A cable theory based biophysical model of resistance change in crab peripheral nerve and human cerebral cortex during neuronal depolarisation: implications for electrical impedance tomography of fast neural activity in the brain.

Electrical impedance tomography (EIT) is a medical imaging method with the potential to image resistance changes which occur during neuronal depolarisation in the brain with a resolution of milliseconds and millimetres. Most biomedical EIT is conducted with applied current over 10 kHz, as this reduces electrode impedance and so instrumentation artefact. However, impedance changes during neuronal depolarization are negligible at such frequencies. In order to estimate optimal recording frequency and specify instrumentation requirements, we have modelled their amplitude and frequency dependence during evoked activity using cable theory. Published values were used for the electrical properties and geometry of cell processes. The model was adjusted for the filtering effect of membrane capacitance and proportion of active neurons. At DC, resistance decreases by 2.8 % in crab nerve during the compound action potential and 0.6 % (range 0.06-1.7 %) locally in cerebral cortex during evoked physiological activity. Both predictions correlate well with independent experimental data. This encourages the view that true tomographic imaging of fast neural activity in the brain is possible, at least with epicortical electrodes in the first instance. It is essential to undertake this at low frequencies below about 100 Hz as above 1 kHz the signal becomes vanishingly small.

Looking for neuronal currents using MRI: an EEG-fMRI investigation of fast MR signal changes time-locked to frequent focal epileptic discharges.

RATIONALE: Reproducible direct measurement of neuronal electrical activity using MRI signal changes due to local magnetic field perturbations would represent a step change in neuroimaging methods. While some previous studies using experiments based on evoked and spontaneous activity provided encouraging results no clear demonstration of neuronal current-related MR changes in the human brain has emerged to date. The availability of simultaneously acquired EEG-fMRI in patients with frequent interictal epileptic discharges (IED), which have significantly greater amplitude than evoked potentials, offers the opportunity to further investigate the phenomenon. METHODS: We re-analysed simultaneously acquired EEG-fMRI data in 6 epilepsy patients with very frequent focal IED and a well-localised generator. A model of MRI signal changes due to fast activity and BOLD signal changes was used to identify fast MR signal changes, potentially directly reflecting neuronal activity. Simultaneously-acquired EEG allowed the comparison of electrical source localisation (ESI), clinical epilepsy localisation and BOLD signal changes with the fast MR signal changes. RESULTS: Clusters of IED-related fast MR signal change were observed in all cases. Spatial correspondence between the IED-related fast MR, BOLD, ESI clusters and irritative zone (IZ) was observed in one slice of a single dataset. The other IED-related fast MR clusters were remote from electro-clinically determined generators of interictal activity. The sign and magnitude of the fast MR signal changes varied across regions and subjects. CONCLUSION: The observed fast MR changes cannot be confidently attributed to the direct effect of neuronal currents due to lack of spatial concordance with generators of interictal activity, IED-related BOLD clusters and ESI estimates.

Hemodynamic correlates of epileptiform discharges: an EEG-fMRI study of 63 patients with focal epilepsy.

Using continuous EEG-correlated fMRI, we investigated the Blood Oxygen Level Dependent (BOLD) signal correlates of interictal epileptic discharges (IEDs) in 63 consecutively recruited patients with focal epilepsy. Semi-automated spike detection and advanced modeling strategies are introduced to account for different EEG event types, and to minimize false activations from uncontrolled motion. We show that: (1) significant hemodynamic correlates were detectable in over 68% of patients in whom discharges were captured and were highly, but not entirely, concordant with site(s) of presumed seizure generation where known; (2) deactivations were less concordant and may non-specifically reflect the consequential or downstream effects of IEDs on brain activity; (3) a striking pattern of retrosplenial deactivation was observed in 7 cases mainly with focal discharges; (4) the basic hemodynamic response to IEDs is physiological; (5) incorporating information about different types of IEDs, their durations and saturation effects resulted in more powerful models for the detection of fMRI correlates; (6) focal activations were more likely when there was good electroclinical localization, frequent stereotyped spikes, less head motion and less background EEG abnormality, but were also seen in patients in whom the electroclinical focus localization was uncertain. These findings provide important new information on the optimal use and interpretation of EEG-fMRI in focal epilepsy and suggest a possible role for EEG-fMRI in providing new targets for invasive EEG monitoring.

EEG-fMRI of idiopathic and secondarily generalized epilepsies.

