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Visual inputs can distort auditory perception, and accurate auditory processing requires the ability to detect and ignore visual input that is simultaneous and incongruent with auditory information. However, the neural basis of this auditory selection from audiovisual information is unknown, whereas integration process of audiovisual inputs is intensively researched. Here, we tested the hypothesis that the inferior frontal gyrus (IFG) and superior temporal sulcus (STS) are involved in top-down and bottom-up processing, respectively, of target auditory information from audiovisual inputs. We recorded high gamma activity (HGA), which is associated with neuronal firing in local brain regions, using electrocorticography while patients with epilepsy judged the syllable spoken by a voice while looking at a voice-congruent or -incongruent lip movement from the speaker. The STS exhibited stronger HGA if the patient was presented with information of large audiovisual incongruence than of small incongruence, especially if the auditory information was correctly identified. On the other hand, the IFG exhibited stronger HGA in trials with small audiovisual incongruence when patients correctly perceived the auditory information than when patients incorrectly perceived the auditory information due to the mismatched visual information. These results indicate that the IFG and STS have dissociated roles in selective auditory processing, and suggest that the neural basis of selective auditory processing changes dynamically in accordance with the degree of incongruity between auditory and visual information. [ABSTRACT FROM AUTHOR]

Objective Resective surgery for mesial temporal lobe epilepsy ( MTLE) with a correspondent lesion has been established as an effective and safe procedure. Surgery for temporal lobe epilepsies with bilateral hippocampal sclerosis or without correspondent lesions, however, carries a higher risk of devastating memory decline, underscoring the importance of establishing the memory-dominant side preoperatively and adopting the most appropriate procedure. In this study, we focused on high gamma activities ( HGAs) in the parahippocampal gyri and investigated the relationship between memory-related HGAs and memory outcomes after hippocampal transection ( HT), a hippocampal counterpart to neocortical multiple subpial transection. The transient nature of memory worsening after HT provided us with a rare opportunity to compare HGAs and clinical outcomes without risking permanent memory disorders. Methods We recorded electrocorticography from parahippocampal gyri of 18 patients with temporal lobe epilepsy while they executed picture naming and recognition tasks. Memory-related HGA was quantified by calculating differences in power amplification of electrocorticography signals in a high gamma range (60-120 Hz) between the two tasks. We compared memory-related HGAs from correctly recognized and rejected trials (hit- HGA and reject- HGA). Using hit- HGA, we determined HGA-dominant sides and compared them with memory outcomes after HT performed on seven patients. Results We observed memory-related HGA mainly between 500 and 600 msec poststimulus. Hit- HGA was significantly higher than reject- HGA. Three patients who had surgery on the HGA-dominant side experienced transient memory worsening postoperatively. The postoperative memory functions of the other four patients remained unchanged. Significance Parahippocampal HGA was indicated to reflect different memory processes and be compatible with the outcomes of HT, suggesting that HGA could provide predictive information on whether the mesial temporal lobe can be resected without causing memory worsening. This preliminary study suggests a refined surgical strategy for atypical MTLE based on reliable memory lateralization. [ABSTRACT FROM AUTHOR]

In this paper we present a brief review of temporal lobe epilepsy from clinical aspects, neuroimaging, pathological and diagnosis that have led us to understand and identify more accurately this disease, as interesting as disturbing and as old as the humanity. [ABSTRACT FROM AUTHOR]

Abstract: Delalande’s vertical hemispherotomy is an innovative evolution of hemispherectomy in minimizing brain resection. We report our modification for this surgical procedure. We modified the original procedure in two aspects for the purpose of less brain resection and confirmation of the complete disconnection. Firstly, all procedures were done via an interhemispheric route instead of a transcortical route. Secondly, we set the anterior disconnection plane as the one that connects the anterior end of the choroidal fissure to the anterior end of the foramen of Monro, instead of the former to the subcallosal area. We applied this modified vertical hemispherotomy to 7 cases. Four cases were children with hemimegalencephaly and other 3 were adults with ulegyric hemisphere. Surgical procedure was completed without complication in all cases. There was no case that required CSF shunting. Seizure outcome was Engel’s class I in 6 and class IV in 1. Postoperative MRI revealed complete disconnection of the affected hemisphere in all patients. We reported our modification of vertical hemispherotomy. Although these are minor modifications, they further minimized brain resection and may serve for less invasiveness of procedure and improvement in completeness of disconnection and its confirmation during surgery. [Copyright &y& Elsevier]

