Tolerability of transcranial magnetic stimulation language mapping in children.

OBJECTIVE: Transcranial Magnetic Stimulation (TMS) has emerged as a viable non-invasive method for mapping language networks. Little is known about the tolerability of transcranial magnetic stimulation language mapping in children. METHODS: Children aged 5-18 years underwent bilateral language mapping using repetitive transcranial magnetic stimulation (rTMS) to target 33 sites/hemisphere. Stimulation was delivered at 5 Hz, in 1-2 second bursts, during visual naming and auditory verb generation. Pain unpleasantness and pain intensity were assessed using an unpleasantness visual analog scale (VAS). RESULTS: 49 participants tolerated motor mapping and had repetitive transcranial magnetic stimulation. 35/49 (71%) completed visual naming and 26/49 (53%) completed both visual naming and verb generation. Mean electrical field per participant was 115 V/m. Young age and lower language ability were associated with lower completion. Visual analogue scale scores were significantly higher (6.1 vs. 2.8) in participants who withdrew early compared to those who completed at least visual naming. CONCLUSIONS: Pain measured by VAS was a major contributor to early withdrawal. However, a complete bilateral map was obtained with one paradigm in 71% of participants. Future studies designed to reduce pain during repetitive transcranial magnetic stimulation over language cortex will boost viability. SIGNIFICANCE: This study represents the first attempt to characterize tolerability of bilateral repetitive transcranial magnetic stimulation language mapping in healthy children.

Neuromagnetic high frequency spikes are a new and noninvasive biomarker for localization of epileptogenic zones.

OBJECTIVE: One barrier hindering high frequency brain signals (HFBS, >80 Hz) from wide clinical applications is that the brain generates both pathological and physiological HFBS. This study was to find specific biomarkers for localizing epileptogenic zones (EZs). METHODS: Twenty three children with drug-resistant epilepsy and age/sex matched healthy controls were studied with magnetoencephalography (MEG). High frequency oscillations (HFOs, > 4 oscillatory waveforms) and high frequency spikes (HFSs, > 1 spiky or sharp waveforms) in 80-250 Hz and 250-600 Hz bands were blindly detected with an artificial intelligence method and validated with visual inspection. The magnitude of HFOs and HFSs were quantified with spectral analyses. Sources of HFSs and HFOs were localized and compared with clinical EZs determined by invasive recordings and surgical outcomes. RESULTS: HFOs in 80-250 Hz and 250-600 Hz were identified in both epilepsy patients (18/23, 12/23, respectively) and healthy controls (6/23, 4/23, respectively). HFSs in 80-250 Hz and 250-600 Hz were detected in patients (16/23, 11/23, respectively) but not in healthy controls. A combination of HFOs and HFSs localized EZs for 22 (22/23, 96%) patients. CONCLUSIONS: The results indicate, for the first time, that HFSs are a newer and more specific biomarker than HFOs for localizing EZs because HFOs appeared in both epilepsy patients and healthy controls while HFSs appeared only in epilepsy patients.

Delineation of epileptogenic zones with high frequency magnetic source imaging based on kurtosis and skewness.

BACKGROUND: Neuromagnetic high frequency brain signals (HFBS, > 80 Hz) are a new biomarker for localization of epileptogenic zones (EZs) for pediatric epilepsy. METHODS: Twenty three children with drug-resistant epilepsy and age/sex matched healthy controls were studied with magnetoencephalography (MEG). Epileptic HFBS in 80-250 Hz and 250-600 Hz were quantitatively determined by comparing with normative controls in terms of kurtosis and skewness. Magnetic sources of epileptic HFBS were localized and then compared to clinical EZs determined by invasive recordings and surgical outcomes. RESULTS: Kurtosis and skewness of HFBS were significantly elevated in epilepsy patients compared to healthy controls (p < 0,001 and p < 0.0001, respectively). Sources of elevated MEG signals in comparison to normative data were co-localized to EZs for 22 (22/23, 96 %) patients. CONCLUSIONS: The results indicate, for the first time, that epileptic HFBS can be noninvasively quantified by measuring kurtosis and skewness in MEG data. Magnetic source imaging based on kurtosis and skewness can accurately localize EZs. SIGNIFICANCE: Source imaging of kurtosis and skewness of MEG HFBS provides a novel way for preoperative localization of EZs for epilepsy surgery.

Kurtosis and skewness of high-frequency brain signals are altered in paediatric epilepsy.

Intracranial studies provide solid evidence that high-frequency brain signals are a new biomarker for epilepsy. Unfortunately, epileptic (pathological) high-frequency signals can be intermingled with physiological high-frequency signals making these signals difficult to differentiate. Recent success in non-invasive detection of high-frequency brain signals opens a new avenue for distinguishing pathological from physiological high-frequency signals. The objective of the present study is to characterize pathological and physiological high-frequency signals at source levels by using kurtosis and skewness analyses. Twenty-three children with medically intractable epilepsy and age-/gender-matched healthy controls were studied using magnetoencephalography. Magnetoencephalographic data in three frequency bands, which included 2-80 Hz (the conventional low-frequency signals), 80-250 Hz (ripples) and 250-600 Hz (fast ripples), were analysed. The kurtosis and skewness of virtual electrode signals in eight brain regions, which included left/right frontal, temporal, parietal and occipital cortices, were calculated and analysed. Differences between epilepsy and controls were quantitatively compared for each cerebral lobe in each frequency band in terms of kurtosis and skewness measurements. Virtual electrode signals from clinical epileptogenic zones and brain areas outside of the epileptogenic zones were also compared with kurtosis and skewness analyses. Compared to controls, patients with epilepsy showed significant elevation in kurtosis and skewness of virtual electrode signals. The spatial and frequency patterns of the kurtosis and skewness of virtual electrode signals among the eight cerebral lobes in three frequency bands were also significantly different from that of the controls (2-80 Hz, P < 0.001; 80-250 Hz, P < 0.00001; 250-600 Hz, P < 0.0001). Compared to signals from non-epileptogenic zones, virtual electrode signals from epileptogenic zones showed significantly altered kurtosis and skewness (P < 0.001). Compared to normative data from the control group, aberrant virtual electrode signals were, for each patient, more pronounced in the epileptogenic lobes than in other lobes(kurtosis analysis of virtual electrode signals in 250-600 Hz; odds ratio = 27.9; P < 0.0001). The kurtosis values of virtual electrode signals in 80-250 and 250-600 Hz showed the highest sensitivity (88.23%) and specificity (89.09%) for revealing epileptogenic lobe, respectively. The combination of virtual electrode and kurtosis/skewness measurements provides a new quantitative approach to distinguishing pathological from physiological high-frequency signals for paediatric epilepsy. Non-invasive identification of pathological high-frequency signals may provide novel important information to guide clinical invasive recordings and direct surgical treatment of epilepsy.