國井 尚人

Delusional misidentification, a rare syndrome in which a patient displays persistent delusional misidentification of individuals or objects, occurs in several types of dementia. However, the pathology of delusional misidentification is still unclear, and there was no data pertaining to striate-frontal projection. Here, we report a case of delusional misidentification following frontotemporal dementia in which complex striate-frontal and some specific frontal gyrus dysfunction were observed. In our presented case, delusional misidentification progressed following frontal atrophy. Believing that her actual daughter had been replaced by her niece, her symptoms of delusional misidentification and frontal atrophy progressed in the short term, and social arrangement was necessary three months after the onset. There were no abnormal neurological findings including parkinsonism and general cognitive function test scores were preserved. Validated by dopamine transporter single-photon emission computed tomography, right unilateral striatal uptake decreased significantly without parkinsonism or Parkinson's disease. In addition, of specific concern, functional magnetic resonance images showed left opercular inferior frontal gyrus and right superior frontal gyrus dysfunctions. Our case study highlights complex striate-frontal projection and specific frontal gyrus dysfunctions associated with the pathology of delusional misidentification syndrome.

BACKGROUND: Chronic inflammation of the thorax, as in tuberculosis-related pyothorax, can cause secondary malignant lymphomas. However, primary malignant lymphoma of the central nervous system, specifically of the dura mater, developing after intracranial infection or inflammation has rarely been reported. Herein, the authors describe a case of primary dural lymphoma that developed secondary to subdural empyema, with an initial presentation mimicking a chronic subdural hematoma. OBSERVATIONS: A 51-year-old man had undergone single burr hole drainage for subdural empyema 2 years prior. The patient subsequently underwent multiple craniotomy and drainage procedures, with successful remission of the subdural empyema. He was subsequently referred to the authors' hospital approximately a year after his initial treatment because of a recollection of subdural fluid, which was suspected to be recurrent empyema. After another single burr hole drainage, which revealed only a subdural hematoma, a histopathological diagnosis of B-cell lymphoma of the dural/subdural membrane was made. Subsequent radiation therapy was completed, with good local control and no recurrence of the subdural hematoma confirmed at 2 months posttreatment. LESSONS: Intracranial lymphoma triggered by chronic inflammation is rare but should be considered a differential diagnosis in subdural hematomas for which the background pathology is unclear. https://thejns.org/doi/10.3171/CASE24153.

Sound frequency and duration are essential auditory components. The brain perceives deviations from the preceding sound context as prediction errors, allowing efficient reactions to the environment. Additionally, prediction error response to duration change is reduced in the initial stages of psychotic disorders. To compare the spatiotemporal profiles of responses to prediction errors, we conducted a human electrocorticography study with special attention to high gamma power in 13 participants who completed both frequency and duration oddball tasks. Remarkable activation in the bilateral superior temporal gyri in both the frequency and duration oddball tasks were observed, suggesting their association with prediction errors. However, the response to deviant stimuli in duration oddball task exhibited a second peak, which resulted in a bimodal response. Furthermore, deviant stimuli in frequency oddball task elicited a significant response in the inferior frontal gyrus that was not observed in duration oddball task. These spatiotemporal differences within the Parasylvian cortical network could account for our efficient reactions to changes in sound properties. The findings of this study may contribute to unveiling auditory processing and elucidating the pathophysiology of psychiatric disorders.

Epileptogenic zones (EZs), where epileptic seizures cease after resection, are localized by assessing the seizure-onset zone using ictal electroencephalography (EEG). Owing to the difficulty in capturing unpredictable seizures, biomarkers capable of identifying EZs from interictal EEG are anticipated. Recent studies using intracranial EEG have identified several potential candidate biomarkers for epileptogenicity. High-frequency oscillation (HFO) was initially expected to be a robust biomarker of abnormal excitatory activity in the ictogenic region. However, HFO-guided resection failed to improve seizure prognosis. Meanwhile, the regularity of low-gamma oscillations (30-80 Hz) indicates inhibitory interneurons' hypersynchronization, which could be used to localize the EZ. Besides resting-state EEG assessments, evoked potentials elicited by single-pulse electrical stimulation, such as corticocortical evoked potentials (CCEP), became valuable tools for assessing epileptogenic regions. CCEP responses recorded in the cortex remote from the stimulation site indicate functional connectivity, revealing increased internal connectivity within the ictogenic region and elevated inhibitory input from the non-involved regions to the ictogenic region. Conversely, large responses close to the stimulation site reflect local excitability, manifesting as an increased N1 amplitude and overriding HFO. Further research is required to establish whether these novel electrophysiological methods, either individually or in combination, can function as robust biomarkers of epileptogenicity and hold promise for improving seizure prognosis.

Auditory sensory processing is assumed to occur in a hierarchical structure including the primary auditory cortex (A1), superior temporal gyrus, and frontal areas. These areas are postulated to generate predictions for incoming stimuli, creating an internal model of the surrounding environment. Previous studies on mismatch negativity have indicated the involvement of the superior temporal gyrus in this processing, whereas reports have been mixed regarding the contribution of the frontal cortex. We designed a novel auditory paradigm, the "cascade roving" paradigm, which incorporated complex structures (cascade sequences) into a roving paradigm. We analyzed electrocorticography data from six patients with refractory epilepsy who passively listened to this novel auditory paradigm and detected responses to deviants mainly in the superior temporal gyrus and inferior frontal gyrus. Notably, the inferior frontal gyrus exhibited broader distribution and sustained duration of deviant-elicited responses, seemingly differing in spatio-temporal characteristics from the prediction error responses observed in the superior temporal gyrus, compared with conventional oddball paradigms performed on the same participants. Moreover, we observed that the deviant responses were enhanced through stimulus repetition in the high-gamma range mainly in the superior temporal gyrus. These features of the novel paradigm may aid in our understanding of auditory predictive coding.

