Assistant Professor, Brain and Mind Research Institute
Assistant Professor, Neurology and Neuroscience
Assistant Professor, Pediatrics, Division of Pediatric Neurology
Weill Cornell Medical College
Blythedale Children's Hospital
We study recovery of motor function after injury to the central nervous system. We focus on the corticospinal system, which connects motor cortex to the spinal cord. We attempt to repair brain-spinal cord connections using activity-based therapies, including electrical stimulation and motor training. The approach capitalizes on the fact that most brain and spinal injuries preserve some corticospinal connections. Also, corticospinal connections are highly activity-dependent and can be strengthened with endogenous activity (practice) or exogenous activity (electrical stimulation). We use a combination of anatomical, behavioral, and electrophysiological techniques to address the roles of injury and activity in promoting plasticity and recovery. We also study how plasticity of the motor systems changes with age and how developmental plasticity can be leveraged to promote recovery after injury. The end goal of our studies is to inform translational efforts to improve neurological function in people with brain and spinal cord injury.
To see how the progress of this research translates to improved treatments for children with chronic brain injury, visit The Early Brain Injury Recovery Program.
Stanford University, Stanford, Calif.
Columbia University, New York
Rutgers University, Piscataway, N.J. in the Laboratory of Wise Young and Ronald Hart
Children’s Hospital of New York, Columbia University, New York
Department of Neurology, Columbia University, New York
Department of Neurology, Columbia University, New York
American Board of Psychiatry and Neurology, Special Qualification in Child Neurology
I am a child neurologist and motor system neuroscientist interested in central nervous system injury and repair. During my postdoctoral fellowship in Jack Martin’s laboratory, I developed expertise in corticospinal injury and response to activity-based treatments. Using a combination of anatomy, physiology (brain mapping), and behavior, I have been able to identify the brain circuits that adapt to developmental brain injury. My laboratory uses activity-based therapies, including brain stimulation and intensive behavioral training to promote recovery of function, both in rodents and humans. In a rodent hemiparesis model, we have demonstrated that stimulation of spared motor circuits causes them to sprout at their terminations in the spinal cord, form functional connections with spinal motor circuits, and restore motor skill. My expertise in animal models of human disease and clinical neurology will allow me to translate the gains in understanding that we hope to achieve in the proposed studies into improved treatments for children with cerebral palsy. This is my goal as a physician-scientist: to direct a truly translational program in which we model activity-based repair strategies in young animals with early brain injury and then use those results to design better treatments for children at risk for cerebral palsy.
Qin L, Jing D, Parauda S, Carmel JB, Ratan RR, Lee FS, Cho S. BDNF met allele promotes stroke recovery through shifting synaptic balance to excitation in the contralateral striatum. Submitted.
Friel KM, Kuo H.-C, Carmel JB, Rowny SB, Gordon AM. Improvements in hand function after bimanual training are not associated with corticospinal tract dysgenesis in children with unilateral cerebral palsy. Submitted.
Carmel JB, Kimura H, Martin JH. After chronic unilateral corticospinal injury, electrical stimulation of motor cortex on the uninjured hemisphere restores skilled locomotion through ipsilateral control. J Neurosci. Accepted with revisions.
Carmel JB, Berrol LJ, Brus-Ramer M, Martin JH. Chronic electrical stimulation of the intact corticospinal system after unilateral injury restores skilled locomotor control and promotes spinal axon outgrowth. J Neurosci. 2010 Aug 11; 30(32): 10918-26.
Brus-Ramer M, Carmel JB, Martin JH. Motor Cortex Bilateral Motor Representation Depends on Subcortical and Interhemispheric Interactions. J Neurosci 2009 May 13; 29(19): 6196-6204. (Co- first author)
Brus-Ramer M, Carmel JB, Chakrabarty S, Martin JH. Electrical stimulation of spared corticospinal axons augments connections with ipsilateral spinal motor circuits after injury. J Neurosci. 2007 Dec 12; 27(50):13793-801.
