Continuous EEG-fMRI in patients with partial epilepsy and focal interictal slow-wave discharges on EEG

Purpose

To verify whether in patients with partial epilepsy and routine electroenecephalogram (EEG) showing focal interictal slow-wave discharges without spikes combined EEG–functional magnetic resonance imaging (fMRI) would localize the corresponding epileptogenic focus, thus providing reliable information on the epileptic source.

Methods

Eight patients with partial epileptic seizures whose routine scalp EEG recordings on presentation showed focal interictal slow-wave activity underwent EEG–fMRI. EEG data were continuously recorded for 24 min (four concatenated sessions) from 18 scalp electrodes, while fMRI scans were simultaneously acquired with a 1.5-Tesla magnetic resonance imaging (MRI) scanner. After recording sessions and MRI artefact removal, EEG data were analyzed offline. We compared blood oxygen level-dependent (BOLD) signal changes on fMRI with EEG recordings obtained at rest and during activation (with and without focal interictal slow-wave discharges).

Results

In all patients, when the EEG tracing showed the onset of focal slow-wave discharges on a few lateralized electrodes, BOLD-fMRI activation in the corresponding brain area significantly increased. We detected significant concordance between focal EEG interictal slow-wave discharges and focal BOLD activation on fMRI. In patients with lesional epilepsy, the epileptogenic area corresponded to the sites of increased focal BOLD signal.

Conclusions

Even in patients with partial epilepsy whose standard EEGs show focal interictal slow-wave discharges without spikes, EEG–fMRI can visualize related focal BOLD activation thus providing useful information for pre-surgical planning.     

Multimodal imaging: an evaluation of univariate and multivariate methods for simultaneous EEG/fMRI

The combination of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) has been proposed as a tool to study brain dynamics with both high temporal and high spatial resolution. Multimodal imaging techniques rely on the assumption of a common neuronal source for the different recorded signals. In order to maximally exploit the combination of these techniques, one needs to understand the coupling (i.e., the relation) between electroencephalographic (EEG) and fMRI blood oxygen level-dependent (BOLD) signals.     

Real-time MR artifacts filtering during continuous EEG/fMRI acquisition

The purpose of this study was the development of a real-time filtering procedure of MRI artifacts in order to monitor the EEG activity during continuous EEG/fMRI acquisition. The development of a combined EEG and fMRI technique has increased in the past few years. Preliminary “spike-triggered” applications have been possible because in this method, EEG knowledge was only necessary to identify a trigger signal to start a delayed fMRI acquisition. In this way, the two methods were used together but in an interleaved manner. In real simultaneous applications, like event-related fMRI study, artifacts induced by MRI events on EEG traces represent a substantial obstacle for a right analysis. Up until now, the methods proposed to solve this problem are mainly based on procedures to remove post-processing artifacts without the possibility to control electrophysiological behavior of the patient during fMRI scan. Moreover, these methods are not characterized by a strong “prior knowledge” of the artifact, which is an imperative condition to avoid any loss of information on the physiological signals recovered after filtering. In this work, we present a new method to perform simultaneous EEG/fMRI study with real-time artifacts filtering characterized by a procedure based on a preliminary analytical study of EPI sequence parameters-related EEG-artifact shapes. Standard EEG equipment was modified in order to work properly during ultra-fast MRI acquisitions. Changes included: high-performance acquisition device; electrodes/cap/wires/cables materials and geometric design; shielding box for EEG signal receiver; optical fiber link; and software. The effects of the RF pulse and time-varying magnetic fields were minimized by using a correct head cap wires-locked environment montage and then removed during EEG/fMRI acquisition with a subtraction algorithm that takes in account the most significant EPI sequence parameters. The on-line method also allows a further post-processing utilization.     

Simultaneous EEG and fMRI in the macaque monkey at 4.7 Tesla

Simultaneous electroencephalography (EEG)/functional magnetic resonance imaging (fMRI) acquisition can identify the brain networks involved in generating specific EEG patterns. Yet, the combination of these methodologies is hampered by strong artifacts that arise due to electromagnetic interference during magnetic resonance (MR) image acquisition. Here, we report corrections of the gradient-induced artifact in phantom measurements and in experiments with an awake behaving macaque monkey during fMRI acquisition at a magnetic field strength of 4.7 T. Ninety-one percent of the amplitude of a 10 microV, 10 Hz phantom signal could successfully be recovered without phase distortions. Using this method, we were able to extract the monkey EEG from scalp recordings obtained during MR image acquisition. Visual evoked potentials could also be reliably identified. In conclusion, simultaneous EEG/fMRI acquisition is feasible in the macaque monkey preparation at 4.7 T and holds promise for investigating the neural processes that give rise to particular EEG patterns.     