Gamma oscillation regularity (GOR) indicates the synchronization of inhibitory interneurons, while the reactivity of cortico-cortical evoked potentials (CCEPs) is supposed to reflect local cortical excitability. Under the assumption that the early response of CCEP near the stimulation site also indicates excitatory activity primarily mediated by pyramidal cells, we aimed to visualize the cortical inhibitory and excitatory activities using GOR and CCEP in combination and to use them to predict the epileptogenic zone (EZ) in mesial temporal lobe epilepsy (MTLE). In five patients who underwent intracranial electrode implantation, GOR and CCEP reactivity in the vicinity of the stimulation site was quantified. The interictal GOR was calculated using multiscale entropy (MSE), the decrease of which was related to the enhanced GOR. These parameters were compared on an electrode-and-electrode basis, and spatially visualized on the brain surface. As a result, elevated GOR and CCEP reactivities, indicative of enhanced inhibitory and excitatory activities, were observed in the epileptogenic regions. Elevated CCEP reactivity was found to be localized to a restricted area centered on the seizure onset region, whereas GOR elevation was observed in a broader region surrounding it. Although these parameters independently predicted the EZ with high specificity, we combined the two to introduce a novel parameter, the excitatory and inhibitory (EI) index. The EI index predicted EZ with increased specificity compared with GOR or CCEP reactivity alone. Our results demonstrate that GOR and CCEP reactivity provided a quantitative visualization of the distribution of cortical inhibitory and excitatory activities and highlighted the relationship between the two parameters. The combination of GOR and CCEP reactivities are expected to serve as biomarkers for localizing the epileptogenic zone in MTLE from interictal intracranial electroencephalograms.

Neurofeedback (NF) shows promise in enhancing memory, but its application to the medial temporal lobe (MTL) still needs to be studied. Therefore, we aimed to develop an NF system for the memory function of the MTL and examine neural activity changes and memory task score changes through NF training. We created a memory NF system using intracranial electrodes to acquire and visualise the neural activity of the MTL during memory encoding. Twenty trials of a tug-of-war game per session were employed for NF and designed to control neural activity bidirectionally (Up/Down condition). NF training was conducted with three patients with drug-resistant epilepsy, and we observed an increasing difference in NF signal between conditions (Up-Down) as NF training progressed. Similarities and negative correlation tendencies between the transition of neural activity and the transition of memory function were also observed. Our findings demonstrate NF's potential to modulate MTL activity and memory encoding. Future research needs further improvements to the NF system to validate its effects on memory functions. Nonetheless, this study represents a crucial step in understanding NF's application to memory and provides valuable insights into developing more efficient memory enhancement strategies.

Removal of the mesial temporal lobe (MTL) is an established surgical procedure that leads to seizure freedom in patients with intractable MTL epilepsy; however, it carries the potential risk of memory damage. Neurofeedback (NF), which regulates brain function by converting brain activity into perceptible information and providing feedback, has attracted considerable attention in recent years for its potential as a novel complementary treatment for many neurological disorders. However, no research has attempted to artificially reorganize memory functions by applying NF before resective surgery to preserve memory functions. Thus, this study aimed (1) to construct a memory NF system that used intracranial electrodes to feedback neural activity on the language-dominant side of the MTL during memory encoding and (2) to verify whether neural activity and memory function in the MTL change with NF training. Two intractable epilepsy patients with implanted intracranial electrodes underwent at least five sessions of memory NF training to increase the theta power in the MTL. There was an increase in theta power and a decrease in fast beta and gamma powers in one of the patients in the late stage of memory NF sessions. NF signals were not correlated with memory function. Despite its limitations as a pilot study, to our best knowledge, this study is the first to report that intracranial NF may modulate neural activity in the MTL, which is involved in memory encoding. The findings provide important insights into the future development of NF systems for the artificial reorganization of memory functions.

There has been tremendous progress in artificial neural networks (ANNs) over the past decade; however, the gap between ANNs and the biological brain as a learning device remains large. With the goal of closing this gap, this paper reviews learning mechanisms in the brain by focusing on three important issues in ANN research: efficiency, continuity, and generalization. We first discuss the method by which the brain utilizes a variety of self-organizing mechanisms to maximize learning efficiency, with a focus on the role of spontaneous activity of the brain in shaping synaptic connections to facilitate spatiotemporal learning and numerical processing. Then, we examined the neuronal mechanisms that enable lifelong continual learning, with a focus on memory replay during sleep and its implementation in brain-inspired ANNs. Finally, we explored the method by which the brain generalizes learned knowledge in new situations, particularly from the mathematical generalization perspective of topology. Besides a systematic comparison in learning mechanisms between the brain and ANNs, we propose "Mental Schema 2.0," a new computational property underlying the brain's unique learning ability that can be implemented in ANNs.

