Facilitation of memory encoding in primate hippocampus by a neuroprosthesis that promotes task-specific neural firing

Abstract

Objective Memory accuracy is a major problem in human disease and is the primary factor that defines Alzheimer’s’, aging and dementia resulting from impaired hippocampal function in medial temporal lobe. Development of a hippocampal memory neuroprosthesis that facilitates normal memory encoding in nonhuman primates (NHPs) could provide the basis for improving memory in human disease states. Approach NHPs trained to perform a short-term delayed match to sample (DMS) memory task were examined with multi-neuron recordings from synaptically connected hippocampal cell fields, CA1 and CA3. Recordings were analyzed utilizing a previously developed nonlinear multi-input multi-output (MIMO) neuroprosthetic model, capable of extracting CA3-to-CA1 spatiotemporal firing patterns during DMS performance. Main Results The MIMO model verified that specific CA3-to-CA1 firing patterns were critical for successful encoding of Sample phase information on more difficult DMS trials. This was validated by delivery of successful MIMO-derived encoding patterns via electrical stimulation to the same CA1 recording locations during the Sample phase which facilitated task performance in the subsequent delayed Match phase on difficult trials that required more precise encoding of Sample information. Significance These findings provide the first successful application of a neuroprosthesis designed to enhance and/or repair memory encoding in primate brain.

Hippocampal Microcircuits, Functional Connectivity, and Prostheses

“…Given also its pivotal roles in memory functions, it has been one of the most studied regions in the brain, and the first target of neural engineers in building cortical prostheses that can restore cognitive functions (Berger et al 2005(Berger et al , 2011Hampson et al 2012Hampson et al , 2013. In this chapter, we will describe the hippocampal microcircuit with an emphasis on its functional consequences in the context of building hippocampal memory prostheses for restoring memory functions.…”

Technological Innovation and Ethical Response in Neurosurgery

“…Limited motor control of robotic prostheses has been achieved through subdural nonpenetrating electrode arrays that do not damage the cortex [28]. Cognitive prosthetics are being developed that actually improve the ability to encode new memories [29].…”

The Function of Cortical Microcircuits: Insights from Biomorphic Ceramic-Based Microelectrode Arrays

“…These arrays were capable of recording single neuron activity from each of their recording sites for at least 6 months during chronic implantation in the somatosensory cortex of rats (Moxon et al 2004), and monkey hippocampus (Hampson et al 2013a) as well as in the prefrontal cortex of nonhuman primates (Opris et al 2011(Opris et al , 2012a. The vertical arrangement of the recording sites on these biomorphic MEAs is ideal for simultaneously recording across the different layers of brain areas such as the cerebral cortex and hippocampus in chronic preparations (Opris et al 2011(Opris et al , 2012a(Opris et al , b, 2013Hampson et al 2012bHampson et al , 2013a.…”

“…The vertical arrangement of the recording sites on these biomorphic MEAs is ideal for simultaneously recording across the different layers of brain areas such as the cerebral cortex and hippocampus in chronic preparations (Opris et al 2011(Opris et al , 2012a(Opris et al , b, 2013Hampson et al 2012bHampson et al , 2013a. Hippocampal pyramidal cells in the rat have been stimulated and recorded (Hampson et al 2013a). Single-unit recordings from nonhuman primate frontal cortex and hippocampus in awake animals have been performed using a specially designed deep recording MEA (not shown) for the primate brain.…”