Estimating functional connectivity using 2D tangential components in MEG sensor space.

BACKGROUND: Connectivity analysis in magnetoencephalography (MEG) sensor space is commonly used for the preliminary estimation of the functional relationship between cortical areas, but the results are difficult to interpret due to the field spread effect. To improve the interpretability of sensor-level connectivity analysis, we introduce and test a new connectivity measure based on imaginary coherence in this study. NEW METHOD: MEG signals from axial gradiometers are subjected to a wavelet transform at a frequency of interest, and are used to reconstruct 2D tangential magnetometer signals. The Euclidean norm of imaginary coherence values obtained from four available pairs between 2D tangential components at two locations is then used to estimate functional connectivity between sensor locations. The use of this new connectivity measure can be extended to 2D planar gradiometer signals or 3D source signals, where the functional relationship between multi-dimensional signals at different locations needs to be quantified as scalar variables. RESULTS: The proposed method was applied to measured and simulated auditory evoked MEG data. The Euclidean norm of imaginary coherence reliably eliminated the field spread effect and showed increased inter-hemispheric coherence between sensors above the left and the right auditory cortex. The significance of the results was tested by introducing variability in spontaneous brain activities in multi-trial evoked data simulations. COMPARISON WITH EXISTING METHOD: The distribution of imaginary coherence among axial gradiometer signals shows peaks not at the sensors directly above the neuronal current sources, but at sensors with field extreme.

Ocular and cardiac artifact rejection for real-time analysis in MEG.

BACKGROUND: Recently, magnetoencephalography (MEG) based real-time brain computing interfaces (BCI) have been developed to enable novel and promising methods for neuroscience research. It is well known that artifact rejection prior to source localization largely enhances the localization accuracy. However, many BCI approaches neglect real-time artifact removal due to its time consuming process. NEW METHOD: The method (referred to as ocular and cardiac artifact rejection for real-time analysis, OCARTA) is based on constrained independent component analysis (cICA), where a priori information of the underlying source signals is used to optimize and accelerate signal decomposition. Thereby, prior information is incorporated by using the subject's individual cardiac and ocular activity. The algorithm automatically uses different separation strategies depending on the underlying source activity. RESULTS: OCARTA was tested and applied to data from three different but most commonly used MEG systems (4D-Neuroimaging, VSM MedTech Inc. and Elekta Neuromag). Ocular and cardiac artifacts were effectively reduced within one iteration at a time delay of 1ms performed on a standard PC (Intel Core i5-2410M). COMPARISON WITH EXISTING METHODS: The artifact rejection results achieved with OCARTA are in line with the results reported for offline ICA-based artifact rejection methods. CONCLUSION: Due to the fast and subject-specific signal decomposition the new approach introduced here is capable of real-time ocular and cardiac artifact rejection.

Implementation of a beam forming technique in real-time magnetoencephalography.

Real-time magnetoencephalography (rtMEG) is an emerging neurofeedback technology that could potentially benefit multiple areas of basic and clinical neuroscience. In the present study, we implemented voxel-based real-time coherence measurements in a rtMEG system in which we employed a beamformer to localize signal sources in the anatomical space prior to computing imaginary coherence. Our rtMEG experiment showed that a healthy subject could increase coherence between the parietal cortex and visual cortex when attending to a flickering visual stimulus. This finding suggests that our system is suitable for neurofeedback training and can be useful for practical brain-machine interface applications or neurofeedback rehabilitation.

A beamformer analysis of MEG data reveals frontal generators of the musically elicited mismatch negativity.

To localize the neural generators of the musically elicited mismatch negativity with high temporal resolution we conducted a beamformer analysis (Synthetic Aperture Magnetometry, SAM) on magnetoencephalography (MEG) data from a previous musical mismatch study. The stimuli consisted of a six-tone melodic sequence comprising broken chords in C- and G-major. The musical sequence was presented within an oddball paradigm in which the last tone was lowered occasionally (20%) by a minor third. The beamforming analysis revealed significant right hemispheric neural activation in the superior temporal (STC), inferior frontal (IFC), superior frontal (SFC) and orbitofrontal (OFC) cortices within a time window of 100-200 ms after the occurrence of a deviant tone. IFC and SFC activation was also observed in the left hemisphere. The pronounced early right inferior frontal activation of the auditory mismatch negativity has not been shown in MEG studies so far. The activation in STC and IFC is consistent with earlier electroencephalography (EEG), optical imaging and functional magnetic resonance imaging (fMRI) studies that reveal the auditory and inferior frontal cortices as main generators of the auditory MMN. The observed right hemispheric IFC is also in line with some previous music studies showing similar activation patterns after harmonic syntactic violations. The results demonstrate that a deviant tone within a musical sequence recruits immediately a distributed neural network in frontal and prefrontal areas suggesting that top-down processes are involved when expectation violation occurs within well-known stimuli.

