John E. Moran

Magnetoencephalographic fields from patients with spontaneous and induced migraine aura.

We investigate and characterize the magnetoencephalographic waveforms from patients during spontaneous and visually induced migraine aura. Direct current neuromagnetic fields were measured during spontaneous onset of migraine auras in 4 migraine patients, and compared with recordings from 8 migraine‐with‐aura patients and 6 normal controls during visual stimulation of the occipital cortex. Complex direct current magnetoencephalographic shifts, similar in waveform, were observed in spontaneous and visually induced migraine patients, but not in controls. Two‐dimensional inverse imaging showed multiple cortical areas activated in spontaneous and visually induced migraine aura patients. In normal subjects, activation was only observed in the primary visual cortex. Results support a spreading, depression‐like neuroelectric event occurring during migraine aura that can arise spontaneously or be visually triggered in widespread regions of hyperexcitable occipital cortex.

Analysis of MEG signals of spreading cortical depression with propagation constrained to a rectangular cortical strip: I. Lissencephalic rabbit model

Magnetic fields arising from the rabbit cortex during spreading cortical depression (SCD) were measured in order to study the currents in the neocortex during SCD. SCD was constrained to propagate in a rectangular cortical strip perpendicular to the midline. This simplified in vivo cortical preparation enabled us to correlate magnetoencephalographic (MEG) signals to their underlying currents within the cortical strip. The propagation of SCD was monitored with an array of electrodes placed along the strip. The propagation speed for SCD in the lissencephalic rabbit brain was 3. 5+/-0.3 mm/min (mean+/-S.E.M., n=14). Slow, quasi-dc, MEG signals were observed as the SCD entered into the longitudinal fissure. The currents giving rise to the MEG signals were perpendicular to the cortical surface and directed from the surface to deeper layers of the cortex. A distributed dipolar source model was used to relate the data to the underlying cortical current. The moment of the single equivalent current dipole source was 38+/-9 nA-m (n=17). This study clarified the nature of the cortical currents during SCD in a lissencephalic in vivo preparation.

Language laterality determined by MEG mapping with MR-FOCUSS

Magnetoencephalography recordings were made on 27 patients with localization related epilepsy during two different language tasks involving semantic and phonological processing (verb generation and picture naming). These patients underwent the semi-invasive intracarotid amobarbital procedure (IAP), also referred to as the Wada test, to determine the language-dominant hemisphere. Magnetoencephalography (MEG) data were analyzed by MR-FOCUSS, a current density imaging technique. A laterality index (LI) was calculated from this solution to determine which hemisphere had more neural activation during these language tasks. The LIs for three separate latencies, within each language task, were calculated to determine the latency that correlated best with each patients IAP result. The LI for all language processing was calculated for the interval 150-550 ms, the second LI was calculated for the interval 230-290 ms (Wernickes activation), and the third LI was calculated for the interval 396-460 ms (Brocas activation). In 23 of 24 epilepsy patients with a successful IAP, the LIs for Brocas activation, during the picture naming task, were in agreement with the results of the IAP (96% agreement). One of three patients who had an undetermined or bilateral IAP had an LI calculated for Brocas activation (396-460 ms) that agreed with intracranial mapping and clinical testing. These results indicate an 89% agreement rate (24 of 27) for magnetoencephalographic LI determination of the hemisphere of language dominance.

Multi-Resolution FOCUSS: A Source Imaging Technique Applied to MEG Data

Summary:A variety of techniques are available for imaging magnetoencephalographic (MEG) data to the corresponding cortical structures. Each performs a functional optimization that includes mathematical and physical restrictions on source activity. Unlike other imaging techniques, MR-FOCUSS (Multi-Resolution FOCal Underdetermined System Solution) utilizes a wavelet statistical operator that allows spatial resolution to be chosen appropriately for focal or extended sources. Control of focal imaging properties is achieved by specifying P in an lP norm distribution template used to construct the wavelets. In addition, incorporation of a multi-resolution wavelet operator desensitizes the mathematical algorithm to noise, (regularization). Like the FOCUSS imaging technique, an initial estimate of cortical activity is recursively enhanced to obtain the final high resolution imaging results. Studies of model MEG data representing all regions of a realistic cortical model are performed to quantify MR-FOCUSS imaging properties. These modeled data studies included single and multiple dipole sources as well as an extended source model. Thus, MR-FOCUSS is found to be very effective for imaging language processing for pre-surgical planning and provides a high-resolution method to image sequential activation of multiple correlated sources involved in language processing.

