Thought-reading Computers, Sleep, And Molecular Imaging Advance Stroke Research

"This is an exciting time in stroke research when new technologies that capture brain signals and behavioral interventions including movement therapy and sleep can be harnessed to promote changes in brain activity," says Carolee Winstein, PhD, of the University of Southern California.

"What is challenging and what will be important for the future of this kind of research is to identify those effects which promote positive neuroplasticity and recovery from the damaging effects of cerebral stroke," Winstein says.

Scientists say that stroke survivors can use their own thoughts to reorganize their brain's electrical activity so that it will closely mimic the activity pattern of the "normal" side of the brain, the hemisphere that escaped stroke's damaging effects. However, in one study at the National Institute of Neurological Diseases and Stroke (NINDS), reorganizing the brain's activity pattern in that hemisphere did not reduce the paralysis in the stroke-affected hand.

"The utility of manipulating this brain reorganization to help improve or restore hand function in these patients remains uncertain," says Ethan Buch, MA, of NINDS.

After a stroke, abnormal patterns of electrical signals spread throughout both sides of the brain -- not just the hemisphere where the stroke occurred -- when patients try to use their paralyzed hands to grasp objects. Paralysis immobilizes the side of the body associated with the brain hemisphere in which the stroke occurred.

The NINDS scientists trained stroke patients to alter their own brain activity in order to move a cursor up or down in the direction of the target on a computer screen. A computer translated the patient's brain signals into the cursor's up or down movements. During these sessions, the patients wore a mechanical glove on their paralyzed hands.

If a patient hit the target with the cursor, the glove would open or close the hand, depending on the target appearing on the screen. The mechanical glove opened and closed only in response to the brain signals that originated in the stroke-affected hemisphere. The glove passively manipulated the patient's paralyzed hand to perform grasping motions that moved a cursor up or down in the direction of the target on a computer screen.

"The cursor was a visual representation of the brain signal that the patients are attempting to control," Buch says. "Modulation of this brain signal, and hence the cursor movement, determined the action of the glove."

The scientists succeeded in training six of the eight stroke survivors enrolled in the study to use the glove to normalize their own brain activation patterns. "By enhancing or diminishing these signals, the patient was able to operate the glove and open or close their hand, respectively," Buch says.

The abnormal signal pattern that emerges when a stroke survivor tries to use the paralyzed hand is believed to be the brain's adaptation to the stroke. Previous research has shown a direct relationship between the amount of abnormal activation and the magnitude of movement impairment.

"However, it is not known if this brain reorganization mediates recovery, or the lack thereof, or is merely a reflection of the disability," Buch says.

In another study, scientists found that the abnormal sense of balance and walking patterns, or gait, that afflict many survivors of stroke and traumatic brain injury were much less in a group of patients whose rehabilitation therapy used an experimental sensory substitution device. This pilot study included 10 patients.

The balance device, BrainPort®, used a sensor to detect head position, which activated electrodes on an array placed on the top of the tongue. The stimulus, which correlated to head and body tilt, cued the patient to correct his or her body position to improve balance.

During training, patients learned to use the feedback by trying to correct their body position in order to keep the stimulus centered on the tongue. The electrical stimulation of the tongue substitutes for the vestibular or balance system, which is often damaged by stroke and traumatic brain injury. This sensory system provides the dominant input about our movement and orientation in space.

Based on positive results of this pilot study, the device's developer, Wicab, Inc., says a controlled, multisite study is planned to determine the efficacy and feasibility of long-term BrainPort® training in rehabilitating stroke and traumatic brain injury patients.

The pilot study trained and evaluated eight patients in Wisconsin and seven in New Jersey. Training sessions included several brief trials of one to five minutes each, followed by one 20-minute trial involving the patient in progressively challenging positions while using the device.

Borrowing the standard tests that physical therapists use to measure balance, the scientists evaluated the patients before training began and after the last training session. Both the patients' subjective reports and the researchers' observations were documented. Some patients continued to use the device independently at home for up to five months.

In all 10 patients, improvement occurred in at least one area, and no negative side effects were noted, says Monica Metea, PhD, of Wicab, Inc. "Taken together, the improvements in test scores are 'clinically significant,' which is an indication of improvement," she says.

"Currently, many people with balance problems because of stroke or traumatic brain injury reach a plateau with conventional therapy," says Metea, adding that the BrainPort® may help patients improve faster or beyond the plateau period.

