September 14, 2010

September 14, 2010 (San Francisco, California) — Specialists are gaining new insights about the brain that are revolutionizing the field and beginning to have an effect on practice. Presenting here at the American Neurological Association 135th Annual Meeting, experts described how new diagnostic technologies such as functional magnetic resonance, diffusion tensor imaging, tractography, magnetoencephalography, and optical imaging are already redefining neurologic disease.

A growing understanding of network and regional brain connectivity are redefining neurologic and psychiatric diseases.

"We're starting to see there is an entire brain response to disease, and that much more is affected than just the site of injury," session chair Frances Jensen, MD, from Harvard University in Boston, Massachusetts, told Medscape Medical News. "We're learning there is actually a structural reorganization that takes place in the brain."

Those changes to network and regional brain connectivity are reportedly present in stroke, dementia, epilepsy, and even neuropsychiatric illnesses.

"We can think of anatomical connectivity like a highway," Maurizio Corbetta, MD, from Washington University in St. Louis, Missouri, said at the meeting. "Functional connectivity is also like a highway, but is weighted by traffic," he explained, noting that heavy traffic leads to high connectivity, and light traffic to low connectivity.

"A network that fires together, wires together, and might even expire together," he suggests.

Dr. Corbetta says that stroke and brain injury produce changes in functional connectivity even in regions of the brain that are not structurally damaged. Still, these physiological changes result in behavioral deficits.

Dr. Corbetta won the Foster Elting Bennett Memorial Lectureship Award for outstanding researchers and educators at the meeting.

Blurring Line Between Neurology and Psychiatry

This increasing understanding has called into question some of the arbitrary division between specialties. "The line between neurology and psychiatry is fading," Dr. Jensen said during an interview.

Dr. Frances Jensen

"In recent years, there is a growing appreciation of large-scale brain networks that support active human mentation," said presenter John Gabrieli, PhD, from the Massachusetts Institute of Technology in Cambridge.

Neuroimaging studies have historically concentrated on localizing mental functions in the brain. However, a growing appreciation of network and regional brain connectivity is shifting that focus. Imaging tools can now be used to examine developmental disorders such as dyslexia, autism, and attention-deficit hyperactivity disorder.

At the meeting here, Dr. Gabrieli described resting-state connectivity of the default-mode network, brain regions associated with introspection. He showed how this network is chronically hyperactivated and hyperconnected in patients with schizophrenia.

When healthy people are at rest, Dr. Gabrieli explained, the medial dorsolateral and prefrontal cortices are not correlated, but in patients with schizophrenia and bipolar disorder, they are linked. This may also explain cognitive dysfunction in both disorders.

Michael Greicius, MD, from Stanford University in Palo Alto, California, also addressed the default-mode network of the brain during his talk on Alzheimer's disease. The posterior regions of the default-mode network tend to overlap considerably with brain regions that show reduced glucose metabolism in the earliest stages of Alzheimer's disease, he pointed out, and even in young, healthy individuals at increased risk.

The default-mode network can be detected, characterized, and quantified using resting-state functional magnetic resonance imaging, Dr. Greicius noted. This measures interregional temporal correlations in signal fluctuations.

"Using these functional connectivity approaches, our group and others have demonstrated reduced functional connectivity in the default-mode network in Alzheimer's disease, mild cognitive impairment, healthy older controls with prominent amyloid plaque burden, and healthy older carriers of the ApoE4 allele," he said.

In addition to functional changes, this brain network also appears to undergo structural changes and overlap to some degree with maps of amyloid plaque distribution, Dr. Greicius explained.

Connectivity may also be altered in epilepsy, Ellen Grant, MD, from Harvard University, pointed out at the meeting. Dr. Grant showed how multiple modalities can be combined with conventional neurophysiology to understand seizure spread.

This work is in practical use right now in epilepsy.

"This work is in practical use right now in epilepsy," Dr. Jensen added. "Epilepsy is a major connectivity disorder, and these imaging techniques are already being applied to patients."

The optimal management of a patient with epilepsy includes determining the focus of ictal onset and evaluating the extent of network involvement, Dr. Grant said at the meeting.

"Currently, 3T imaging with 32 channel coils and motion-corrected sequences provide the highest-quality images for detection of subtle structural lesions," she said. "But confirming ictal onset from identified structural lesions currently requires electroencephalography, magnetoencephalography, and intracranial grids and depth electrodes for validation."

Evaluating functional network involvement is performed with functional magnetic resonance imaging, neurological exam, and neuropsychological testing, as well as Wada tests in some centers, she notes.

"I hope clinicians will understand that the patient in front of them who is dealing with a deficit has this issue not only from a structural lesion, but also network involvement," Alex Carter, MD, who works with Dr. Corbetta at Washington University, told Medscape Medical News.

"We now have tools to assess these secondary abnormalities that we were previously unable to even look for," he noted.

The presenters have disclosed no relevant financial relationships.

American Neurological Association 135th Annual Meeting: Neurobiology of Disease Symposium. Presented September 12, 2010.