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Objective evaluation of language function is critical for children with intractable epilepsy under consideration for epilepsy surgery. The purpose of this preliminary study was to evaluate word recognition in children with intractable epilepsy by using magnetoencephalography (MEG). Ten children with intractable epilepsy (M/F 6/4, mean ± SD 13.4 ± 2.2 years) were matched on age and sex to healthy controls. Common nouns were presented simultaneously from visual and auditory sensory inputs in "match" and "mismatch" conditions. Neuromagnetic responses M1, M2, M3, M4, and M5 with latencies of ~100 ms, ~150 ms, ~250 ms, ~350 ms, and ~450 ms, respectively, elicited during the "match" condition were identified. Compared to healthy children, epilepsy patients had both significantly delayed latency of the M1 and reduced amplitudes of M3 and M5 responses. These results provide neurophysiologic evidence of altered word recognition in children with intractable epilepsy.

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Recent studies have revealed the importance of high-frequency brain signals (>70 Hz). One challenge of high-frequency signal analysis is that the size of time-frequency representation of high-frequency brain signals could be larger than 1 terabytes (TB), which is beyond the upper limits of a typical computer workstation's memory (<196 GB). The aim of the present study is to develop a new method to provide greater sensitivity in detecting high-frequency magnetoencephalography (MEG) signals in a single automated and versatile interface, rather than the more traditional, time-intensive visual inspection methods, which may take up to several days. To address the aim, we developed a new method, accumulated source imaging, defined as the volumetric summation of source activity over a period of time. This method analyzes signals in both low- (1~70 Hz) and high-frequency (70~200 Hz) ranges at source levels. To extract meaningful information from MEG signals at sensor space, the signals were decomposed to channel-cross-channel matrix (CxC) representing the spatiotemporal patterns of every possible sensor-pair. A new algorithm was developed and tested by calculating the optimal CxC and source location-orientation weights for volumetric source imaging, thereby minimizing multi-source interference and reducing computational cost. The new method was implemented in C/C++ and tested with MEG data recorded from clinical epilepsy patients. The results of experimental data demonstrated that accumulated source imaging could effectively summarize and visualize MEG recordings within 12.7 h by using approximately 10 GB of computer memory. In contrast to the conventional method of visually identifying multi-frequency epileptic activities that traditionally took 2-3 days and used 1-2 TB storage, the new approach can quantify epileptic abnormalities in both low- and high-frequency ranges at source levels, using much less time and computer memory.

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PURPOSE: Magnetoencephalography (MEG) has been shown a useful diagnostic tool for presurgical evaluation of pediatric medically intractable partial epilepsy as MEG source localization has been shown to improve the likelihood of seizure onset zone (SOZ) sampling during subsequent evaluation with intracranial EEG (ICEEG). We investigated whether ictal MEG onset source localization further improves results of interictal MEG in defining the SOZ. METHODS: We identified 20 pediatric patients with one habitual seizure during MEG recordings between October 2007 and April 2011. MEG was recorded with sampling rates of 600Hz and 4000Hz for 10 and 2min respectively. Continuous head localization (CHL) was applied. Source localization analyses were applied using multiple algorithms, both at the beginning of ictal onset and for interictal MEG discharges. Ictal MEG onsets were identified by visual inspection and power spectrum using short-time Fourier transform (STFT). Source localizations were compared with ICEEG, surgical procedure and outcome. KEY FINDINGS: Eight patients met all inclusion criteria. Five of the 8 patients (63%) had concordant ictal MEG onset source localization and interictal MEG discharge source localizations in the same lobe, but the source of ictal MEG onset was closer to the SOZ defined by ICEEG. SIGNIFICANCE: Although the capture of seizures during MEG recording is challenging, the source localization for ictal MEG onset proved to be a useful tool for presurgical evaluation in our pediatric population with medically intractable epilepsy.

