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A new technique combining intracranial electroencephalography (icEEG) with functional magnetic resonance imaging (fMRI) in patients with focal epilepsy reveals widespread changes across the brain in locally recorded epileptic activity. David Carmichael, PhD, from the Institute of Neurology, University of London, United Kingdom, presented preliminary results in 2 patients at the 9th European Congress on Epileptology.

"Our results showed that there is brain activity seen on the fMRI which is distant to the location of the intracranial electrodes which recorded interictal epileptic activity. This suggests we can measure the activity of an epileptic network over a greater range of spatial and temporal scales than previously possible," he told Medscape Medical News.

This is the first time this type of investigation has been conducted in human subjects, the British neurologist noted.

In Dr. Carmichael's study, 2 patients undergoing presurgical evaluation for epilepsy surgery received icEEG-fMRI. As part of their clinical assessment, the investigators implanted electrodes into the temporal lobe of one patient and in the frontal lobe of the other. Electrical signals were then recorded, which provided information on where the seizures might originate.

Before this, the patients received a routine clinical assessment encompassing a battery of tests, including structural MRI, scalp EEG, magnetoencephalography, and neuropsychometric testing to help identify any particular performance-related deficits to facilitate localization of the abnormal area of the brain. This information was used to guide the electrode implantation for icEEG-fMRI.

"Recording electrical activity from directly within the brain means there is exquisite sensitivity to the brain's electrical activity. Because the electrode contacts record from approximately 1 cm of surrounding brain tissue, they provide a precise spatial location," Dr. Carmichael pointed out.

Each patient underwent 2 icEEG-fMRI scans lasting 10 minutes each. Scanning patients with implants requires a careful assessment of safety, Dr. Carmichael explained, and the scan was conducted following a strict safety protocol using a 1.5T scanner, a head RF-coil, low-SAR sequences (≤0.1-W/Kg head-average), and an exact external electrode cable configuration, allowing for 64-channels of invasive EEG to be recorded with MR compatible equipment. Details on the procedure are described at http://www.ncbi.nlm.nih.gov/pubmed/19651221.

Using intracranial electrodes in combination with fMRI gives a better picture of epileptic activity across the brain, Dr. Carmichael reported. "It is impossible to implant the electrodes throughout the whole brain, so in conjunction with the intracranial EEG we have added fMRI, which allows us to measure epileptic activity both very locally with the intracranial electrodes and then look at associated responses over the entire brain," he explained.

The investigators used the technique to identify activity across the brain associated with spikes of interictal activity. After the scan, they identified spikes that signified epileptic activity on the icEEG recording and compared them with the fMRI scan. Comparisons were made between the signal changes seen in the fMRI scan and the icEEG spikes.

"One ongoing clinical question asks to what extent the area of brain in which a seizure starts overlaps with the irritative zone which contains ongoing epileptic activity," remarked Dr. Carmichael.

Although this is an early, proof-of-principle study, it holds promise for application in situations where imaging of the brain needs to be expanded but is limited by the number of electrodes that can be placed in the brain at 1 time.

"It might help in uncovering regions of activity [seen on] the fMRI which may not be where the epileptic events were recorded from. So it may reveal distant areas of activity, and these can then be compared to the patient's outcome following surgery to see if these areas were important in generating seizures. This will be the validation of what these extra areas might tell us and their relevance to the patient," the British researcher told Medscape Medical News.

Commenting on the presentation, Megan McGill, BS, a PhD student at the Comprehensive Epilepsy Center of New York University in New York City, who presented a neuroimaging poster at the meeting, said she found the work represented an interesting intersection between new technology and use in patients.

"Intracranial EEG is more specific than scalp EEGs and allows the researcher to map areas which show seizure activity or any sort of functional activity which can be seen on fMRI as well. Intracranial EEG also allows you to map activity exactly when it occurs, and it can be correlated to a brain image. This has implications for surgical resections and for identifying where seizures are happening," Ms. McGill explained.

Ms. McGill has also researched the brains of patients with epilepsy in the resting state, but she aimed to characterize aberrant networks in people with idiopathic generalized epilepsy and to define and quantify to what extent these networks are different from healthy brains.

Using an fMRI scanner, Ms. McGill looked for regions of the brain that were positively correlated in 15 patients compared with the same areas in 15 age- and sex-matched controls.

"I chose 2 well-established areas of the default mode network (DMN), namely, the posterior cingulate and the ventral anterior cingulate, and found that both controls and patients show that large areas of the DMN show positive correlation when at rest."

However, Ms. McGill also found certain areas in the brains of the patients that showed a much smaller extent of activation, especially in the dorsal medial prefrontal cortex. "Here, not only was there a lack of correlation, but they showed an anticorrelation, and this was unexpected. Their functional connectivity actually appears to be opposite for some reason."

She also discovered a marked difference in an area in the right interparietal sulcus in which 15 of 15 controls showed an anticorrelation, whereas 13 of 15 epilepsy patients showed a positive correlation.  

"People with epilepsy, either because of their seizures or as a precursor to seizures have functional networks which are atypical and show different patterns of activation," added Ms. McGill.

"In addition, even though these patients have normal IQs, they often show deficits in executive functioning attributed to the frontal lobe, so it could be that what we see in the resting state is correlated to specific cognitive deficits," Ms. McGill told Medscape Medical News.

Her next step is to find out if there is any relationship between the degree of cognitive deficit and the degree to which areas of the frontal cortex are different from the rest of the DMN.

Commenting on Ms. McGill's work, Dr. Carmichael said that he and his colleagues had found some default mode changes in patients with temporal lobe focal epilepsy. "In patient 2 [in his study], there were DMN changes. It is not clear if these changes are downstream and caused by a spike or upstream and due to changes in conscious attention, which facilitate spike generation and propagation," he said.

Dr. Carmichael and Ms. McGill have declared no relevant financial relations

Source: Medscape Medical News