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Panagiotis G. Simos, Eduardo M. Castillo, Jack M. Fletcher, David J. Francis, Fernando Maestu, Joshua I. Breier, William W. Maggio, and Andrew C. Papanicolaou

Object. There are conflicting claims in the functional imaging literature concerning whether different languages are represented by distinct brain mechanisms in individuals who are proficient in more than one language. This interesting theoretical issue has practical implications when functional imaging methods are used for presurgical language mapping. To address this issue the authors compared the location and extent of receptive language cortex specific to English and Spanish in neurologically intact bilingual volunteers by using magnetic source imaging.

Methods. Areas of the cortex that were specialized for receptive language functions were identified separately for each language in 11 healthy adults who were bilingual in English and Spanish. The authors performed exactly the same procedures used routinely for presurgical receptive language mapping. In each bilingual individual, the receptive language—specific map always encompassed the posterior portion of the superior temporal gyrus. In every case, however, substantial differences in the receptive language maps were also observed for the two languages, regardless of whether each participant's first language was English or Spanish.

Conclusions. Although the reasons for such differences and their ultimate significance in identifying the cerebral mechanisms of language are subject to continuing investigation, their presence is noteworthy and has practical implications for the surgical management of patients with lesions in the temporal and parietal regions of the dominant hemisphere.

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Po Ching Chen, Steven A. Messina, Eduardo Castillo, James Baumgartner, Joo Hee Seo, Holly Skinner, Elakkat D. Gireesh, and Ki Hyeong Lee


Generalized-onset seizures are usually conceptualized as engaging bilaterally distributed networks with no clear focus. However, the authors previously reported a case series demonstrating that in some patients with generalized-onset seizures, focal seizure onset could be discovered after corpus callosotomy. The corpus callosum is considered to be a major pathway for seizure generalization in this group of patients. The authors hypothesized that, in patients with generalized-onset seizures, the structure of the corpus callosum could be different between patients who have lateralized seizures and those who have nonlateralized seizures after corpus callosotomy. The authors aimed to evaluate the structural difference through statistical analysis of diffusion tensor imaging (DTI) scalars between these two groups of patients.


Thirty-two patients diagnosed with generalized-onset motor seizures and without an MRI lesion were included in this study. Among them, 16 patients developed lateralized epileptic activities after corpus callosotomy, and the remaining 16 patients continued to have nonlateralized seizures after corpus callosotomy. Presurgical DTI studies were acquired to quantify the structural integrity of the corpus callosum.


The DTI analysis showed significant reduction of fractional anisotropy (FA) and increase in radial diffusivity (RD) in the body of the corpus callosum in the lateralized group compared with the nonlateralized group.


The authors’ findings indicate the existence of different configurations of bilateral epileptic networks in generalized epilepsy. Generalized seizures with focal onset relying on rapid spread through the corpus callosum might cause more structural damage related to demyelination in the corpus callosum, showing reduced FA and increased RD. This study suggests that presurgical DTI analysis of the corpus callosum might predict the seizure lateralization after corpus callosotomy.

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Elakkat D. Gireesh, Kihyeong Lee, Holly Skinner, Joohee Seo, Po-Ching Chen, Michael Westerveld, Richard D. Beegle, Eduardo Castillo, and James Baumgartner


The goal of this study was to assess the success rate and complications of stereo-electroencephalogra-phy (sEEG) and laser interstitial thermal therapy (LITT) in the treatment of nonlesional refractory epilepsy in cingulate and insular cortex.


The authors retrospectively analyzed the treatment response in 9 successive patients who underwent insular or cingulate LITT for nonlesional refractory epilepsy at their center between 2011 and 2019. Localization of seizures was based on inpatient video-EEG monitoring, neuropsychological testing, 3-T MRI, PET scan, magnetoencephalography scan, and/or ictal SPECT scan. Eight patients underwent sEEG, and 1 patient had implantation of both sEEG electrodes and subdural grids for localization of epileptogenic zones. LITT was performed in 5 insular cases (4 left and 1 right) and 3 cingulate cases (all left-sided). One patient also underwent both insular and cingulate LITT on the left side. All of the patients who underwent insular LITT as well as 2 of the 3 who underwent cingulate LITT were right-hand dominant. The patient who underwent insular plus cingulate LITT was also right-hand dominant.