Cortical hyperexcitability in migraine patients before and after sodium valproate treatment.

DC-magnetoencephalography (DC-MEG)waveforms arising during migraine aura were used to determine the effectiveness of prophylactic medication therapy on neuronal hyperexcitability. Nine patients were prescribed valproate (Depakote) for migraine prophylaxis. MEG scans were recorded during visual stimulation before commencing medication and again after 30 days of daily use of valproate. Cortical brain activity was recorded during stimulation with a black-and-white circular checkerboard pattern alternating at 8 Hz and were analyzed with MR-FOCUSS. Large-amplitude DC-MEG signals, imaged to extended areas of occipital cortex, were seen before therapy. After 30 days of prophylactic treatment, reduced DC-MEG shifts in the occipital cortex and reduced incidence of migraine attacks were observed. Using visual stimulation, the authors demonstrated the hyperexcitability of widespread regions throughout occipital cortex in migraine patients, explaining the susceptibility for triggering spreading cortical depression and migraine aura. This study confirms that MEG can noninvasively determine the status of neuronal excitability before and after therapy. This finding may be helpful in determining which prophylactic medications will be most effective in reducing hyperexcitability in particular patients.

MEG localization of language-specific cortex utilizing MR-FOCUSS

Objective:To demonstrate noninvasive localization of cognitive cortical areas involved in language processing with magnetoencephalography (MEG) interpreted by multiresolution FOCUSS (MR-FOCUSS), a current density imaging technique. Method:MEG data were collected during verb-generation and picture-naming tasks from 18 right-handed control subjects and 24 right-handed patients with epilepsy. Results: The averaged epic data from the verb-generation task, analyzed by MR-FOCUSS, showed initial activation in the left supramarginal gyrus, superior temporal gyrus, and angular gyrus at 239 ± 31 ms in all subjects, consistent with other language mapping studies. Average amplitude of underlying cortical sources was ~452 pAm. The averaged epic data from the picture-naming task, analyzed by MR-FOCUSS, showed activation in the left inferior frontal gyrus (IFG) area starting at 436 ± 40 ms in all subjects. Average amplitudes of underlying cortical sources were ~380 pAm. Conclusion:The time course of neuronal language processing can be imaged noninvasively with millisecond resolution by magnetoencephalography using the multiresolution FOCUSS technique.To the Editor: Bowyer et al.1 present a novel mathematical approach for determining patterns of brain activity associated with performance of language tasks. The software developed by the authors has two main advantages, which could, in theory, ensure a level of confidence sufficient for presurgical planning applications. First, it takes into account the anatomy of the brain, constraining potential “sources” of magnetic activity based on physiologic and physical considerations. Second, and perhaps most important, the software is designed to operate unsupervised, significantly reducing the impact of subjective input from the user, a limitation characteristic of the “standard” method of the iterative application of the single equivalent current dipole (ECD) that the Bowyer et al. method claims to surpass in efficiency. Incidentally, the ECD method remains the “gold standard” in magnetoencephalography (MEG) studies on the cerebral mechanisms of basic sensory functions and of language, because it is the only one that has been validated against invasive brain mapping techniques and postoperative outcome,2–5 yet Bowyer et al. do not acknowledge this. As with previous attempts to outline brain activity profiles using alternative mathematical approaches, the results reported by Bowyer et al. are both interesting and promising. Clinical applications of MEG will be greatly facilitated by the use of userindependent analysis techniques, provided, however, that the key requirement of external validation of activation maps that applies to every functional imaging method is fully met. External validation is particularly crucial for techniques that model activity in terms of spatially extensive sources (like the Bowyer et al. technique does), given the inherent uncertainty surrounding threshold selection for displaying activation images. Adopting different image thresholding criteria may modify the extent of cortical regions that appear active, thereby seriously affecting the utility of the technique for presurgical mapping applications. Hopefully, the method that Bowyer et al. advocate will soon meet the validation requirement and emerge as a “more sensitive and useful technique” than the “standard” one which has been validated. Yet until this transpires, we believe it is advisable not to confound hope with fact. Incidentally, we also believe it is advisable not to confound literary genres (i.e. epic) with segments or durations of time-series (i.e. epochs) which the authors repeatedly do in their text.

