Comparing electrical stimulation functional mapping with subdural electrodes and stereoelectroencephalography.

OBJECTIVE: Electrical stimulation mapping (ESM) is the clinical standard for functional localization with subdural electrodes (SDE). As stereoelectroencephalography (SEEG) has emerged as an alternative option, we compared functional responses, afterdischarges (ADs), and unwanted ESM-induced seizures (EISs) between the two electrode types. METHODS: Incidence and current thresholds for functional responses (sensory, motor, speech/language), ADs, and EISs were compared between SDE and SEEG using mixed models incorporating relevant covariates. RESULTS: We identified 67 SEEG ESM and 106 SDE ESM patients (7207 and 4980 stimulated contacts, respectively). We found similar incidence of language and motor responses between electrode types; however, more SEEG patients reported sensory responses. ADs and EISs occurred less commonly with SEEG than SDE. Current thresholds for language, face motor, and upper extremity (UE) motor responses and EIS significantly decreased with age. However, they were not affected by electrode type, premedication, or dominant hemispheric stimulation. AD thresholds were higher with SEEG than with SDE. For SEEG ESM, language thresholds remained below AD thresholds up to 26 years of age, whereas this relationship was inverse for SDE. Also, face and UE motor thresholds fell below AD thresholds at earlier ages for SEEG than SDE. AD and EIS thresholds were not affected by premedication. SIGNIFICANCE: SEEG and SDE have clinically relevant differences for functional brain mapping with electrical stimulation. Although evaluation of language and motor regions is comparable between SEEG and SDE, SEEG offers a higher likelihood of identifying sensory areas. A lower incidence of ADs and EISs, and a favorable relationship between functional and AD thresholds suggest superior safety and neurophysiologic validity for SEEG ESM than SDE ESM.

Development of information sharing in language neocortex in childhood-onset drug-resistant epilepsy.

OBJECTIVE: We studied age-related dynamics of information sharing among cortical language regions with electrocorticographic high-gamma modulation during picture-naming and story-listening tasks. METHODS: Seventeen epilepsy patients aged 4-19 years, undergoing extraoperative monitoring with left-hemispheric subdural electrodes, were included. Mutual information (MI), a nondirectional measure of shared information, between 16 pairs of cortical regions of interest, was computed from trial-averaged 70-150 Hz power modulations during language tasks. Impact of age on pairwise MI between language regions and their determinants were ascertained with regression analysis. RESULTS: During picture naming, significant increase in MI with age was seen between pairwise combinations of Broca's area, inferior precentral gyrus (iPreC), and frontal association cortex (FAC); Wernicke's area and posterior association cortex (PAC); and Broca's and Wernicke's areas. During story listening, significant age-related increase in MI was seen between Wernicke's area and either Broca's area, FAC, or PAC; and between Broca's area and FAC. Significant impact of baseline intelligence quotient was seen on the relationship between age and MI for all pairs, except between Broca's area and iPreC. The mean MI was higher during naming compared to listening for pairs including iPreC with Broca's area, FAC, or PAC and was lower for pairs of Wernicke's area or PAC with anterior language regions. SIGNIFICANCE: Information sharing matures with age "within" frontal and temporoparietal language cortices, and "between" Broca's and Wernicke's areas. This study provides evidence for distinct patterns of developmental plasticity within perisylvian language cortex and has implications for planning epilepsy surgery.

Electrocorticographic high-gamma modulation with passive listening paradigm for pediatric extraoperative language mapping.

