Miami Project Researchers Receive $1.1 Million Grant to Study Neuroplasticity

Martin Oudega, Ph.D., and Monica A. Perez, P.T., Ph.D., both associate professors of neurological surgery and researchers at The Miami Project to Cure Paralysis at the University of Miami Miller School of Medicine, have received a $1.1 million Veterans Administration grant to study neuroplasticity.

The funded research project, titled “Maximizing Spike-Timing Dependent Plasticity after Spinal Cord Injury,” will explore new clinical approaches to restoring upper-limb function after incomplete cervical spinal cord injury (SCI). The corticospinal tract axons are involved in controlling upper-limb function. Paired-pulse induced spike-timing dependent plasticity (STDP) enhances synaptic strength between residual corticospinal tract axons and spinal motoneurons, resulting in temporary improvements in upper-limb function in humans with incomplete cervical SCI.

The goals of the research are to develop methods to maximize STDP-induced aftereffects in a pre-clinical setting of incomplete SCI, and ultimately to translate this knowledge to humans to maximize STDP-mediated motor function recovery after incomplete cervical SCI.

“This joint award will give us the opportunity to translate knowledge gathered from pre-clinical studies to humans to maximize current approaches aiming at restoring motor function after SCI,” said Oudega.

STDP aftereffects depend on the parameters of stimulation and the activation of postsynaptic glutamate receptors causing increased synaptic transmission. The researchers will use a research model of incomplete cervical SCI to examine the effects of increasing paired-pulse frequencies and duration, as well as extended use of clinically-relevant receptors on the strength of electrophysiological and forelimb functional STDP aftereffects. Motor training will be combined with paired-pulse STDP stimulation to further enhance plasticity and behavioral recovery.

Comprehensive assessment of cellular and molecular plasticity in the brain and spinal cord will be used to study neuronal mechanisms underlying the effects of the approaches. Secondarily, the researchers will translate the knowledge from their research to humans with incomplete cervical SCI. The most effective stimulation parameters and pharmacological agents will be used in humans during functionally relevant reach to grasp motor tasks. Motor training of reach and grasp movements will be combined with the learned STDP-paradigms to further enhance behaviorally relevant plasticity and recovery of function.

The researchers hope to establish new knowledge on STDP-mediated aftereffect mechanisms in a model of incomplete cervical SCI, which will then be used to maximize STDP aftereffects in humans with incomplete cervical SCI. They also hope the results will support the development of more effective clinically relevant STDP protocols to improve daily use of upper-limb function in humans with SCI. The importance of this research is highlighted by the restricted efficacy of current strategies to improve hand function after SCI, which can ultimately have a positive effect on an injured person’s quality of daily life.

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