Functional Magnetic Resonance Imaging- and Magnetoencephalography-based Brain Mapping for Identifying Language Functions and Its Validation by Electrocortical Stimulation.Purpose:Functional magnetic resonance imaging (fMRI) detects changes in cerebral blood flow and has been applied to the identification of the dominant hemisphere in language functions. Most of the fMRI-language studies disclose frontal activation by various lexico-semantic tasks. Magnetoencephalography (MEG) directly detects neuronal activity and records intracellular electric current flow in the brain. It localizes semantic responses peaking at approximately 400 msec after word presentation (late responses) in the temporoparietal regions, and the MEG responses are suspected to be strongly related to the receptive language function. We have, therefore, utilized these two modalities to independently visualize the expressive- and receptive-language functions. The successful mapping results by noninvasive techniques were verified by electrocortical stimulation.Methods:We investigated two patients with intractable epilepsy; a right-handed patient with left frontal epilepsy (Patient 1) and a left-handed patient with bilateral temporal lobe epilepsy (Patient 2). Neurological examinations disclosed no language deficits in both patients. They were asked to generate verbs related to acoustically presented nouns (verb generation) and to categorize visually presented words as abstract or concrete (A/C categorization) for fMRI and MEG investigations, respectively. The averaged magnetic signals were digitally filtered between 0.1 and 30 Hz. Significant MEG deflections were visually identified on the basis of the root mean squared fields of more than 10 sensors in the fronto-temporal (FT) or temporo-occipital (TO) regions. Locations and dipole moments of equivalent current dipoles were calculated every 2 msec from 250 to 600 msec after the stimulus was started, using the single equivalent dipole model. After subdural electrodes were placed over the hemisphere, the results of fMRI and MEG, and postoperative CT scan demonstrating the electrode positions were co-registered and superimposed on the anatomical MRI by maximizing the mutual information of all data sets with Affine transformation. The noninvasive functional mapping results were validated by 60Hz bipolar stimulation with the subdural electrodes. During the stimulation, patients were instructed to keep reading words, naming pictures, or generating verbs.Results:FMRI demonstrated activations in the inferior (IFG) and middle frontal gyri (MFG) of the suspected dominant hemisphere. While MEG disclosed highly concentrated semantic dipoles in the superior temporal (STG), supramarginal (SmG) and fusiform gyri (FuG) of the dominant hemisphere, FMRI and MEG clearly indicated language dominancy on the left hemisphere in Patient 1 and on the right in Patient 2. During locus validations, the electrocortical stimulation to the IFG and STG consistently induced speech arrest and sensory aphasia including dyslexia, respectively. In addition, the stimulation to the right FuG in Patient 2 revealed pure dyslexia with no suppression in the picture-naming task. Since the cortical stimulation to the MFG caused no neurological symptom, the MFG activation on fMRI did not correspond to the results of the stimulation. These findings suggest that the MFG might play roles in speech association or working memory and might be outside the critical language area compared to the other activated areas on fMRI and MEG.Conclusion:Noninvasive functional mapping techniques are powerful tools to identify language dominancy. IFG activation on fMRI, as well as STG, SmG, and FuG dipole clusters on MEG, are highly reliable for the detection of the critical language areas. MFG activation on fMRI, however, needs more careful validation and interpretation. It is necessary to modify and improve the lexico-semantic tasks of functional brain mapping for appropriate visualization of the critical language areas. Anterior Temporal Language Area with Respect to Verbal Memory Impairment after Temporal Lobectomy with Hippocampal Preservation.Purpose:It is well known that verbal memory loss occurs after resection of the hippocampus in the dominant hemisphere. From the viewpoint of improving verbal memory within 1 year after hippocampal resection, restoration of memory function may depend, not only on the hippocampal resection on the affected side, but also the resection of the language area within the lateral and basal cortex detected by electrical cortical stimulation study.Case Report:A 44-year-old, right-handed man was referred to our hospital because of intractable seizures. When he was 19 years of age, he had a traffic accident and a left temporal hemorrhage due to contusion was removed. At 32 years of age, the first generalized seizure occurred, followed by the onset of complex partial seizures consisting of unresponsiveness, oral and verbal automatism. The seizure frequency was three times per week. A scalp electroencephalogram revealed frequent spikes over the left frontotemporal region and ictal activity starting from the left sphenoid lead. Imaging studies showed evidence for prior contusion in the left superior and middle temporal gyri. Neurological examination revealed mild nonfluent dysphasia.Methods and Results:Subdural grid recording and functional mapping: To confirm epileptogenic areas and the exact language areas, chronically implanted subdural grid recordings and electrical cortical stimulation studies were conducted. Ictal seizure onset was localized within 6 cm posterior to the temporal tip. According to functional language mapping, Wernicke's area was detected in a region of 12 electrodes just posterior to the area of the prior contusion area. Surprisingly, the anterior temporal language area was also detected in a region of six electrodes within the above-mentioned epileptogenic area.Resective surgery: A 6-cm en bloc left temporal lobectomy, including the lateral and basal cortex, was performed. An electrocorticogram was recorded over the surface of the left hippocampus. A few spikes were recorded every 10 seconds, but the hippocampus was not resected, because preoperative MRI revealed no atrophy or change of signal intensity, and the findings from the Wada test were consistent with left hemisphere dominance for speech and memory. For 22 months after surgery, the patient had only one complex partial seizure.Cognitive functions: Postoperative Standard Language Test of Aphasia (in Japanese) revealed language dysfunction, especially object naming, verbal fluency in a word generation task, and ability to follow auditory instruction. Verbal memory and delayed recall on the Wechsler Memory Scale Revised showed declines just after surgery and relative improvement after 1 year. The score changes were 79→59→83→69 for verbal memory and 85→less than 50→87→80 for delayed recall before operation, 1 month, 4 months, and 1 year after operation, respectively.Discussions:Postoperative verbal memory was impaired after temporal lobectomy even though the hippocampus was not resected in this case. This finding infers an interesting hypothesis that the language area was included within the resected areas located in the lateral and basal cortex. According to the results of the stimulation study using a chronically implanted subdural grid, the language area was detected within 45 mm from the temporal tip in 11 of 24 patients (48%), and involved 45 of 182 electrodes (25%). All five patients with cortical resection, which included the language areas detected by cortical stimulation showed decreased word recall after surgery, compared with three of eight patients with resection not including the language area (p= 0.04).Conclusions: Verbal memory dysfunction sometimes occurs in patients with temporal resection, irrespective of hippocampal preservation in the dominant hemisphere. According to functional mapping, speech impairment and verbal memory dysfunction also occur after resection of the lateral and basal temporal cortex including language areas detected by cortical stimulation. SISCOM Analysis by 99mTc-ECD and 123I-IMP in Patients with Temporal Lobe Epilepsy: Comparison with SPM Analysis of Ictal and Interictal SPECT.Purpose:The ictal single-photon emission computed tomography (SPECT) has diagnostic significance when an increase in regional cerebral blood flow (rCBF) is detected in the suspected area of seizure onset compared to the interictal image. For a long time, we compared the ictal and interictal images by visual inspection and used them for the detection of epileptogenetic zone. More objective evaluation became possible after the statistical image analysis of SPECT was introduced for clinical use. Recently, the method of subtracting interictal from ictal SPECT and co-registering to three-dimensional MRI (SISCOM) has been introduced. We tried to evaluate the usability of the SISCOM analysis by comparing it with the statistical parametric mapping (SPM) analysis of ictal and interictal SPECT in patients with temporal lobe epilepsy.Methods:We retrospectively studied the patients with temporal lobe epilepsy who underwent anterior temporal lobectomy or amygdala-hippocampectomy in our hospital between April 1996 and April 2003. Patients with surgical outcomes classified as Class 1 or 2 according to Engel's definition were included in the study. In these conditions, the epileptogenetic zone should be located within the site of the resection. Ictal SPECT, interictal SPECT, and MRI images were necessary for SISCOM analysis. For ictal and interictal SPECT analysis, the same radiotracer of either 99mTc-ECD (ECD) or 123I-IMP (IMP) should be used in both imagings. Patients with ictal ECD and interictal IMP SPECT, or ictal IMP and interictal ECD SPECT were excluded. Finally, 52 patients who had undergone ictal and interictal SPECT as well as preoperative MRI were analyzed. The ECD group consisted of 37 patients with 46 ictal and 43 interictal data. The IMP group comprised 22 patients with 22 ictal and 29 interictal data. The SISCOM analyses were done with the most recent data set. These patients were classified according to the radiotracer of SPECT, the mode of surgical resection, and invasive EEG monitoring. Among the 52 patients, the histopathological diagnoses of specimens were mesial temporal sclerosis in 38, dysembryoplastic neuroepithelial tumor in four, cortical dysplasia in two, scar in one, and unknown in seven patients. The SPECT images were acquired with the Shimazu SET-070 system. Image data of SPECT were transferred to the workstation, recalculated with a converting program to the DICOM format, and stored. The MRI images were acquired with the GE Sierra system. The T1-weighted images of whole brain (thin-sliced 3D-MRI were preferred) were used, which were previously stored in the DICOM image server. The DICOM data of both SPECT and MRI were changed to the ANAYZE format for analyses in the workstation. The modified SPM99 program specialized for jackknife test using the z-score expression was used (eZIS ver.2, Daiichi Pharmaceutical Co. Ltd, Japan). For the SPM analysis, controls were selected among the epilepsy patients who had no abnormal findings both in interictal SPECT and MRI. Sixteen control patients consisting of ten males and six females were selected (ECD group; aged 24.8± 5.86 years, IMP group; aged 24.7± 5.41 years). One-side test for hypoperfusion of rCBF was used to analyze the interictal SPECT, and one-side test for hyperperfusion of rCBF for the ictal SPECT. The statistical parameter was as follows: z≥ 2, Extent n≥ 1000. For the SISCOM analysis, a Windows-based SISCOM program was used. In this program, SPECT images were automatically co-registered to MRI using the AIR algorithm and the subtraction images of interictal from ictal SPECT were constructed. The statistical parameter of Z-score was greater than 2. The results of the SISCOM and SPM analyses were classified into six steps according to the laterality and the localization of the view: (1) finding centered on the mesial temporal lobe; (2) finding centered on the temporal lobe; (3) finding centered on the hemisphere; (4) finding centered on bilateral temporal lobes; (5) no definite finding; and (6) finding centered on the contralateral side from the focus. In the main statistical analysis, (1)+ (2)+ (3) was used for focus detection.Results:When using ECD-SPECT, the focus detection rate was 44.2% by interictal SPM, 32.6% by ictal SPM, and 60.9% by SISCOM. When using IMP-SPECT, the rate was 55.2% by interictal SPM, 40.9% by ictal SPM, and 68.2% by SISCOM. In both groups, the focus detection rate was higher by SISCOM than by interictal or ictal SPM. The SISCOM analysis had a detection rate approximately 15% higher compared to interictal SPM. The focus detection rate by SISCOM for all patients with temporal lobe epilepsy was 60.9% for ECD and 68.2% for IMP. The rate of false positive was 17.4% for ECD and 4.5% for IMP. However, the timing of radiotracer injection and the seizure conditions at that time was not uniform for all cases; IMP-SPECT appeared to be superior for the detection of the epileptogenetic zone in temporal lobe epilepsy. In seven patients with both ECD and IMP sets of interictal and ictal SPECT, the IMP results of SISCOM analysis tended to be superior. The focus detection rate was compared by the difference in the mode of resection surgery. The choice of amygdala-hippocampectomy or anterior temporal lobectomy was an indicator of the focus location in the mesial or lateral region of the temporal lobe. However, the focus detection rates in mesial temporal lobe using ECD-SPECT and analyzed by interictal and ictal SPM were 35.3% and 30%, respectively, and were lower than when using IMP-SPECT. The focus detection rate using ECD-SPECT and analyzed by SISCOM was 60%, and not significantly different from that using IMP-SPECT. It is supposed that the combination of subtle findings in interictal and ictal SPECT works well in SISCOM analysis. On the other hand, the focus detection rate was compared by whether invasive EEG monitoring was required for focus detection. Invasive EEG monitoring with intracranial or subdural electrodes has been used only in difficult cases to determine the epileptogenetic zone or the precise location in the temporal lobe. The focus detection rate by SISCOM analysis in difficult cases was 50% using IMP-SPECT and 50% using ECD-SPECT, whereas the rate by ictal SPM analysis was only 16.7% using IMP-SPECT and 27.3% using ECD-SPECT.Conclusion:for the detection of the epileptogenetic zone of temporal lobe epilepsy, SISCOM analysis was shown to be effective. SISCOM analysis was clearly superior to the SPM analysis for patients with temporal lobe epilepsy. Generally, complex partial seizures last for a relatively long duration in temporal lobe epilepsy. The difference between the SISCOM results of ECD-SPECT and IMP-SPECT is suspected to reflect more stable images obtained by IMP-SPECT compared to ECD-SPECT. Multimodal Navigation-guided Temporal Lobe Epilepsy Surgery Using Focus Detection by F-18 Fluorodeoxyglucose