We used simultaneous EEG and functional MRI (EEG-fMRI) to study generalized spike wave activity (GSW) in idiopathic and secondary generalized epilepsy (SGE). Recent studies have demonstrated thalamic and cortical fMRI signal changes in association with GSW in idiopathic generalized epilepsy (IGE). We report on a large cohort of patients that included both IGE and SGE, and give a functional interpretation of our findings. Forty-six patients with GSW were studied with EEG-fMRI; 30 with IGE and 16 with SGE. GSW-related BOLD signal changes were seen in 25 of 36 individual patients who had GSW during EEG-fMRI. This was seen in thalamus (60%) and symmetrically in frontal cortex (92%), parietal cortex (76%), and posterior cingulate cortex/precuneus (80%). Thalamic BOLD changes were predominantly positive and cortical changes predominantly negative. Group analysis showed a negative BOLD response in the cortex in the IGE group and to a lesser extent a positive response in thalamus. Thalamic activation was consistent with its known role in GSW, and its detection in individual cases with EEG-fMRI may in part be related to the number and duration of GSW epochs recorded. The spatial distribution of the cortical fMRI response to GSW in both IGE and SGE involved areas of association cortex that are most active during conscious rest. Reduction of activity in these regions during GSW is consistent with the clinical manifestation of absence seizures.

Analysis of EEG-fMRI data in focal epilepsy based on automated spike classification and Signal Space Projection.

Simultaneous acquisition of EEG and fMRI data enables the investigation of the hemodynamic correlates of interictal epileptiform discharges (IEDs) during the resting state in patients with epilepsy. This paper addresses two issues: (1) the semi-automation of IED classification in statistical modelling for fMRI analysis and (2) the improvement of IED detection to increase experimental fMRI efficiency. For patients with multiple IED generators, sensitivity to IED-correlated BOLD signal changes can be improved when the fMRI analysis model distinguishes between IEDs of differing morphology and field. In an attempt to reduce the subjectivity of visual IED classification, we implemented a semi-automated system, based on the spatio-temporal clustering of EEG events. We illustrate the technique's usefulness using EEG-fMRI data from a subject with focal epilepsy in whom 202 IEDs were visually identified and then clustered semi-automatically into four clusters. Each cluster of IEDs was modelled separately for the purpose of fMRI analysis. This revealed IED-correlated BOLD activations in distinct regions corresponding to three different IED categories. In a second step, Signal Space Projection (SSP) was used to project the scalp EEG onto the dipoles corresponding to each IED cluster. This resulted in 123 previously unrecognised IEDs, the inclusion of which, in the General Linear Model (GLM), increased the experimental efficiency as reflected by significant BOLD activations. We have also shown that the detection of extra IEDs is robust in the face of fluctuations in the set of visually detected IEDs. We conclude that automated IED classification can result in more objective fMRI models of IEDs and significantly increased sensitivity.

The MR detection of neuronal depolarization during 3-Hz spike-and-wave complexes in generalized epilepsy.

Previously, an analysis of activations observed in a patient with idiopathic generalized epilepsy using electroencephalogram-correlated functional magnetic resonance imaging (MRI) during runs of 3-Hz generalized spike-wave discharge (GSWD) was presented by Salek-Haddadi. Time-locked, bilateral, thalamic blood oxygenation level-dependent increases were reported to be accompanied by widespread, symmetric, cortical deactivation with a frontal maximum. In light of recent investigations into MRI detection of the magnetic field perturbations caused by neuronal current loops during depolarization, we revisited the analysis of the data of Salek-Haddadi as a preliminary search for a neuroelectric signal. We modeled the MRI response as the sum of a fast signal and a slower signal and demonstrated significant MRI activity at a time scale of the order of 30 ms associated with GSWDs. Further work is necessary before firm conclusions may be drawn about the nature of this signal.

Electrical impedance tomography of human brain function using reconstruction algorithms based on the finite element method.

Electrical impedance tomography (EIT) is a recently developed technique which enables the internal conductivity of an object to be imaged using rings of external electrodes. In a recent study, EIT during cortical evoked responses showed encouraging changes in the raw impedance measurements, but reconstructed images were noisy. A simplified reconstruction algorithm was used which modelled the head as a homogeneous sphere. In the current study, the development and validation of an improved reconstruction algorithm are described in which realistic geometry and conductivity distributions have been incorporated using the finite element method. Data from computer simulations and spherical or head-shaped saline-filled tank phantoms, in which the skull was represented by a concentric shell of plaster of Paris or a real human skull, have been reconstructed into images. There were significant improvements in image quality as a result of the incorporation of accurate geometry and extracerebral layers in the reconstruction algorithm. Image quality, assessed by blinded subjective expert observers, also improved significantly when data from the previous evoked response study were reanalysed with the new algorithm. In preliminary images collected during epileptic seizures, the new algorithm generated EIT conductivity changes which were consistent with the electrographic ictal activity. Incorporation of realistic geometry and conductivity into the reconstruction algorithm significantly improves the quality of EIT images and lends encouragement to the belief that EIT may provide a low-cost, portable functional neuroimaging system in the foreseeable future.