Comparison of analytical strategies for EEG-correlated fMRI data in patients with epilepsy

The simultaneous recording of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) can be used to localize interictal epileptiform discharges (IEDs). Previous studies have reported varying degrees of concordance of EEG-fMRI with electroclinical findings. The aim of the present study is to evaluate to what extent this variability is determined by the analytical strategy or by the properties of the EEG data. For that purpose, 42 IED sets obtained in 29 patients with epilepsy were reanalyzed using a finite impulse response approach, which estimates the hemodynamic response function (HRF) from the data and allows non-causal effects. Cardiac effects were treated as additional confounders in the model. This approach was compared to the classical approach assuming a fixed HRF for each voxel in the brain. The performance of each method was assessed by comparing the fMRI results to the EEG focus. The flexible model revealed more significantly activated voxels, which resulted in more activated brain regions concordant with the EEG focus (26 vs. 16). Correction for cardiac effects improved the results in 7 out of the 42 data sets. Furthermore, design theory for event-related experiments was applied in order to determine the influence of the number of IEDs and their temporal distribution on the success of an experiment. It appeared that this success is highly dependent upon the number of IEDs present during the recording and less on their temporal spacing. We conclude that the outcome of EEG-fMRI can be improved by using an optimized analytical strategy, but also depends on the number of IEDs occurring during the recording.     

Hemodynamic response (BOLD/fMRI) in focal epilepsy with reference to benzodiazepine effect

We studied a new procedure of BOLD/fMRI acquisition in epilepsy. They use the benzodiazepine effect to achieve a more reliable baseline for statistical analysis. The method works only in the MR domain without EEG correlation. It compares the EPI images during interictal epileptic discharges and the images “inactivated” by benzodiazepine.

The results in five out of eight patients show that this procedure in comparison with the EEG/fMRI method gives a net improvement of spatial definition of BOLD areas. These preliminary results seem to confirm the hypothesis that the better BOLD/fMRI procedure in epilepsy is to make use of physical features of MR that, unlike EEG, is not influenced by the distance of intercerebral sources and consequently allows a more complete and undistorted display of BOLD areas.     

The BOLD response and the gamma oscillations respond differently than evoked potentials: an interleaved EEG-fMRI study

Background  

The integration of EEG and fMRI is attractive because of their complementary precision regarding time and space. But the relationship between the indirect hemodynamic fMRI signal and the more direct EEG signal is uncertain. Event-related EEG responses can be analyzed in two different ways, reflecting two different kinds of brain activity: evoked, i.e. phase-locked to the stimulus, such as evoked potentials, or induced, i.e. non phase-locked to the stimulus such as event-related oscillations. In order to determine which kind of EEG activity was more closely related with fMRI, EEG and fMRI signals were acquired together, while subjects were presented with two kinds of rare events intermingled with frequent distractors. Target events had to be signaled by pressing a button and Novel events had to be ignored.     

EEG-fMRI mapping of asymmetrical delta activity in a patient with refractory epilepsy is concordant with the epileptogenic region determined by intracranial EEG

