Brain injury can cause detrimental functional changes in brain regions far from the site of the actual injury

A study of patients who have difficulty paying attention to the left side of their environment has provided some of the first direct evidence that brain injury can cause detrimental functional changes in brain regions far from the site of the actual injury.

"We normally don't consider changes in function beyond the site of brain injuries," says Maurizio Corbetta, M.D., the Norman J. Stupp Professor of Neurology at Washington University School of Medicine in St. Louis and lead author of the paper. "Our findings suggest that looking for functional changes beyond the injury site is critical to understanding the behavioral deficits caused by injury and assessing the options to accelerate recovery from those deficits."

The new study, published online Oct. 16 in Nature Neuroscience, focused on patients with injuries located on the right side of the brain, approximately between the temple and the ear, in areas known as the temporoparietal and ventral frontal cortex. In 25 to 30 percent of stroke patients, injuries in these regions lead to a condition known as spatial neglect.

"Soon after the injury, these patients may forget to shave the left side of their face, fail to eat food on the left side of a plate or seem to be unaware of their left arm," says Corbetta, who is clinical director of the Stroke and Brain Injury Program at the Rehabilitation Institute of St. Louis, where the patients were recruited. "But if you explicitly tell them to pay attention to the left side, then for a brief time they can. It's as if their brain can voluntarily overcome the impairment, but that rebalancing act is very temporary."

The condition, which annually afflicts an estimated 3 to 5 million patients worldwide, is typically most acute in the days and weeks immediately following a stroke but can become a chronic problem. Approximately 90 percent of all cases of spatial neglect are linked to right-brain injuries and lead to difficulty paying attention to the left side; however, the condition can also result from left-brain injury and undermine right-side attention.

Clinicians who treat patients with stroke and other traumatic brain injury traditionally have looked to changes in patient behavior and abilities as indicators of the functions normally performed by the area impacted by the injury. However, because each brain area is connected to many others, some researchers have suggested a theory of distributed injury.

Previous studies have provided only circumstantial evidence for the theory, which notes that brain regions can only perform their functions properly through connections with other brain regions. Alter the function of one brain region through injury, the theory proposes, and the connections that usually enable normal function will lead to alterations in the function of other potentially distant brain areas.

To determine if distributed injury plays a role in stroke patients with spatial neglect, Corbetta and his colleagues took functional magnetic resonance imaging scans of patients as they performed a series of tests of their ability to pay attention to visual targets, one of the cognitive abilities most severely impaired by spatial neglect. Researchers scanned patients' brains during these tasks one month after injury and again six months later, when many had recovered from the problem to some extent.

As expected, both sets of patient scans showed decreased activity in injured areas. But they also revealed changes in other areas that were anatomically intact.

"Although all patients in this study had right-side injuries, at one month post-injury we found increases in activity in attention-controlling centers of the brain's left hemisphere, as well as sharp decreases in activity in corresponding areas of the injured hemisphere," Corbetta says. "We could also detect functional changes in activity in visual areas located at the back of the head--as far as 10 to 15 centimeters away from the injury site."

These activity changes in distant brain regions were correlated with the severity of impairment in visual target detection, providing direct evidence for the distributed injury theory.

In the six-month scans, these changes, including the large spikes in activity in attention centers in the left hemisphere of the brain, had mostly faded away, and the level of activity normalized in parallel to the recovery from attention deficits.

Corbetta says these results show that the ability to pay attention to the environment and be aware of one's body depends on a competive balance between the two halves of the brain. Normally, attention-controlling regions on each side of the brain actively compete with each other to establish a balance that can temporarily be shunted to one side or the other. In the aftermath of injury, the uninjured hemisphere becomes hyperactive, pulling the brain's attention away from the side normally attended by the injured -- and now less active -- hemisphere.

In patients who do not recover well from spatial neglect, Corbetta speculates that devices known as transcranial magnetic stimulators may be able to help. The stimulators can be used to decrease activity in a particular region of the brain. If physicians can use them to reduce hyperactivity in the left brain's attention-controlling centers, that may help the patient's brain more quickly establish a balance between the competing centers and give a more normal share of attention to both left and right sides.

"We need to start looking at recovery of function as a dynamic process in which neural systems on both sides of the brain reach a new equilibrium point," Corbetta says.

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