PET.Purpose:We investigated the clinical role of multimodal navigation surgery using focus detection by F-18 fluorodeoxyglucose (FDG) PET as a surgical modality for temporal lobe epilepsy.Patients and Method:In April and May of 2004, four patients with intractable temporal lobe epilepsy and organic lesions underwent epilepsy surgery without preoperative chronic electrocorticography (ECoG) monitoring. Histological examinations of the surgical specimens demonstrated benign tumors in two patients, a cavernous angioma in one patient, and hippocampal sclerosis in one patient. After presurgical assessments by repeated EEGs, video-EEG monitoring, MRI and neuropsychological testing, three of the four patients underwent C-11 flumazenil (FMZ)-PET, and all four patients underwent FDG-PET. We first examined the relationships between the organic lesions and hypometabolic areas on FDG-PET, and then compared the FDG-hypometabolic areas and low-uptake areas on FMZ-PET. To examine the epileptogenicity of the hypometabolic areas on FDG-PET, we recorded intraoperative ECoG in and around the hypometabolic areas under the guidance of an intraoperative navigation system.Results:(1) The hypometabolic areas on FDG-PET were wider than the low-uptake areas on FMZ-PET in three patients. (2) Spikes on intraoperative ECoG were recorded in areas within the hypometabolic areas in all four patients.Conclusion:Multimodal navigation surgery using preoperative FDG-PET in combination with intraoperative ECoG may become an important method for focus detection in patients with temporal lobe epilepsy and organic lesions. Magnetoencephalography in Children with Intractable Epilepsy Secondary to Tuberous Sclerosis Complex.Background:Tuberous sclerosis complex (TSC) often causes medically intractable seizures, usually as a result of cortical tubers, cortical dysplasia, and reactive gliosis. Epilepsy surgery for the TSC is often discouraged because of the difficulties in obtaining concordant findings in various imaging modalities such as CT, MRI, EEG, SPECT, and PET. Magnetoencephalography (MEG) has been used for presurgical evaluation of epilepsy patients to localize the epileptic foci noninvasively. This study classifies MEG spike sources (MEGSSs) from TSC patients and correlates them to EEG and MRI results.Methods:We retrospectively reviewed the medical records of seven patients who underwent MEG examination for intractable epilepsy secondary to TSC at the Hospital for Sick Children in Toronto between 2001 and 2003. All patients received an epilepsy evaluation that included previous history, physical and neurological examinations, prolonged video-scalp EEG (VEEG), and MRI.Results:All patients had multiple cortical tubers on MRI. The number of cortical tubers ranged from 6 to 27 (mean, 16). Five patients had prominent tubers (>25 mm in size) in one region. On interictal VEEG examination, four patients had hemispheric interictal epileptiform discharges, while three showed multiple independent spike foci (MISF). The interictal epileptiform discharges were localized predominantly in the frontal region in six of the seven patients. Four patients had ictal onset zones that lateralized, two patients had only frontal onset seizures, and two patients had ictal onset zones in two regions with different seimiologies. One patient had independent ictal onset zones in bilateral hemispheres. Two had nonlocalized, generalized seizures. MEGSSs were distributed as clusters (six or more spike sources, 1 cm or less between sources) or scatters (fewer than six spike sources, regardless of the distance between sources, or sources with greater than 1 cm between sources regardless of the number of sources). Four patients had one or more clusters with coexisting scatters. Three patients had bilateral scatters alone. The MEGSS distribution patterns were classified into three groups: Group A (two patients), unilateral single cluster with scatters; Group B (two patients), bilateral clusters with scatters; and Group C (three patients), bilateral scatters alone. Group C had fewer MEGSSs (mean, 25) than Group A and B (mean, 50). In Group A, the location of the single cluster in each patient was concordant with the prominent regional or hemispheric MRI tuber, and with the ictal onset and the interictal epileptiform discharge zones on VEEG. In Group B, the bilateral clusters did not completely correlate with the multiple prominent MRI tubers, bilateral or diffuse interictal discharges, or multiple or generalized seizure VEEG findings. In Group C with bilateral scatters, the locations of predominantly lateralized MEGSSs in two patients did not completely overlap with the prominent tubers on MRI. Yet, the scatters covered the interictal epileptiform discharge and ictal onset zones. In one patient with equally bilateral scatters, a prominent tuber and interictal/ictal onset zones in the right frontal region indicated a right frontal epileptic zone.Conclusions:MEG showed multiple spike sources in all the patients with TSC. A single MEGSS cluster that correlates with the ictal onset zone and the prominent tuber on MRI likely indicates a potential epileptogenic zone. Bilaterally clustered and scattered MEGSS together with discordant prominent tubers, multiple seizure types, or generalized seizure probably indicate multiple potential epileptogenic zones. Bilaterally scattered MEGSS may be a reflection of multifocal structural abnormalities, multiple independent spike foci, and abnormal background activities. Clinical Evaluation of Patients with Preoperative Magnetoencephalography Showing Multiple Equivalent Current Dipole Clusters.Purpose:To evaluate the clinical and location differences among patients with preoperative multiple equivalent current dipole (ECD) clusters measured using magnetoencephalography (MEG), and to evaluate surgical results.Subjects and Methods:We studied 10 epileptic patients (eight men, two women) with a mean age of 26 years (range, 6–53 years), who underwent cortical resective surgery at our institution between July 2000 and July 2003. The mean duration of follow-up was 3 years (range, 1.2–4.2 years). Pathologies comprised temporal lobe epilepsy (TLE, n= 3), frontal lobe epilepsy (FLE, n= 4), parietal lobe epilepsy (PLE, n= 2), and occipital lobe epilepsy (OLE, n= 1). All patients displayed multiple ECD clusters measured on preoperative MEG. Preoperative ECD clustering patterns were divided into three categories: (1) bilateral symmetrical ECD clusters (n= 3; TLE in one patient, FLE in two patients); (2) multiple asymmetrical ECD clusters limited to the ipsilateral hemisphere (n= 4; TLE in two patients, OLE in one patient, FLE in one patient); and (3) multiple randomized ECD clusters in both hemispheres (n= 3; PLE in two patients, FLE in one patient). Focus resective surgery was performed on the basis of semiology, electroencephalography (EEG), long-term video EEG, MEG, and chronic subdural electrodes findings.Results:Among the three patients with bilaterally symmetrical ECD clusters preoperatively, both FLE patients experienced no seizures (Engel's class 1) and the TLE patient was Engel's class 2 after surgery with no ECD clusters on the postoperative MEG. Among the four patients with multiple asymmetrical ECD clusters in the ipsilateral hemisphere, both TLE patients were assessed as Engel's class 3 while the FLE and OLE patients were class 2 after surgery. All three patients with multiple randomized ECD clusters were Engel's class 3.Conclusion:Patients with bilateral symmetrical ECD clusters on preoperative MEG achieve good clinical results after focus resective surgery. Bilateral symmetrical ECD on MEG may indicate that one ECD cluster is the primary focus, while the other side is the propagated area from the contralateral side (focus). Surgical results for multiple asymmetrical ECD clusters in the ipsilateral hemisphere and multiple randomized ECD clusters in bilateral hemispheres are poor. Individual ECD clusters in these cases may display epileptogenicity, and even if the dominant focus is removed, one of the less dominant foci will take over as the next main focus. Two Cases of Status Epilepticus Showing Changes on Transient Diffusion-weighted Magnetic Resonance Imaging.Case reports:Case 1 was a 36-year-old woman who was admitted for convulsive status epilepticus. She had a history of generalized convulsive seizure at the age of 17 years and frequently experienced simple partial seizures before admission. After the first event of convulsive status epilepticus, she presented with tonic–clonic seizures for 10–20 seconds occurring every 5–10 minutes. Interictal EEG demonstrated mild focal background slowing and some small spikes over the right frontal cortex. Diffusion-weighted MRI (DWI) during status epilepticus showed marked gyriform cortical hyperintensity over the right temporal and occipital lobes. Both T2-weighted image and fluid-attenuated inversion recovery (FLAIR) image showed no abnormality. The cerebrospinal fluid showed no increase in protein and no pleocytosis. Following intubation for the treatment of respiratory insufficiency, sedative medications were added to the antiepileptic therapy. Convulsions continued for 24 hours. Seven days after the onset, the abnormalities on DWI disappeared.Case 2 was a 52-year-old man who experienced partial seizure involving the left side of the body, followed by symptoms of altered mental status and visual hallucinations over the 2 weeks before presentation. He had a history of subcortical hemorrhage in the right parietal lobe. EEG showed diffuse background slowing and additional focal slowing over the right occipital cortex with spikes in the right hemisphere. DWI demonstrated gyriform cortical hyperintensity over the right parietal and occipital lobe beside the focal hypointensity. The T2-weighted and FLAIR images depicted cortical hyperintensity in the regions showing abnormality on DWI. The patient was treated with antiepileptic drugs with additional therapy for acute cerebral infarction. Two weeks after admission, the initial abnormalities on MRI disappeared, but new hyperintensity appeared over the right temporal cortex and ipsilateral hippocampus. The patient experienced transient amnesia up to the disappearance of the latter abnormalities.Conclusions:In patients with status epilepticus, transient structural changes have been demonstrated recently with the use of DWI. These changes consist of the redistribution of intracellular and extracellular water, presumably due to altered permeability through the cell membrane or cytotoxic edema. We report two cases of status epilepticus showing transient DWI changes. Case 1 experienced convulsive status epilepticus with electrical changes suggesting an origin in the right frontal cortex, whereas the DWI changes appeared in distant temporal and occipital cortex. Case 2 was diagnosed as having complex partial status epilepticus with a suggested origin in the right occipital and temporal structures, corresponding with the findings of DWI. In Case 2, DWI and T2 signal changes appeared to be roughly synchronous. Our cases suggest that periictal imaging changes may occur in the region of the epileptic discharge or in distant structures. Both types of changes were reversible, implying that decreased diffusion associated with ongoing status epilepticus is reversible without subsequent tissue injury. The DWI changes are speculated to be mainly caused by activity-induced injury with cytotoxic edema. High-frequency Oscillations in the Epileptogenic Zone Using Multiple Band Frequency Analysis.Purpose:Multiple band frequency analysis (MBFA) was used to detect sustained high-frequency oscillation during ictal electrocorticography in a child with intractable neocortical epilepsy. We hypothesized that the sustained ictal high-frequency oscillations may delineate the epileptogenic zone.Methods:A 14-year-old left-handed girl developed partial seizures at the age of 11 years, consisting of an aura of a dizzy sensation and a visual phenomenon, followed by staring, unresponsiveness, and automatisms. MRI showed a heterogeneous mass in the right occipital lobe. During scalp video-EEG monitoring, her seizures originated from right posterior head region. Lesionectomy was performed at the age of 12 years. Pathological study disclosed an oligoastrocytoma. Although her visual phenomena disappeared, seizure frequency increased, at 11 months after the first surgery, in the form of dizzy spells similar to preoperative seizures. Postoperative MRI showed gliosis around the resection area. No recurrent or residual tumor was evident. Intracranial video-EEG monitoring was done at the age of 14 years. A subdural grid with 75 electrodes was used to cover the right occipital, posterior temporal, and parietal regions. Sampling rate was 1 kHz. Thirty-three seizures were recorded during 72 hours. The ictal onset in all 33 EEG seizures was identical, and was located anterior to the previous resection area. Cortical excision of the right posterior temporo-occipital regions, anterior to the previous cortical excision was performed. Pathologic diagnosis was dysembryoplastic neuroepithelial tumor. She had been seizure free for 5 months at the time of study. To analyze EEG seizures using MBFA, 25 electrodes were retrospectively selected, consisting of 20 electrodes located in the resection area delineated by intracranial video-EEG monitoring and 5 electrodes outside of the excision area. All 33 seizures at 10 seconds before and 38 seconds after the ictal electrographical onset were subjected to MBFA (minimum bandwidth 2 Hz, between 5 Hz and 300 Hz, Notch filter at 60 Hz). The minimum time window was 100 msec. Power value was calculated asμV2 rms. We defined the sustained high-frequency oscillations as the maximum power value>15μV2 rms and sustained duration>500 msec. The frequency of each of the sustained high-frequency oscillations was obtained and the number of electrodes and seizures with sustained high1-frequency oscillations were counted.Results:Twenty-seven of the 33 seizures (82%) showed sustained high-frequency oscillations. Seventeen out of the 25 electrodes (68%) recorded sustained high-frequency oscillations. Fifteen of the 17 electrodes (88%) were located in the resection area. The range of the high-frequency oscillations was from 78 to 158 Hz with a mean frequency of 124 Hz. Four of the 25 electrodes (16%) with only a spike and wave pattern and no sustained high-frequency oscillations were located in the resection area. The remaining four electrodes (16%) showed neither sustained high-frequency oscillations nor spike- and -wave patterns, including one electrode that was located in the resection area.Conclusion:Electrocorticography at a sampling rate of 1 kHz was able to record high-frequency oscillations at the ictal onset in a patient with neocortical epilepsy. The locations of the electrodes that recorded sustained high-frequency oscillations at ictal onset delineated the epileptogenic zone. This case of neocortical epilepsy demonstrates the utility of MBFA to evaluate the epileptogenic high-frequency oscillation. [ABSTRACT FROM AUTHOR]