OBJECTIVE: This prospective study compared the topography of high-gamma modulation (HGM) during a story-listening task requiring negligible patient cooperation, with the conventional electrical stimulation mapping (ESM) using a picture-naming task, for presurgical language localization in pediatric drug-resistant epilepsy. METHODS: Patients undergoing extraoperative monitoring with subdural electrodes were included. Electrocorticographic signals were recorded during quiet baseline and a story-listening task. The likelihood of 70- to 150-Hz power modulation during the listening task relative to the baseline was estimated for each electrode and plotted on a cortical surface model. Sensitivity, specificity, accuracy, and diagnostic odds ratio (DOR) were estimated compared to ESM, using a meta-analytic framework. RESULTS: Nineteen patients (10 with left hemisphere electrodes) aged 4-19 years were analyzed. HGM during story listening was observed in bilateral posterior superior temporal, angular, supramarginal, and inferior frontal gyri, along with anatomically defined language association areas. Compared to either cognitive or both cognitive and orofacial sensorimotor interference with naming during ESM, left hemisphere HGM showed high specificity (0.82-0.84), good accuracy (0.66-0.70), and DOR of 2.23 and 3.24, respectively. HGM was a better classifier of ESM language sites in the left temporoparietal cortex compared to the frontal lobe. Incorporating visual naming with the story-listening task substantially improved the accuracy (0.80) and DOR (13.61) of HGM mapping, while the high specificity (0.85) was retained. In the right hemisphere, no ESM sites for aphasia were seen, and the results of HGM and ESM comparisons were not significant. SIGNIFICANCE: HGM associated with story listening is a specific determinant of left hemisphere ESM language sites. It can be used for presurgical language mapping in children who cannot cooperate with conventional language tasks requiring active engagement. Incorporation of additional language tasks, if feasible, can further improve the diagnostic accuracy of language localization with HGM.

Cortical morphology, epileptiform discharges, and neuropsychological performance in BECTS.

OBJECTIVES: The aim of this study was to understand the relationship between cortical morphology, centrotemporal spike (CTS), and neuropsychological functioning in children with BECTS compared to their typically developing peers. MATERIALS AND METHODS: To examine whole-brain differences in cortical thickness between groups, a general linear model approach was applied to T1-weighted structural magnetic resonance imaging (MRI) in children with BECTS and typically developing children. Further region-of-interest (ROI) analyses were performed to examine the effects of frequency and lateralization of CTS. In addition, the relationship between Processing Speed Index (PSI) and cortical thickness was investigated. RESULTS: Twenty-three patients with BECTS and thirty-two controls were included. There was no statistically significant difference in global cortical thickness between groups. With ROI analyses, we found significantly thinner cortex within right pars opercularis when comparing children with right predominant CTS, and with very frequent right CTS (>10/min) to the control group (P = 0.028 and P = 0.026, respectively). A statistically significant interaction of group (controls vs BECTS) and PSI was seen in bilateral frontal and right superior parietal cortices, indicating a positive relationship between cortical thickness and PSI in healthy controls but not BECTS. CONCLUSION: A region of cortex where right CTS may originate was thinner in BECTS compared to children without BECTS. Typically developing children with faster processing speed had thicker cortices in regions supporting visuomotor integration, motor, and executive function, but this relationship was not observed in BECTS. These results suggest that BECTS is associated with atypical cortical morphology that may underlie poorer neuropsychological performance.

Presurgical language localization with visual naming associated ECoG high- gamma modulation in pediatric drug-resistant epilepsy.

OBJECTIVE: This prospective study compared presurgical language localization with visual naming-associated high-γ modulation (HGM) and conventional electrical cortical stimulation (ECS) in children with intracranial electrodes. METHODS: Patients with drug-resistant epilepsy who were undergoing intracranial monitoring were included if able to name pictures. Electrocorticography (ECoG) signals were recorded during picture naming (overt and covert) and quiet baseline. For each electrode the likelihood of high-γ (70-116 Hz) power modulation during naming task relative to the baseline was estimated. Electrodes with significant HGM were plotted on a three-dimensional (3D) cortical surface model. Sensitivity, specificity, and accuracy were calculated compared to clinical ECS. RESULTS: Seventeen patients with mean age of 11.3 years (range 4-19) were included. In patients with left hemisphere electrodes (n = 10), HGM during overt naming showed high specificity (0.81, 95% confidence interval [CI] 0.78-0.85), and accuracy (0.71, 95% CI 0.66-0.75, p < 0.001), but modest sensitivity (0.47) when ECS interference with naming (aphasia or paraphasic errors) and/or oral motor function was regarded as the gold standard. Similar results were reproduced by comparing covert naming-associated HGM with ECS naming sites. With right hemisphere electrodes (n = 7), no ECS-naming deficits were seen without interference with oral-motor function. HGM mapping showed a high specificity (0.81, 95% CI 0.78-0.84), and accuracy (0.76, 95% CI 0.71-0.81, p = 0.006), but modest sensitivity (0.44) compared to ECS interference with oral-motor function. Naming-associated ECoG HGM was consistently observed over Broca's area (left posterior inferior-frontal gyrus), bilateral oral/facial motor cortex, and sometimes over the temporal pole. SIGNIFICANCE: This study supports the use of ECoG HGM mapping in children in whom adverse events preclude ECS, or as a screening method to prioritize electrodes for ECS testing.

