A cortical neural prosthesis for restoring and enhancing memory

TLDR

A primary objective in developing a neural prosthesis is to replace nonfunctional neural circuitry, requiring artificial reconstruction of neuron‑to‑neuron connections that can be recognized by remaining circuitry and promote appropriate interaction; hippocampal CA3/CA1 ensembles in rats performing a delayed‑nonmatch‑to‑sample task encode trial‑specific lever information in distinct spatiotemporal firing patterns. The study demonstrates a neural prosthesis that uses a multi‑input/multi‑output nonlinear model to replace hippocampal ensemble firing patterns with electrical stimulation pulses. The prosthesis identifies MIMO patterns online in real time and delivers them as electrical stimulation in a closed‑loop behavioral paradigm. The model predicted successful performance on the same trial, improved performance under normal conditions, and restored performance in animals with hippocampal activity blocked, demonstrating that a neural prosthesis can restore and enhance mnemonic processes.

Abstract

A primary objective in developing a neural prosthesis is to replace neural circuitry in the brain that no longer functions appropriately. Such a goal requires artificial reconstruction of neuron-to-neuron connections in a way that can be recognized by the remaining normal circuitry, and that promotes appropriate interaction. In this study, the application of a specially designed neural prosthesis using a multi-input/multi-output (MIMO) nonlinear model is demonstrated by using trains of electrical stimulation pulses to substitute for MIMO model derived ensemble firing patterns. Ensembles of CA3 and CA1 hippocampal neurons, recorded from rats performing a delayed-nonmatch-to-sample (DNMS) memory task, exhibited successful encoding of trial-specific sample lever information in the form of different spatiotemporal firing patterns. MIMO patterns, identified online and in real-time, were employed within a closed-loop behavioral paradigm. Results showed that the model was able to predict successful performance on the same trial. Also, MIMO model-derived patterns, delivered as electrical stimulation to the same electrodes, improved performance under normal testing conditions and, more importantly, were capable of recovering performance when delivered to animals with ensemble hippocampal activity compromised by pharmacologic blockade of synaptic transmission. These integrated experimental-modeling studies show for the first time that, with sufficient information about the neural coding of memories, a neural prosthesis capable of real-time diagnosis and manipulation of the encoding process can restore and even enhance cognitive, mnemonic processes.