Realignment of magnetoencephalographic data for group analysis in the sensor domain.

Magnetoencephalography (MEG) is a neuroimaging modality with high temporal resolution for studying functional brain processes in relatively small neural assemblies on the time scale of <100 milliseconds and with synchrony and coherence in the recorded signals at high frequencies. Advanced MEG signal analysis gained importance for clinical applications, e.g., as a sensitive classifier for the diagnosis of neuropsychiatric disorders. Despite tremendous improvements in magnetic source imaging, MEG analysis often does not require explicit source estimation and can be performed in the sensor domain. However, group analysis of MEG sensor data is complicated by variable positioning of the sensor array relative to the head and needs realignment of the sensor configuration. Here, the authors provide an algorithm for transforming the magnetic field data as recorded at various sensor positions onto a common sensor array. Based on the measured magnetic field at the original sensor position, they estimate a source distribution and project it onto a virtual sensor array using the leadfield description of the magnetic forward solution. First, they analyzed the variation of sensor positioning in a typical MEG study and reported the impact on the leadfield matrix. Then they evaluated the realignment algorithm and reported its properties. Including efficient regularization to the inverse solution, they demonstrated that the introduced error is in the order of the sensor noise, and smoothing of data is limited to the set of smallest eigenvalues of the data. They demonstrated the performance of the algorithm with dipole source modeling on group averaged MEG data and comparison of grand averaged auditory evoked responses with and without sensor realignment.

Differential neural responses to acupuncture revealed by MEG using wavelet-based time-frequency analysis: a pilot study.

Acupoint specificity, lying at the core of the Traditional Chinese Medicine, still faces many controversies. As previous neuroimaging studies on acupuncture mainly adopted relatively low time-resolution functional magnetic resonance imaging (fMRI) technology and inappropriate block-designed experimental paradigm due to sustained effect, in the current study, we employed a single block-designed paradigm together with high temporal-resolution magnetoencephalography (MEG) technology. We applied time-frequency analysis based upon Morlet wavelet transforming approach to detect differential oscillatory brain dynamics induced by acupuncture at Stomach Meridian 36 (ST36) using a nearby nonacupoint (NAP) as control condition. We observed that frequency power changes were mainly restricted to delta band for both ST36 group and NAP group. Consistently increased delta band power in contralateral temporal regions and decreased power in the counterparts of ipsilateral hemisphere were detected following stimulation at ST36 on the right leg. Compared with ST36, no significant delta ranges were found in temporal regions in NAP group, illustrating different oscillatory brain patterns. Our results may provide additional evidence to support the specificity of acupuncture modulation effects.

Verification of fetal brain responses by coregistration of fetal ultrasound and fetal magnetoencephalography data.

Fetal magnetoencephalography (fMEG) is used to study neurological functions of the developing fetus by measuring magnetic signals generated by electrical sources within the fetal brain. For this aim either auditory or visual stimuli are presented and evoked brain activity or spontaneous activity is measured at the sensor level. However a limiting factor of this approach is the low signal to noise ratio (SNR) of recorded signals. To overcome this limitation, advanced signal processing techniques such as spatial filters (e.g., beamformer) can be used to increase SNR. One crucial aspect of this technique is the forward model and, in general, a simple spherical head model is used. This head model is an integral part of a model search approach to analyze the data due to the lack of exact knowledge about the location of the fetal head. In the present report we overcome this limitation by a coregistration of volumetric ultrasound images with fMEG data. In a first step we validated the ultrasound to fMEG coregistration with a phantom and were able to show that the coregistration error is below 2 cm. In the second step we compared the results gained by the model search approach to the exact location of the fetal head determined on pregnant mothers by ultrasound. The results of this study clearly show that the results of the model search approach are in accordance with the location of the fetal head.

