The proposed projects will investigate behavioral adaptation and synaptic plasticity in the primate motor system, using a novel implantable recurrent brain-computer interface (rBCI). We will use the rBCI to create artificial corticospinal and corticocortical connections and document the effects of prolonged operation on motor behavior and strength of neural connections. The rBCI records neural activity and uses a programmable computer chip to deliver activity-contingent stimuli in real time to nervous system sites during hours of free behavior. One application is to bridge impaired biological connections, a paradigm we have demonstrated for cortically controlled electrical stimulation of paralyzed arm muscles (Moritz et al, Nature, 2008). Our proposed experiments will investigate the ability of intact monkeys to incorporate an artificial corticospinal connection into normal behavior. A second application of the rBCI is to produce Hebbian plasticity through spike-triggered stimulation, which can strengthen physiological connections (Jackson et al, Nature, 2006). Our experiments will investigate whether this plasticity can be induced with minimally invasive procedures and whether the resultant changes can be prolonged through additional interventions. Our experiments will investigate the induction of spike-timing dependent plasticity of corticospinal and intracortical neural connections and the influence of behavioral state. We will also develop a powerful multichannel rBCI to implement a wide range of transforms between recorded activity and stimulation. These studies will provide crucial evidence to inform clinical applications of this novel rBCI paradigm to more effective treatments of stroke, traumatic brain injury and spinal cord injury -- namely to use implantable computers to facilitate transmission of neural signals across lost connections and to strengthen weakened neural connections.

Public Health Relevance

Recovery of function after stroke, traumatic brain injury or spinal cord injury is a significant medical challenge for millions of patients in the United States The proposed projects will investigate new treatment modalities using implantable computers to allow the brain to control electrical stimulation of other brain regions and spinal cord. Clinicall, the resultant artificial connections can be used to bypass lost physiological pathways, and can also promote the strengthening of weakened neural connections. A key feature of these autonomous implantable devices is continuous operation during prolonged periods of free behavior.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Sensorimotor Integration Study Section (SMI)
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Ludwig, Kip A
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University of Washington
Schools of Medicine
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Wu, Guoji; Perlmutter, Steve I (2013) Sensitivity of spinal neurons to GABA and glycine during voluntary movement in behaving monkeys. J Neurophysiol 109:193-201
Lucas, Timothy H; Fetz, Eberhard E (2013) Myo-cortical crossed feedback reorganizes primate motor cortex output. J Neurosci 33:5261-74
Fetz, Eberhard E (2013) Volitional control of cortical oscillations and synchrony. Neuron 77:216-8
Seki, Kazuhiko; Fetz, Eberhard E (2012) Gating of sensory input at spinal and cortical levels during preparation and execution of voluntary movement. J Neurosci 32:890-902
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Zanos, Stavros (2009) Neural correlates of high-frequency intracortical and epicortical field potentials. J Neurosci 29:3673-5
Smith, W S; Fetz, E E (2009) Synaptic linkages between corticomotoneuronal cells affecting forelimb muscles in behaving primates. J Neurophysiol 102:1040-8
Smith, W S; Fetz, E E (2009) Synaptic interactions between forelimb-related motor cortex neurons in behaving primates. J Neurophysiol 102:1026-39

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