Neuromagnetic correlates of audiovisual word processing in the developing brain.

The brain undergoes enormous changes during childhood. Little is known about how the brain develops to serve word processing. The objective of the present study was to investigate the maturational changes of word processing in children and adolescents using magnetoencephalography (MEG). Responses to a word processing task were investigated in sixty healthy participants. Each participant was presented with simultaneous visual and auditory word pairs in "match" and "mismatch" conditions. The patterns of neuromagnetic activation from MEG recordings were analyzed at both sensor and source levels. Topography and source imaging revealed that word processing transitioned from bilateral connections to unilateral connections as age increased from 6 to 17 years old. Correlation analyses of language networks revealed that the path length of word processing networks negatively correlated with age (r = -0.833, p < 0.0001), while the connection strength (r = 0.541, p < 0.01) and the clustering coefficient (r = 0.705, p < 0.001) of word processing networks were positively correlated with age. In addition, males had more visual connections, whereas females had more auditory connections. The correlations between gender and path length, gender and connection strength, and gender and clustering coefficient demonstrated a developmental trend without reaching statistical significance. The results indicate that the developmental trajectory of word processing is gender specific. Since the neuromagnetic signatures of these gender-specific paths to adult word processing were determined using non-invasive, objective, and quantitative methods, the results may play a key role in understanding language impairments in pediatric patients in the future.

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.

Spatial Heterogeneity of Cortical Excitability in Migraine Revealed by Multifrequency Neuromagnetic Signals.

UNLABELLED: To investigate the spatial heterogeneity of cortical excitability in adolescents with migraine, magnetoencephalography (MEG) recordings at a sampling rate of 6,000 Hz were obtained from 35 adolescents with an acute migraine and 35 age- and sex-matched healthy control participants during an auditory-motor task. Neuromagnetic activation from low- to high-frequency ranges (5-1,000 Hz) was measured at sensor and source levels. The heterogeneity of cortical excitability was quantified within each functional modality (auditory vs motor) and hemispherical lateralization. MEG data showed that high-frequency, not low-frequency neuromagnetic signals, showed heterogeneous cortical activation in migraine subjects compared with control participants (P < .001). The alteration of the heterogeneity of cortical excitability in migraine subjects was independent of age and sex. The degree of the neuromagnetic heterogeneity of cortical activation was significantly correlated with headache frequency (r = .71, P < .005). The alteration of cortical excitability in migraine subjects was spatially heterogeneous and frequency dependent, which previously has not been reported. The finding may be critical for developing spatially targeted therapeutic strategies for normalizing cortical excitability with the purpose of reducing headache attacks. PERSPECTIVE: This article presents a new approach to quantitatively measure the spatial heterogeneity of cortical excitability in adolescents with migraine using MEG signals in a frequency range of 5 to 1,000 Hz. The characteristics of the location and degree of cortical excitability may be critical for spatially targeted treatment for migraine.

Multi-frequency localization of aberrant brain activity in autism spectrum disorder.

OBJECTIVE: The abnormality of intrinsic brain activity in autism spectrum disorders (ASDs) is still inconclusive. Contradictory results have been found pointing towards hyper-activity or hypo-activity in various brain regions. The present research aims to investigate the spatial and spectral signatures of aberrant brain activity in an unprecedented frequency range of 1-2884 Hz at source levels in ASD using newly developed methods. MATERIALS AND METHODS: Seven ASD subjects and age- and gender-matched controls were studied using a high-sampling rate magnetoencephalography (MEG) system. Brain activity in delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), low gamma (30-55 Hz), high gamma (65-90 Hz), ripples (90-200 Hz), high-frequency oscillations (HFOs, 200-1000 Hz), and very high-frequency oscillations (VHFOs, 1000-2884 Hz) was volumetrically localized and measured using wavelet and beamforming. RESULTS: In comparison to controls, ASD subjects had significantly higher odds of alpha activity (8-12 Hz) in the sensorimotor cortex (mu rhythm), and generally high-frequency activity (90-2884 Hz) in the frontal cortex. The source power of HFOs (200-1000 Hz) in the frontal cortex in ASD was significantly elevated as compared with controls. CONCLUSION: The results suggest that ASD has significantly altered intrinsic brain activity in both low- and high-frequency ranges. Increased intrinsic high-frequency activity in the frontal cortex may play a key role in ASD.

Filling Predictable and Unpredictable Gaps, with and without Similarity-Based Interference: Evidence for LIFG Effects of Dependency Processing.

One of the most replicated findings in neurolinguistic literature on syntax is the increase of hemodynamic activity in the left inferior frontal gyrus (LIFG) in response to object relative (OR) clauses compared to subject relative clauses. However, behavioral studies have shown that ORs are primarily only costly when similarity-based interference is involved and recently, Leiken and Pylkkänen (2014) showed with magnetoencephalography (MEG) that an LIFG increase at an OR gap is also dependent on such interference. However, since ORs always involve a cue indicating an upcoming dependency formation, OR dependencies could be processed already prior to the gap-site and thus show no sheer dependency effects at the gap itself. To investigate the role of gap predictability in LIFG dependency effects, this MEG study compared ORs to verb phrase ellipsis (VPE), which was used as an example of a non-predictable dependency. Additionally, we explored LIFG sensitivity to filler-gap order by including right node raising structures, in which the order of filler and gap is reverse to that of ORs and VPE. Half of the stimuli invoked similarity-based interference and half did not. Our results demonstrate that LIFG effects of dependency can be elicited regardless of whether the dependency is predictable, the stimulus materials evoke similarity-based interference, or the filler precedes the gap. Thus, contrary to our own prior data, the current findings suggest a highly general role for the LIFG in dependency interpretation that is not limited to environments involving similarity-based interference. Additionally, the millisecond time-resolution of MEG allowed for a detailed characterization of the temporal profiles of LIFG dependency effects across our three constructions, revealing that the timing of these effects is somewhat construction-specific.

