There is a fundamental knowledge gap about how the human brain controls one of the most fundamental hand actions, grasping. Developing solutions for the manual impairments that ensue from brain injuries and neurological diseases hinges on closing this knowledge gap. The long-term goal is to determine how cortical and subcortical structures in the brain integrate sensory information into accurate hand actions. The objective of this proposal, which is a stepping-stone towards the long-term goal, is to determine the functional organizations of the parietal-frontal pathways that mediate grasping in monkeys. The central hypothesis is that three parietal-frontal pathways control successive stages of grasping (approach, contact, lift). Each pathway node is further organized into modules that are specific to grip posture (precision and whole hand). This hypothesis has been formulated primarily from studies conducted during the applicant's postdoctoral work. The rationale for the proposed research is that it will close a pressing knowledge gap about how a parietal-frontal networks controls one of the most sophisticated and clinically relevant motor functions.
Two specific aims will be pursued to test this hypothesis: (1) Determine how the parietal-frontal pathways control successive stages of grasping;and (2) Determine how modules within nodes of the parietal-frontal pathways encode grip posture. Under the first aim (K-99 phase), optical imaging will be used to identify the parietal and frontal nodes on the cortical surface that are activated during grasping. Electrophysiological recordings in each node identified with optical imaging will be used to determine the relationships between spike train modulations and grasping stages. Under the second aim (R-00 phase), optical imaging and electrophysiological recordings from modules of the same network nodes will show the spatial organizations of clusters of neurons tuned to specific grip postures. Electrical stimulation of the same modules during grasping will be used to temporarily manipulate its mechanisms and further test the contributions of individual modules to grasping. The functional connections of individual modules will be tested with concurrent electrical stimulation and optical imaging, which has already been proven feasible in the applicant's hands. The chief innovation of this proposal is the use of a multi- pronged approach that centers on optical imaging in behaving monkeys to determine how the parietal-frontal network controls grasping. The proposed research is significant because it is expected to vertically expand the understanding of how the parietal-frontal network in the primate brain controls grasping. Ultimately, such knowledge has the potential to advance the design of brain-machine interfaces that rely on recording neuronal signals from the brain to aid hand use for patients who have lost the ability to use their hands due to central nervous system injury or amputation.

Public Health Relevance

The proposed research is relevant to public health because it will determine how the brains of monkeys control grasping, which is one of the most fundamental functions of the human hand. The expected outcome is a critical stepping-stone to improving the design of treatments that aid patients with motor disabilities. Thus, the proposed research is relevant to the part of the NIH mission that pertains to creating the knowledge foundation for reducing the burden of disability caused by central nervous system injury or amputation.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Career Transition Award (K99)
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NST-2 Subcommittee (NST)
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Chen, Daofen
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Vanderbilt University Medical Center
Schools of Arts and Sciences
United States
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Gharbawie, Omar A; Stepniewska, Iwona; Kaas, Jon H (2016) The origins of thalamic inputs to grasp zones in frontal cortex of macaque monkeys. Brain Struct Funct 221:3123-40
Liao, Chia-Chi; DiCarlo, Gabriella E; Gharbawie, Omar A et al. (2015) Spinal cord neuron inputs to the cuneate nucleus that partially survive dorsal column lesions: A pathway that could contribute to recovery after spinal cord injury. J Comp Neurol 523:2138-60
Roe, Anna Wang; Chernov, Mykyta M; Friedman, Robert M et al. (2015) In Vivo Mapping of Cortical Columnar Networks in the Monkey with Focal Electrical and Optical Stimulation. Front Neuroanat 9:135
Qi, Hui-Xin; Reed, Jamie L; Gharbawie, Omar A et al. (2014) Cortical neuron response properties are related to lesion extent and behavioral recovery after sensory loss from spinal cord injury in monkeys. J Neurosci 34:4345-63
Stepniewska, Iwona; Gharbawie, Omar A; Burish, Mark J et al. (2014) Effects of muscimol inactivations of functional domains in motor, premotor, and posterior parietal cortex on complex movements evoked by electrical stimulation. J Neurophysiol 111:1100-19
Qi, Hui-Xin; Gharbawie, Omar A; Wynne, Katherine W et al. (2013) Impairment and recovery of hand use after unilateral section of the dorsal columns of the spinal cord in squirrel monkeys. Behav Brain Res 252:363-76
Liao, Chia-Chi; Gharbawie, Omar A; Qi, Huixin et al. (2013) Cortical connections to single digit representations in area 3b of somatosensory cortex in squirrel monkeys and prosimian galagos. J Comp Neurol 521:3768-90