Abstract Epilepsy is a neurological disorder that may affect the autonomic nervous system (ANS) from 15 to 20 min before seizure onset, and disturbances of ANS affect R–R intervals (RRI) on an electrocardiogram (ECG). This study aims to develop a machine learning algorithm for predicting focal epileptic seizures by monitoring R–R interval (RRI) data in real time. The developed algorithm adopts a self-attentive autoencoder (SA-AE), which is a neural network for time-series data. The results of applying the developed seizure prediction algorithm to clinical data demonstrated that it functioned well in most patients; however, false positives (FPs) occurred in specific participants. In a future work, we will investigate the causes of FPs and optimize the developing seizure prediction algorithm to further improve performance using newly added clinical data.

OBJECTIVE: The impact of the coronavirus disease 2019 (COVID-19) pandemic on epilepsy care across Japan was investigated by conducting a multicenter retrospective cohort study. METHODS: This study included monthly data on the frequency of (1) visits by outpatients with epilepsy, (2) outpatient electroencephalography (EEG) studies, (3) telemedicine for epilepsy, (4) admissions for epilepsy, (5) EEG monitoring, and (6) epilepsy surgery in epilepsy centers and clinics across Japan between January 2019 and December 2020. We defined the primary outcome as epilepsy-center-specific monthly data divided by the 12-month average in 2019 for each facility. We determined whether the COVID-19 pandemic-related factors (such as year [2019 or 2020], COVID-19 cases in each prefecture in the previous month, and the state of emergency) were independently associated with these outcomes. RESULTS: In 2020, the frequency of outpatient EEG studies (-10.7%, p<0.001) and cases with telemedicine (+2,608%, p=0.031) were affected. The number of COVID-19 cases was an independent associated factor for epilepsy admission (-3.75*10-3 % per case, p<0.001) and EEG monitoring (-3.81*10-3 % per case, p = 0.004). Further, the state of emergency was an independent factor associated with outpatient with epilepsy (-11.9%, p<0.001), outpatient EEG (-32.3%, p<0.001), telemedicine for epilepsy (+12,915%, p<0.001), epilepsy admissions (-35.3%; p<0.001), EEG monitoring (-24.7%: p<0.001), and epilepsy surgery (-50.3%, p<0.001). SIGNIFICANCE: We demonstrated the significant impact that the COVID-19 pandemic had on epilepsy care. These results support those of previous studies and clarify the effect size of each pandemic-related factor on epilepsy care.

Decoding the inner representation of a word meaning from human cortical activity is a substantial challenge in the development of speech brain-machine interfaces (BMIs). The semantic aspect of speech is a novel target of speech decoding that may enable versatile communication platforms for individuals with impaired speech ability; however, there is a paucity of electrocorticography studies in this field. We decoded the semantic representation of a word from single-trial cortical activity during an imageability-based property identification task that required participants to discriminate between the abstract and concrete words. Using high gamma activity in the language-dominant hemisphere, a support vector machine classifier could discriminate the 2-word categories with significantly high accuracy (73.1 ± 7.5%). Activities in specific time components from two brain regions were identified as significant predictors of abstract and concrete dichotomy. Classification using these feature components revealed that comparable prediction accuracy could be obtained based on a spatiotemporally targeted decoding approach. Our study demonstrated that mental representations of abstract and concrete word processing could be decoded from cortical high gamma activities, and the coverage of implanted electrodes and time window of analysis could be successfully minimized. Our findings lay the foundation for the future development of semantic-based speech BMIs.

Neurofeedback through visual, auditory, or tactile sensations improves cognitive functions and alters the activities of daily living. However, some people, such as children and the elderly, have difficulty concentrating on neurofeedback for a long time. Constant stressless neurofeedback for a long time may be achieved with auditory neurofeedback using music. The primary purpose of this study was to clarify whether music-based auditory neurofeedback increases the power of the alpha wave in healthy subjects. During neurofeedback, white noise was superimposed on classical music, with the noise level inversely correlating with normalized alpha wave power. This was a single-blind, randomized control crossover trial in which 10 healthy subjects underwent, in an assigned order, normal and random feedback (NF and RF), either of which was at least 4 weeks long. Cognitive functions were evaluated before, between, and after each neurofeedback period. The secondary purpose was to assess neurofeedback-induced changes in cognitive functions. A crossover analysis showed that normalized alpha-power was significantly higher in NF than in RF; therefore, music-based auditory neurofeedback facilitated alpha wave induction. A composite category-based analysis of cognitive functions revealed greater improvements in short-term memory in subjects whose alpha-power increased in response to NF. The present study employed a long period of auditory alpha neurofeedback and achieved successful alpha wave induction and subsequent improvements in cognitive functions. Although this was a pilot study that validated a music-based alpha neurofeedback system for healthy subjects, the results obtained are encouraging for those with difficulty in concentrating on conventional alpha neurofeedback.Trial registration: 2018077NI, date of registration: 2018/11/27.

Gamma oscillations are physiological phenomena that reflect perception and cognition, and involve parvalbumin-positive γ-aminobutyric acid-ergic interneuron function. The auditory steady-state response (ASSR) is the most robust index for gamma oscillations, and it is impaired in patients with neuropsychiatric disorders such as schizophrenia and autism. Although ASSR reduction is known to vary in terms of frequency and time, the neural mechanisms are poorly understood. We obtained high-density electrocorticography recordings from a wide area of the cortex in 8 patients with refractory epilepsy. In an ASSR paradigm, click sounds were presented at frequencies of 20, 30, 40, 60, 80, 120, and 160 Hz. We performed time-frequency analyses and analyzed intertrial coherence, event-related spectral perturbation, and high-gamma oscillations. We demonstrate that the ASSR is globally distributed among the temporal, parietal, and frontal cortices. The ASSR was composed of time-dependent neural subcircuits differing in frequency tuning. Importantly, the frequency tuning characteristics of the late-latency ASSR varied between the temporal/frontal and parietal cortex, suggestive of differentiation along parallel auditory pathways. This large-scale survey of the cortical ASSR could serve as a foundation for future studies of the ASSR in patients with neuropsychiatric disorders.