Preresection intraoperative electrocorticography (ECoG) abnormalities predict seizure-onset zone and outcome in pediatric epilepsy surgery.

OBJECTIVE: The predictive value of intraoperative electrocorticography (ECoG) in pediatric epilepsy surgery is unknown. In a population of children undergoing ECoG followed typically by invasive extraoperative monitoring (IEM) and resection, we aimed to determine the relationship between frequent ECoG abnormalities and the seizure onset zone and outcome after resection. METHODS: We retrospectively identified 103 children with preresection ECoG of sufficient technical quality. ECoG records were scored based on electrode location and frequency, blinded to the seizure-onset zone and outcome. Electrographic seizure and spike locations were identified. Locations of seizures and spike populations were then compared to the location of seizure-onset zone defined by IEM using subdural electrodes and resection margin. RESULTS: Electrographic seizures were identified in 11 (11%) of 103 patients. A spike population of one or more was noted in 79 (77%) of 103 patients. In 50 (63%) of 79 patients, spike populations correlated with seizure-onset zone location. The overall surgical outcome was good (ILAE 1 to 3) in 53 (52%) of 101 patients. Outcome was good in seven (78%) of nine patients when electrographic seizure location was resected. The best outcomes were obtained with resection of both the seizure-onset zone and ECoG abnormalities to include seizures and spike locations (22/33 good outcome, 67%, p = 0.008). There was a significantly better outcome in children with complete resection of ECoG-identified spike populations (14/26, 62% good outcome) compared to when none were resected (4/14, 29%, p = 0.043). SIGNIFICANCE: Electrographic seizures and frequent spikes are frequently seen on pre-resection ECoG in children. The brain locations corresponding to these discharges are highly concordant with the seizure-onset zone; resection of these regions is correlated with good seizure outcome. Further research is needed to design interventions that increase the reliability of ECoG prediction of the epileptogenic zone and obviate the need for IEM.

Quantitative neuromagnetic signatures of aberrant cortical excitability in pediatric chronic migraine.

BACKGROUND: Reports have suggested that abnormal cortical excitability may be associated with acute migraines. The present study quantitatively assesses the degree of cortical excitability in chronic migraine as compared to acute migraine and healthy controls within the pediatric population. METHODS: We investigated 27 children suffering from chronic migraine, 27 children suffering from acute migraine, and 27 healthy controls using a magnetoencephalography (MEG) system, recording at a sampling rate of 6000 Hz. All groups were age-matched and gender-matched. Neuromagnetic brain activation was elicited by a finger-tapping motor task. The spatiotemporal and spectral signatures of MEG data within a 5-2884 Hz range were analyzed using Morlet wavelet transform and beamformer analyses. RESULTS: Compared with controls, the chronic migraine group showed (1) significantly prolonged latencies of movement-elicited magnetic fields (MEFs) between 5 and 100 Hz; (2) increased spectral power between 100 and 200 Hz, and between 2200 and 2800 Hz; and (3) a higher likelihood of neuromagnetic activation in the ipsilateral sensorimotor cortices, supplementary motor area, and occipital regions. Compared with acute migraine group, chronic migraine patients showed (1) significantly higher odds of having strong MEFs after 150 ms; and (2) significantly higher odds of having neuromagnetic activation from the deep brain areas. CONCLUSIONS: Results demonstrated that chronic migraine subjects were not only different from the healthy controls, but also different from acute migraine subjects. The chronification of migraines may be associated with elevated cortical excitability, delayed and spread neural response, as well as aberrant activation from deep brain areas.

Low- and high-frequency oscillations reveal distinct absence seizure networks.