Presents a study that tested the hypothesis that the optimal schedule for the power plant start-up scheduling problem lies on the edge of the feasible space. Problems of power plant start-up scheduling; Location of the optimal schedule; Details of the enforcement operation; Use of genetic algorithms for enforcement operations.

Global cerebral ischemia models for genetically engineered mice are of particular importance for the study of delayed neuronal death, but have been complicated by variability of vascular anatomy. Here we developed a 5-min cardiac arrest model that was not affected by vascular anatomy, and evaluated the hippocampal neuronal injury in BL/6 and SV129 mice. Despite prolonged anoxic depolarization for approximately 7 min, however, no consistent ischemic neuronal injury was noted in the CA1 sector of the hippocampus in both strains. Thus, our observations suggested that murine hippocampal neurons are relatively resistant to ischemia compared with those in other rodents. [Copyright &y& Elsevier]

Presents a genetic algorithm with an adaptive-enforcement operation for addressing problems in power plant start-up scheduling. Common start-up scheduling problems; Efficiency of the proposed genetic algorithm in finding the optimal or near-optimal schedules.

Focuses on the ultracytochemical demonstration of the polarity of Ca[sup 2+]-adenosine triphosphate activity in microglia in rat cerebral cortices. Use of the lead salt technique; Manifestation of interactions between perineuronal microglia and neurons in the polarity; Distribution of the reaction product along the plasma membrane without polarity.

Background The lesionectomy is a general surgical procedure for treating focal epilepsy resulting from a structural abnormality, but a favorable outcome cannot be achieved in some patients, especially patients whose symptomatogenic zone is located in remote regions. Herein we propose the surgical disconnection of the seizure propagation pathway, which consists of short and long associating fibers linking the epileptogenic zone to the remote symptomatogenic zone, as an effective method of achieving favorable seizure outcomes in patients with posterior cortex epilepsy. Methods Three patients with intractable epilepsy showing a structural abnormality in the medial posterior cortex participated in this study. Their habitual seizures were complex partial seizures stemming from remote symptomatogenic zones. Seizure propagation-related fibers were assumed by non-invasive examination and semiology. Results Cingulum and superior/inferior longitudinal fasciculus were considered to form main seizure propagation pathway. Based on the preoperative assumption and the intraoperative intracranial electroencephalogram findings, a lesionectomy and corticectomy were performed for 2 patients while a clusterectomy and corticectomy were performed for the remaining patient. The resection area was extended in the direction of the association fibers to disconnect the remote symptomatogenic zone completely from the epileptogenic zone. Engel class I was achieved in all the patients. Conclusion The current study suggested that assuming the presence of association fibers was an important factor for achieving a favorable outcome in the surgical treatment of posterior cortex epilepsy. Though further study is required, disconnection surgery is recommended as a treatment option for cases in which the epileptogenic zone is located in an eloquent area. [ABSTRACT FROM AUTHOR]

Objective Cortico-cortical evoked potential (CCEP) has been utilized to evaluate connectivity between cortices. However, previous reports have rarely referred to the impact of volume-conducted potential (VCP) which must be a confounding factor of large potential around the stimulation site. To address this issue, we challenged the null hypothesis that VCP accounts for the majority of the recorded potential, particularly around the stimulation site. Methods CCEP was recorded with high-density intracranial electrodes in 8 patients with intractable epilepsy. First, we performed regression analysis for describing the relationship between the distance and potential of each electrode. Second, we performed principal component analysis (PCA) to reveal the temporal features of recorded waveforms. Results The regression curve, declining by the inverse square of the distance, fitted tightly to the plots ( R 2 : 0.878–0.991) with outliers. PCA suggested the responses around the stimulation site had the same temporal features. We also observed the continuous declination over the anatomical gap and the phase reversal phenomena around the stimulation site. Conclusions These results were consistent with the null hypothesis. Significance This study highlighted the risk of misinterpreting CCEP mapping, and proposed mathematical removal of VCP, which could lead to more reliable mapping based on CCEP. [ABSTRACT FROM AUTHOR]

We report two extremely rare cases involving the development of transient selective retrograde amnesia for simple machine operation lasting for several hours. A 61-year-old male taxi driver suddenly became unable to operate a taximeter, and a 66-year-old female janitor suddenly became unable to use a fax machine. They could precisely recount their episodes to others both during and after the attacks, and their memories during their attacks corresponded to the memory of the witness and the medical records of the doctor, respectively. Therefore, it appears that these individuals remained alert and did not develop anterograde amnesia during their attacks. On day 4, they underwent high-resolution magnetic resonance imaging (MRI), and diffusion-weighted MRI with 2-mm section thickness revealed small high-intensity signal lesions in the left hippocampal cornu ammonis area 1 (CA1) region. However, these lesions disappeared during the chronic phase. This is the first report describing lesions detected by MRI in patients with transient selective amnesia without anterograde amnesia. Reversible damage to the hippocampal CA1 region may cause transient selective amnesia by impairing the retrieval of relevant memories. [ABSTRACT FROM AUTHOR]

