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Focal neuroinflammation is considered one of the hypotheses for the cause of temporal lobe epilepsy (TLE) with amygdala enlargement (AE). Here, we report a case involving an adult female patient with TLE-AE characterized by late-onset seizures and cognitive impairment. Anti-N-methyl-d-aspartate receptor (NMDAR) antibodies were detected in her cerebrospinal fluid. However, administration of appropriate anti-seizure drugs (ASD), without immunotherapy, improved TLE-AE associated with NMDAR antibodies. In the present case, two clinically significant observations were made: 1) anti-NMDAR antibody-mediated autoimmune processes may be associated with TLE-AE, and 2) appropriate administration of ASD alone can improve clinical symptoms in mild cases of autoimmune epilepsy.

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Humans recognize body parts in categories. Previous studies have shown that responses in the fusiform body area (FBA) and extrastriate body area (EBA) are evoked by the perception of the human body, when presented either as whole or as isolated parts. These responses occur approximately 190 ms after body images are visualized. The extent to which body-sensitive responses show specificity for different body part categories remains to be largely clarified. We used a decoding method to quantify neural responses associated with the perception of different categories of body parts. Nine subjects underwent measurements of their brain activities by magnetoencephalography (MEG) while viewing 14 images of feet, hands, mouths, and objects. We decoded categories of the presented images from the MEG signals using a support vector machine (SVM) and calculated their accuracy by 10-fold cross-validation. For each subject, a response that appeared to be a body-sensitive response was observed and the MEG signals corresponding to the three types of body categories were classified based on the signals in the occipitotemporal cortex. The accuracy in decoding body-part categories (with a peak at approximately 48%) was above chance (33.3%) and significantly higher than that for random categories. According to the time course and location, the responses are suggested to be body-sensitive and to include information regarding the body-part category. Finally, this non-invasive method can decode category information of a visual object with high temporal and spatial resolution and this result may have a significant impact in the field of brain-machine interface research.

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INTRODUCTION: Identification of language-related cortical functions can be carried out noninvasively by transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG), which allow for lesion-based interrogation and global temporospatial investigation of cortices, respectively. Combining these two modalities can improve the accuracy of the identification, but the relationships between them remain unclear. We compared TMS and MEG responses during the same language task to elucidate their temporospatial relationships and used the results to develop a novel method to identify language-related cortical functions. METHODS: Twelve healthy right-handed volunteers performed a picture-naming task during TMS and MEG. TMS was applied on the right or left inferior frontal gyrus (IFG) at five time points, and the reaction times (RTs) for naming the pictures were measured. The temporospatial oscillatory changes measured by MEG during the same task were then compared with the TMS results. RESULTS: Transcranial magnetic stimulation of the left IFG significantly lengthened RTs at 300 and 375 msec after picture presentation, whereas TMS of the right IFG did not change RTs significantly. Interestingly, the stimulus time point at which RTs increased significantly for each individual was correlated with when the low gamma event-related desynchronizations (ERDs) peaked in the left IFG. Moreover, combining the results of TMS and MEG improved the detection rate for identifying the laterality of language function. CONCLUSIONS: These results suggest that the low gamma ERDs measured by MEG strongly relate to the language function of picture naming in the left IFG. Finally, we propose a novel method to identify language-related cortical functions by combining TMS and MEG.

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In this study, we aimed to identify the cerebellum-related electromyographic (EMG) response that appeared in the upper limbs musculature. Thirty times averaged transcranial magnetic stimulation (TMS) with a double-cone coil placed over the cerebellar hemisphere elicited long latency EMG responses at the bilateral extensor carpi radialis (ECR) muscles. The peak latency of this EMG response was 70.7±12.7 ms in the ipsilateral ECR and 62.9±10.2 ms in the contralateral ECR of the TMS side. These latencies were much longer than the latency of the muscle evoked potential when we stimulated pyramidal tracts at the foramen magnum level. Cerebellar hemisphere loading by the finger target pursuit test made this EMG response faster during TMS on the ipsilateral side of the cerebellum and slower during TMS on the contralateral side of the cerebellum. Furthermore, the deeper the level of drowsiness, the slower the peak latency of this EMG response became. These results suggest that this EMG potential is a specific response of the cerebellum and brainstem reticular formation, and may be conducted from the cerebellar structure to the ECR muscle through the polysynaptic transmission of the reticulospinal tract.

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Gamma-secretase is a multimeric membrane protein complex composed of presenilin (PS), nicastrin, Aph-1 and, Pen-2 that is responsible for the intramembrane proteolysis of various type I transmembrane proteins, including amyloid beta-precursor protein and Notch. The direct labeling of PS polypeptides by transition-state analogue gamma-secretase inhibitors suggested that PS represents the catalytic center of gamma-secretase. Here we show that one of the major gamma-secretase inhibitors of dipeptidic type, N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT), targets the C-terminal fragment of PS, especially the transmembrane domain 7 or more C-terminal region, by designing and synthesizing DAP-BpB (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-(S)-phenylglycine-4-(4-(8-biotinamido)octylamino)benzoyl)benzyl)methylamide), a photoactivable DAPT derivative. We also found that DAP-BpB selectively binds to the high molecular weight gamma-secretase complex in an activity-dependent manner. Photolabeling of PS by DAP-BpB is completely blocked by DAPT or its structural relatives (e.g. Compound E) as well as by arylsulfonamides. In contrast, transition-state analogue inhibitor L-685,458 or alpha-helical peptidic inhibitor attenuated the photolabeling of PS1 only at higher concentrations. These data illustrate the DAPT binding site as a novel functional domain within the PS C-terminal fragment that is distinct from the catalytic site or the substrate binding site.

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