Naoaki Tanaka

Task-free presurgical mapping using functional magnetic resonance imaging intrinsic activity.

OBJECT Low-frequency components of the spontaneous functional MR imaging signal provide information about the intrinsic functional and anatomical organization of the brain. The ability to use such methods in individual patients may provide a powerful tool for presurgical planning. The authors explore the feasibility of presurgical motor function mapping in which a task-free paradigm is used. METHODS Six surgical candidates with tumors or epileptic foci near the motor cortex participated in this study. The investigators directly compared task-elicited activation of the motor system to activation obtained from intrinsic activity correlations. The motor network within the unhealthy hemisphere was identified based on intrinsic activity correlations, allowing distortions of functional anatomy caused by the tumor and epilepsy to be directly visualized. The precision of the motor function mapping was further explored in 1 participant by using direct cortical stimulation. RESULTS The motor regions localized based on the spontaneous activity correlations were quite similar to the regions defined by actual movement tasks and cortical stimulation. Using intrinsic activity correlations, it was possible to map the motor cortex in presurgical patients. CONCLUSIONS This task-free paradigm may provide a powerful approach to map functional anatomy in patients without task compliance and allow multiple brain systems to be determined in a single scanning session.

Altered Structural Connectome in Temporal Lobe Epilepsy

PURPOSE To study differences in the whole-brain structural connectomes of patients with left temporal lobe epilepsy (TLE) and healthy control subjects. MATERIALS AND METHODS This study was approved by the institutional review board, and all individuals gave signed informed consent. Sixty-direction diffusion-tensor imaging and magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) magnetic resonance imaging volumes were analyzed in 24 patients with left TLE and in 24 healthy control subjects. MP-RAGE volumes were segmented into 1015 regions of interest (ROIs) spanning the entire brain. Deterministic white matter tractography was performed after voxelwise tensor calculation. Weighted structural connectivity matrices were generated by using the pairwise density of connecting fibers between ROIs. Graph theoretical measures of connectivity networks were compared between groups by using linear models with permutation testing. RESULTS Patients with TLE had 22%-45% reduced (P < .01) distant connectivity in the medial orbitofrontal cortex, temporal cortex, posterior cingulate cortex, and precuneus, compared with that in healthy subjects. However, local connectivity, as measured by means of network efficiency, was increased by 85%-270% (P < .01) in the medial and lateral frontal cortices, insular cortex, posterior cingulate cortex, precuneus, and occipital cortex in patients with TLE as compared with healthy subjects. CONCLUSION This study suggests that TLE involves altered structural connectivity in a network that reaches beyond the temporal lobe, especially in the default mode network.

Localization of focal epileptic discharges using functional connectivity magnetic resonance imaging

OBJECT In patients with medically refractory epilepsy the accurate localization of the seizure onset zone is critical for successful surgical treatment. The object of this study was to investigate whether the degree of coupling of spontaneous brain activity as measured with functional connectivity MR imaging (fcMR imaging) can accurately identify and localize epileptic discharges. METHODS The authors studied 6 patients who underwent fcMR imaging presurgical mapping and subsequently underwent invasive electroencephalography. RESULTS Focal regions of statistically significant increases in connectivity were identified in 5 patients when compared with an ad hoc normative sample of 300 controls. The foci identified by fcMR imaging overlapped the epileptogenic areas identified by invasive encephalography in all 5 patients. CONCLUSIONS These results suggest that fcMR imaging may provide an effective high-spatial resolution and noninvasive method of localizing epileptic discharges in patients with refractory epilepsy.

Clinical applications of magnetoencephalography

Magnetoencephalography (MEG), in which magnetic fields generated by brain activity are recorded outside of the head, is now in routine clinical practice throughout the world. MEG has become a recognized and vital part of the presurgical evaluation of patients with epilepsy and patients with brain tumors. We review investigations that show an improvement in the postsurgical outcomes of patients with epilepsy by localizing epileptic discharges. We also describe the most common clinical MEG applications that affect the management of patients, and discuss some applications that are close to having a clinical impact on patients. Hum Brain Mapp, 2009.