Objective Multiple hippocampal transection ( MHT) is a surgical procedure developed to avoid postoperative memory decline. Its efficacy has been documented in only a few small series with relatively short observation periods. We prospectively evaluated the long-term seizure and cognitive outcomes of MHT combined with multiple subpial transection or lesionectomy ( MHT + MST/L). Moreover, we quantitatively evaluated the structural and metabolic neuroradiologic changes after the procedure to elucidate the anatomofunctional correlates of memory preservation. Methods Twenty-four patients underwent MHT + MST/L for treatment of drug-resistant mesial temporal lobe epilepsy ( mTLE) and were followed for more than 5 years. Indications for the procedure were the following: (1) verbally dominant-sided surgery in patients with a radiologically normal hippocampus or normal/near normal memory, and (2) surgery for patients with concomitant epileptic activity on the contralateral side, that is, when the surgery was considered a high risk for severe postoperative memory decline. Seizure outcome was evaluated using Engel's classification 1, 2, and 3 years after surgery, and at the last visit ( LV). Three subgroups were evaluated as well: magnetic resonance imaging ( MRI) negative ( MN), hippocampal sclerosis ( HS), and normal hippocampus with extrahippocampal lesion ( NHEL). The long-term cognitive outcome was followed through to LV in patients who underwent verbally dominant-sided surgery. Hippocampal volume ( HV), diffusion tensor parameters ( DTP), and glucose utilization ( GU) were determined from MRI and fluorodeoxyglucose-positron emission tomography ( FDG- PET) studies performed before and >6 months after surgery. Results Whereas the rate of Engel class I as a whole was 71% at 1 year and 67% at LV, the rates in the MN, HS, and NHEL groups were 60%, 67%, and 100% at 1 year, respectively, and 70%, 56%, and 80% at LV, respectively. Memory indices after verbally dominant-sided surgery transiently declined at 1 month but recovered to and remained at the preoperative level through LV. The HV, DTP of the fornix, and GU of the temporal lobe on the treated side showed pathologic changes even when the transiently declined memory indices had recovered to the preoperative level. Significance The long-term outcome for complex partial seizures after MHT + MST/L was comparable to that seen after anterior temporal lobectomy. The long-term cognitive outcome was favorable, even for patients with a high risk of severe postoperative memory decline. MHT + MST/L may be a treatment option for mTLE in which resective surgery carries a risk of postoperative memory decline, particularly in patients without MRI lesion. A discrepancy between the preserved memory and the pathologic neuroradiologic changes indicates the necessity for further studies including functional MRI. [ABSTRACT FROM AUTHOR]

Astrocytes are the cells that actively participate in the process of lesion repair in the central nervous system (CNS), and reactive astrocytosis of varying degrees becomes apparent with time in any pathological condition occurring in the normally developed postnatal CNS. Ganglioside GD3 (II[sup 3]a(NeuAca2-8NeuAc)-LacCer, GD3) in reactive astrocytes from autopsied patients with Creutzfeldt–Jakob disease (CJD) and old cerebral infarction was investigated immunocytochemically, using mouse IgM anti-GD3 monoclonal antibody (DSG-1). Reactive astrocytes in CJD and cerebral infarction demonstrated GD3-immunoreactivity within the cytoplasm. Normal astrocytes were negative. The present data raise the possibility that GD3 in reactive astrocytes has biological implications for the properties of the cells, such as cellular motility. [ABSTRACT FROM AUTHOR]

Background Safe entry to the inferior horn is required for a selective approach to the medial temporal region. This can be challenging sometimes for inexperienced surgeons. Our objective was to verify the usefulness of the deep medullary vein (DMV) as an intraoperative landmark for safely entering the inferior horn during the transsylvian selective approach to the mesial temporal region. Methods Videos of 8 cases of transsylvian selective amygdalohippocampectomies performed at the University of Tokyo Hospital from 2013 to 2015 were reviewed. Consistency of the DMV and time required to open the inferior horn via the temporal stem through the inferior limiting sulcus were retrospectively evaluated. Results DMVs were identified in all cases; the average number identified was 2.5 ± 0.3 (mean ± SE). The inferior horn was opened without disorientation in all cases, with mean dissecting time of 7.0 minutes ± 1.1. No complications were caused by disorientation within the temporal stem white matter. Conclusions Consideration of the venous system within the white matter and following the DMV could reduce the risk of disorientation and enable the surgeon to reach the inferior horn in a straightforward manner without accidental white matter damage. [ABSTRACT FROM AUTHOR]

SUMMARY Vagus nerve stimulation (VNS) is a palliative treatment for intractable epilepsy. Therapeutic mechanisms of VNS have not been elucidated. In this study, we measured the local field potential (LFP) with high-spatial resolution using a microelectrode array in adult rats, and analyzed VNS-induced phase modulation at a local network level. Eight adult Wistar rats (270-330 g) were used. Each rat underwent implantation of a VNS system under 1.5% isoflurane anesthesia. One week after implantation, right temporal craniotomy was performed under the same anesthesia as previously. Subsequently, a microelectrode array was placed in the temporal lobe cortex, and the LFP was recorded with a sampling rate of 1000 Hz. Phase-locking values (PLV) between all pairs of electrodes in varied frequency bands were calculated in order to evaluate the effect of VNS in terms of synchrony of neuronal activities. The PLV was calculated both in a normal state and in an epileptic state induced by kainic acid. VNS increased the PLV in a normal state, particularly in the high-γ band. In an epileptic state, on the other hand, VNS increased the PLV in the high-γ band and decreased the PLV in the δ and low-β bands. These results suggest that VNS modulates neural activities in a band-specific and state-dependent manner so as to keep cortical synchrony within the optimal state. [ABSTRACT FROM AUTHOR]

Objective. The determination of language lateralisation is important for patients with medically intractable epilepsy or a brain tumour near the language areas to avoid the risk of post-surgical language deficits. The aim of this study was to evaluate the clinical usefulness of near-infrared spectroscopy (NIRS) to identify language lateralisation compared with functional MRI (fMRI) and magnetoencephalography (MEG) in multiple language tasks. Methods. We investigated 28 patients whose language dominance was evaluated by the Wada test. fMRI, MEG and NIRS were performed to investigate language representation. All patients were as'ked to read three-letter words silently for fMRI and MEG ( Kana reading) and to write words beginning with a visually presented letter (word generation) for NIRS. The laterality index was calculated to assess language lateralisation in each investigation. Results. In 24 cases (85.7%%), of which two investigations showed the same laterality, the results had perfect concordance with the Wada test. In patients with left dominance, the sensitivity and specificity of fMRI, MEG and NIRS was 95.0%% and 62.5%%, 100%% and 87.5%%, 75.0%% and 87.5%%, respectively. In three patients with right lateralization, only NIRS showed a significant increase of oxygenated-haemoglobin in the right inferior frontal region, indicating right dominance. Conclusion. We established a method to determine language lateralisation by co-utilising fMRI, MEG and NIRS with high reliability. NIRS recognised atypical language representation, in addition to fMRI and MEG. While fMRI, MEG and NIRS are not currently as accurate as the Wada test in determining language lateralisation, this non-invasive and repeatable method has great potential as an alternative to the Wada test in time following further research and refinement of these techniques. [ABSTRACT FROM AUTHOR]

The safety and high efficiency of adeno-associated virus (AAV) vectors has facilitated their wide-scale use to deliver therapeutic genes for experimental and clinical purposes in diseases affecting the central nervous system (CNS). AAV1, 2, 5, 8, 9, and rh10 are the most commonly used serotypes for CNS applications. Most AAVs are known to transduce genes predominantly into neurons. However, the precise tropism of AAVs in the dentate gyrus (DG), the region where persistent neurogenesis occurs in the adult brain, is not fully understood. We stereotaxically injected 1.5 × 1010 viral genomes of AAV2, 5, or rh10 carrying green fluorescent protein (GFP) into the right side of gerbil hippocampus, and performed immunofluorescent analysis using differentiation stage-specific markers 1 week after injection. We found that AAV5 showed a significantly larger number of double-positive cells for GFP and Sox2 in the DG, compared with the AAV2 and rh10 groups. On the contrary, AAVrh10 presented a substantially larger number of double-positive cells for GFP and NeuN in the DG, compared with AAV2 and AAV5. Our findings indicated that AAV5 showed high transduction efficiency to neural stem cells and precursor cells, whereas AAVrh10 showed much higher efficiency to mature neurons in the DG. [ABSTRACT FROM AUTHOR]

We studied the postoperative development of 14 children with cortical dysgenesis who underwent modified functional hemispherectomy (hemispherotomy) at the age of 6 years or younger. At follow-up of 24–72 months (median of 47 months), six (43%) were seizure-free, six achieved>90% reduction, one achieved 50–90% reduction, and one achieved 0–50% reduction in seizure frequency. At the preoperative and final postoperative examinations, mean scores of developmental quotient (DQ) were as follows: 25.5 and 31.9 in total DQ, 26.0 and 33.7 in intellectual DQ, and 27.4 and 22.9 in motor DQ. Children scoring >50 points in preoperative intellectual DQ score obtained near-normal intellectual DQ postoperatively, while, those scoring <10 DQ preoperatively remained at a low developmental level. Among children with DQ scores in the range from 10 to 50, two children who obtained seizure-free outcome and were operated upon in the first 3 years of life achieved marked developmental progress. The present study indicated that high preoperative intellectual DQ and cessation of seizures seem to be associated with better postoperative intellectual development. However, long-term observation of postoperative development and an accumulation of more cases will be needed before we can reach a firm conclusion. [Copyright &y& Elsevier]

