Abstracts

Rationale: High-frequency brain signals (HFBS) up to 1,500 Hz have been identified with invasive recordings. It has been found that HFBS in 100-200 Hz (ripples) and 250-500 Hz (fast ripples) are potential new biomarkers for epileptogenesis and epileptogenicity(Worrell et al., 2008; Engel, Jr. et al., 2009; Jacobs et al., 2009; Staley, 2007). Since our research has been focusing on noninvasive detection of HFBS over the past decades, the present study was designed to characterize the spatial and frequency signatures of pathological HFBS in tuberous sclerosis complex (TSC) with noninvasive methodologies. Methods: Fourteen patients with TSC and eighty normal volunteers were studied. Magnetoencephalography (MEG) data were recorded with a 275-Channel MEG system in a magnetically shielded room. Spontaneous brain activity was recorded without any task. The length of each epoch of MEG data was 120 seconds (2 minutes). At least two epochs of MEG data were recorded for each subject. Three-dimensional magnetic resonance imaging (MRI) was obtained for all subjects with a 3T scanner. Seven out of the 14 patients had intracranial recordings. MEG data were transformed from time-domain to frequency domain with Morlet continuous wavelet transform. An accumulated spectrogram was developed and optimized to detect and quantify HFBS (see Figure 1 for example). Neuromagnetic sources of HFBS were volumetrically localized with wavelet-based beamformer. Results: MEG data recorded from healthy subjects showed very weak HFBS around 800-900 Hz without any detectable signals in 100-600 Hz. However, MEG data from patients with TSC showed rhythmic and very strong activities in a range of 100-600 Hz. Therefore, our data analyses focused on two frequency bands: 100-200 Hz and 250-500 Hz. High-frequency components in 100-200 Hz and in 250-500Hz were identified in 11 patients (11/14, 78%) and in 12 patients (12/14, 85%), respectively. We observed that 13 patients (13/14, 93%) had more than one high-frequency component. HFBS in 100-200Hz were localized closely to tubers on MRI in 9 patients (9/14, 64%). HFBS In 250-500Hz were localized closely to tubers on MRI in 12 patients (12/14, 85%). When intracranial recording was considered to be a "gold standard” for localization of epileptogenic zones, the concordances of the epileptogenic zones and the loci of epileptic activities in100-200Hz and 250-500Hz were 71% (5/7) and 86% (6/7), respectively. Figure 1 shows an example. Conclusions: Our preliminary results have demonstrated that HFBS could be noninvasively detected in patients with TSC using MEG and advanced signals processing methods. The high-frequency components, ripples and fast ripples, could accurately localize the epileptogenic zones defined by intracranial recordings. The results indicate that noninvasive detection of HFBS has the potential to be clinically very useful.