Propagation of epileptic spikes reconstructed from spatiotemporal magnetoencephalographic and electroencephalographic source analysis

The purpose of this study is to assess the accuracy of spatiotemporal source analysis of magnetoencephalography (MEG) and scalp electroencephalography (EEG) for representing the propagation of frontotemporal spikes in patients with partial epilepsy. This study focuses on frontotemporal spikes, which are typically characterized by a preceding anterior temporal peak followed by an ipsilateral inferior frontal peak. Ten patients with frontotemporal spikes on MEG/EEG were studied. We analyzed the propagation of temporal to frontal epileptic spikes on both MEG and EEG independently by using a cortically constrained minimum norm estimate (MNE). Spatiotemporal source distribution of each spike was obtained on the cortical surface derived from the patients MRI. All patients underwent an extraoperative intracranial EEG (IEEG) recording covering temporal and frontal lobes after presurgical evaluation. We extracted source waveforms of MEG and EEG from the source distribution of interictal spikes at the sites corresponding to the location of intracranial electrodes. The time differences of the ipsilateral temporal and frontal peaks as obtained by MEG, EEG and IEEG were statistically compared in each patient. In all patients, MEG and IEEG showed similar time differences between temporal and frontal peaks. The time differences of EEG spikes were significantly smaller than those of IEEG in nine of ten patients. Spatiotemporal analysis of MEG spikes models the time course of frontotemporal spikes as observed on IEEG more adequately than EEG in our patients. Spatiotemporal source analysis may be useful for planning epilepsy surgery, by predicting the pattern of IEEG spikes.

Dynamic statistical parametric mapping for analyzing ictal magnetoencephalographic spikes in patients with intractable frontal lobe epilepsy

The purpose of this study is to assess the clinical value of spatiotemporal source analysis for analyzing ictal magnetoencephalography (MEG). Ictal MEG and simultaneous scalp EEG was recorded in five patients with medically intractable frontal lobe epilepsy. Dynamic statistical parametric maps (dSPMs) were calculated at the peak of early ictal spikes for the purpose of estimating the spatiotemporal cortical source distribution. DSPM solutions were mapped onto a cortical surface, which was derived from each patients MRI. Equivalent current dipoles (ECDs) were calculated using a single-dipole model for comparison with dSPMs. In all patients, dSPMs tended to have a localized activation, consistent with the clinically determined ictal onset zone, whereas most ECDs were considered to be inappropriate sources according to their goodness-of-fit values. Analyzing ictal MEG spikes by using dSPMs may provide useful information in presurgical evaluation of epilepsy.

Generalized spike-wave discharges involve a default mode network in patients with juvenile absence epilepsy: A MEG study

This study uses magnetoencephalography (MEG) to examine whether cortical regions that constitute a default mode network are involved during generalized spike-wave discharges (GSWs) in patients with juvenile absence epilepsy (JAE). We studied five JAE patients for whom MEG was recorded using a 204-channel, whole-head gradiometer system. Dynamic statistical parametric mapping (dSPM) was done to estimate the cortical source distribution of GSW. The dSPM results showed strong medial prefrontal activation in all patients, with activation in the posterior cingulate and precuneus in three of five patients simultaneously or slightly after medial prefrontal activation. Furthermore, dSPM showed that the initial activation of a GSW appears in the focal cortical regions. Cortical regions that constitute a default mode network are strongly involved in the GSW process in some patients with JAE. Results also show that focal cortical activation appears at the onset of a GSW.