Quantification of Interictal Neuromagnetic Activity in Absence Epilepsy with Accumulated Source Imaging.

Aberrant brain activity in childhood absence epilepsy (CAE) during seizures has been well recognized as synchronous 3 Hz spike-and-wave discharges on electroencephalography. However, brain activity from low- to very high-frequency ranges in subjects with CAE between seizures (interictal) has rarely been studied. Using a high-sampling rate magnetoencephalography (MEG) system, we studied ten subjects with clinically diagnosed but untreated CAE in comparison with age- and gender-matched controls. MEG data were recorded from all subjects during the resting state. MEG sources were assessed with accumulated source imaging, a new method optimized for localizing and quantifying spontaneous brain activity. MEG data were analyzed in nine frequency bands: delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), low-gamma (30-55 Hz), high-gamma (65-90 Hz), ripple (90-200 Hz), high-frequency oscillation (HFO, 200-1,000 Hz), and very high-frequency oscillation (VHFO, 1,000-2,000 Hz). MEG source imaging revealed that subjects with CAE had higher odds of interictal brain activity in 200-1,000 and 1,000-2,000 Hz in the parieto-occipito-temporal junction and the medial frontal cortices as compared with controls. The strength of the interictal brain activity in these regions was significantly elevated in the frequency bands of 90-200, 200-1,000 and 1,000-2,000 Hz for subjects with CAE as compared with controls. The results indicate that CAE has significantly aberrant brain activity between seizures that can be noninvasively detected. The measurements of high-frequency neuromagnetic oscillations may open a new window for investigating the cerebral mechanisms of interictal abnormalities in CAE.

MEG evidence that the LIFG effect of object extraction requires similarity-based interference.

This study addresses a much-debated effect on a much-debated region: the increase of left inferior frontal gyrus (LIFG) activation associated with object-extracted relative clauses. This haemodynamic result is one of the most central and most cited findings in the cognitive neuroscience of syntax and it has robustly contributed to the popular association of Broca's region with syntax. Our study had two goals: (1) to characterise the timing of this classic effect with magnetoencephalography (MEG) and (2) to connect it to psycholinguistic research on the effects of similarity-based interference during sentence processing. Specifically, behavioural studies have shown that object relatives are primarily only costly when the two preverbal noun phrases are parallel in their surface syntax, for example, both consisting of a definite determiner and a noun (e.g. the reporter who the senator attacked), as opposed to employing, for example, a definite noun phrase and a proper name (the reporter who Bill attacked). This finding suggests that the difficulty of object extraction lies not within its syntax but rather in similarity-based interference affecting working memory processes. Although working memory is a prominent hypothesis for the LIFG engagement in object extraction, the haemodynamic literature has routinely employed stimuli involving parallel as opposed to non-parallel syntax. Using written sentences presented word-by-word, we tested whether an LIFG effect of object extraction is obtained with MEG, allowing us to characterise its timing, and whether it reduces or disappears if the two preverbal noun phrases are non-parallel in their surface syntax. Our results show an LIFG increase for object relatives at around 600 ms after verb onset, but only when the preverbal arguments are parallel. These findings are consistent with memory and competition-based explanations of the LIFG effect of object extraction and challenge accounts attributing it to displacement.

Magnetoencephalography detection of high-frequency oscillations in the developing brain.

Increasing evidence from invasive intracranial recordings suggests that the matured brain generates both physiological and pathological high-frequency signals. The present study was designed to detect high-frequency brain signals in the developing brain using newly developed magnetoencephalography (MEG) methods. Twenty healthy children were studied with a high-sampling rate MEG system. Functional high-frequency brain signals were evoked by electrical stimulation applied to the index fingers. To determine if the high-frequency neuromagnetic signals are true brain responses in high-frequency range, we analyzed the MEG data using the conventional averaging as well as newly developed time-frequency analysis along with beamforming. The data of healthy children showed that very high-frequency brain signals (>1000 Hz) in the somatosensory cortex in the developing brain could be detected and localized using MEG. The amplitude of very high-frequency brain signals was significantly weaker than that of the low-frequency brain signals. Very high-frequency brain signals showed a much earlier latency than those of a low-frequency. Magnetic source imaging (MSI) revealed that a portion of the high-frequency signals was from the somatosensory cortex, another portion of the high-frequency signals was probably from the thalamus. Our results provide evidence that the developing brain generates high-frequency signals that can be detected with the non-invasive technique of MEG. MEG detection of high-frequency brain signals may open a new window for the study of developing brain function.