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Recent studies in adults have found consistent contralateral high gamma activities in the sensorimotor cortex during unilateral finger movement. However, no study has reported on this same phenomenon in children. We hypothesized that contralateral high gamma activities also exist in children during unilateral finger movement. Sixty normal children (6-17 years old) were studied with a 275-channel MEG system combined with synthetic aperture magnetometry (SAM). Sixty participants displayed consistently contralateral event-related synchronization (C-ERS) within high gamma band (65-150 Hz) in the primary motor cortices (M1) of both hemispheres. Interestingly, nineteen younger children displayed ipsilateral event-related synchronization (I-ERS) within the high gamma band (65-150 Hz) just during their left finger movement. Both I-ERS and C-ERS were localized in M1. The incidence of I-ERS showed a significant decrease with age. Males had significantly higher odds of having ipsilateral activity compared to females. Noteworthy, high gamma C-ERS appeared consistently, while high gamma I-ERS changed with age. The asymmetrical patterns of neuromagnetic activities in the children's brain might represent the maturational lateralization and/or specialization of motor function. In conclusion, the present results have demonstrated that contralateral high-gamma neuromagnetic activities are potential biomarkers for the accurate localization of the primary motor cortex in children. In addition, the interesting finding of the ipsilateral high-gamma neuromagnetic activities opens a new window for us to understand the developmental changes of the hemispherical functional lateralization in the motor system.

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OBJECT: Recent reports suggest that high-frequency epileptic activity is highly localized to epileptogenic zones. The goal of the present study was to investigate the potential usefulness of noninvasive localization of high-frequency epileptic activity for epilepsy surgery. METHODS: Data obtained in 4 patients, who had seizures during routine magnetoencephalography (MEG) tests, were retrospectively studied. The MEG data were digitized at 4000 Hz, and 3D MR images were obtained. The magnetic sources were volumetrically localized with wavelet-based beamformer. The MEG results were subsequently compared with clinical data. RESULTS: The 4 patients had 1-4 high-frequency neuromagnetic components (110-910 Hz) in ictal and interictal activities. The loci of high-frequency activities were concordant with intracranial recordings therein 3 patients, who underwent presurgical evaluation. The loci of high-frequency ictal activities were in line with semiology and neuroimaging in all 4 of the patients. High-frequency epileptic activity was highly localized to the epileptogenic zones. CONCLUSIONS: High-frequency epileptic activity can be volumetrically localized with MEG. Source analysis of high-frequency neuromagnetic signals has the potential to determine epileptogenic zones noninvasively and preoperatively for epilepsy surgery.

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In recent years, there has been a growing interest on the role of gamma band (>30 Hz) neural oscillations in motor control, although the function of this activity in motor control is unknown clearly. With the goal of discussing the high frequency sources non-invasively and precisely during unilateral index finger movement, we investigated gamma band oscillations in 20 right-handed normal adults with magnetoencephalography (MEG). The results showed that gamma band activity appeared only during finger movement. Nineteen subjects displayed consistently contralateral event-related synchronization (C-ERS) within high gamma band (70-150 Hz) in primary motor cortex (M1) of both hemispheres. Interestingly, 15 subjects displayed ipsilateral event-related desynchronization (I-ERD) and C-ERS within broad gamma band (30-150 Hz). The locations of the broad gamma band I-ERD and C-ERS revealed hemispherical symmetry in M1. These findings demonstrate that there are consistent high gamma C-ERS and inconsistent low gamma I-ERD during a simple finger movement in the motor cortex. This study provides new evidence for the use of high gamma frequency oscillations as biomarkers in the analyses of functional brain activity and the localization of the motor cortex.

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BACKGROUND: Magnetoencephalography (MEG) is increasingly used in the presurgical evaluation of pediatric seizure patients. Many pediatric patients require sedation or anesthesia to tolerate these exams. However, the available literature on anesthetic management in this population is very limited. METHODS: We retrospectively reviewed the records of all patients who underwent MEG scanning at our institution with regard to the interaction of anesthetic management and quality of scan data. RESULTS: High-dose propofol infusions (> or =200 microg.kg(-1).min(-1)) were associated with high frequency artifacts that interfered with the identification of epileptiform discharges. Lower-dose propofol infusions (< or =100 microg.kg(-1).min(-1)) did not produce artifacts but required co-administration of fentanyl to prevent patient motion. Dexmedetomidine infusions were not associated with signal artifacts and prevented patient motion very well in our initial patients and became our standard technique. CONCLUSION: In our experience, dexmedetomidine infusions are preferable to propofol-based techniques for pediatric MEG scans due to the absence of adverse effect on interictal activity.