Language Lateralization Represented by Spatiotemporal Mapping of Magnetoencephalography

BACKGROUND AND PURPOSE: Determination of hemispheric language dominance is critical for planning epilepsy surgery. We assess the usefulness of spatiotemporal source analysis of magnetoencephalography for determining language laterality. MATERIALS AND METHODS: Thirty-five patients with epilepsy were studied. The patients performed a semantic word-processing task during MEG recording. Epochs containing language-related neuromagnetic activity were averaged after preprocessing. The averaged data between 250 and 550 ms after stimulus were analyzed by using dynamic statistical parametric mapping. ROIs were obtained in the opercular and triangular parts of the inferior frontal gyrus, superior temporal gyrus, and supramarginal gyrus in both hemispheres. We calculated laterality indices according to 1) dSPM-amplitude method, based on the amplitude of activation in the ROIs, and 2) dSPM-counting method, based on the number of unit dipoles with activation over a threshold in the ROIs. The threshold was determined as half of the maximum value in all ROIs for each patient. A LI ≥0.10 or ≤−0.10 was considered left- or right-hemisphere dominance, respectively; a LI between −0.10 and 0.10 was considered bilateral. All patients underwent an intracarotid amobarbital procedure as part of presurgical evaluation. RESULTS: The dSPM-counting method demonstrated laterality consistent with the IAP in 32 of 35 patients (91.4%), the remaining 3 (8.6%) demonstrated bilateral language representation, whereas the dSPM-amplitude method showed 18 (51.4%) concordant and 17 (48.6%) bilateral. No laterality opposite to the IAP was found. CONCLUSIONS: Spatiotemporal mapping of language lateralization with the dSPM-counting method may reduce the necessity for an IAP in as many as 90% of patients.

State-dependent variability of dynamic functional connectivity between frontoparietal and default networks relates to cognitive flexibility.

The brain is a dynamic, flexible network that continuously reconfigures. However, the neural underpinnings of how state-dependent variability of dynamic functional connectivity (vdFC) relates to cognitive flexibility are unclear. We therefore investigated flexible functional connectivity during resting-state and task-state functional magnetic resonance imaging (rs-fMRI and t-fMRI, resp.) and performed separate, out-of-scanner neuropsychological testing. We hypothesize that state-dependent vdFC between the frontoparietal network (FPN) and the default mode network (DMN) relates to cognitive flexibility. Seventeen healthy subjects performed the Stroop color word test and underwent t-fMRI (Stroop computerized version) and rs-fMRI. Time series were extracted from a cortical atlas, and a sliding window approach was used to obtain a number of correlation matrices per subject. vdFC was defined as the standard deviation of connectivity strengths over these windows. Higher task-state FPN-DMN vdFC was associated with greater out-of-scanner cognitive flexibility, while the opposite relationship was present for resting-state FPN-DMN vdFC. Moreover, greater contrast between task-state and resting-state vdFC related to better cognitive performance. In conclusion, our results suggest that not only the dynamics of connectivity between these networks is seminal for optimal functioning, but also that the contrast between dynamics across states reflects cognitive performance.

Magnetoencephalographic analysis in patients with vagus nerve stimulator.

The objective of this study was to assess the feasibility of magnetoencephalography in epilepsy patients with a vagus nerve stimulator. Magnetoencephalography was performed in two patients with medically intractable epilepsy who had a vagus nerve stimulator. Because of the artifacts caused by the vagus nerve stimulator, no spikes could be identified in the original magnetoencephalographic data in either patient. The temporally extended signal space separation method was used to remove artifacts. After processing by this method, left temporoparietal spikes were clearly identified in patient 1. Equivalent current dipoles calculated from these spikes were localized in the left posterior-temporal and parietal lobes. The location of the dipoles was consistent with the spike distribution on intracranial electroencephalography. In patient 2, bilateral diffuse spikes were seen in the processed data. The contour maps demonstrated a bilateral pattern, not in agreement with a single focal source. These findings supported the diagnosis of symptomatic generalized epilepsy in this patient. Magnetoencephalography may thus be a useful option for evaluating patients with intractable epilepsy who have a vagus nerve stimulator.