OBJECTIVE: The aim of this study was to determine the frequency-dependent, spatiotemporal involvement of corticothalamic networks to the generation of absence seizures. METHODS: Magnetoencephalography recordings were obtained in 12 subjects (44 seizures) with untreated childhood absence seizures. Time-frequency analysis of each seizure was performed to determine bandwidths with significant power at ictal onset. Source localization was then completed to determine brain regions contributing to generalized spike and wave discharges seen on electroencephalogram. RESULTS: Significant power in the time-frequency analysis was seen within 1 to 20Hz, 20 to 70Hz, and 70 to 150Hz bandwidths. Source localization revealed that sources localized to the frontal cortex similarly for the low- and gamma-frequency bandwidths, whereas at the low-frequency bandwidth (3-20Hz) significantly more sources localized to the parietal cortex (odds ratio [OR] = 16.7). Cortical sources within the high-frequency oscillation (HFO) bandwidth (70-150Hz) localized primarily to the frontal region compared to the parietal (OR = 7.32) or temporal (OR = 2.78) areas. INTERPRETATION: Neuromagnetic activity within frontal and parietal cortical regions provides further confirmation of hemodynamic changes reported using functional magnetic resonance imaging that have been associated with absence seizures. The frequency-dependent nature of these networks has not previously been reported, and the presence of HFOs during absence seizures is a novel finding. Co-occurring frontal and parietal corticothalamic networks may interact to produce a pathological state that contributes to the generation of spike and wave discharges. The clinical and pathophysiological implications of HFOs within the frontal cortical region are unclear and should be further investigated.

Comparison of magnetic source estimation to intracranial EEG, resection area, and seizure outcome.

OBJECTIVES: Magnetoencephalography (MEG) is used to guide intracranial electroencephalography (ICEEG) monitoring and determine areas for resection. The purpose of this retrospective cross-sectional study was to report our experience using dipole modeling/dipole scanning, current density reconstructions, and beam-forming methods in a large cohort of pediatric patients with intractable epilepsy. METHODS: Source localization results for each algorithm and seizure-onset zone, defined by ICEEG, were described by three blinded reviewers according to five location criteria. The accuracy of each algorithm was then compared to ICEEG. The relationships between the accuracy of these algorithms (discordant, lobar concordant, sublobar concordant) and long-term seizure outcome was calculated using positive and negative predictive values. RESULTS: Thirty-two patients (mean age ± SD, 10.8 ± 5 years) were included in this retrospective review. No algorithms had sublobar concordance with ICEEG in all patients, including when algorithms were grouped by type (dipole modeling/dipole scanning, current density reconstruction, beam forming). Synthetic aperture magnetometry (SAM) with excess kurtosis tended to be the most accurate, but there were no significant differences between algorithms. When comparing the source modeling with ICEEG findings, significantly more patients with a seizure-free outcome were found to have lobar or sublobar concordance of multiple signal classification (MUSIC) (61.1%) and standardized low resolution brain electromagnetic tomography (sLORETA) (52.9%). Positive predictive values were highest for MUSIC (61.9%) and equivalent current dipole (ECD) (57.1%). Negative predictive values were highest for SAM(g2 )-VS (83%), minimum norm estimate (MNE) (75%), MUSIC (73.7%), and ECD (73.5%). SIGNIFICANCE: This study describes the use of multiple MEG source estimation techniques and demonstrates that all algorithms have similar rates of concordance with ICEEG. Also, the concordance or discordance of MUSIC with ICEEG was the best predictor of long-term seizure outcome.

Correlation of NICU anthropometry in extremely preterm infants with brain development and language scores at early school age.

Growth in preterm infants in the neonatal intensive care unit (NICU) is associated with increased global and regional brain volumes at term, and increased postnatal linear growth is associated with higher language scores at age 2. It is unknown whether these relationships persist to school age or if an association between growth and cortical metrics exists. Using regression analyses, we investigated relationships between the growth of 42 children born extremely preterm (< 28 weeks gestation) from their NICU hospitalization, standardized neurodevelopmental/language assessments at 2 and 4-6 years, and multiple neuroimaging biomarkers obtained from T1-weighted images at 4-6 years. We found length at birth and 36 weeks post-menstrual age had positive associations with language scores at 2 years in multivariable linear regression. No growth metric correlated with 4-6 year assessments. Weight and head circumference at 36 weeks post-menstrual age positively correlated with total brain volume and negatively with global cortical thickness at 4-6 years of age. Head circumference relationships remained significant after adjusting for age, sex, and socioeconomic status. Right temporal cortical thickness was related to receptive language at 4-6 years in the multivariable model. Results suggest growth in the NICU may have lasting effects on brain development in extremely preterm children.