Background: Vagus nerve stimulation (VNS) is an established palliative surgical treatment for refractory epilepsy. Recently, pairing VNS with rehabilitation received growing attention for their joint effect on neural plasticity. However, objective biological measurements proving the interaction between VNS effects and cortical recruitment are lacking. Studies reported that VNS induced little blood flow increase in the cerebral cortex. Objective: This study tested the hypothesis that pairing VNS with a cognitive task amplifies task-induced cerebral blood flow (CBF). Methods: This study included 21 patients implanted with vagus nerve stimulator to treat refractory epilepsy. Near-infrared spectroscopy (NIRS) with sensors on the forehead measured CBF changes in the frontal cortices in response to VNS. Cerebral blood flow was measured when VNS was delivered during a resting state or a verbal fluency task. We analyzed the VNS effect on CBF in relation to stimulation intensity and clinical responsiveness. Results: We observed no CBF change when VNS was delivered during rest, irrespective of stimulation intensity or responsiveness. Cerebral blood flow changed significantly when a verbal fluency task was paired with VNS in a stimulation intensity-dependent manner. Cerebral blood flow changes in the non-responders showed no intensity-dependency. Conclusion: Our results could be an important biological proof of the interaction between VNS effects and cortical recruitment, supporting the validity of pairing VNS with rehabilitation.

OBJECTIVE: In long-term video-monitoring, automatic seizure detection holds great promise as a means to reduce the workload of the epileptologist. A convolutional neural network (CNN) designed to process images of EEG plots demonstrated high performance for seizure detection, but still has room for reducing the false-positive alarm rate. METHODS: We combined a CNN that processed images of EEG plots with patient-specific autoencoders (AE) of EEG signals to reduce the false alarms during seizure detection. The AE automatically logged abnormalities, i.e., both seizures and artifacts. Based on seizure logs compiled by expert epileptologists and errors made by AE, we constructed a CNN with 3 output classes: seizure, non-seizure-but-abnormal, and non-seizure. The accumulative measure of number of consecutive seizure labels was used to issue a seizure alarm. RESULTS: The second-by-second classification performance of AE-CNN was comparable to that of the original CNN. False-positive seizure labels in AE-CNN were more likely interleaved with "non-seizure-but-abnormal" labels than with true-positive seizure labels. Consequently, "non-seizure-but-abnormal" labels interrupted runs of false-positive seizure labels before triggering an alarm. The median false alarm rate with the AE-CNN was reduced to 0.034 h-1, which was one-fifth of that of the original CNN (0.17 h-1). CONCLUSIONS: A label of "non-seizure-but-abnormal" offers practical benefits for seizure detection. The modification of a CNN with an AE is worth considering because AEs can automatically assign "non-seizure-but-abnormal" labels in an unsupervised manner with no additional demands on the time of the epileptologist.

Altered gamma oscillations have attracted considerable attention as an index of the excitation/inhibition (E/I) imbalance in schizophrenia and other neuropsychiatric disorders. The auditory steady-state response (ASSR) has been the most robust probe of abnormal gamma oscillatory dynamics in schizophrenia. Here, we review recent ASSR studies in patients with schizophrenia and other neuropsychiatric disorders. Preclinical ASSR research, which has contributed to the elucidation of the underlying pathophysiology of these diseases, is also discussed. The developmental trajectory of the ASSR has been explored and may show signs of the maturation and disruption of E/I balance in adolescence. Animal model studies have shown that synaptic interactions between parvalbumin-positive GABAergic interneurons and pyramidal neurons contribute to the regulation of E/I balance, which is related to the generation of gamma oscillation. Therefore, ASSR alteration may be a significant electrophysiological finding related to the E/I imbalance in neuropsychiatric disorders, which is a cross-disease feature and may reflect clinical staging. Future studies regarding ASSR generation, especially in nonhuman primate models, will advance our understanding of the brain circuit and the molecular mechanisms underlying neuropsychiatric disorders.

Although aberrations in the number and function of glutamate AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors are thought to underlie neuropsychiatric disorders, no methods are currently available for visualizing AMPA receptors in the living human brain. Here we developed a positron emission tomography (PET) tracer for AMPA receptors. A derivative of 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluoro-phenoxyacetamide radiolabeled with 11C ([11C]K-2) showed specific binding to AMPA receptors. Our clinical trial with healthy human participants confirmed reversible binding of [11C]K-2 in the brain according to Logan graphical analysis (UMIN000020975; study design: non-randomized, single arm; primary outcome: dynamics and distribution volumes of [11C]K-2 in the brain; secondary outcome: adverse events of [11C]K-2 during the 4-10 d following dosing; this trial met prespecified endpoints). In an exploratory clinical study including patients with epilepsy, we detected increased [11C]K-2 uptake in the epileptogenic focus of patients with mesial temporal lobe epilepsy, which was closely correlated with the local AMPA receptor protein distribution in surgical specimens from the same individuals (UMIN000025090; study design: non-randomized, single arm; primary outcome: correlation between [11C]K-2 uptake measured with PET before surgery and AMPA receptor protein density examined by biochemical study after surgery; secondary outcome: adverse events during the 7 d following PET scan; this trial met prespecified endpoints). Thus, [11C]K-2 is a potent PET tracer for AMPA receptors, potentially providing a tool to examine the involvement of AMPA receptors in neuropsychiatric disorders.