Efecto de la estimulación auditiva a una frecuencia de 5 Hz en la memoria verbal / Impact of auditory stimulation at a frequency of 5 Hz in verbal memory

Introducción. El objetivo de este estudio es establecer si la estimulación a 5 Hz favorece el recuerdo inmediato de palabras. Método. Veinte participantes recibieron estimulación auditiva a frecuencias de 5 Hz-theta, 13 Hz-beta, ruido blanco (RB) y palabras. Resultados. Los resultados indican diferencias significativas en número de palabras recordadas por día entre las frecuencias. A partir del día 3 hasta el día 5 se observó una asociación significativa entre un mayor número de palabras recordadas con 5 Hz comparadas con las demás frecuencias. Si tenemos en cuenta el número de palabras recordadas durante el registro en la magnetoencefalogrofia, en la segunda medida se encontró diferencias significativas con mayor número de palabras entre 5 Hz y 13 Hz y entre 5 Hz y RB. En la frecuencia mediana sólo se presentaron diferencias significativas en estimulación a una frecuencia de 5 Hz. Conclusión. La estimulación auditiva durante largo tiempo a una frecuencia de 5 Hz genera un acoplamiento de la actividad cerebral a dicho ritmo que aumenta la capacidad de memoria verbal inmediata (AU)

Introduction. The objective of this study was to establish whether stimulation at 5 Hz enables immediate words recall. Method. A total of 20 participants received auditory stimulation at 5 Hz-theta, beta-13 Hz frequencies, white noise (WN) and words. Results. The results indicate significant differences in the number of recalled words per day depending on the stimulation frequencies. From the third to the fifth day a significant association was shown between increasing numbers of recalled words at 5 Hz compared with the rest of the frequencies. If we take the number of words recorded during the recording of the magnetoencephalography into account, significant differences with greater numbers of words between 5 Hz and between13 Hz and 5 Hz and WN were found in the second measure. The median frequency only showed significant differences in stimulation at a frequency of 5 Hz. Conclusion. Auditory stimulation over a long time at a frequency of 5 Hz generates a coupling of brain activity that increases the capacity of immediate verbal memory (AU)

Spatiotemporal mapping the neural correlates of acupuncture with MEG.

Acupuncture is an ancient Eastern healing modality with putative therapeutic applications. Unfortunately, little is known about the central mechanisms by which acupuncture may exert its effects. In this study, 16 [corrected] healthy subjects were evaluated with magnetoencephalography (MEG) to map the location and timing of brain activity during low-frequency electroacupuncture (EA) and mechanical, noninsertive, sham acupuncture (SA) given at acupoint PC-6. Both EA and SA evoked brain responses that localized to contralateral primary somatosensory (SI) cortex. However, initial responses for EA peaked slightly earlier than those for SA and were located inferiorly within SI. Average equivalent current dipole strength was stronger (particularly at latencies >60 ms) for SA. These spatiotemporal differences between activations elicited by EA and SA are likely attributable to stimulus modality (electrical versus mechanical) and differences in the underlying somatosensory fibers transmitting these signals. The present data confirm that acupuncture modulates activity within somatosensory cortex, providing support for previous studies that suggest that the therapeutic effects of acupuncture are linked to SI modulation. Thus, MEG provides excellent spatiotemporal characterization of the somatosensory component of acupuncture, and future studies can contrast derived brain response parameters in healthy controls with those found in a diseased state.

Stochastic resonance seen as increase in phase synchrony or power in auditory steady-state responses in MEG.

This report shows the first evidence that stochastic resonance can be triggered in the auditory steady state re-sponses (ASSRs) in MEG (magnetoencephalogram) which was indicated either by increased synchrony to the stimulus or by increase in power of ASSR when there was certain amount of noise in addition to the sinusoidal AM sound compared with the ASSR when there was no noise. To obtain the above conclusion, we applied statistical analysis to each subject's data rather than to the whole set of the data of all subjects because individual differences smoothed out the effect of noise addition when the data were averaged over all the subjects.

Serial magnetoencephalographic study of fetal and newborn auditory discriminative evoked responses.

The mismatch negativity (MMN) response elicited to auditory stimuli is an indicator for cognitive function of sound discrimination in humans. MMN was successfully recorded in previous studies in newborns and fetuses (33-40 weeks of gestation) with magnetoencephalography (MEG). The aim of our study was to perform systematic serial MMN recordings on fetuses starting at 28 weeks of gestation with a follow up recording within 2 weeks after birth. The recording of weak magnetic fields from the fetal brain were performed with the 151 channel MEG system called SARA (SQUID Array for Reproductive Assessment). Two tone bursts were presented in a sequence of a standard complex tone of 500 Hz intermixed with a deviant complex tone of 750 Hz in 12% of the stimuli, inter-stimulus interval 800+/-100 ms. Eighteen pregnant women between 28th and 39th gestational weeks participated in the study. Measurements were performed every two weeks and once after delivery. The averaged evoked responses to standard and deviant tones were obtained and subtraction between them was calculated. A successful detection of response to the frequency change was found in 66% of the fetal data and 89% of the neonatal data. Responses to the standard tone were detected in 56% of all records. In the 28-39 week gestational age group, the discriminative brain responses to tone frequency change could be detected as early as 28 weeks. Although not statistically significant, a decrease in latency was observed with increase in gestational age. The ability of the fetus to detect changes in sounds is a prerequisite to normal development for cognitive function; related to language learning and clinical aspects of auditory disorders.

