable identification of the primary motor area (PMA), diffusion tensor imaging (DTI) data were acquired and corticospinal tractography was mathematically visualized. METHODS: Data sets of DTI, anatomic magnetic resonance imaging, and functional magnetic resonance imaging with finger-tapping tasks were acquired during the same investigation in 30 patients with a brain lesion affecting the motor system. Off-line processing of DTI data was performed to visualize the corticospinal tract, placing a seed area in the cerebral peduncle of the midbrain, where the corticospinal tract is densely concentrated. Somatosensory evoked magnetic fields and intraoperative cortical somatosensory evoked potentials were recorded with electrical stimulation of the median nerve to confirm the results of the corticospinal tractography. RESULTS: Functional magnetic resonance imaging and somatosensory evoked magnetic fields failed to identify the PMA in eight patients (16.7%) and one patient (3.8%) investigated, respectively, because of cortical dysfunctions caused by brain lesions. DTI data were acquired within 3 minutes without patient tasks. Using the appropriate seed area and fractional anisotropy, corticospinal tractography successfully indicated the PMA location in all patients. The suspected PMA and central sulcus locations were confirmed by the cortical somatosensory evoked potentials. CONCLUSION: Corticospinal tractography enables identification of the PMA and is beneficial, particularly for patients who present with dysfunction of the PMA.

Neuromagnetic source localization of epileptiform activity in patients with graphogenic epilepsy.

PURPOSE: To clarify the source localization of epileptiform activity by using magnetoencephalography (MEG) in patients with graphogenic epilepsy. METHODS: MEG and simultaneous EEG were recorded with a 204-channel whole-head MEG system in two patients with graphogenic epilepsy. During the MEG recordings, the patients performed a set of tasks comprising mental arithmetic calculation, speaking, moving the right arm in a manner resembling writing, writing, and thinking of writing. Equivalent current dipoles (ECD) were calculated for epileptiform discharges on MEG by using a single-dipole model. The ECD were superimposed on the magnetic resonance images of the patients. RESULTS: The task of writing provoked seizures, in which both patients jerked the right arms. Thinking of writing also induced these seizures. In both patients, EEG associated with the seizures showed bursts of spike-and-slow-wave complexes predominantly in the centroparietal region. MEG also showed epileptiform discharges corresponding to the EEG bursts. ECDs obtained from the discharges were clustered in the left centroparietal area. CONCLUSIONS: Thinking of writing was a trigger for the seizures, as well as the task of writing. The source of the epileptiform discharge associated with the seizures was localized in the unilateral centroparietal area. The findings suggest that the centroparietal region plays an important role in the pathophysiology underlying these two graphogenic epilepsy cases.