Auditory mismatch negativity (MMN) is an electrophysiological response to a deviation from regularity. This response is considered pivotal to understanding auditory processing, particularly in the pre-attentive phase. However, previous findings suggest that MMN is a product of N1 adaptation/enhancement, which reflects lower-order auditory processing. The separability of these two components remains unclear and is considered an important issue in the field of neuroscience. The aim of the present study was to spatiotemporally differentiate MMN from N1 adaptation using human electrocorticography (ECoG). Auditory evoked potentials under the classical oddball (OD) task as well as the many standards (MS) task were recorded in three patients with epilepsy whose lateral cortices were widely covered with high-density electrodes. Close observation identified an electrode at which N1 adaptation was temporally separated from MMN, whereas N1 adaptation was partially incorporated into MMN at other electrodes. Since N1 adaptation occurs in the N1 population, we spatially compared MMN with N1 obtained from the MS task instead of N1 adaptation. As a result, N1 was observed in a limited area around the Sylvian fissure adjacent to A1, whereas MMN was noted in wider areas, including the temporal, frontal, and parietal lobes. MMN was thus considered to be differentiated from N1 adaptation. The results suggest that MMN is not merely a product of the neural adaptation of N1 and instead represents higher-order processes in auditory deviance detection. These results will contribute to strengthening the foundation of future research in this field.

Mismatch negativity (MMN) reduction is one of the most robust findings among several neurophysiological and neurocognitive measures in patients with schizophrenia. MMN is a promising biomarker for schizophrenia because of the following properties: 1) its relationship with early psychosis, including clinical high-risk (CHR); 2) its relationship with the functional abilities of patients; and 3) its translatability into basic research using animal models. Specifically, the utility of the passive auditory oddball paradigm that does not require subjects to make behavioral responses enables identical physiological activities to be obtained from both experimental animals and patients. This advantage has contributed to clarifying the generating mechanism of MMN in various animal studies. We reviewed clinical reports focused on early psychosis; specifically differential effects of deviance type and relationships to clinical and functional outcome. For the utility of MMN as a tool for translational research, we next reviewed recent MMN studies in rodents and nonhuman primates (NHP) as well as studies using intracranial recordings in humans, a rare opportunity to detect neural signals in vivo in humans. Neural computations of MMN, such as adaptation, deviance detection, and predictive coding, have been recent topics for understanding MMN generating mechanisms. Finally, several significant research questions were provided for future directions. MMN research could contribute to innovative, novel, therapeutic strategies in the future by becoming a bridge between basic and clinical research.

INTRODUCTION: Epileptologists could benefit from a diagnosis support system that automatically detects seizures because visual inspection of long-term electroencephalograms (EEGs) is extremely time-consuming. However, the diversity of seizures among patients makes it difficult to develop universal features that are applicable for automatic seizure detection in all cases, and the rarity of seizures results in a lack of sufficient training data for classifiers. METHODS: To overcome these problems, we utilized an autoencoder (AE), which is often used for anomaly detection in the field of machine learning, to perform seizure detection. We hypothesized that multichannel EEG signals are compressible by AE owing to their spatio-temporal coupling and that the AE should be able to detect seizures as anomalous events from an interictal EEG. RESULTS: Through experiments, we found that the AE error was able to classify seizure and nonseizure states with a sensitivity of 100% in 22 out of 24 available test subjects and that the AE was better than the commercially available software BESA and Persyst for half of the test subjects. CONCLUSIONS: These results suggest that the AE error is a feasible candidate for a universal seizure detection feature.

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.

Restoration of speech communication for locked-in patients by means of brain computer interfaces (BCIs) is currently an important area of active research. Among the neural signals obtained from intracranial recordings, single/multi-unit activity (SUA/MUA), local field potential (LFP), and electrocorticography (ECoG) are good candidates for an input signal for BCIs. However, the question of which signal or which combination of the three signal modalities is best suited for decoding speech production remains unverified. In order to record SUA, LFP, and ECoG simultaneously from a highly localized area of human ventral sensorimotor cortex (vSMC), we fabricated an electrode the size of which was 7 by 13 mm containing sparsely arranged microneedle and conventional macro contacts. We determined which signal modality is the most capable of decoding speech production, and tested if the combination of these signals could improve the decoding accuracy of spoken phonemes. Feature vectors were constructed from spike frequency obtained from SUAs and event-related spectral perturbation derived from ECoG and LFP signals, then input to the decoder. The results showed that the decoding accuracy for five spoken vowels was highest when features from multiple signals were combined and optimized for each subject, and reached 59% when averaged across all six subjects. This result suggests that multi-scale signals convey complementary information for speech articulation. The current study demonstrated that simultaneous recording of multi-scale neuronal activities could raise decoding accuracy even though the recording area is limited to a small portion of cortex, which is advantageous for future implementation of speech-assisting BCIs.