Frequency specific impairment of automatic pitch change detection by fMRI acoustic noise: an MEG study.

The loud acoustic noise produced by the magnetic resonance scanner is a major source of interference in auditory fMRI research. Whole-head magnetoencephalography (MEG) was used to investigate the interaction between the frequency range of auditory stimulation and fMRI acoustic noise. Pure tones and 3-harmonic complexes varying between 240 and 1240 Hz in frequency were presented while participants attended to a silent subtitled film. Continuous fMRI acoustic noise was presented during half of the blocks. The activity in six regions of interest was analyzed in 100-200 and 200-300 ms time windows to evaluate the magnetic counterparts of the mismatch negativity (MMN) and P3a brain responses. The results suggested that fMRI noise significantly reduced the amplitude of these responses. The effect of the noise on the automatic processing of the tones was more prominent for the tones with frequencies higher than 500 Hz. It is recommended that in the MMN protocols using continuous fMRI acquisition the sound stimuli should be spectrally separated from the fMRI scanner noise spectrum.

Fetal magnetoencephalography--a multimodal approach.

Past studies have shown the feasibility of recording fetal evoked responses to external stimuli using a non-invasive technique called magnetoencephalography (MEG). These studies were all performed using either auditory or visual stimuli and showed a fairly low detection rate for each modality, thus making this technology currently unreliable for fetal clinical applications. This study is based on the hypothesis that a multimodal approach of applying both auditory and visual stimulation paradigms in successive recording sessions could improve the probability of obtaining a fetal evoked response. A total of 34 studies were performed on 11 normal healthy fetuses at different stages of gestation starting as early as 28 weeks with a 151-channel fetal MEG system. The success rate of obtaining a response to either (or both) stimuli from a study at a given gestation age was 91%. All the 11 fetuses showed a response at least once over the gestation period the recordings were performed. A multimodal testing approach can improve the ability of the MEG technique to reliably monitor the functional development of the fetal brain.

Magnetoencephalography is feasible for infant assessment of auditory discrimination.

Magnetoencephalography (MEG) detects the brain's magnetic fields as generated by neuronal electric currents arising from synaptic ion flow. It is noninvasive, has excellent temporal resolution, and it can localize neuronal activity with good precision. For these reasons, many scientists interested in the localization of brain functions have turned to MEG. The technique, however, is not without its drawbacks. Those reluctant to employ it cite its relative awkwardness among pediatric populations because MEG requires subjects to be fairly still during experiments. Due to these methodological challenges, infant MEG studies are not commonly pursued. In the present study, MEG was employed to study auditory discrimination in infants. We had two goals: first, to determine whether reliable results could be obtained from infants despite their movements; and second, to improve MEG data analysis methods. To get more reliable results from infants we employed novel hardware (real-time head-position tracking system) and software (signal space separation method, SSS) solutions to better deal with noise and movement. With these solutions, the location and orientation of the head can be tracked in real time and we were able to reduce noise and artifacts originating outside the helmet significantly. In the present study, these new methods were used to study the biomagnetic equivalents of event-related potentials (ERPs) in response to duration changes in harmonic tones in sleeping, healthy, full-term newborns. Our findings indicate that with the use of these new analysis routines, MEG will prove to be a very useful and more accessible experimental technique among pediatric populations.

The neurophysiological basis of the auditory continuity illusion: a mismatch negativity study.