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.

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. METHODS: We identified 48 patients who underwent surgical treatment after the surgical evaluation with intracranial EEG, and 44 patients met criteria for this retrospective study. Results were not used in surgical decision making. Intracranial EEG recordings were collected with a sampling rate of 2,000 Hz. Recordings were first inspected visually to determine ictal onset and then analyzed further with time-frequency analysis. Forty-one (93%) of 44 patients had ictal HFOs determined with time-frequency analysis of intracranial EEG. KEY FINDINGS: Twenty-two (54%) of the 41 patients with ictal HFOs had complete resection of HFO regions, regardless of frequency bands. Complete resection of HFOs (n = 22) resulted in a seizure-free outcome in 18 (82%) of 22 patients, significantly higher than the seizure-free outcome with incomplete HFO resection (4/19, 21%). SIGNIFICANCE: Our study shows that ictal HFOs are commonly found with intracranial EEG in our population largely of children with cortical dysplasia, and have localizing value. The use of ictal HFOs may add more promising information compared to interictal HFOs because of the evidence of ictal propagation and followed by clinical aspect of seizures. Complete resection of HFOs is a favorable prognostic indicator for surgical outcome.

Improving Detection of Hippocampal Epileptiform Activity Using Magnetoencephalography.

PURPOSE: Magnetoencephalography (MEG) defines the spike-generating zone and provides targets for invasive monitoring with stereotactic electroencephalography. This retrospective, blinded, cross-sectional study determined whether MEG virtual sensors could identify hippocampal epileptiform activity. METHODS: Using MEG beamformer analysis, virtual sensors were manually placed in bilateral hippocampi and corresponding virtual sensor waveforms were analyzed for the presence of epileptiform activity. These findings were compared with hippocampal stereotactic electroencephalography in the same patients. Concordance was determined using sensitivity and specificity. RESULTS: Thirty patients (mean age 12.5 ± 5.9 years) and 35 hippocampi were included. Patients were also placed into subgroups based on conventional MEG analysis: temporal (n = 19), extratemporal (n = 10), and normal (n = 1). Overall, sensitivity and specificity were 57.9% and 50.0%, respectively (n = 35). Patients with temporal sources based on conventional MEG analysis had sensitivity and specificity of 80.0% and 36.4%, respectively (n = 21). Those with extratemporal sources based on conventional MEG had sensitivity and specificity of 42.9% and 80.0%, respectively (n = 12). CONCLUSIONS: When grouped by conventional MEG analysis, virtual sensors can be useful to confirm mesial temporal dipoles seen with conventional analysis. SIGNIFICANCE: This work may help support the use of MEG for the detection of epileptiform activity in the hippocampus and influence the planning of invasive electrode placement.

Clinical validation of magnetoencephalography network analysis for presurgical epilepsy evaluation.

OBJECTIVE: To clinically validate the connectivity-based magnetoencephalography (MEG) analyses to identify seizure onset zone (SOZ) with comparing to equivalent current dipole (ECD). METHODS: The ECD cluster was quantitatively analyzed by calculating the centroid of the cluster and maximum distance (the largest distance between all dipoles). The "primary hub" was determined by the highest eigencentrality. The distribution of nodes in the top 5% of eigenvector centrality values was quantified by generating the convex hull between each node. RESULTS: Thirty-one patients who underwent MEG, stereotactic-EEG, and focal surgery were included. The primary hub was significantly closer to the sEEG-defined SOZ compared to ECD (p = 0.009). The seizure freedom positive and negative predictive values of complete ECD cluster and primary hub resections did not significantly differ, although complete resection of the primary hub showed slightly better negative predictive value (ECD: 50.0% NPV, hub: 64.7% NPV). Both quantitative ECD and functional connectivity analyses suggested that spatially restricted dipole distributions and higher connectivity in a smaller region correlate with better seizure outcomes. CONCLUSIONS: Our findings suggest that MEG network analysis could be a valuable complement to the ECD methods. SIGNIFICANCE: The results of this study are an important step towards using non-invasive neurophysiologic recordings to accurately define the epileptic network.

High gamma oscillations of sensorimotor cortex during unilateral movement in the developing brain: a MEG study.

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.

Impaired auditory information processing during acute migraine: a magnetoencephalography study.