We studied a patient with refractory focal epilepsy using continuous EEG-correlated fMRI. Seizures were characterized by head turning to the left and clonic jerking of the left arm, suggesting a right frontal epileptogenic region. Interictal EEG showed occasional runs of independent nonlateralized slow activity in the delta band with right frontocentral dominance and had no lateralizing value. Ictal scalp EEG had no lateralizing value. Ictal scalp EEG suggested right-sided central slow activity preceding some seizures. Structural 3-T MRI showed no abnormality. There was no clear epileptiform abnormality during simultaneous EEG-fMRI. We therefore modeled asymmetrical EEG delta activity at 1-3 Hz near frontocentral electrode positions. Significant blood oxygen level-dependent (BOLD) signal changes in the right superior frontal gyrus correlated with right frontal oscillations at 1-3 Hz but not at 4-7 Hz and with neither of the two frequency bands when derived from contralateral or posterior electrode positions, which served as controls. Motor fMRI activations with a finger-tapping paradigm were asymmetrical: they were more anterior for the left hand compared with the right and were near the aforementioned EEG-correlated signal changes. A right frontocentral perirolandic seizure onset was identified with a subdural grid recording, and electric stimulation of the adjacent contact produced motor responses in the left arm and after discharges. The fMRI localization of the left hand motor and the detected BOLD activation associated with modeled slow activity suggest a role for localization of the epileptogenic region with EEG-fMRI even in the absence of clear interictal discharges.     

Coupling of simultaneously acquired electrophysiological and haemodynamic responses during visual stimulation

We investigate the relationship between the temporal variation in the magnitude of occipital visual evoked potentials (VEPs) and of haemodynamic measures of brain activity obtained using both blood oxygenation level dependent (BOLD) and perfusion sensitive (ASL) functional magnetic resonance imaging (fMRI). Volunteers underwent a continuous BOLD fMRI scan and/or a continuous perfusion-sensitive (gradient and spin echo readout) ASL scan, during which 30 second blocks of contrast reversing visual stimuli (at 4 Hz) were interleaved with 30 second blocks of rest (visual fixation). Electroencephalography (EEG) and fMRI were simultaneously recorded and following EEG artefact cleaning, VEPs were averaged across the whole stimulation block (120 reversals, VEP₁₂₀) and at a finer timescale (15 reversals, VEP₁₅). Both BOLD and ASL time-series were linearly modelled to establish: (1) the mean response to visual stimulation, (2) transient responses at the start and end of each stimulation block, (3) the linear decrease between blocks, (4) the nonlinear between-block variation (covariation with VEP₁₂₀), (5) the linear decrease within block and (6) the nonlinear variation within block (covariation with VEP₁₅).     

Gradient induced artifacts in simultaneous EEG-fMRI: Effect of synchronization on spiral and EPI k-space trajectories

The nature of the gradient induced electroencephalography (EEG) artifact is analyzed and compared for two functional magnetic resonance imaging (fMRI) pulse sequences with different k-space trajectories: echo planar imaging (EPI) and spiral. Furthermore, the performance of the average artifact subtraction algorithm (AAS) to remove the gradient artifact for both sequences is evaluated. The results show that the EEG gradient artifact for spiral sequences is one order of magnitude higher than for EPI sequences due to the chirping spectrum of the spiral sequence and the dB/dt of its crusher gradients. However, in the presence of accurate synchronization, the use of AAS yields the same artifact suppression efficiency for both pulse sequences below 80 Hz. The quality of EEG signal after AAS is demonstrated for phantom and human data. EEG spectrogram and visual evoked potential (VEP) are compared outside the scanner and use both EPI and spiral pulse sequences. MR related artifact residues affect the spectra over 40 Hz (less than 0.2 μV up to 120 Hz) and modify the amplitude of P1, N2 and P300 in the VEP. These modifications in the EEG signal have to be taken into account when interpreting EEG data acquired in simultaneous EEG-fMRI experiments.     

Choosing Strategies to Deal with Artifactual EEG Data in Children with Cognitive Impairment

Rett syndrome is a disease that involves acute cognitive impairment and, consequently, a complex and varied symptomatology. This study evaluates the EEG signals of twenty-nine patients and classify them according to the level of movement artifact. The main goal is to achieve an artifact rejection strategy that performs well in all signals, regardless of the artifact level. Two different methods have been studied: one based on the data distribution and the other based on the energy function, with entropy as its main component. The method based on the data distribution shows poor performance with signals containing high amplitude outliers. On the contrary, the method based on the energy function is more robust to outliers. As it does not depend on the data distribution, it is not affected by artifactual events. A double rejection strategy has been chosen, first on a motion signal (accelerometer or EEG low-pass filtered between 1 and 10 Hz) and then on the EEG signal. The results showed a higher performance when working combining both artifact rejection methods. The energy-based method, to isolate motion artifacts, and the data-distribution-based method, to eliminate the remaining lower amplitude artifacts were used. In conclusion, a new method that proves to be robust for all types of signals is designed.     

