A Hippocampal Cognitive Prosthesis: Multi-Input, Multi-Output Nonlinear Modeling and VLSI Implementation

Abstract

This paper describes the development of a cognitive prosthesis designed to restore the ability to form new long-term memories typically lost after damage to the hippocampus. The animal model used is delayed nonmatch-to-sample (DNMS) behavior in the rat, and the “core” of the prosthesis is a biomimetic multi-input/multi-output (MIMO) nonlinear model that provides the capability for predicting spatio-temporal spike train output of hippocampus (CA1) based on spatio-temporal spike train inputs recorded presynaptically to CA1 (e.g., CA3). We demonstrate the capability of the MIMO model for highly accurate predictions of CA1 coded memories that can be made on a single-trial basis and in real-time. When hippocampal CA1 function is blocked and long-term memory formation is lost, successful DNMS behavior also is abolished. However, when MIMO model predictions are used to reinstate CA1 memory-related activity by driving spatio-temporal electrical stimulation of hippocampal output to mimic the patterns of activity observed in control conditions, successful DNMS behavior is restored. We also outline the design in very-large-scale integration for a hardware implementation of a 16-input, 16-output MIMO model, along with spike sorting, amplification, and other functions necessary for a total system, when coupled together with electrode arrays to record extracellularly from populations of hippocampal neurons, that can serve as a cognitive prosthesis in behaving animals.

Restoration of function after brain damage using a neural prosthesis

“…Further, closed-loop approaches are under development in animal models of spinal cord injury (38,39). Other investigators have proposed a closed-loop approach for a cognitive prosthesis that has shown promise in animal models (40). Other potential clinical applications based on the current model include stroke, focal TBI, and surgical resections.…”

Use of multi-electrode array recordings in studies of network synaptic plasticity in both time and space

“…Conductor and Mobius) make it possible to perform a broad set of analyses for different kinds of application. hippocampus, which provides the capability for predicting spatio-temporal spike train outputs of CA1 based on the inputs recorded in CA3 (pre-synaptic input to CA1), successfully restored the functions of the damaged hippocampus in animal's delayed nonmatch-to-sample behavioral test [53] .…”

Identifying and Predicting Rat Behavior Using Neural Networks

“…Alzheimer's disease and other forms of dementia are typically associated with loss of neurons in the EC region, the region that provides input to the hippocampus [9] Understanding the electrophysiological signal encoding of hippocampal neurons from the EC to CA1 region in a rat hippocampus may provide insight concerning the relation of electrophysiological activity between the EC and CA1 hippocampal regions and rat behavior, which has not been as extensively studied as electrophysiological activity between the CA3 to CA1 region [1], [8]. This thesis aims to use neurological patterns simultaneously recorded from the EC and CA1 region in a rat to identify whether the neurological activity is associated with wheel running, T-maze or open exploration behavior.…”

“…Information is stored by transferring processed spatiotemporal neurological activity from the entorhinal cortex (EC) region to the CA1 region [1], where the information is projected into long-term memory. The anatomical location of the CA1, CA3 and EC region is shown in Figure 1, along with a graphic illustration of what neurological spatial-temporal activity may look like in a rat hippocampus [2], [3].…”

“…Many aspects of neurological activity have been extensively researched, including mechanisms underlying synaptic transmission and generation of electrical activity for individual neurons [8], transfer of information based on spatio-temporal neural activity of neuron ensembles in the CA3 to CA1 region in rats [1], [5], [8], [16], and transfer of information in the prefrontal cortex in nonhuman primates [15]. These studies contribute to modeling dynamic properties of neural activity and behavior associated with neural activity.…”