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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS012542-40
Application #
8726492
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Ludwig, Kip A
Project Start
1978-09-30
Project End
2018-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
40
Fiscal Year
2014
Total Cost
$683,039
Indirect Cost
$299,309
Name
University of Washington
Department
Physiology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Zanos, Stavros; Rembado, Irene; Chen, Daofen et al. (2018) Phase-Locked Stimulation during Cortical Beta Oscillations Produces Bidirectional Synaptic Plasticity in Awake Monkeys. Curr Biol 28:2515-2526.e4
Clausen, Jens; Fetz, Eberhard; Donoghue, John et al. (2017) Help, hope, and hype: Ethical dimensions of neuroprosthetics. Science 356:1338-1339
Lajoie, Guillaume; Krouchev, Nedialko I; Kalaska, John F et al. (2017) Correlation-based model of artificially induced plasticity in motor cortex by a bidirectional brain-computer interface. PLoS Comput Biol 13:e1005343
Eaton, Ryan W; Libey, Tyler; Fetz, Eberhard E (2017) Operant conditioning of neural activity in freely behaving monkeys with intracranial reinforcement. J Neurophysiol 117:1112-1125
Seeman, Stephanie C; Mogen, Brian J; Fetz, Eberhard E et al. (2017) Paired Stimulation for Spike-Timing-Dependent Plasticity in Primate Sensorimotor Cortex. J Neurosci 37:1935-1949
Rembado, Irene; Zanos, Stavros; Fetz, Eberhard E (2017) Cycle-Triggered Cortical Stimulation during Slow Wave Sleep Facilitates Learning a BMI Task: A Case Report in a Non-Human Primate. Front Behav Neurosci 11:59
Smith, William A; Mogen, Brian J; Fetz, Eberhard E et al. (2016) Exploiting Electrocorticographic Spectral Characteristics for Optimized Signal Chain Design: A 1.08 Analog Front End With Reduced ADC Resolution Requirements. IEEE Trans Biomed Circuits Syst 10:1171-1180
Wander, Jeremiah D; Sarma, Devapratim; Johnson, Lise A et al. (2016) Cortico-Cortical Interactions during Acquisition and Use of a Neuroprosthetic Skill. PLoS Comput Biol 12:e1004931
Weaver, Kurt E; Wander, Jeremiah D; Ko, Andrew L et al. (2016) Directional patterns of cross frequency phase and amplitude coupling within the resting state mimic patterns of fMRI functional connectivity. Neuroimage 128:238-251
Moorjani, Samira (2016) Erratum: Addendum: Miniaturized Technologies for Enhancement of Motor Plasticity. Front Bioeng Biotechnol 4:51

Showing the most recent 10 out of 83 publications