Experimental study of the time-dependent rate of K → πππ

The time-dependence of the decay rate of initially pure K⁰ into the final state (π⁺π⁻π⁰) has been studied in search for the decay k_S⁰→π⁺π⁻π⁰. No evidence is found in a sample of 384 observed events. The ratio of the CP -violating K_S⁰ amplitude and the K_L⁰ amplitude is η₊₋₀ = (0.13_−0.20^+0.17) + i(0.17_−0.26^+0.27); the ratio of the CP-conserving K_S⁰ amplitude and the K_L⁰ amplitude is < 0.4. The energy dependence of the K⁰→π⁺π⁻π⁰ matrix element is found to be a₊₋₀ = −0.31 ± 0.03.     

An empirical investigation of motion effects in eMRI of interictal epileptiform spikes

We recently developed a functional neuroimaging technique called encephalographic magnetic resonance imaging (eMRI). Our method acquires rapid single-shot gradient-echo echo-planar MRI (repetition time=47 ms); it attempts to measure an MR signal more directly linked to neuronal electromagnetic activity than existing methods. To increase the likelihood of detecting such an MR signal, we recorded concurrent MRI and scalp electroencephalography (EEG) during fast (20-200 ms), localized, high-amplitude (>50 μV on EEG) cortical discharges in a cohort of focal epilepsy patients. Seen on EEG as interictal spikes, these discharges occur in between seizures and induced easily detectable MR magnitude and phase changes concurrent with the spikes with a lag of milliseconds to tens of milliseconds. Due to the time scale of the responses, localized changes in blood flow or hemoglobin oxygenation are unlikely to cause the MR signal changes that we observed. While the precise underlying mechanisms are unclear, in this study, we empirically investigate one potentially important confounding variable — motion. Head motion in the scanner affects both EEG and MR recording. It can produce brief “spike-like” artifacts on EEG and induce large MR signal changes similar to our interictal spike-related signal changes. In order to explore the possibility that interictal spikes were associated with head motions (although such an association had never been reported), we had previously tracked head position in epilepsy patients during interictal spikes and explicitly demonstrated a lack of associated head motion. However, that study was performed outside the MR scanner, and the root-mean-square error in the head position measurement was 0.7 mm. The large inaccuracy in this measurement therefore did not definitively rule out motion as a possible signal generator. In this study, we instructed healthy subjects to make deliberate brief (<500 ms) head motions inside the MR scanner and imaged these head motions with concurrent EEG and MRI. We compared these artifactual MR and EEG data to genuine interictal spikes. While per-voxel MR and per-electrode EEG time courses for the motion case can mimic the corresponding time courses associated with a genuine interictal spike, head motion can be unambiguously differentiated from interictal spikes via scalp EEG potential maps. Motion induces widespread changes in scalp potential, whereas interictal spikes are localized and have a regional fall-off in amplitude. These findings make bulk head motion an unlikely generator of the large spike-related MR signal changes that we had observed. Further work is required to precisely identify the underlying mechanisms.     

Source-to-sensation level ratio of transmitted biosonar pulses in an echolocating false killer whale

Transmitted biosonar pulses, and the brain auditory evoked potentials (AEPs) associated with those pulses, were synchronously recorded in a false killer whale Pseudorca crassidens trained to accept suction-cup EEG electrodes and to detect targets by echolocation. AEP amplitude was investigated as a function of the transmitted biosonar pulse source level. For that, a few thousand of the individual AEP records were sorted according to the spontaneously varied amplitude of synchronously recorded biosonar pulses. In each of the sorting bins (in 5-dB steps) AEP records were averaged to extract AEP from noise; AEP amplitude was plotted as a function of the biosonar pulse source level. For comparison, AEPs were recorded to external (in free field) sound pulses of a waveform and spectrum similar to those of the biosonar pulses; amplitude of these AEPs was plotted as a function of sound pressure level. A comparison of these two functions has shown that, depending on the presence or absence of a target, the sensitivity of the whale's hearing to its own transmitted biosonar pulses was 30 to 45 dB lower than might be expected in a free acoustic field.     

BOLD functional MRI in disease and pharmacological studies: room for improvement?

