To restore neurological function in children who sustain injury to the developing nervous system by accelerating the incorporation of new neurorehabilitation treatments into clinical practice.
In recent years, our understanding of brain plasticity has grown substantially. Work at the Burke Medical Research Institute demonstrates how the developing brain responds to injury and how preserved brain regions take over functions of injured ones. We have also developed procedures to stimulate neural plasticity and improve function in brain-injured animals. The goal of our recovery program is to translate these insights into therapies for children with chronic brain injury.
The strategy of the program is to use patterned neural activity—a fundamental determinant of brain plasticity—to improve the function of the damaged brain. First, we will identify brain connections spared by injury, and then improve the function of those connections using either high-intensity training alone or in combination with electrical brain stimulation. The benefits of this approach have been substantiated in animal studies and preliminary clinical trials. In addition, this approach is practical, safe, and well-tolerated by patients.
The Early Brain Injury Recovery Program consists of two basic science laboratories that study activity-based therapies for brain repair and one clinical laboratory to study these therapies in children. The labs are linked by two common themes: response of the young brain to injury, and repair of the injured brain using activity.
Motor Recovery Laboratory: Led by Jason Carmel, MD, PhD, the lab uses electrical stimulation to promote recovery of movement in rodents with neonatal brain injury. Dr. Carmel is a neurologist and neuroscientist with expertise in recovery of movement using brain electrical stimulation. He has shown that brain stimulation can promote recovery of movement in rodents with brain injury, even when applied long after injury.
Early Brain Injury Recovery Laboratory: Led by Kathleen Friel, PhD, the lab uses non-invasive brain stimulation to promote recovery of movement in children with weakness on one side of the body. Dr. Friel is a neuroscientist with expertise in techniques to safely stimulate the human brain. She has shown that intensive hand therapy not only restores function but also strengthens brain connections in children with cerebral palsy.
Vision Rehabilitation Laboratory: Led by Glen Prusky, PhD, the lab uses visual experience to enhance recovery of vision in rodents with brain injury. Dr. Prusky is a neuroscientist with expertise in the visual system and the role of visual experience in restoring vision. He created Optomotry, a virtual reality system that tests rodents, and enhances visual experience. Remarkably, the visual experience can also restore visual attention in rodents with developmental brain injury.
Our end goal is to enroll children with brain injuries into clinical trials to test new modalities for treatment, such as high intensity training programs and non-invasive brain stimulation. These treatments will employ the understanding gained from basic research programs at the Burke Medical Research Institute to create safe and practical treatments to restore neurological function. For recovery of movement in children with weakness on one side of their bodies, we will test whether brain connections spared by injury can be strengthened with non-invasive brain stimulation. For children with impaired visual attention, we investigate how patterned visual stimulation with a novel computer program can enable them to follow visual stimuli with their eyes. These approaches differ from conventional treatments in that they have been validated in animal models by researchers with a deep understanding of how structured neural activity affects brain plasticity.
Project 1: High intensity training to promote hand function in children with hemiplegic cerebral palsy. Directed by Dr. Kathleen Friel, the goal is to use new methods of hand training to improve function in children with cerebral palsy affecting one half of the body. Dr. Friels’s research focuses on the importance of motor activity in neurorehabilitation. Her laboratory studies how brain structure and function change as children receive hand rehabilitative training. By better understanding brain structure and function in children with CP, it is hoped that scientists will best be able to improve therapies for these children.
Project 2: Transcranial direct current stimulation to promote recovery of hand function in children with hemiplegic cerebral palsy. One way to alter brain excitability is to pass a weak current from a scalp electrode on one side to another electrode on the other side of the head. This technique, called transcranial direct current stimulation (tDCS), has been shown to augment the speed with which healthy adults learn a skilled hand task. tDCS also improves recovery of arm function in adults with stroke. We will apply this promising therapy to children with cerebral palsy affecting one side of the body (hemiplegia). Our first goal will be to determine the safety and feasibility of this intervention. We will also determine which parts of the brain are excited by tDCS and whether this results in better skill learning with the impaired hand. We will apply the tDCS to areas of the brain that are best adapted for restoring control of the impaired hand. This innovative targeting of the therapy is made possible by our understanding of brain changes that occur after early brain injury and by two advanced research techniques. The first technique, magnetic brain stimulation, allows us to map which parts of the brain controls each body part. The second technique uses MRI to map connections between different regions of the brain. We will use these techniques to apply tDCS in the safest and most effective way to restore hand function in children with hemiplegic cerebral palsy.
Project 3: Computer-generated visual stimulation to increase visual attention in children with brain injury. Visual experience is critical for the proper wiring of the visual system and for the acquisition of sight during development. Experience can also be used as therapy to help rewire the visual system and restore sight after brain injury. Studies in the laboratory of Dr. Glen Prusky have used visual experience in rodents to increase brain plasticity and restore visual function in rodents. We have applied the same visual therapy to a child with brain injury and have found remarkable increase in their visual attention. Whereas we are encouraged by this result, we are limited by two factors:
- the interface, which consists of black and white lines that move horizontally, is not very engaging, and
- the system is limited in its ability to measure visual attention.
In this project we intend to address each of these deficiencies in innovative ways. To make the interface more engaging, we will use colorful computer graphics paired with sound to simulate salient cues in the environment. To test visual attention, we will adopt a preferential looking task, which presents two pictures to the subject and looks for response when the subject directs their gaze on one of the objects. The pictures can vary by contrast, size, and color; attention is measured by the limit of these variables at which the pictures stop drawing the subject’s gaze. Thus, we intend to translate a therapy that has restored vision in rodents with developmental brain injury into a child-friendly computer program to deliver visual therapy to children with brain injury, and to precisely measure the response to therapy.
In neurology, anatomy is considered destiny: the pattern of brain injury determines which neurological functions are lost. But brain connections can be altered to restore function—this is particularly true in childhood. With our understanding of how neural activity shapes brain connections, we can harness activity to selectively strengthen those brain circuits that are best adapted for restoring function. While anatomy can predict the initial disability following injury, we can now reduce that disability with targeted therapy. Thus, we believe that for children with early brain injury, anatomy is not destiny. By employing novel brain plasticity treatments, we are confident that we can improve neurological outcomes in children with injury to the developing nervous system.