Following LITT, 67% of the patients were seizure free (Engel class I) at follow-up (mean 1.35 years, range 0.6–2.8 years). All patients responded favorably to treatment (Engel class I–III). Two patients developed small intracranial hemorrhages during the sEEG implantation that did not require surgical management. One patient developed a large intracranial hemorrhage during an insular LITT procedure that did require surgical management. That patient experienced aphasia, incoordination, and hemiparesis, which resolved with inpatient rehabilitation. No permanent neurological deficits were noted in any of the patients at last follow-up. Neuropsychological status was stable in this cohort before and after LITT.


sEEG can be safely used to localize seizures originating from insular and cingulate cortex. LITT can successfully treat seizures arising from these deep-seated structures. The insula and cingulum should be evaluated more frequently for seizure onset zones.

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Hideaki Ishibashi, Panagiotis G. Simos, Eduardo M. Castillo, William W. Maggio, James W. Wheless, Howard L. Kim, Vijay Venkataraman, Daniel K. Sanders, Joshua I. Breier, Wenbo Zhang, Robert N. Davis, and Andrew C. Papanicolaou

Object. Magnetoencephalography (MEG) is a novel noninvasive diagnostic tool used to determine preoperatively the location of the epileptogenic zone in patients with epilepsy. The presence of focal slowing of activity recorded by electroencephalography (EEG) is an additional indicator of an underlying pathological condition in cases of intractable mesial temporal lobe epilepsy (MTLE). In the present study the authors examined the significance of focal, slow-wave and interictal spike activity detected using MEG in 29 patients who suffered from MTLE that was not associated with structural brain lesions.

Methods. All patients underwent resective surgery after MEG and EEG monitoring. Equivalent single-dipole modeling was applied to focal low-frequency magnetic activity (LFMA) and interictal paroxysmal activity. Lateralized LFMA was defined as trains of rhythmic activity over the temporal area, with frequencies lower than 7 Hz, which were easily distinguished from background activity.

Lateralized LFMA was found in 17 patients (58.6%); it always occurred on the side ipsilateral to the side of resection and displayed a maximum amplitude over the temporal area. Dipolar sources of magnetic flux computed during slow-wave trains were found in the majority of cases in the posterior superior temporal region and, occasionally, in mesial temporal structures that were subsequently resected. With respect to lateralization there was never disagreement between LFMA and MEG interictal spike sources. Thus, in patients with MTLE that is not associated with a mass lesion LFMA is topographically related to the epileptogenic area and, therefore, has value for reliable determination of the side and, possibly, the location of this area.

Conclusions. Although focal slowing of EEG background activity is generally considered to be a nonspecific sign of functional disturbance, interictal LFMA in patients with MTLE should be conceptualized as a distinct electrographic phenomenon that is directly related to the epileptogenic abnormality. Analyzing the interictal MEG distribution of LFMA and sharp activity improves the diagnostic utility of MEG in patients with suspected TLE who are undergoing surgical evaluation.

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Andrew C. Papanicolaou, Panagiotis G. Simos, Eduardo M. Castillo, Joshua I. Breier, Shirin Sarkari, Ekaterina Pataraia, Rebecca L. Billingsley, Scott Buchanan, James Wheless, Vijayalakshmi Maggio, and William W. Maggio

Object. In this study the authors evaluated the sensitivity and selectivity of a noninvasive language mapping procedure based on magnetoencephalography (MEG), for determining hemispheric dominance for language functions.

Methods. Magnetic activation profiles of the brain were obtained from 100 surgical candidates (age range 8–56 years) with medically intractable seizure disorder by using a whole-head MEG system within the context of a word recognition task. The degree of language-specific activity was indexed according to the number of consecutive sources (modeled as single, moving current dipoles) in perisylvian brain areas. Only activity sources that were observed with a high degree of spatial and temporal overlap in two split-half data sets were used to compute the MEG laterality index. Independently, all patients underwent Wada testing for the determination of hemispheric dominance for language.

Independent clinical judgments based on MEG and Wada data showed a high degree of concordance (87%). Magnetoencephalography laterality judgments had an overall sensitivity of 98%, but a lower selectivity of 83%, which was due to the fact that MEG detected more activity in the nondominant hemisphere than was predicted based on the Wada test. A number of objective criteria were derived based on this large patient series to ensure data quality and bolster the clinical usefulness of MEG for language mapping.

Conclusions. Although the availability of MEG is still limited across epilepsy surgery centers, this study method may be substituted for the Wada procedure in assessing hemispheric dominance for language in select cases.