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.
|Lei, Yuming; Ozdemir, Recep A; Perez, Monica A (2018) Gating of Sensory Input at Subcortical and Cortical Levels during Grasping in Humans. J Neurosci 38:7237-7247|
|Christiansen, Lasse; Perez, Monica A (2018) Targeted-Plasticity in the Corticospinal Tract After Human Spinal Cord Injury. Neurotherapeutics 15:618-627|
|Aguiar, Stefane A; Choudhury, Supriyo; Kumar, Hrishikesh et al. (2018) Effect of central lesions on a spinal circuit facilitating human wrist flexors. Sci Rep 8:14821|
|Tazoe, Toshiki; Perez, Monica A (2017) Cortical and reticular contributions to human precision and power grip. J Physiol 595:2715-2730|
|Long, Jinyi; Federico, Paolo; Perez, Monica A (2017) A novel cortical target to enhance hand motor output in humans with spinal cord injury. Brain 140:1619-1632|
|Federico, Paolo; Perez, Monica A (2017) Altered corticospinal function during movement preparation in humans with spinal cord injury. J Physiol 595:233-245|
|Federico, Paolo; Perez, Monica A (2017) Distinct Corticocortical Contributions to Human Precision and Power Grip. Cereb Cortex 27:5070-5082|
|Macklin, Richard A; Bae, Jihye; Orell, Melanie et al. (2017) Time-Dependent Discrepancies between Assessments of Sensory Function after Incomplete Cervical Spinal Cord Injury. J Neurotrauma 34:1778-1786|
|Urbin, M A; Ozdemir, Recep A; Tazoe, Toshiki et al. (2017) Spike-timing-dependent plasticity in lower-limb motoneurons after human spinal cord injury. J Neurophysiol 118:2171-2180|
|Lei, Yuming; Perez, Monica A (2017) Cortical contributions to sensory gating in the ipsilateral somatosensory cortex during voluntary activity. J Physiol 595:6203-6217|
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