Brian Noga, Ph.D.

The long-term goal of Dr. Noga's research is to develop and optimize treatments for spinal cord injury (SCI) based on neuromodulation strategies that enhance the activity of spinal locomotor circuits. In particular, he is interested in the influence of descending monoaminergic pathways on the activity of these neurons and their networks. Toward this end, he has developed biosensors and methods to localize, identify and characterize spinal monoamine release with the high spatial and temporal resolution method of fast cyclic voltammetry. He is currently involved in characterizing the effects of deep brain stimulation for improving locomotion following incomplete spinal cord injury. Deep brain stimulation (DBS) has been shown to be an effective, relatively safe, reversible, and adjustable treatment for difficult-to-treat movement disorders, such as Parkinson’s Disease. To date, it has had little application in persons with spinal cord injury (SCI), even though a significant percentage of persons with new and chronic injuries have spared connections between brain and spinal cord (National SCI Statistical Center). Recent work in Dr. Noga's laboratory has pointed to a potential target for controlling walking after partial SCI and has led to obtaining 2 major federally-funded research grants. Research funded by the Department of Defense will provide a much needed proof-of-concept for stimulation strategies targeting spared pathways in persons with incomplete SCI in a translational animal model of neurological and neurosurgical disorders, using a technique that is already available and FDA approved. This technology offers the prospect of early application in the rehabilitation process, to significantly enhance walking ability when it would not otherwise occur. That is, persons with incomplete injuries that may not normally achieve ambulation, may have the ability to do so with this treatment. The improved physical ability may result in a wide range of benefits including the ability to exercise, bone-load, and strengthen muscle, and a reduction in secondary complications associated with a sedentary lifestyle, with improved participation and quality of life. If successful, gait training after SCI could become more efficient, ultimately reducing costs of care. The use of state-of-the-art, high-resolution DBS probes (NIH funded study) will enable precise, selective and tunable stimulation of deep brain structures with greater flexibility in positioning for precise current delivery. This will reduce side effects associated with stimulation of adjacent, functionally unrelated structures. This study will be important for seamless transition to the next-generation, steerable, human DBS electrodes and BMI currently in development. This research is expected to directly lead to a Phase 1 clinical study, and to further preclinical studies which may involve supplementary transmitter replacement in combination with locomotor training and functional electrical stimulation.

Major accomplishments: 1) characterized monoaminergic control of spinal reflexes important for sensory control of spinal locomotion; 2) identified and characterized hindlimb locomotor-activated neurons in the lumbar spinal cord (location, activity, transmitter phenotype, etc.); 3) characterized the monoaminergic innervation of and identified the major monoaminergic receptors on spinal locomotor-activated neurons that are implicated in the neuromodulatory control of locomotion; 4) identified key components of the descending brainstem pathway for the initiation of locomotion; and, 5) demonstrated that monoaminergic neuromodulatory control of spinal function is mediated in part by extrasynaptic (volume) neurotransmission.