Although an increasing number of cases of temporal lobe epilepsy (TLE) with ipsilateral amygdala enlargement (AE) have been reported, there are few pathological reports, and no clear consensus has been established. Oligodendroglia or oligodendroglia-like cells (OLCs) have recently attracted attention in epilepsy studies. Here, we report the clinical and pathological findings of a 40-year-old male TLE patient with AE and hippocampal sclerosis, in whom histopathological study demonstrated remarkable clustering of OLCs around the uncus. The patient began to have refractory seizures at the age of 14, and preoperative MRI revealed left amygdala enlargement and left hippocampal atrophy. Other examinations were consistent with left mesial temporal epileptogenicity. He underwent surgical resection and achieved seizure freedom. Histopathological study of the amygdala showed swollen neurons with relatively large bodies and thick neurites, accompanied by vacuolar degeneration in the background. Additionally, there were marked clusters of OLCs with round nuclei and densely stained chromatin around the uncus. The OLCs were Olig2-positive. In the hippocampus, severe cell loss in CA1 and granule cell dispersion in the dentate gyrus were found. These findings may provide some insights for further pathological investigations of TLE with non-neoplastic AE.

Objective. Several neuroimaging studies have demonstrated that the ventral temporal cortex contains specialized regions that process visual stimuli. This study investigated the spatial and temporal dynamics of electrocorticographic (ECoG) responses to different types and colors of visual stimulation that were presented to four human participants, and demonstrated a real-time decoder that detects and discriminates responses to untrained natural images. Approach. ECoG signals from the participants were recorded while they were shown colored and greyscale versions of seven types of visual stimuli (images of faces, objects, bodies, line drawings, digits, and kanji and hiragana characters), resulting in 14 classes for discrimination (experiment I). Additionally, a real-time system asynchronously classified ECoG responses to faces, kanji and black screens presented via a monitor (experiment II), or to natural scenes (i.e. the face of an experimenter, natural images of faces and kanji, and a mirror) (experiment III). Outcome measures in all experiments included the discrimination performance across types based on broadband γ activity. Main results. Experiment I demonstrated an offline classification accuracy of 72.9% when discriminating among the seven types (without color separation). Further discrimination of grey versus colored images reached an accuracy of 67.1%. Discriminating all colors and types (14 classes) yielded an accuracy of 52.1%. In experiment II and III, the real-time decoder correctly detected 73.7% responses to face, kanji and black computer stimuli and 74.8% responses to presented natural scenes. Significance. Seven different types and their color information (either grey or color) could be detected and discriminated using broadband γ activity. Discrimination performance maximized for combined spatial-temporal information. The discrimination of stimulus color information provided the first ECoG-based evidence for color-related population-level cortical broadband γ responses in humans. Stimulus categories can be detected by their ECoG responses in real time within 500 ms with respect to stimulus onset.

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.

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. (C) 2017 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

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 &gt;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-termoutcome for complex partial seizures afterMHT + 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.

Background and Purpose: We analyzed the ability of a machine learning approach that uses diffusion tensor imaging (DTI) structural connectomes to determine lateralization of epileptogenicity in temporal lobe epilepsy (TLE). Materials and Methods: We analyzed diffusion tensor and 3-dimensional (3D) T-1-weighted images of 44 patients with TLE (right, 15, left, 29; mean age, 33.0 +/- 11.6 years) and 14 age-matched controls. We constructed a whole brain structural connectome for each subject, calculated graph theoretical network measures, and used a support vector machine (SVM) for classification among 3 groups (right TLE versus controls, left TLE versus controls, and right TLE versus left TLE) following a feature reduction process with sparse linear regression. Results: In left TLE, we found a significant decrease in local efficiency and the clustering coefficient in several brain regions, including the left posterior cingulate gyrus, left cuneus, and both hippocampi. In right TLE, the right hippocampus showed reduced nodal degree, clustering coefficient, and local efficiency. With use of the leave-one-out cross-validation strategy, the SVM classifier achieved accuracy of 75.9 to 89.7% for right TLE versus controls, 74.4 to 86.0% for left TLE versus controls, and 72.7 to 86.4% for left TLE versus right TLE. Conclusion: Machine learning of graph theoretical measures from the DTI structural connectome may give support to lateralization of the TLE focus. The present good discrimination between left and right TLE suggests that, with further refinement, the classifier should improve presurgical diagnostic confidence.

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.

Recognition of faces and written words is associated with category-specific brain activation in the ventral occipitotemporal cortex (vOT). However, topological and functional relationships between face-selective and word-selective vOT regions remain unclear. In this study, we collected data from patients with intractable epilepsy who underwent high-density recording of surface field potentials in the vOT. "Faces" and "letterstrings" induced outstanding category-selective responses among the 24 visual categories tested, particularly in high-gamma band powers. Strikingly, within-hemispheric analysis revealed alternation of face-selective and letterstring-selective zones within the vOT. Two distinct face-selective zones located anterior and posterior portions of the mid-fusiform sulcus whereas letterstring-selective zones alternated between and outside of these 2 face-selective zones. Further, a classification analysis indicated that activity patterns of these zones mostly represent dedicated categories. Functional connectivity analysis using Granger causality indicated asymmetrically directed causal influences from face-selective to letterstring-selective regions. These results challenge the prevailing view that different categories are represented in distinct contiguous regions in the vOT.

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.

ObjectiveResective 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. MethodsWe 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 (60-120Hz) 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. ResultsWe observed memory-related HGA mainly between 500 and 600msec 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. SignificanceParahippocampal 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.

