“Biomimetic micro-electronic systems as neural prostheses: Restoration of lost memory function and enhancement of normal memory function with implantable spatio-temporal models of hippocampal input-output activity”

Abstract

Dr. Berger leads a multi-disciplinary collaboration with Dr. Sam Deadwyler (Wake Forest Univ.), Dr. John Granacki (USC), Dr. Vasilis Marmarelis (USC), and Dr. Greg Gerhardt (Univ. of Kentucky), that is developing a microchip-based neural prosthesis for the hippocampus, a region of the brain responsible for long-term memory. Damage to the hippocampus is frequently associated with epilepsy, stroke, and dementia (Alzheimer's disease), and is considered to underlie the memory deficits characteristic of these neurological conditions. The essential goals of Dr. Berger's multi-laboratory effort include: (1) experimental study of neuron and neural network function — how does the hippocampus encode information?, (2) formulation of biologically realistic models of neural system dynamics -- can that encoding process be described mathematically to realize a predictive model of how the hippocampus responds to any event?, (3) microchip implementation of neural system models -- can the mathematical model be realized as a set of electronic circuits to achieve parallel processing, rapid computational speed, and miniaturization?, and (4) creation of hybrid neuron-silicon interfaces -- can structural and functional connections between electronic devices and neural tissue be achieved for long-term, bi-directional communication with the brain? By integrating solutions to these component problems, the team is realizing a microchip-based model of hippocampal nonlinear dynamics that can perform the same function as part of the hippocampus. Through bi-directional communication with other neural tissue that normally provides the inputs and outputs to/from a damaged hippocampal area, the biomimetic model could serve as a neural prosthesis. A proof-of-concept will be presented using rats that have been chronically implanted with stimulation/recording micro-electrodes throughout the dorsoventral extent of the hippocampus, and that have been trained using a delayed, non-match-to-sample task. Normal hippocampal functioning is required for successful delayed non-match-to-sample memory. Memory/behavioral function of the hippocampus is blocked pharmacologically, and then in the presence of the blockade, hippocampal memory/behavioral function is restored by a multi-input, multi-output model of hippocampal nonlinear dynamics that interacts bi-directionally with the hippocampus. The model is used to predict output of the hippocampus in the form of spatio-temporal patterns of neural activity in the CA1 region; electrical stimulation of CA1 cells is used to “drive” the output of hippocampus to the desired (predicted) state. These results show for the first time that it is possible to create “hybrid electro-biological” systems that display normal physiological properties, and thus, may be used as neural prostheses to restore damaged brain regions.