Magnetic fields associated with spreading depression in anaesthetised rabbits

Magnetic fields were measured with SQUID magnetometry outside the skull of anaesthetised rabbits during initiation and propagation of spreading depression (SD) in the cortex. Slowly changing fields (up to 1.4 pT) were observed during the propagation phase, from 4-8.5 min after initiation of SD with KCl application, with maxima at about 6 min. The peak amplitude of the equivalent net dipole generators in the brain was ca. 28 microA.mm, substantially less than previously observed with SD in vitro, but large enough that similar signals might be detectable in man.

An Assessment of MEG Coherence Imaging in the Study of Temporal Lobe Epilepsy

Purpose:  This study examines whether magnetoencephalographic (MEG) coherence imaging is more sensitive than the standard single equivalent dipole (ECD) model in lateralizing the site of epileptogenicity in patients with drug‐resistant temporal lobe epilepsy (TLE).

Conversation effects on neural mechanisms underlying reaction time to visual events while viewing a driving scene: fMRI analysis and asynchrony model

This neuroimaging study investigated the neural mechanisms of the effect of conversation on visual event detection during a driving-like scenario. The static load paradigm, established as predictive of visual reaction time in on-road driving, measured reaction times to visual events while subjects watched a real-world driving video. Behavioral testing with twenty-eight healthy volunteers determined the reaction time effects from overt and covert conversation tasks in this paradigm. Overt and covert conversation gave rise to longer visual event reaction times in the surrogate driving paradigm compared to just driving with no conversation, with negligible effect on miss rates. The covert conversation task was then undertaken by ten right-handed healthy adults in a 4-Tesla fMRI magnet. We identified a frontal-parietal network that maintained event detection performance during the conversation task while watching the driving video. Increased brain activations for conversation vs. no conversation during such simulated driving was found not only in language regions (Brocas and Wernickes areas), but also specific regions in bilateral inferior frontal gyrus, bilateral anterior insula and orbitofrontal cortex, bilateral lateral prefrontal cortex (right middle frontal gyrus and left frontal eye field), supplementary motor cortex, anterior and posterior cingulate gyrus, right superior parietal lobe, right intraparietal sulcus, right precuneus, and right cuneus. We propose an Asynchrony Model in which the frontal regions have a top-down influence on the synchrony of neural processes within the superior parietal lobe and extrastriate visual cortex that in turn modulate the reaction time to visual events during conversation while driving.

Cortical locations of maximal spindle activity: magnetoencephalography (MEG) study

The aim of this study was to determine the main cortical regions related to maximal spindle activity of sleep stage 2 in healthy individual subjects during a brief morning nap using magnetoencephalography (MEG). Eight volunteers (mean age: 26.1 ± 8.7, six women) all right handed, free of any medical psychiatric or sleep disorders were studied. Whole‐head 148‐channel MEG and a conventional polysomnography montage (EEG; C3, C4, O1 and O2 scalp electrodes and EOG, EMG and ECG electrodes) were used for data collection. Sleep MEG/EEG spindles were visually identified during 15 min of stage 2 sleep for each participant. The distribution of brain activity corresponding to each spindle was calculated using a combination of independent component analysis and a current source density technique superimposed upon individual MRIs. The absolute maximum of spindle activation was localized to frontal, temporal and parietal lobes. However, the most common cortical regions for maximal source spindle activity were precentral and/or postcentral areas across all individuals. The present study suggests that maximal spindle activity localized to these two regions may represent a single event for two types of spindle frequency: slow (at 12 Hz) and fast (at 14 Hz) within global thalamocortical coherence.