A sound turned off for a short moment can be perceived as continuous if the silent gap is filled with noise. The neural mechanisms underlying this "continuity illusion" were investigated using the mismatch negativity (MMN), an event-related potential reflecting the perception of a sudden change in an otherwise regular stimulus sequence. The MMN was recorded in four conditions using an oddball paradigm. The standards consisted of 500-Hz, 120-msec tone pips that were either physically continuous (Condition 1) or were interrupted by a 40-msec silent gap (Condition 2). The deviants consisted of the interrupted tone, but with the silent gap filled by a burst of bandpass-filtered noise. The noise either occupied the same frequency region as the tone and elicited the continuity illusion (Conditions 1a and 2a), or occupied a remote frequency region and did not elicit the illusion (Conditions 1b and 2b). We predicted that, if the continuity illusion is determined before MMN generation, then, other things being equal, the MMN should be larger in conditions where the deviants are perceived as continuous and the standards as interrupted or vice versa, than when both were perceived as continuous or both interrupted. Consistent with this prediction, we observed an interaction between standard type and noise frequency region, with the MMN being larger in Condition 1a than in Condition 1b, but smaller in Condition 2a than in Condition 2b. Because the subjects were instructed to ignore the tones and watch a silent movie during the recordings, the results indicate that the continuity illusion can occur outside the focus of attention. Furthermore, the latency of the MMN (less than approximately 200 msec postdeviance onset) places an upper limit on the stage of neural processing responsible for the illusion.

Source distribution of neuromagnetic slow-wave activity in schizophrenic patients--effects of activation.

When slow waves in the EEG delta and theta frequency range appear in the waking state, they may indicate pathological conditions including psychopathology. The generators of focal slow waves can be mapped using magnetic source imaging. The resulting brain maps may possibly characterize dysfunctional brain areas. The present study examined the stability of the density and distribution of MEG slow waves during three conditions-rest, mental arithmetic and imagery-in 30 schizophrenic patients and 17 healthy controls. Schizophrenic patients displayed a higher density of delta and theta generators primarily in temporal and parietal areas. The group difference was not affected by the particular conditions. The focal concentration of delta and theta slow waves did not differ between patients with and without neuroleptic medication, whereas the prominence of theta dipoles in the temporal area correlated with neuroleptic dosage. The relative amount of temporal slow waves was correlated with the negative symptoms score (PANSS-N) suggesting that temporal dysfunction may be related to negative symptomatology.Results suggest that the distribution of slow-wave activity, measured in a standardized setting, might add diagnostic information about brain abnormalities in schizophrenia.

Neuropsychiatric thalamocortical dysrhythmia: surgical implications.

Clearly, more clinical experience must be amassed to define in detail the possibilities of this surgical approach in disabling neuropsychiatric disorders. We propose, however, that the evidence for benign and efficient surgical intervention against the neuropsychiatric TCD syndrome is already compelling. The potential appearance of strong postoperative reactive manifestations requires a close association between surgery and psychotherapy, with the latter providing support for the integration of the new situation as well as the resolution of old unresolved issues.

Signal analysis of auditory evoked cortical fields in fetal magnetoencephalography.

Magnetoencephalography (MEG) using auditory evoked cortical fields (AEF) is an absolutely non-invasive method of passive measurement which utilizes magnetic fields caused by specific cortical activity. By applying the exceptionally sensitive SQUID technology to record these fields of dipolar configuration produced by the fetal brain, MEG as an investigational tool could provide new insights into the development of the human brain in utero. The major constraint to this application is a very low signal-to-noise ratio (SNR) that has to be attributed to a variety of factors including the magnetic signals generated by the fetal and maternal hearts which inevitably obscure a straightforward signal analysis. By applying a new algorithm of specific heart artefact reduction based on the relative regularity of the heart signals, we were able to increase the chance of extracting a fetal AEF from the raw data by the means of averaging techniques and principle component analysis. Results from 27 pregnant, healthy women (third trimester of their uncomplicated pregnancy) indicate an improved detection rate and the reproducibility of the fetal MEG. We evaluate and discuss a-priori criteria for signal analyses which will enable us to systematically analyze additional limiting factors, to further enhance the efficiency of this method and to promote the assessment of its possible clinical value in the future.

Magnetic field tomography of cortical and deep processes: examples of "real-time mapping" of averaged and single trial MEG signals.

Magnetic field tomography (MFT) provides 3-dimensional estimates of brain activity, from non-contact, non-invasive measurements of the magnetic field generated by coherent electrical activity in the brain. MFT analysis of averaged auditory "odd-ball" data show cortical and deep activation, presumably from the amygdala and hippocampus. These results are compared with MFT estimates obtained from a patient who had undergone lobectomy which removed these structures. The variability from subject to subject is confounded by variability between trials for the same subject; the relationship between the averaged and single trials is probed by bi-hemispheric simultaneous measurements performed under the same odd-ball paradigm and by MFT analysis of auditory evoked data and interictal epileptic activity.