BACKGROUND: There has been growing interest in clinical single-neuron recording to better understand epileptogenicity and brain function. It is crucial to compare this new information, single-neuronal activity, with that obtained from conventional intracranial electroencephalography during simultaneous recording. However, it is difficult to implant microwires and subdural electrodes during a single surgical operation because the stereotactic frame hampers flexible craniotomy. OBJECTIVE: To describe newly designed electrodes and surgical techniques for implanting them with subdural electrodes that enable simultaneous recording from hippocampal neurons and broad areas of the cortical surface. METHODS: We designed a depth electrode that does not protrude into the dura and pulsates naturally with the brain. The length and tract of the depth electrode were determined preoperatively between the lateral subiculum and the lateral surface of the temporal lobe. A frameless navigation system was used to insert the depth electrode. Surface grids and ventral strips were placed before and after the insertion of the depth electrodes, respectively. Finally, a microwire bundle was inserted into the lumen of the depth electrode. We evaluated the precision of implantation, the recording stability, and the recording rate with microwire electrodes. RESULTS: Depth-microwire electrodes were placed with a precision of 3.6 mm. The mean successful recording rate of single-or multiple-unit activity was 14.8%, which was maintained throughout the entire recording period. CONCLUSION: We achieved simultaneous implantation of microwires, depth electrodes, and broad-area subdural electrodes. Our method enabled simultaneous and stable recording of hippocampal single-neuron activities and multichannel intracranial electroencephalography.

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 100 ms after stimulus onsets, subsequently in the left posterior middle temporal gyrus, in the left ventral premotor cortex at 200 ms and in the left middle and left inferior frontal gyri at 300 ms 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 100-600 ms. 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. (C) 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

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 (60-120 Hz) 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. (C) 2012 Elsevier Inc. All rights reserved.

We compared electrocorticography (ECoG) with invasive intracranial noninvasive functional MRI using language-related tasks. Twenty patients underwent bilateral implantation of subdural electrodes (more than 80 channels) for diagnosing intractable epilepsy. Before implantation of the electrodes, language-related fMRI was performed, and the fMR images were superimposed on individual brain images. Brain mapping with electrocortical stimulation was performed on the basis of the fused fMR and brain MR images, and the specificity and sensitivity of language-related fMRI was calculated. For careful interpretation of spatial and temporal ECoG changes with semantic tasks, we developed a software to visualize semantic-ECoG dynamics in the brain. Semantic-ECoG was recorded during word, figure, and face recognition as well as memory tasks. The raw ECoG data were processed by averaging and time-frequency analysis, and the functional profiles were projected onto the individual brain surface. Acquired ECoG was classified using Support Vector Machine and Sparse Logistic Regression to decode brain signals. Because of variations in electrode locations, we normalized the ECoG electrodes by using SPM8. Although fMRI has 90% sensitivity, its specificity is only up to 50%. The basal temporal-occipital cortex was activated within 250 ms after visual object presentation. Compared to other stimuli, face stimulation evoked significantly higher ECoG amplitudes. Among different brain regions, the hippocampus was predominantly activated during the memory task. The prediction rate of ECoG classification was 90%, which was sufficient for clinical use. Semantic-ECoG is a powerful technique to detect and decode human brain functions.

Purpose: To evaluate whether the use of diffusion-tensor tractography (DTT) of the corticospinal tract could reduce motor complications after stereotactic radiosurgery (SRS). Methods and Materials: Patients with arteriovenous malformation (AVM) in the deep frontal lobe, deep parietal lobe, basal ganglia, and thalamus who had undergone radiosurgery since 2000 and were followed up for more than 3 years were studied. DTT of the corticospinal tract had been integrated into treatment planning of SRS since 2004, and the maximum dose received by the corticospinal tract was attempted to be less than 20 Gy. Treatment outcomes before (28 patients, Group A) and after (24 patients, Group B) the introduction of this technique were compared. Results: There were no statistical differences between the two groups (Group A vs. Group B) in patients' age (34 years vs. 33 years, p = 0.76), percentage of patients with hemorrhagic events before treatment (50% vs. 29%, p = 0.12), or percentage of AVM involving the basal ganglia and thalamus (36% vs. 46%, p = 0.46). Obliteration rates were 69% and 76% at 4 years in Groups A and B, respectively (p = 0.68), which were not significantly different. Motor complications were observed in 5 patients in Group A (17.9%) but only in 1 patient in Group B (4.2%), which was significantly less frequent (p = 0.021). Conclusion: Integrating DTT of the corticospinal tract into treatment planning contributed to reduction of motor complications without compromising the obliteration rate for AVM adjacent to the corticospinal tract. (C) 2012 Elsevier Inc.

Purpose: To analyze the effect of use of tractography of the critical brain white matter fibers created from diffusion tensor magnetic resonance imaging on reduction of morbidity associated with radiosurgery. Methods and Materials: Tractography of the pyramidal tract has been integrated since February 2004 if lesions are adjacent to it, the optic radiation since May 2006, and the arcuate fasciculus since October 2007. By visually con.. firming the precise location of these fibers, the dose to these fiber tracts was optimized. One hundred forty-four consecutive patients with cerebral arteriovenous malformations who underwent radiosurgery with this technique between February 2004 and December 2009 were analyzed. Results: Tractography was prospectively integrated in 71 of 155 treatments for 144 patients. The pyramidal tract was visualized in 45, the optic radiation in 22, and the arcuate fasciculus in 13 (two tracts in 9). During the follow-up period of 3 to 72 months (median, 23 months) after the procedure, 1 patient showed permanent worsening of pre-existing dysesthesia, and another patient exhibited mild transient hemiparesis 12 months later but fully recovered after oral administration of corticosteroid agents. Two patients had transient speech disturbance before starting integration of the arcuate fasciculus tractography, but no patient thereafter. Conclusion: Integrating tractography helped prevent morbidity of radiosurgery in patients with brain arteriovenous malformations. (C) 2012 Elsevier Inc.