Cao Z, Gao Y, Bryson JB, Hou J, Chaudhry N, Siddiq M, Martinez J, Spencer T, Carmel J, Hart RP, Filbin MT. The cytokine interleukin-6 is sufficient but not necessary to mimic the peripheral conditioning lesion effect on axonal growth. J Neurosci. 2006 May 17; 26(20):5565-73.
Carmel JB, Kakinohana O, Mestril R, Young W, Marsala M, Hart RP. Mediators of ischemic preconditioning identified by microarray analysis of rat spinal cord. Exp Neurol. 2004 Jan;185(1):81-96.
Cizkova D, Carmel JB, Yamamoto K, Kakinohana O, Sun D, Hart RP, Marsala M. Characterization of spinal HSP72 induction and development of ischemic tolerance after spinal ischemia in rats. Exp Neurol. 2004 Jan; 185(1):97-108.
Carmel JB, Galante A, Soteropolous P, Tolias P, Young W, Hart RP. Gene expression profiling of acute spinal cord injury reveals inflammatory signals and neuron loss. Physiological Genomics. 2001 Dec 21;7(2):201-213.
Hsaio M, Tse V, Carmel J, Tsai Y, Felgner PL, Haas M, Silverberg GD. Intracavitary liposome-mediated p53 gene transfer into glioblastoma with endogenous wild-type p53 in vivo results in tumor suppression and long-term survival. Biochem Biophys Res Commun. 1997 Apr 17; 233(2):359-64.
Hsaio M, Tse V, Carmel J, Constanzi E, Strauss B, Haas M, Silverberg GD. Functional expression of human p21 (WAF1/CIP1) gene in rat glioma cells suppresses tumor growth in vivo and induces radio-sensitivity. Biochem Biophys Res Commun. 1997 Apr 17; 233(2): 329-35.
Thelma Bethea, B.S.
Laboratory Manager/Research Technician
B.S., Rochester Institute of Technology, Rochester, NY
My background and experience in neuroscience stems from work in a psychiatric lab at the Children’s Hospital of Philadelphia where we observed the effects of stress, depression, and anxiety on the brain’s noradrenergic system. My interests have since shifted to motor function loss as a result of demyelinating diseases such as Multiple Sclerosis, and the role of the Corticospinal tract in motor injury and repair. Since joining the motor recovery lab, my projects include the use of behavioral and anatomical techniques to observe activity-based therapeutic effects on axonal plasticity and functional recovery after brain and/or spinal cord insult.
Brendan Flynn, B.S.
Post-Baccalaureate Pre-Med Student
Postdoctoral Associate, Yale University, CT
with Hal Blumenfeld, M.D., Ph.D.
Associate Research Scientist, Yale University, CT
with Hal Blumenfeld, M.D., Ph.D.
B.Sc., Gorakhpur University, Gorakhpur, U.P., India
M.Sc., University of Lucknow, Lucknow, U.P., India
Ph.D., Neuroimaging and Biochemistry, SG Postgraduate Inst. of Med. Sciences, Lucknow, India
with Rakesh Gupta, M.D.
I am interested in understanding the physiology and anatomy of motor functions in the corticospinal system. We use electrical stimulation on intact as well as injured brain and spinal cord to study physiology of plasticity in the corticospinal system. I have gained experience in studying neurophysiology and brain anatomy changes in epilepsy and brain injury models using electrophysiology, brain stimulation, and multi-modal functional and structural magnetic resonance imaging. As a motor recovery laboratory team, our goal is to improve understanding of motor functions in patients with brain and spinal cord injury.
B.A., Occidental College, Los Angeles, CA (2006)
Ph.D., Systems Biology and Disease, University of Southern California, Los Angeles, CA (2012)
with Nina S. Bradley, P.T., Ph.D.
I am a neuroscientist with an abiding interest in development of the motor systems. My doctoral training in developmental neuroscience focused on acquisition of a motor control skill in an animal model (chick embryo) during embryonic development. My research was primarily dedicated to understanding motor control development under influence of environmental factors. During my graduate training I developed tools to study muscle movement patterns that were previously thought to be unavailable at early stages of development. In the Carmel laboratory, I have been working on a rat model of hemiplegic cerebral palsy with primary focus on restoring forepaw function after corticospinal injury. Working on a translational animal model has made me passionate about understanding prenatal injuries that can lead to motor disabilities. I am particularly excited about applying electrical brain stimulation for neuromodulation, because it is a targeted therapy and has enormous translational potential.