The DYNC1H1 gene encodes the heavy chain of cytoplasmic dynein 1, a core structure of the cytoplasmic dynein complex. Dominant DYNC1H1 mutations are implicated in Charcot–Marie–Tooth disease, axonal, type 20, spinal muscular atrophy, lower extremity-predominant 1, and autosomal dominant mental retardation 13 with neuronal migration defects. We report two patients with DYNC1H1 mutations who had intractable epilepsy and intellectual disability (ID), one with and one without pachygyria. Patient 1 had severe ID. At the age of 2 months, she presented myoclonic seizures and tonic seizures, and later experienced atonic seizures and focal impaired-awareness seizures (FIAS). EEG showed slow waves in right central areas during myoclonic seizures. Brain MRI revealed pachygyria, predominantly in the occipital lobe. After callosal transection her atonic seizures disappeared, but FIAS remained. Patient 2 was diagnosed with autism spectrum disorder (ASD) and severe ID. At the age of 7 years, he presented generalized tonic–clonic seizures, myoclonic seizures, and FIAS. Interictal EEG showed generalized spike-and-wave complexes, predominantly in the left frontal area. Brain MRI was unremarkable. Exome sequencing revealed novel de novo mutations in DYNC1H1 : c.4691A > T, p.(Glu1564Val) in Patient 1 and c.12536 T > C, p.(Leu4179Ser) in Patient 2. DYNC1H1 comprises a stem, stalk, and six AAA domains. Patient 2 is the second report of an AAA6 domain mutation without malformations of cortical development. The p.(Gly4072Ser) mutation in the AAA6 domain was also reported in a patient with ASD. It may be that the AAA6 domain has little effect on neuronal movement of DYNC1H1 along microtubules. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction is significantly associated with neurological deficits and age-related neurological diseases. While mitochondria are dynamically regulated and properly maintained during neurogenesis, the manner in which mitochondrial activities are controlled and contribute to these processes is not fully understood. Mitochondrial transcription factor A (TFAM) contributes to mitochondrial function by maintaining mitochondrial DNA (mtDNA). To clarify how mitochondrial dysfunction affects neurogenesis, we induced mitochondrial dysfunction specifically in murine neural stem cells (NSCs) by inactivating Tfam. Tfam inactivation in NSCs resulted in mitochondrial dysfunction by reducing respiratory chain activities and causing a severe deficit in neural differentiation and maturation both in vivo and in vitro. Brain tissue from Tfam-deficient mice exhibited neuronal cell death primarily at layer V and microglia were activated prior to cell death. Cultured Tfam-deficient NSCs showed a reduction in reactive oxygen species produced by the mitochondria. Tfam inactivation during neurogenesis resulted in the accumulation of ATF4 and activation of target gene expression. Therefore, we propose that the integrated stress response (ISR) induced by mitochondrial dysfunction in neurogenesis is activated to protect the progression of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Neuromodulation achieved by vagus nerve stimulation (VNS) induces various neuropsychiatric effects whose underlying mechanisms of action remain poorly understood. Innervation of neuromodulators and a microcircuit structure in the cerebral cortex informed the hypothesis that VNS exerts layer-specific modulation in the sensory cortex and alters the balance between feedforward and feedback pathways. To test this hypothesis, we characterized laminar profiles of auditory-evoked potentials (AEPs) in the primary auditory cortex (A1) of anesthetized rats with an array of microelectrodes and investigated the effects of VNS on AEPs and stimulus specific adaptation (SSA). VNS predominantly increased the amplitudes of AEPs in superficial layers, but this effect diminished with depth. In addition, VNS exerted a stronger modulation of the neural responses to repeated stimuli than to deviant stimuli, resulting in decreased SSA across all layers of the A1. These results may provide new insights that the VNS-induced neuropsychiatric effects may be attributable to a sensory gain mechanism: VNS strengthens the ascending input in the sensory cortex and creates an imbalance in the strength of activities between superficial and deep cortical layers, where the feedfoward and feedback pathways predominantly originate, respectively. [ABSTRACT FROM AUTHOR]

We herein present three cases of a rare type of spinal AVF, an intradural radicular AVF, which mimicked a dural AVF. A 65-year-old male presented with congestive myelopathy. On angiography, right vertebral angiogram (VAG) showed a suspected dural AVF; however, left VAG showed the same intradural dilated vein fed by the anterior spinal artery (ASA). Intraoperative and histological results suggested that a single AVF was located on the right C1 nerve root fed by the right C1 radicular artery and branch of the anterior spinal artery. Two additional patients with a radicular AVF at the C3 or C5 level were presented. Intradural radicular AVFs and dural AVFs have very similar appearances; however, there is a difference that makes the risk of the endovascular treatment of radicular AVFs markedly higher because of blood supply from the ASA. In our case, the AVF was completely occluded by direct surgery without major complications. [ABSTRACT FROM AUTHOR]

Background: Inventing an optimal curve on a microcatheter is required for successful intracranial aneurysm coiling. Shaping microcatheters for vertebrobasilar artery aneurysm coiling is difficult because of the vessel's long, tortuous and mobile anatomy. To overcome this problem, we devised a new method of shaping the microcatheter by using the patient's specific vessel anatomy and the highly shapable microcatheter. We report our preliminary results of treating posterior circulation aneurysms by this method. Methods: An unshaped microcatheter (Excelsior XT-17; Stryker Neurovascular, Fremont, CA, USA) was pretreated by exposure to the patient's vessel for five minutes. The microcatheter was placed in the vicinity of the targeted aneurysm and was left in contact with the patient's vessel before extraction. This treatment precisely formed a curve on the microcatheter shaft identical to the patient's vessel anatomy. Following the pretreatment, the tip of the microcatheter was steam shaped according to the long axis of the target aneurysm. Five consecutive vertebrobasilar aneurysms were treated using this shaping method and evaluated for the clinical and anatomical outcomes and microcatheter accuracy and stability. Results: All of the designed microcatheters matched the vessel and aneurysm anatomy except in one case that required a single modification. All aneurysms were successfully catheterized without the assistance of a microguidewire, and matched the long axis of the aneurysm. All microcatheters retained stability until the end of the procedure. Conclusions: A precise microcatheter shaping for a vertebrobasilar artery aneurysm may be achieved by using the patient's actual vessel anatomy and the highly shapable microcatheter. [ABSTRACT FROM AUTHOR]

Auditory contextual processing has been assumed to be based on a hierarchical structure consisting of the primary auditory cortex, superior temporal gyrus (STG), and frontal lobe. Recent invasive studies on mismatch negativity (MMN) have revealed functional segregation for auditory contextual processing such as neural adaptation in the primary auditory cortex and prediction in the frontal lobe. However, the role of the STG remains unclear. We obtained induced activity in the high gamma band as mismatch response (MMR), an electrocorticographic (ECoG) counterpart to scalp MMN, and the components of MMR by analyzing ECoG data from patients with refractory epilepsy in an auditory oddball task paradigm. We found that MMR localized mainly in the bilateral posterior STGs, and that deviance detection largely accounted for MMR. Furthermore, adaptation was identified in a limited number of electrodes on the superior temporal plane. Our findings reveal a mixed contribution of deviance detection and adaptation depending on location in the STG. Such spatial considerations could lead to further understanding of the pathophysiology of relevant psychiatric disorders. [ABSTRACT FROM AUTHOR]

Survivin, a member of the inhibitors of apoptosis protein gene family, inhibits the activity of caspase, leading to a halt of the apoptotic process. Our study focused on the neuroprotective effect of survivin after transient middle cerebral artery occlusion (MCAO) with intraparenchymal administration of an adeno‐associated virus (AAV) vector. His‐tagged survivin was cloned and packaged into the AAV‐rh10 vector. Four‐week‐old Sprague–Dawley rats were injected with 4 × 109 vg of AAV‐GFP or AAV‐His‐survivin into the right striatum and were treated 3 weeks later with transient MCAO for 90 min. Twenty‐four hours after MCAO, functional and histological analyses of the rats were performed. The result showed that rats that had been treated with AAV‐green fluorescent protein (GFP) and those that had been treated with AAV‐His‐survivin did not show a significant difference in neurological scores 24 hr after MCAO, however, infarction volume was significantly reduced in the AAV‐His‐survivin group compared to that in the AAV‐GFP group. Although the neutrophil marker myeloperoxidase did not show a significant difference in the ischemic boundary zone, cells positive for active caspase‐3 and terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick end labeling were significantly decreased in the AAV‐His‐survivin group. In conclusion, survivin overexpression in the ischemic boundary zone induced by using an AAV vector has the potential for amelioration of ischemic damage via an antiapoptotic mechanism. Rats were injected with 4×109 vg of adeno‐associated virus (AAV)‐green fluorescent protein (GFP) or AAV‐His‐survivin into the right striatum and were treated three weeks later with transient middle cerebral artery occlusion (MCAO) for 90 minutes. Twenty‐four hours after MCAO, functional analysis did not show significant difference. Histological analyses showed that AAV‐His‐survivin treatment significantly reduced the infarction volume and decreased apoptotic markers in the ischemic boundary zone, but not the neutrophil infiltration. [ABSTRACT FROM AUTHOR]