BACKGROUND: Functional magnetic resonance imaging (fMRI) is a less invasive way of mapping brain functions. The reliability of fMRI for localizing language-related function is yet to be determined. OBJECTIVE: We performed a detailed analysis of language fMRI reliability by comparing the results of 3-T fMRI with maps determined by extraoperative electrocortical stimulation (ECS). METHODS: This study was performed on 8 epileptic patients who underwent subdural electrode placement. The tasks performed during fMRI included verb generation, abstract/concrete categorization, and picture naming. We focused on the frontal lobe, which was effectively activated by these tasks. In extraoperative ECS, 4 tasks were combined to determine the eloquent areas: spontaneous speech, picture naming, reading, and comprehension. We calculated the sensitivity and specificity with different Z score thresholds for each task and appropriate matching criteria. For further analysis, we divided the frontal lobe into 5 areas and investigated intergyrus variations in sensitivity and specificity. RESULTS: The abstract/concrete categorization task was the most sensitive and specific task in fMRI, whereas the picture naming task detected eloquent areas most efficiently in ECS. The combination of the abstract/concrete categorization task and a 3-mm matching criterion gave the best tradeoff (sensitivity, 83%; specificity, 61%) when the Z score was 2.24. As for intergyrus variation, the posterior inferior frontal gyrus showed the best tradeoff (sensitivity, 91%; specificity, 59%), whereas the anterior middle frontal gyrus had low specificity. CONCLUSION: Despite different tasks for fMRI and extraoperative ECS, the relatively low specificity might be caused by a fundamental discrepancy between the 2 techniques. Reliability of language fMRI activation might differ, depending on the brain region.

BACKGROUND AND IMPORTANCE: Tumor-induced osteomalacia (TIO) is an uncommon paraneoplastic syndrome rarely encountered in neurosurgical practice. We report on 2 cases of TIO caused by skull base tumors. Although the diagnosis of TIO is difficult to make and often is delayed because of the insidious nature of the symptoms, mostly systemic pain and weakness, it is curable once it is diagnosed and properly treated. CLINICAL PRESENTATION: Both patients presented with severe pain developing in the lower extremities and moving out to the entire body, as well as difficulty moving. They were diagnosed with TIO several years after onset. A high level of serum FGF23 was confirmed, and whole-body imaging studies demonstrated tumors in the middle and anterior cranial base, respectively. The patient with the anterior cranial base tumor had a history of hemorrhage into the frontal lobe and partial resection. En bloc resection of tumor with surrounding skull bone was performed. The histological diagnosis for both cases was phosphaturic mesenchymal tumor, mixed connective tissue variant. CONCLUSION: The level of FGF23 normalized immediately after surgery. Both patients experienced a dramatic relief of pain and recovery of muscle power. Although reports of osteomalacia caused by tumors in the neurosurgical field are extremely rare in the literature, its true incidence is unknown. We emphasize the importance of recognition of this syndrome and recommend total resection of tumors when possible.

OBJECTIVE: To present an angiographic classification of attachment of meningiomas at the cerebellopontine angle (CPA) based on tumor feeding and to validate the utility of this classification in predicting meningioma attachments at the CPA. METHODS: The authors retrospectively analyzed 34 consecutive patients with meningioma at the CPA. Based on operative findings, tumors were classified into four types: the petroclival type, in which the trigeminal nerve is displaced laterally; the tentorial type, in which the center of tumor attachment is located at the medial tentorium; the anterior petrous type, in which the center of tumor attachment is located anterior to the meatus; and the posterior petrous type, in which the center of tumor attachment is located posterior to the meatus. Magnetic resonance imaging (MRI) was sufficient to confirm attachment of the posterior petrous type. Another 26 cases were analyzed angiographically and classified into three types: abnormal ipsilateral tentorial artery type (type A); bilateral internal carotid artery (ICA) type (type B); and nontentorial, non-ICA type (type N). This angiographic classification was validated by comparison with the attachment classification. RESULTS: Angiographic types A, B, and N corresponded to tentorial, petroclival, and anterior petrous types of attachment. Observed agreement was very high, particularly for tumors greater than 30 mm in diameter (kappa statistic 0.83; 95% confidence interval [CI] 0.62-1.0). Angiographic type in this paired attachment typing offered high sensitivity and specificity greater than 0.80 in tumors larger than 30 mm. CONCLUSIONS: This angiographic classification seems to be useful in predicting meningioma attachments at the CPA. The existence of an abnormally developed tentorial artery seems highly indicative of tumor attachment to the tentorium.

Three patients undergoing surgery for cerebello-pontine angle meningioma suffered transient episodes of asystole. All patients exhibited return to the previous heart rate with cessation of surgical manipulations and administration of anticholinergic agents. These reactions were apparently elicited by activation of the trigeminocardiac reflex (TCR) by direct stimulation of the trigeminal nerve or branches in the dura mater or cerebellar tentorium. Remifentanil was used in all three cases as an anesthetic agent, so may be a cause of the TCR. The possibility of activation of the TCR should be considered during surgical manipulation around the trigeminal nerve or the distribution of the trigeminal nerve branches. Transient bradycardia, hypotension, or asystole can occur regardless of whether there is pressure on the brainstem during posterior fossa meningioma surgery.