Epilepsy patients exhibit altered brain connections, study shows

Patients with the most common form of focal epilepsy exhibit widespread, abnormal connections in their brains, according to a Radiology study published today by a team of researchers at the MGH Martinos Center for Biomedical Imaging in Boston. The new findings could help to advance diagnosis and treatment of the condition.

The study looked at patients suffering temporal lobe epilepsy, a condition characterized by recurrent seizures arising from one or both temporal lobes of the brain. Previously, researchers believed this stemmed from isolated injuries of structures within the temporal lobe. But recent investigations point to the involvement of the default mode network, or DMN, a set of brain regions that are active during the resting state.

The implication of these regions led the Martinos Center group to apply a unique approach to ‘connectomics,’ the high-speed, high-throughput mapping of neural connections in the brain. “Epilepsy may be the best example of an abnormal human connectome,” said Steven M. Stufflebeam, MD, director of clinical MEG at the Martinos Center and principal investigator of the Radiology study, “so it was a natural thing to study with connectomics.”

The study grew out of earlier research by Stufflebeam and colleagues, who several years ago published a paper demonstrating the functional abnormalities of the DMN. Following this research, Matthew N. DeSalvo, MD, then a Harvard Medical School student and the first author of the paper published today, decided to use network theory to investigate abnormalities in the structural connections.

To this end, the researchers performed diffusion tensor imaging (DTI) on 24 patients with left temporal lobe epilepsy who were scheduled to have surgery to remove the site from which the seizures emanated. DTI – developed at the Martinos Center and now used for brain imaging studies the world over – is a type of MRI that tracks diffusion of water in the brain’s white matter and thus allows imaging of the neural tracts connecting distant regions of the brain. The researchers compared these data with those from 24 healthy controls, analyzing the results with a novel technique designed to identify and quantify structural connections in the brain.

The analyses indicated that the abnormal connections are even more widespread than previously thought. “Using diffusion tensor imaging, we found alterations in the structural connectivity beyond the medial temporal lobe, particularly in the default mode network,” Stufflebeam said.

They also revealed an 85 to 270 percent increase in local connectivity both within and beyond the DMN. The researchers note that this may be an adaptation to the loss of the long-range connections.

Stufflebeam and DeSalvo and colleagues continue to explore the widespread, abnormal connections, using the Connectom MRI at the Martinos Center to better define these connections in other types of epilepsy. The Connectom, which utilizes exceptionally strong gradients to enhance data acquisition with both structural and functional images, is the only one of its kind and thus offers a unique opportunity to study the connections.

“The Connectom can image crossing white matter fibers with more precision,” Stufflebeam said. “Because it was designed specifically to do diffusion MRI, which requires a tremendous amount of power, it will allow us to image white matter connections more accurately and at a higher resolution.”