Recurrent bacterial meningitis is not a frequent clinical condition. We describe here the case of a woman with recurrent pneumococcal meningitis caused by the leakage of CSF due to an occult middle fossa encephalocele related to chronic otitis media. To detect an extremely small encephalocele, detailed evaluation by bone CT and RI cisternography are very useful. In the treatment of recurrent bacterial meningitis, clinicians should examine for the presence of a small encephalocele early and perform an appropriate surgical therapy, because the condition could be fatal. [ABSTRACT FROM AUTHOR]

Background In superficial temporal artery−middle cerebral artery (STA-MCA) anastomosis, there is a certain risk of intraoperative acute occlusion of the bypass that can cause operative complications. Objective We sought to assess the efficacy of resuturing at the same site after intraoperative acute occlusion of the bypass. Methods In total, 129 STA-MCA anastomosis operations were performed on 125 patients at our institution. The electronic medical records of each patient were reviewed to gather information regarding intraoperative occlusion events, and the operative videos and postoperative radiologic images were also reviewed. Results Twelve intraoperative acute occlusions were identified. In each case, resuturing was performed after cutting all knots, flushing the thrombus, and trimming the edges of the STAs. In 11 cases, indocyanine green videoangiography and/or Doppler sonography revealed patency during the operation, which was confirmed by postoperative magnetic resonance angiography. None of the 12 cases exhibited high-signal intensities in the MCA area on diffusion-weighted images. Conclusion If intraoperative acute occlusion of STA-MCA anastomosis occurs, reanastomosis at the site should be the first option. [ABSTRACT FROM AUTHOR]

Adeno-associated virus (AAV) is an ideal vector for gene transduction into the central nervous system because of its safety and efficiency. While it is currently widely used for clinical trials and is expected to become more widespread, the appropriate combination of viral serotypes and promoters have not been fully investigated. In this study, we compared the transduced gene expression of AAVrh10 to AAV5 in gerbil hippocampus using three different promoters, including cytomegalovirus (CMV), chicken β-actin promoter with the CMV immediate-early enhancer (CAG), and the Synapsin 1 (Syn1) promoter. Four-week-old male gerbils underwent stereotaxic injection with 1 × 10 10 viral genome of AAV carrying green fluorescent protein (GFP). Quantification of the GFP-positive areas 3 weeks after injection showed that AAVrh10-CMV and AAVrh10-CAG were the most efficient ( p  < 0.001, compared with the control) and AAVrh10-Syn1 and AAV5-CMV were the next most efficient ( p  < 0.05, compared with the control). On the other hand, AAV5-Syn1 showed little expression, which was only observed at the injected site. In conclusion, we should note that some combinations of viral capsids and promoters can result in failure of gene delivery, while most of them will work appropriately in the transgene expression in the brain. [ABSTRACT FROM AUTHOR]

SUMMARY Vagus nerve stimulation (VNS) causes neuromodulatory effects in the cerebral cortex, which are useful not only for therapy on intractable epilepsy but also for enhancement of higher brain functions such as cognition and memory. Recently, it has been reported that VNS may also affect auditory-evoked neutral activities. However, it remains to be elucidated how and where VNS modulates neutral activities in the auditory cortex. Here, we examined effects of VNS on adaptation of neutral activities in response to repeated stimuli in the rat auditory cortex. Both a surface and depth microelectrode array recorded auditory-evoked potentials in response to click train and oddball stimuli. We quantified a repetition rate transfer function and common stimulus-specific adaptation (SSA) index from the amplitude of middle-latency response (PI). Consequently, VNS affected temporal response property and increased SSA in the layer 1 and 5/6 of auditory cortex. This result suggests that VNS strengthens adaptation in the auditory cortex in a layer-specific manner. [ABSTRACT FROM AUTHOR]

Background Refractory temporal lobe epilepsy due to spontaneous temporal pole encephalocele is a rare but increasingly recognized condition. Optimal surgical management is complicated by the lack of knowledge regarding both the extent of the epileptogenic area and the need for repair of the encephalocele. Case Description We report two cases that add significant information to these issues. In Case 1, with a 5-year history of refractory seizures, implantation of diagnostic subdural electrodes into the anterior temporal base happened to abolish the seizures completely. No structural changes were evident on postoperative magnetic resonance imaging. In Case 2, with a large encephalocele and a 5-year history of refractory seizures, surgical disconnection of the temporal pole successfully abolished seizures without any need for encephalocele repair. Conclusions These two cases support the view that the epileptogenic area is confined to within the temporal pole for spontaneous temporal pole encephalocele. Temporopolar disconnection represents one surgical option for this entity that achieves seizure cessation without requiring extra repair procedures. [ABSTRACT FROM AUTHOR]

SUMMARY Vagus nerve stimulation (VNS) is a surgical treatment for intractable epilepsy. Although VNS has been used to treat more than 60,000 patients, the precise therapeutic mechanism of action has not been elucidated. Here, we hypothesize that VNS modulates the local synchronization of cortical activities and thus inhibits seizures. In order to verify this hypothesis, we mapped local field potentials (LFPs) with high-spatial resolution using a microelectrode array from the temporal cortices of adult rats and analyzed VNS-induced phase modulation at the local network level. VNS significantly increased the phase locking value (PLV), an index of synchronization, specifically at the gamma band. The optimal stimulation pulse of VNS was 0.5 mA delivered at 10 Hz. This PLV modulation was most effective when the interelectrode distance was about 1.6 mm. Gamma-band PLVs within the auditory cortex increased more significantly than those between the auditory and nonauditory cortices, while alpha- and low-beta PLV exhibited more synchronization between the auditory and nonauditory cortices. These results demonstrate that VNS modulates cortical synchronization in a band specific manner, and has some implications for the mechanism of action of VNS. [ABSTRACT FROM AUTHOR]

• A change in Broadmann area 10 activity was detected by fMRI in a lvPPA case. • The change in Broadmann area 10 activity preceded a change in CBF. • It is possible that Broadmann area 10 is a key brain region of lvPPA. [ABSTRACT FROM AUTHOR]

Abstract: How visual object categories are represented in the brain is one of the key questions in neuroscience. Studies on low-level visual features have shown that relative timings or phases of neural activity between multiple brain locations encode information. However, whether such temporal patterns of neural activity are used in the representation of visual objects is unknown. Here, we examined whether and how visual object categories could be predicted (or decoded) from temporal patterns of electrocorticographic (ECoG) signals from the temporal cortex in five patients with epilepsy. We used temporal correlations between electrodes as input features, and compared the decoding performance with features defined by spectral power and phase from individual electrodes. While using power or phase alone, the decoding accuracy was significantly better than chance, correlations alone or those combined with power outperformed other features. Decoding performance with correlations was degraded by shuffling the order of trials of the same category in each electrode, indicating that the relative time series between electrodes in each trial is critical. Analysis using a sliding time window revealed that decoding performance with correlations began to rise earlier than that with power. This earlier increase in performance was replicated by a model using phase differences to encode categories. These results suggest that activity patterns arising from interactions between multiple neuronal units carry additional information on visual object categories. [Copyright &y& Elsevier]

Abstract: High gamma activity (HGA) has been shown to be positively correlated with blood oxygenation level-dependent (BOLD) responses in the primary cortices with simple tasks. It is, however, an open question whether the correlation is simply applied to the association areas related to higher cognitive functions. The aim of this study is to investigate quantitative correlation between HGA and BOLD and their spatial and temporal profiles during semantic processing. Thirteen patients with intractable epilepsy underwent fMRI and electrocorticography (ECoG) with a word interpretation task to evoke language-related responses. Percent signal change of BOLD was calculated at each site of ECoG electrode, which has power amplification of high gamma band (60–120Hz) activity. We transformed locations of individual electrodes and brains to a universal coordination using SPM8 and made the quantitative comparisons on a template brain. HGAs were increased in several language-related areas such as the inferior frontal and middle temporal gyri and were positively correlated with BOLD responses. The most striking finding was different temporal dynamics of HGAs in the different brain regions. Whereas the frontal lobe showed longer-lasting HGA, the HGA-intensity on the temporal lobe quickly declined. The different temporal dynamics of HGA might explain why routine language-fMRI hardly detected BOLD in the temporal lobe. This study clarified different neural oscillation and BOLD response in various brain regions during semantic processing and will facilitate practical utilization of fMRI for evaluating higher-order cognitive functions not only in basic neuroscience, but also in clinical practice. [Copyright &y& Elsevier]

