Most of our daily life activities involve bilateral hand and arm movements. This ability is largely disrupted in individuals with cervical spinal cord injury (SCI). This proposal has two main goals: 1). examine the physiology of CNS pathways contributing to the control of bilateral hand and arm movements in individuals with cervical SCI, and 2). study approaches to promote recovery of upper-limb motor function. We focus on bilateral elbow flexion/extension and precision grip, which are basic movements in our daily life activities.
In Aim 1, we will examine the contribution of the motor cortex, corticospinal drive, and spinal cord to the control of bilateral hand and arm movements after cervical SCI. Transcranial magnetic stimulation (TMS) will be used to examine excitability of intracortical pathways and corticospinal drive. Electroencephalography (EEG) and electromyography (EMG) and EMG/EMG coherence will be used to examine transmission in corticospinal inputs to spinal motoneurons. We will assess motoneuronal excitability by using peripheral nerve stimulation. Together, these studies will identify the effects of SCI on physiological pathways involved in functionally relevant actions.
In Aim 2, we propose to study two novel approaches to promote recovery of upper-limb motor function. First, we plan to strengthen transmission in the corticospinal pathway by using spike-timing- dependent plasticity (STDP) protocols. Repeated pairs of TMS and peripheral nerve stimuli will be precisely timed to arrive at the motor cortex and spinal cord, respectively, to induce synaptic plasticity. Second, we plan to enhance voluntary control of upper-limb muscles by combining myoelectric-controlled training with STDP protocols, targeting physiological sites affected by SCI (identified in Aim 1). Training will consist of controlling a 2-D cursor using EMG signals from bilateral hand and arm muscles.
The specific Aims i n this proposal tightly couple basic scientific human research and translational neuroscience. This work will advance our understanding of how bilateral actions are controlled and could lead to the development of novel interventional approaches to restore bilateral control of upper-limb muscles. The absence of universally accepted treatments for hand and arm motor disability after SCI, and other CNS disorders, and the limited behavioral improvements with present interventions highlight the importance of these investigations.
The control of bilateral hand and arm movements is largely disrupted in individuals with cervical SCI. This proposal will examine the contribution of the motor cortex, corticospinal drive, and spinal cord to hand and arm muscle activity during functionally relevant bilateral actions. Novel methods will be used to strengthen transmission in the corticospinal pathway and to enhance voluntary control of upper-limb muscles. Because deficits in bilateral arm movements and corticospinal transmission are a major problem after stroke, amyotrophic lateral sclerosis, multiple sclerosis, and other motor disorders, our work may also be relevant for patients with other lesions of the CNS.
|Cirillo, John; Calabro, Finnegan J; Perez, Monica A (2016) Impaired Organization of Paired-Pulse TMS-Induced I-Waves After Human Spinal Cord Injury. Cereb Cortex 26:2167-77|
|Long, Jinyi; Tazoe, Toshiki; Soteropoulos, Demetris S et al. (2016) Interhemispheric connectivity during bimanual isometric force generation. J Neurophysiol 115:1196-207|
|Macklin, R A; Brooke, V J; Calabro, F J et al. (2016) Discrepancies between clinical assessments of sensory function and electrical perceptual thresholds after incomplete chronic cervical spinal cord injury. Spinal Cord 54:16-23|
|Calabro, Finnegan J; Perez, Monica A (2016) Bilateral reach-to-grasp movement asymmetries after human spinal cord injury. J Neurophysiol 115:157-67|
|Cirillo, John; Perez, Monica A (2015) Subcortical contribution to late TMS-induced I-waves in intact humans. Front Integr Neurosci 9:38|
|Tazoe, Toshiki; Perez, Monica A (2015) Effects of repetitive transcranial magnetic stimulation on recovery of function after spinal cord injury. Arch Phys Med Rehabil 96:S145-55|
|Bunday, Karen L; Tazoe, Toshiki; Rothwell, John C et al. (2014) Subcortical control of precision grip after human spinal cord injury. J Neurosci 34:7341-50|
|Tazoe, Toshiki; Perez, Monica A (2014) Selective activation of ipsilateral motor pathways in intact humans. J Neurosci 34:13924-34|
|Perez, Monica A; Butler, Jane E; Taylor, Janet L (2014) Modulation of transcallosal inhibition by bilateral activation of agonist and antagonist proximal arm muscles. J Neurophysiol 111:405-14|
|Bunday, Karen L; Oudega, Martin; Perez, Monica A (2013) Aberrant crossed corticospinal facilitation in muscles distant from a spinal cord injury. PLoS One 8:e76747|
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