In another study, scientists for the first time compared motor training for only the paralyzed arm with training using both of the arms moving together symmetrically, says doctoral candidate Mary Ellen Stoykov, MS, OTR/L, of the University of Illinois-Chicago and the Rehabilitation Institute of Chicago.

Bilateral training, involving both the paralyzed arm and the fully functioning arm, has been proposed as a potentially more effective rehabilitation intervention to help more stroke survivors. Currently only 30 to 62 percent of patients regain any functional use of their arm after six months of rehabilitation, according to long-term studies.

A total of 24 stroke patients participated in the new study, which required either unilateral or bilateral training sessions three times a week for eight weeks. For 12 patients in the study group, the training involved both the paralyzed arm and the fully functioning arm. The 12 other patients used only their impaired arm during the training sessions, which emphasized continuous, rhythmic movements and included reaching and pointing to various targets in the work space, opening and closing drawers, and pushing and pulling movements. Auditory cueing with a metronome facilitated the continuous rhythmic movement.

To determine whether improvements occurred due to the training, the scientists measured each patient's strength and range of motion as well as arm motor function. Stoykov says that the results showed a significant advantage for the bilateral group for improving shoulder function and strength. However, both groups made considerable gains in overall arm motor function. While unilateral and bilateral training were both effective, Stoykov notes that the improvements observed in both groups may have been due to the nature of the activities, which included continuous, cyclical movements paced with the metronome.

A good night's sleep is generally believed to help older stroke survivors as well as healthy, young individuals to remember motor skills that they were taught that day. However, a new study also shows that sleep is even more important to stroke survivors because it helps them to remember new skills when explicit instructions are not given.

"You practice something, you sleep, and then you do it better," says doctoral candidate Catherine Siengsukon, PT, who conducted the study, which was the first to examine the interaction of sleep and the type of instruction given for learning a new motor task after stroke.

"Understanding the role of sleep in memory consolidation and learning in the damaged brain has tremendous implications for rehabilitation and recovery from stroke," she says.

This new research data may change the way therapists teach motor skills to patients who have suffered from a stroke and may help insure that training sessions during research studies as well as clinical treatment are scheduled so that each is followed by a good night's sleep.

"Sleep may be the reason that the motor skills improve between sessions when overnight delays are built into research designs," she adds.

The study, conducted at the University of Kansas Medical Center, included 31 stroke survivors. One group practiced a continuous tracking task in the evening and then underwent a retest the following morning. Another group of participants practiced the tracking task in the morning and conducted the retest the same day in the evening. Prior to practice of the tracking task, half of the participants received instructions regarding the presence of a repeating wave pattern (explicit instruction condition) while the other half did not (implicit condition).

"We discovered that both sleep and the type of instruction provided influenced memory consolidation of a continuous tracking task following stroke," Siengsukon says.

Sleep enhanced learning of explicit motor skills. In previous studies, sleep did not help young, healthy people with implicit motor learning. But in this study, sleep also benefited the older individual's implicit motor learning after stroke.

In studies using molecular imaging techniques, Stanford University scientists have demonstrated in live rodents that the process of new blood vessel formation in the brain starts very early after strokes occur.

These results suggest that molecular imaging and other technologies that enable scientists to visualize and quantify biological processes at the cellular and molecular level as they occur could accelerate the application of drug or cell-based therapies to improve the brain's formation of the blood vessels that help repair brain damage from stroke and other neurological disorders, says Raphael Guzmán, MD, of Stanford University.

"To date, we don't know the timing or the ideal place for cell or drug delivery in potential future clinical stroke trials," explains Guzmán. "It is conceivable that molecular imaging techniques not only will help us monitor the therapy's effects but also will help us define patient specific treatment strategies."

Through in vivo molecular imaging, Guzmán says, scientists also may be able to identify early molecular and biological activities that predict clinical outcome of a specific therapy -- for example, transplants of human stem cells to replace brain cells to enhance new blood vessel formation in brain tissue damaged by stroke.

In this collaborative project between the neurosurgery department and the molecular imaging program at Stanford, scientists analyzed the time course and natural kinetics of the cell receptor vascular endothelial growth factor receptor. The ligand to this receptor, the protein vascular endothelial growth factor, plays an important role in neurovascular repair after stroke. This noninvasive study was conducted in a rat experimental stroke model.