Abstract: Objective: We developed a novel technique of spatial normalization of subdural electrode positions across subjects and assessed the spatial–temporal dynamics of high-gamma activity (HGA) in the dominant hemisphere elicited by three distinct language tasks. Methods: The normalization process was applied to 1512 subdural electrodes implanted in 21 patients with intractable epilepsy. We projected each task-related HGA profile onto a normalized brain. Results: The word interpretation task initially elicited HGA augmentation in the bilateral fusiform gyri at 100ms after stimulus onsets, subsequently in the left posterior middle temporal gyrus, in the left ventral premotor cortex at 200ms and in the left middle and left inferior frontal gyri at 300ms and after. The picture naming task elicited HGA augmentation in few sites in the left frontal lobe. The verb generation task elicited HGA in the left superior temporal gyrus at 100–600ms. Common HGA augmentation elicited by all three tasks was noted in the left posterior-middle temporal and left ventral premotor cortices. Conclusions: The spatial–temporal dynamics of language-related HGA were demonstrated on a spatially-normalized brain template. Significance: This study externally validated the spatial and temporal dynamics of language processing suggested by previous neuroimaging and electrophysiological studies. [Copyright &y& Elsevier]

Accurate prediction of epileptic seizures will open novel therapeutic possibilities for patients with intractable epilepsy. We attempted to identify precursors of seizures in the functional networks of electrocorticograms by applying graph theory. Long-term electrocorticograms for periods of 39-76 h from three patients with temporal lobe epilepsy were investigated using pair-wise cross-correlations. Time-varying network properties suggested that there were several distinct brain states. Although functional networks during seizures could be characterized as having a regular topography, no consistent characteristics of functional networks were found immediately prior to seizure onsets. However, it was found that seizures under an identical state were followed by similar transients of the network properties. These results suggest that network properties themselves could not serve as reliable predictors of seizure onset. Yet, some significant pre-seizure changes in the parameters tested appear likely to depend on the brain state. To predict seizures, it may be necessary to take into consideration the states of the brain. In addition to stationary network properties we characterized in the present study, dynamic interactions of epileptic activities with the network might be taken into account to predict the spread of a seizure. [ABSTRACT FROM AUTHOR]

Abstract: We recorded human orbitofrontal electrocorticogram during wakefulness and sleep in epileptic patients using subdural electrodes. During wakefulness and rapid eye movement (REM) sleep, we observed beta activity in the raw orbitofrontal signals. Power spectral analysis demonstrated beta enhancement during wakefulness and REM sleep when compared to slow wave sleep (SWS). During the phasic REM periods, the beta power was significantly lower than during the tonic REM periods. Gamma enhancement manifested itself in four out of six subjects during the phasic periods. This study is the first that has focused on electrical activity in the human orbitofrontal cortex. Although the role of the orbitofrontal cortex during sleep still remains unclear, high frequency activities give us important suggestions in elucidating the human sleep mechanism. [Copyright &y& Elsevier]

Ten epileptic patients each with subdural electrodes surgically attached to the anterior cingulate cortex (ACC; two cases), the orbitofrontal cortex (OFC; seven cases), or both (one case) were included in this study. We recorded each patient''s ACC or OFC electrocorticogram (ECoG) during the time period that the patient was awake and naturally asleep. We performed a Fast Fourier Transformation (FFT) power spectral analysis on each ECoG to examine its frequency component. We found that the ACC showed regular and continuous theta oscillation (5–7Hz) during wakefulness and rapid eye movement (REM) sleep, but not during slow wave sleep. Theta waves observed in REM sleep were not as distinct as those found in wakefulness. We also discovered that the orbitofrontal signals represented spectral peaks in the theta band only during wakefulness. This suggests the coexistence of theta oscillation in the ACC. Considering our previous observations of gamma and beta oscillations in the human hippocampus, we hypothesize that the human limbic system manifests two oscillatory activities. The results obtained in this study suggest that electrophysiological activity in the ACC could be related to particular psychological functions in wakefulness and in REM sleep. These results are useful in elucidating the human brain mechanism. [Copyright &y& Elsevier]

The purpose of this study is to propose and investigate a new approach for discriminating between focal and non-focal hemispheres in intractable temporal lobe epilepsy, based on applying multivariate time series analysis to the discharge-free background brain activity observed in nocturnal electrocorticogram (ECoG) time series.Five unilateral focal patients and one bilateral focal patient were studied. In order to detect the location of epileptic foci, linear multivariate autoregressive (MAR) models were fitted to the ECoG data; as a new approach for the purpose of summarizing these models in a single relevant parameter, the behavior of the corresponding impulse response functions was studied and described by an attenuation coefficient.In the majority of unilateral focal patients, the averaged attenuation coefficient was found to be almost always significantly larger in the focal hemisphere, as compared to the non-focal hemisphere. Also the amplitude of the fluctuations of the attenuation coefficient was significantly larger in the focal hemisphere. Moreover, in one patient showing a typical regular sleep cycle, the attenuation coefficient in the focal hemisphere tended to be larger during REM sleep and smaller during Non-REM sleep. In the bilateral focal patient, no statistically significant distinction between the hemispheres was found.This study provides encouraging results for new investigations of brain dynamics by multivariate parametric modeling. It opens up the possibility of relating diseases like epilepsy to the properties of inconspicuous background brain dynamics, without the need to record and analyze epileptic seizures or other evidently pathological waveforms. [Copyright &y& Elsevier]

Purpose: We assessed the diagnostic value of [11C]methionine (MET) positron emission tomography (PET) in the differential diagnosis of dysembryoplastic neuroepithelial tumors (DNETs) among benign tumors associated with temporal lobe epilepsy (TLE). Methods: This series consisted of seven TLE patients with benign tumors in the temporal lobe. After MET-PET study, all seven patients underwent tumor resection along with focus excision. The uptake of tracers was evaluated by the lesion-to-contralateral ratio (L/C ratio) and the standardized uptake value (SUV). We also assessed the relation between MET uptake and proliferation capacity observed in the surgical specimens. Results: Whereas four patients with DNETs did not show high MET uptake visually, the ganglioglioma and gliomas of the remaining three patients were identified as high–MET-uptake lesions. In the DNETs, the SUV ranged from 1.03 to 1.41, and the L/C ratio ranged from 0.99 to 1.14. MET uptake was significantly lower in the patients with DNETs than in the patients with ganglioglioma and brain gliomas (SUV, p = 0.045; L/C ratio, p = 0.0079). The Ki-67 labeling index was 4% in one patient with DNET and 5% in one patient with pleomorphic xanthoastrocytoma (higher labeling index). The higher labeling index was not related to high MET uptake based on the SUV (p = 0.91) and L/C ratio (p = 0.38). Conclusions: Negative MET uptake in benign temporal lobe tumors with TLE is consistent with a preoperative diagnosis of DNET. [ABSTRACT FROM AUTHOR]

To investigate the sleep spindle activity of the human prefrontal cortex (PFC), we simultaneously recorded whole nights of polysomnographic and electrocorticographic (ECoG) activities during the natural sleep of epileptic patients. Subjects were nine patients with intractable epilepsy who had subdural electrodes surgically attached to the orbital (seven cases), medial (three cases), or dorsolateral (two cases) PFC, and in one case to the frontal pole. To examine spindle frequencies, fast Fourier transformation (FFT) and auto-correlation analyses were performed on the PFC ECoG and Cz EEG data, primarily on epochs of stage 2 sleep. Lower sigma band ECoG oscillations of about 12 Hz were widely distributed across all prefrontal cortical areas including the frontal limbic regions, but none of the PFC sigma frequency peaks coincided with the faster (about 14 Hz) Cz EEG sleep spindles. Combining our results with anatomical and electrophysiological facts, it is suggested that the thalamofrontal circuit involving the rostral reticular and the mediodorsal nucleus of the thalamus is responsible for the generation of 12 Hz frontal spindles in humans. [Copyright &y& Elsevier]

Many reports have described loss of neurons in the substantia nigra in Pick''s disease (PiD). In those reports, however, “Pick''s disease” includes PiD without Pick bodies (PB), and there is only limited data available on regional nigral pathology in PiD with PB. To elucidate the pathological changes of the substantia nigra in PiD with PB, we examined five cases and 12 age-matched controls by morphometry. The number and size of pigmented and nonpigmented neurons, as well as the area of the substantia nigra were examined. The area of the substantia nigra was significantly reduced in PiD with PB. The pigmented and nonpigmented neuron counts in PiD with PB were not statistically different from those in controls. There was a significant reduction in the size of pigmented neurons in PiD with PB to 82% with that in the controls. In addition, after reviewing 48 cases of PiD with PB reported in the literature, we found that none of the cases with typical frontotemporal lobe symptoms exhibited parkinsonism until the terminal stage. These data are useful for discriminating PiD with PB from other diseases showing frontotemporal characteristics, including the frontal lobe degeneration type and the motor neuron disease type of frontotemporal dementia. [Copyright &y& Elsevier]