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PURPOSE: Invasive intracranial recordings have suggested that high-frequency oscillation is involved in epileptogenesis and is highly localized to epileptogenic zones. The aim of the present study is to characterize the frequency and spatial patterns of high-frequency brain signals in childhood epilepsy using a non-invasive technology. METHODS: Thirty children with clinically diagnosed epilepsy were studied using a whole head magnetoencephalography (MEG) system. MEG data were digitized at 4,000 Hz. The frequency and spatial characteristics of high-frequency neuromagnetic signals were analyzed using continuous wavelet transform and beamformer. Three-dimensional magnetic resonance imaging (MRI) was obtained for each patient to localize magnetic sources. RESULTS: Twenty-six patients showed high-frequency (100-1,000 Hz) components (26/30, 86%). Nineteen patients showed more than one high-frequency component (19/30, 63%). The frequency range of high-frequency components varied across patients. The highest frequency band was identified around 910 Hz. The loci of high-frequency epileptic activities were concordant with the lesions identified by magnetic resonance imaging for 21 patients (21/30, 70%). The MEG source localizations of high-frequency components were found to be concordant with intracranial recordings for nine of the eleven patients who underwent epilepsy surgery (9/11, 82%). CONCLUSION: The results have demonstrated that childhood epilepsy was associated with high-frequency epileptic activity in a wide frequency range. The concordance of MEG source localization, MRI and intracranial recordings suggests that measurement of high-frequency neuromagnetic signals might provide a novel approach for clinical management of childhood epilepsy.

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Recent studies have found that the brain generates very fast oscillations. The objective of the present study was to investigate the spectral, spatial and coherent features of high-frequency brain oscillations in the developing brain. Sixty healthy children and 20 healthy adults were studied using a 275-channel magnetoencephalography (MEG) system. MEG data were digitized at 12,000 Hz. The frequency characteristics of neuromagnetic signals in 0.5-2000 Hz were quantitatively determined with Morlet wavelet transform. The magnetic sources were volumetrically estimated with wavelet-based beamformer at 2.5 mm resolution. The neural networks of endogenous brain oscillations were analyzed with coherent imaging. Neuromagnetic activities in 8-12 Hz and 800-900 Hz were found to be the most reliable frequency bands in healthy children. The neuromagnetic signals were localized in the occipital, temporal and frontal cortices. The activities in the occipital and temporal cortices were strongly correlated in 8-12 Hz but not in 800-900 Hz. In comparison to adults, children had brain oscillations in intermingled frequency bands. Developmental changes in children were identified for both low- and high-frequency brain activities. The results of the present study suggest that the development of the brain is associated with spatial and coherent changes of endogenous brain activities in both low- and high-frequency ranges. Analysis of high-frequency neuromagnetic oscillation may provide novel insights into cerebral mechanisms of brain function. The noninvasive measurement of neuromagnetic brain oscillations in the developing brain may open a new window for analysis of brain function.

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Hemispheric specialization or asymmetry in higher brain functions such as language is well accepted. This study was designed to quantitatively determine if the hemispheric asymmetry is measurable in the somatosensory system. Twenty-two participants were studied with magnetoencephalography (MEG) while their left and right index fingers were stimulated in randomized order. The finger representation in the cortex was volumetrically localized using a wavelet based beamformer. The strength of functional activity was estimated with an intensity volume while the waveforms of the virtual sensors were computed with a virtual sensor placed in the center of localized finger area. The results showed that the latency of the first identifiable response evoked by left finger stimulation was significantly shorter than that evoked by right finger stimulation (p<0.05). The left somatosensory cortex generated higher frequency neuromagnetic signals than did the right somatosensory cortex (p<0.05). Moreover, the volume of neuromagnetic activation elicited by right finger stimulation was significantly larger than that elicited by left finger stimulation in males (p<0.001). The neuromagnetic activation revealed by virtual sensors was more consistent than that revealed by physical sensors across participants. We conclude that neuromagnetic activities in the left and right somatosensory cortices have significant differences in terms of response latency, oscillation frequency and activation volume in high-frequency neuromagnetic signals. An investigation of the hemispheric specific features of neuromagnetic activation in the somatosensory cortex lays a foundation for the study of psychophysiologic asymmetries in the brain.

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