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Adult Neurorecovery: Neurophysiological Pathways

This proposal addresses a critical need in spinal cord injury research, the need for quantitative, sensitive tools to measure neuroplasticity in the human after injury to detect change preceding functional changes. Recently, an individual who had complete motor paralysis below T1 for over three years regained the ability to voluntarily move his toes, ankles, knees and hips during epidural stimulation identifying connectivity from supraspinal centers to the lumbosacral spinal cord, however the specific pathways mediating these responses cannot be determined using available clinical measures. In addition, neural repair and regeneration strategies are emerging; however the sensitive measures to assess improvement in connectivity are not available. The objective of this proposal is to assess the viability of corticospinal, vestibulospinal, reticulospinal and long propriospinal pathways after human spinal cord injury and in response to interventions that induce neuroplasticity by using sensitive, quantifiable neurophysiological assessments. The tibialis anterior, vastus lateralis and soleus motor evoked responses and soleus H-reflex response to neurostimulation that represents specific regions of the brain will be utilized to identify residual supraspinal input after injury. We propose to use a sequence of established methodologies with the specific customized experimental design that will allow us to probe the viability of supraspinal pathways. We will first study individuals with chronic injury who presumably have reached a relatively stable neurologic state with varied levels of severity of injury as classified by the INSCI, AIS grade (1-3). Next, we will follow individuals with the spinal cord injury from the first week throughout the first year to examine the responsiveness of these measures to the natural history of recovery and relate these measures to functional recovery. We will initially compare the neurophysiological measures with the INSCI motor and sensory scores and walking measures (6 minute walk). And finally, we will assess the responsiveness of the neurophysiological measures to an activity-based intervention, Locomotor Training, that has shown functional improvements in walking and balance in individuals with chronic incomplete spinal cord injury. We will also get the radiological images over time, and compare them with the neurophysiological assessment, and relate them to functional recovery. These results will advance our understanding of neuroplasticity after injury and in response to therapeutic interventions at a mechanistic level and anatomic level, thus filling a well identified need in the field of spinal cord injury research.

Basic scientists working with animal models of spinal cord injury (SCI) have been testing a wide array of potential methods to protect spinal cord cells from further damage following injury, replace subsequently lost cells, and repair damaged neural circuitry. However, translating these strategies to treat humans with spinal cord injury (SCI) presents significant challenges. One of these challenges is the current lack of objective, quantitative outcome measures with sufficient sensitivity to monitor neurologic changes during recovery. The current gold standard for clinical assessment of spinal cord injury is the American Spinal Injury Association’s (ASIA) neurological classification which includes tests of motor and cutaneous sensory function. There are limitations to the ASIA impairment scale (AIS). For sensory function, there is a limiting component of subjectivity with sensory cutaneous evaluation of each dermatome scored simply as either normal, absent or abnormal sensation. For motor function only five muscle groups of the upper and lower limbs are assessed and graded on a subjective ordinal scale. The trunk is not evaluated, making assessment of neurological level spinal cord injury in the thoracic region dependent solely on the sensory evaluation. The Brain Motor control Assessment (BMCA) was originally designed to quantitatively identify and characterize residual supraspinal central nervous system influence on motor output following a severe SCI. We propose to augment the BMCA to include motor testing of the trunk musculature, as well as test the upper and lower extremities in further detail. This revised exam is to be called the Functional NeuroPhysiological Assessment (FNPA), and it will encompass tests that will allow us to further understand level of injury and the capacity for neurologic and functional recovery over time. Determining if the FNPA is a valid and reliable, quantitative outcome measure will allow for its utilization in multi-center clinical trials that are trying to determine if existing and developing therapies are producing the neurologic recovery they are proposing.