'Big Picture' Of Brain Changes May Be Crucial To Recovery From Stroke Injury

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

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

"Soon after the injury, thesepatients may forget to shave the left side of their face, fail to eatfood on the left side of a plate or seem to be unaware of their leftarm," says Corbetta, who is clinical director of the Stroke and BrainInjury Program at the Rehabilitation Institute of St. Louis, where thepatients were recruited. "But if you explicitly tell them to payattention to the left side, then for a brief time they can. It's as iftheir brain can voluntarily overcome the impairment, but thatrebalancing act is very temporary."

The condition, which annuallyafflicts an estimated 3 to 5 million patients worldwide, is typicallymost acute in the days and weeks immediately following a stroke but canbecome a chronic problem. Approximately 90 percent of all cases ofspatial neglect are linked to right-brain injuries and lead todifficulty paying attention to the left side; however, the conditioncan also result from left-brain injury and undermine right-sideattention.

Clinicians who treat patients with stroke and othertraumatic brain injury traditionally have looked to changes in patientbehavior and abilities as indicators of the functions normallyperformed by the area impacted by the injury. However, because eachbrain area is connected to many others, some researchers have suggesteda theory of distributed injury.

Previous studies have providedonly circumstantial evidence for the theory, which notes that brainregions can only perform their functions properly through connectionswith other brain regions. Alter the function of one brain regionthrough injury, the theory proposes, and the connections that usuallyenable normal function will lead to alterations in the function ofother potentially distant brain areas.

To determine ifdistributed injury plays a role in stroke patients with spatialneglect, Corbetta and his colleagues took functional magnetic resonanceimaging scans of patients as they performed a series of tests of theirability to pay attention to visual targets, one of the cognitiveabilities most severely impaired by spatial neglect. Researchersscanned patients' brains during these tasks one month after injury andagain six months later, when many had recovered from the problem tosome extent.

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

"Although all patientsin this study had right-side injuries, at one month post-injury wefound increases in activity in attention-controlling centers of thebrain's left hemisphere, as well as sharp decreases in activity incorresponding areas of the injured hemisphere," Corbetta says. "Wecould also detect functional changes in activity in visual areaslocated at the back of the head—as far as 10 to 15 centimeters awayfrom the injury site."

These activity changes in distant brainregions were correlated with the severity of impairment in visualtarget detection, providing direct evidence for the distributed injurytheory.

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

Corbettasays these results show that the ability to pay attention to theenvironment and be aware of one's body depends on a competive balancebetween the two halves of the brain. Normally, attention-controllingregions on each side of the brain actively compete with each other toestablish a balance that can temporarily be shunted to one side or theother. In the aftermath of injury, the uninjured hemisphere becomeshyperactive, pulling the brain's attention away from the side normallyattended by the injured — and now less active — hemisphere.

Inpatients who do not recover well from spatial neglect, Corbettaspeculates that devices known as transcranial magnetic stimulators maybe able to help. The stimulators can be used to decrease activity in aparticular region of the brain. If physicians can use them to reducehyperactivity in the left brain's attention-controlling centers, thatmay help the patient's brain more quickly establish a balance betweenthe competing centers and give a more normal share of attention to bothleft and right sides.

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

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Corbetta M, Kincade MJ, Lewis C, Snyder AZ, Sapir A. Neural basisand recovery of spatial attention deficits in spatial neglect. NatureNeuroscience, online edition, Oct. 16, 2005.

Funding from the J.S.McDonnell Foundation and the National Institute of Neurological Disorders supported this research.