2002 to 2007, Assistant Professor, Emory University School of Medicine, Atlanta, GA
2007-2011, Director of Lab, MidAtlantic Neonatology Associates, Morristown, NJ
B.A., Binzhou Medical College, China
M.D., Binzhou Medical College, China
M.S., Xian Medical University, China
Ph.D., Ehime University School of Medicine, Japan
In my 25 years as a scientist, I have focused on animal models of stroke and have spent the last ten years devoted to neonatal brain injury. We have created a neonatal rat model of arterial ischemic stroke and have used the model to investigate aspects of neuroprotection and neurological recovery. Since joining Dr. Carmel’s lab, I have focused on experiments on the plasticity of corticospinal connections after neonatal pyramidotomy.
The Thomas and Agnes Carvel Foundation
Title: Using Neural Activity to Repair the Brain
Dates of project: 9/13-8/15
Goals: To use behavioral training and brain electrical stimulation to repair motor circuit connections in a rat model of neonatal stroke.
National Institutes of Health
K08 NS073796, NINDS-NIH
Title: Injury and adaptation in the developing rat corticospinal and rubrospinal tracts
Dates of project: 9/11-8/15
Goals: To determine 1) how brain circuits can compensate for one another after early brain injury, and 2) if electrical stimulation can enhance brain-spinal cord connection and enhance motor recovery in rats.
March of Dimes Basil O'Connor Starter Award
Title: Electrical Stimulation to Strengthen Corticospinal Circuits and Prevent Cerebral Palsy
Dates of project: 2/12-1/14
Goals: In rat pups with PVL-like injury, we hypothesize that electrical stimulation of spared CST connections will strenthen their spinal cord connections and that this will prevent the development of cerebral palsy.
In addition, we have applied for funding to understand how a form of non-invasive brain stimulation, called transcranial direct current stimulation, affects motor cortex excitability. We will test how various stimulation paradigms affect stimulation-induced movement and motor learning.
The Early Brain Injury Recovery Program
Mission: 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.
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: 1) the interface, which consists of black and white lines that move horizontally, is not very engaging, and 2) 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.
Visit the clinic page for more information.
April 1, 2014
Dr. Carmel is featured in this month's Wag Magazine in a story about spinal cord injury.
December 30, 2013
Dr. Carmel and other advocates' work to reinstate full funding to New York's Spinal Cord Injury Research Program is featured on lohud.com.
December 20, 2013
Dr. Carmel's research has received support from the Travis Roy Foundation, which highlights his recent achievements on their website.
October 24, 2013
Dr. Carmel has been selected as one of the 2013 Doctors of Distinction, awarded annually to distinguished physicians in Westchester County. He will receive the Research Excellence Award, which "recognizes a physician whose clinical research in a particular area has caught the attention of his or her peers and deserves special acknowledgement." The awards ceremony will be held on October 24 at The Bristal in White Plains, NY.
November 7, 2012
Dr. Carmel teams up again with Dr. Adam Wolfberg, author of Fragile Beginnings, for the ISIS Parenting webinar, 'As Preemies Grow: From Preterm Birth to Preschool & Beyond.'
October 7, 2012
Dr. Carmel talks with Jack M. Parent, M.D., of the University of Michigan, about his Rehabilitation and Regeneration poster presentation at the ANA's 2012 Annual Meeting. Watch the interview on YouTube.
February 7, 2012
In Fragile Beginnings, author Dr. Adam Wolfberg takes readers into the complex world of newborn intensive care and into the lab of researchers who are working to improve the futures of children born too soon. He follows the work of Dr. Jason Carmel, who was inspired to study how the brain adapts to injury when his twin brother was paralyzed in an accident. Wolfberg details current scientific practices and discoveries, and explores the profound emotional and ethical issues raised by the advancing technology that allows people to save the lives of increasingly undeveloped preemies. The book is published today.
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.