Acute migraine could be associated with neurophysiological and cognitive changes. This study evaluates the neurophysiological changes in auditory information processing in adolescents with acute migraine by means of magnetoencephalography. The multifeature sound mismatch negativity (MMN) paradigm was used to study nine adolescents with an acute migraine and nine age- and gender-matched healthy controls. Latencies and amplitudes of M100, M150, M200, and MMNm responses were evaluated. Migraine subjects had smaller M150 amplitudes than healthy subjects. The latencies of MMNm response for the frequency change were delayed in both hemispheres in migraine subjects, as compared with healthy controls. Our results indicate that the function of neural substrates, responsible for different stages of auditory information processing, is impaired during the acute migraine. The identification of underlying cortical dysfunction during an acute migraine can lead to future identification of neurophysiological biomarkers for studying acute migraine and response to treatment.

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.

Functional Hyperconnectivity during a Stories Listening Task in Magnetoencephalography Is Associated with Language Gains for Children Born Extremely Preterm.

Extreme prematurity (EPT, <28 weeks gestation) is associated with language problems. We previously reported hyperconnectivity in EPT children versus term children (TC) using magnetoencephalography (MEG). Here, we aim to ascertain whether functional hyperconnectivity is a marker of language resiliency for EPT children, validating our earlier work with a distinct sample of contemporary well-performing EPT and preterm children with history of language delay (EPT-HLD). A total of 58 children (17 EPT, 9 EPT-HLD, and 32 TC) participated in stories listening during MEG and functional magnetic resonance imaging (fMRI) at 4-6 years. We compared connectivity in EPT and EPT-HLD, investigating relationships with language over time. We measured fMRI activation during stories listening and parcellated the activation map to obtain "nodes" for MEG connectivity analysis. There were no significant group differences in age, sex, race, ethnicity, parental education, income, language scores, or language representation on fMRI. MEG functional connectivity (weighted phase lag index) was significantly different between groups. Preterm children had increased connectivity, replicating our earlier work. EPT and EPT-HLD had hyperconnectivity versus TC at 24-26 Hz, with EPT-HLD exhibiting greatest connectivity. Network strength correlated with change in standardized scores from 2 years to 4-6 years of age, suggesting hyperconnectivity is a marker of advancing language development.

Beta synchrony for expressive language lateralizes to right hemisphere in development.

A left perisylvian network is known to support language in healthy adults. Low-beta (13-23 Hz) event-related desynchrony (ERD) has been observed during verb generation, at approximately 700-1200 ms post-stimulus presentation in past studies; the signal is known to reflect increased neuronal firing and metabolic demand during language production. In contrast, concurrent beta event-related synchrony (ERS) is thought to reflect neuronal inhibition but has not been well studied in the context of language. Further, while low-beta ERD for expressive language has been found to gradually shift from bilateral in childhood to left hemispheric by early adulthood, developmental lateralization of ERS has not been established. We used magnetoencephalography to study low beta ERS lateralization in a group of children and adolescents (n = 78), aged 4 to less than 19 years, who performed covert verb generation. We found that the youngest children had bilateral ERD and ERS. By adolescence, low-beta ERD was predominantly left lateralized in perisylvian cortex (i.e., Broca's and Wernicke's regions), while beta ERS was predominantly right lateralized. Increasing lateralization was significantly correlated to age for both ERD (Spearman's r = 0.45, p < 0.01) and ERS (Spearman's r = - 0.44, p < 0.01). Interestingly, while ERD lateralized in a linear manner, ERS lateralization followed a nonlinear trajectory, suggesting distinct developmental trajectories. Implications to early-age neuroplasticity and neuronal inhibition are discussed.

The Value of Source Localization for Clinical Magnetoencephalography: Beyond the Equivalent Current Dipole.

Source localization for clinical magnetoencephalography recordings is challenging, and many methods have been developed to solve this inverse problem. The most well-studied and validated tool for localization of the epileptogenic zone is the equivalent current dipole. However, it is often difficult to summarize the richness of the magnetoencephalography data with one or a few point sources. A variety of source localization algorithms have been developed to more fully explain the complexity of clinical magnetoencephalography data used to define the epileptogenic network. In this review, various clinically available source localization methods are described and their individual strengths and limitations are discussed.