Hisako Fujiwara

Resection of ictal high-frequency oscillations leads to favorable surgical outcome in pediatric epilepsy

Purpose:  Intracranial electroencephalography (EEG) is performed as part of an epilepsy surgery evaluation when noninvasive tests are incongruent or the putative seizure‐onset zone is near eloquent cortex. Determining the seizure‐onset zone using intracranial EEG has been conventionally based on identification of specific ictal patterns with visual inspection. High‐frequency oscillations (HFOs, >80 Hz) have been recognized recently as highly correlated with the epileptogenic zone. However, HFOs can be difficult to detect because of their low amplitude. Therefore, the prevalence of ictal HFOs and their role in localization of epileptogenic zone on intracranial EEG are unknown.

Frequency and spatial characteristics of high-frequency neuromagnetic signals in childhood epilepsy

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.

Focal corticothalamic sources during generalized absence seizures: A MEG study

Magnetoencephalography (MEG) was used to determine cortical and subcortical contributions to the formation of spike and wave discharges in twelve newly diagnosed, drug naïve children during forty-four generalized absence seizures. Previous studies have implicated various cortical areas and thalamic nuclei in the generation of absence seizures, but the relative timing of their activity remains unclear. Beamformer analysis using synthetic aperture magnetometry (SAM) was used to confirm the presence of independent thalamic activity, and standardized Low Resolution Brain Electromagnetic Topography (sLORETA) was used to compute statistical maps indicating source locations during absence seizures. Sources detected in the 50ms prior to the start of the seizure were more likely to be localized to the frontal cortex or thalamus. At the time of the first spike on EEG, focal source localization was seen in the lateral frontal cortex with decreased thalamic localization. Following the spike, localization became more widespread throughout the cortex. Comparison of the earliest spike and wave discharge (SWD) (Ictal Onset) and a SWD occurring 3s into the seizure (mid-Ictal) revealed significant differences during the slow wave portion of the SWDs. This study of MEG recordings in childhood absence seizures provides additional evidence that there are focal brain areas responsible for these seizures which appear bilaterally symmetric and generalized with a conventional 10-20 placement scalp EEG.

Ictal MEG onset source localization compared to intracranial EEG and outcome: improved epilepsy presurgical evaluation in pediatrics.

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.

Noninvasive localization of epileptogenic zones with ictal high-frequency neuromagnetic signals

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.

Low‐ and high‐frequency oscillations reveal distinct absence seizure networks

The aim of this study was to determine the frequency‐dependent, spatiotemporal involvement of corticothalamic networks to the generation of absence seizures.

Accumulated source imaging of brain activity with both low and high-frequency neuromagnetic signals

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 workstations 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.

Gamma oscillations in the primary motor cortex studied with MEG

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.

Time, frequency and volumetric differences of high-frequency neuromagnetic oscillation between left and right somatosensory cortices.

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.

Neuromagnetic evidence of impaired cortical auditory processing in pediatric intractable epilepsy.

PURPOSE We aimed to determine the changes in neural correlates of auditory information processing such as auditory detection, encoding, and sensory discrimination in pediatric patients with intractable epilepsy. METHODS In this magnetoencephalography (MEG) study, 10 patients and 10 age- and gender-matched healthy controls were investigated with the multi-feature mismatch negativity (MMN) paradigm. Latencies and amplitudes of M100, M150, M200, and MMN event-related fields were evaluated. RESULTS All event-related fields in response to standard stimuli (M100, M150 and M200) and responses to occasional five deviant sounds, deviating from the standard stimuli either in duration, frequency, intensity, location, or by including a silent gap were reduced in amplitude in epilepsy patients compared with healthy controls. CONCLUSIONS Our study suggests that auditory information processing is impaired in patients with drug-resistant epilepsy, being evident both in stimulus feature encoding (as reflected by changes of early event-related components, e.g., M100) and in cortical sound discrimination (as reflected by MMNm). The neural changes involving diminished M100 as well as MMNms for all five deviant sound types suggest wide-spread auditory information processing impairments in these patients.