At the Burke Medical Research Institute, Jason Carmel, M.D., Ph.D., is investigating ways to help the brain and spinal cord reconnect after injury. The translational nature of Dr. Carmel’s research not only aligns with the mission of BMRI but has personal resonance as well.
During Dr. Carmel’s second year of medical school at Columbia University, his twin brother, David, dove head first into a shallow sandbar and broke his neck, leaving him with permanent spinal cord injury. Dr. Carmel took a break from medical school and began working in a neuroscience lab at Rutgers, eventually earning a Ph.D. in addition to completing his clinical training in pediatric neurology. At the time, “I didn’t know what my balance would be between treating patients and research,” he recalls.
These days, as the director of the Motor Recovery Laboratory at BMRI, Dr. Carmel devotes most of his time to research. But the driving force behind his research is improving treatments for patients with brain and spinal cord injuries. He leads a team of scientists trying to understand the body’s capacity to adapt after corticospinal injury, which damages the neurons connecting the brain and the spinal cord. Ultimately they hope to enhance that capacity to help patients regain motor function. As a child neurologist at both Weill Cornell Medical Center and Blythedale Children’s Hospital, Carmel sees first hand the future beneficiaries of his efforts in the lab.
To that end, the Carmel lab is focusing on electrical brain stimulation, in which a low electrical current is applied to the surface of the brain to alter the excitability of particular neurons. Research has shown that electrical brain stimulation can boost the repair of brain-spinal cord connections and restore movement after spinal cord injury. Although people have toyed with electrical brain stimulation since the 1700s, only in recent years has the field gained scientific validation and clinical acceptance. Even in the 1990s, electrical brain stimulation usually meant electroconvulsive therapy, which was about as little understood as slapping the side of television set, says Dr. Carmel.
The brain stimulation used in his lab is much milder and can be carefully targeted to specific brain regions. Studies in rodents use electrodes implanted inside the skull, but a non-invasive form, known as transcranial direct current stimulation (tDCS), has been developed for human patients. It’s a technique that “capitalizes on our understanding of neuroscience,” says Dr. Carmel. “Now we think of electrical stimulation as a way to selectively support certain areas or connections in the brain.”
The brain is sculpted by activity, explains Dr. Carmel, and electrical brain stimulation is a way to harness that activity to strengthen weak brain-spinal cord connections. The corticospinal system in humans is crossed—the left brain controls the right hand, for example, and the right brain controls the left hand. Although these crossed connections between brain and spinal cord dominate, sparser same-side connections exist as well. Stroke, cerebral palsy, and spinal cord injuries often affect one side, damaging the crossed connections, but leaving intact these same-side connections, which then have a chance to step up.
Indeed, Dr. Carmel’s lab has found that the left and right hemispheres of the brain can compensate for each other after injury. In a rat model, cutting the spinal connections from the left motor cortex (the motor cortex controls voluntary movements) disables the right forelimb. “We use this model because it mimics the major problem that we see in restoring movement after paralyzing injury: the connections between brain and spinal cord are too weak to be effective,” says Dr. Carmel. Electrically stimulating the right motor cortex can induce same-side spinal connections to grow—and these strengthened connections between the right motor cortex and right forelimb can restore the movements previously controlled by the damaged left motor cortex. Over time, one side of the brain can learn to control both forelimbs. These findings suggest that instead of trying to revive the injured brain regions, electrical brain stimulation can recruit alternative brain regions to take over lost motor function.
Dr. Carmel is pursuing related research on the use of behavior training and brain stimulation in a rat model of neonatal stroke. The encouraging results from animal studies have also paved the way for clinical trials in children with chronic brain injury. As part of the Early Brain Injury Recovery Program at BMRI and a new collaboration with Blythedale Children’s Hospital, Carmel will test tDCS therapy in children with cerebral palsy affecting one side of the body (hemiplegia). Both projects will be funded by a new grant from the Thomas and Agnes Carvel Foundation.
Dr. Carmel joined BMRI in 2012 after meeting executive director Rajiv Ratan, M.D., Ph.D., on an advocacy trip to Albany. They were there to urge state lawmakers to restore spinal cord research funding, a campaign that is ongoing. (A 1998 bill had instituted a surcharge on moving violations and a portion of that revenue, $8.5 million a year, was dedicated to the Spinal Cord Injury Research Fund. Since 2010, however, that money has been diverted to balance the state’s budget.) This week, spinal cord injury advocates, Dr. Carmel’s brother among them, are again heading to Albany to continue the fight.