In the past decade the use of blood oxygen level-dependent (BOLD) fMRI to investigate the effect of diseases and pharmacological agents on brain activity has increased greatly. BOLD fMRI does not measure neural activity directly, but relies on a cascade of physiological events linking neural activity to the generation of MRI signal. However, most of the disease and pharmacological studies performed so far have interpreted changes in BOLD fMRI as "brain activation," ignoring the potential confounds that can arise through drug- or disease-induced modulation of events downstream of the neural activity. This issue is especially serious in diseases (like multiple sclerosis, brain tumours and stroke) and drugs (like anaesthetics or those with a vascular action) that are known to influence these physiological events. Here we provide evidence that, to extract meaningful information on brain activity in patient and pharmacological BOLD fMRI studies, it is important to identify, characterise and possibly correct these influences that potentially confound the results. We suggest a series of experimental measures to improve the interpretability of BOLD fMRI studies. We have ranked these according to their potential information and current practical feasibility. First-line, necessary improvements consist of (1) the inclusion of one or more control tasks, and (2) the recording of physiological parameters during scanning and subsequent correction of possible between-group differences. Second-line, highly recommended important aim to make the results of a patient or drug BOLD study more interpretable and include the assessment of (1) baseline brain perfusion, (2) vascular reactivity, (3) the inclusion of stimulus-related perfusion fMRI and (4) the recording of electrophysiological responses to the stimulus of interest. Finally, third-line, desirable improvements consist of the inclusion of (1) simultaneous EEG-fMRI, (2) cerebral blood volume and (3) rate of metabolic oxygen consumption measurements and, when relevant, (4) animal studies investigating signalling between neural cells and blood vessels.     

高功率毫米波辐照大鼠失能效应的脑电观察

使用高功率8毫米波辐照清醒的大鼠,同时测量其脑电图。用小波进行多分辨分析,将脑电信号分解成各个节律信号,分析其变化。辐照时,大鼠出现了非节律性的高幅δ波,而且在慢波中夹杂着癫痫样放电,这说明大鼠在受到辐照时产生高度节律紊乱,提示了其受到强烈刺激而进入失能状态。大鼠受到辐照时失能期为辐照第(1.3±0.5)s到(17.2±2.3)s,辐照于30 s时结束,第(62.7±2.6)s时,其脑电图开始恢复。结果表明:大鼠受到高功率毫米波辐照时最佳失能发生在表皮温升较快、表皮损伤较轻的时候,过长时间的辐照不会延长其失能时间,反而会导致其损伤加大。因此,应用高功率毫米波的失能效应时须控制一定剂量。     

Changes of summating potentials in the guinea pig cochlea after impulse sound exposure

Compound action potentials(CAP)and action potential-summatingpotential complex(AP-SP)evoked by click and tone burst respectively were re-corded from the round window in guinea pigs.Correlations between the posi-tive and negative summating potentials(SP and SP-)were examined beforeand after impulse sound exposure.The results show that the SP- is related tothe threshold shift of CAP.In comparison to normal condtion,it appears witha high incidence when the auditory threshold shift reaches 30 dB or more.SP-increases in amplitude when SP decreases.The smaller the amplitude of SP ,the larger that of SP-.This suggests that in normal hearing condition SP- maybe suppressed by SP .Such suppression may be released if OHCs are injured.The dominant SP- as a sign of recruitment may be due to the change in thenonlinear character of IHC following OHC damage.     

fMRI在经颅直流电刺激研究中的应用进展

经颅直流电刺激（tDCS）是一种新颖的神经系统疾病治疗手段,可非侵入性调控中枢神经活动.它具有安全、成本低、疗效显著等特点,因此在神经科学等领域被大量研究和应用.功能磁共振成像（fMRI）具备高时空分辨率的优势,近年来被广泛用于tDCS治疗效果的评估及其作用机制的研究.本文从临床研究与动物模型实验两方面总结fMRI技术应用于tDCS研究中的最新进展,并讨论其应用前景.     

Brain oscillatory activity during motor imagery in EEG-fMRI coregistration

The purpose of the present work was to investigate the correlation between topographical changes in brain oscillatory activity and the blood oxygenation level-dependent (BOLD) signal during a motor imagery (MI) task using electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) coregistration.