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. 2012 Mar;20(2):198-211.
doi: 10.1109/TNSRE.2012.2189133.

A hippocampal cognitive prosthesis: multi-input, multi-output nonlinear modeling and VLSI implementation

Theodore W Berger  1 , Dong Song, Rosa H M Chan, Vasilis Z Marmarelis, Jeff LaCoss, Jack Wills, Robert E Hampson, Sam A Deadwyler, John J Granacki
Affiliations

A hippocampal cognitive prosthesis: multi-input, multi-output nonlinear modeling and VLSI implementation

Theodore W Berger et al. IEEE Trans Neural Syst Rehabil Eng. 2012 Mar.

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.

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Figures

Fig. 1
Fig. 1
Nonlinearity of input–output relations in brain. Single pulse: With intensity set near threshold, single pulses may or may not elicit an action potential (AP). Dual pulses: if the first pulse of the pair does not elicit an AP, then pre-synaptic facilitation (residual Ca2+ in the presynaptic terminal) and/or NMDA receptor activation causes an AP; if the first pulse does cause an AP, then the response to second pulse is suppressed (possibly due to GABAergic feedback) and elicits only an EPSP. Triplets can cause an EPSP-AP-EPSP predictable from the dual pulse response. Bursts of APs can generate Ca2+ influx triggering hyperpolarizations that block subsequent APs. The main point to be made here is that in almost no case is simple “additivity” of the responses observed—two inputs do not cause two outputs that simply add together. There is almost always a nonadditivity caused by underlying mechanisms.
Fig. 2
Fig. 2
Top: Drawing of the rabbit brain, with the neocortex removed to expose the hippocampus. Shaded portion represents a section transverse to the longitudinal axis that is subsequently shown in the bottom panel. Bottom: Internal circuitry of the hippocampus, i.e., the “tri-synaptic pathway,” indicating the entorhinal cortex (ENTO), perforant path (pp) input to the dentate gyrus (DG), CA3 pyramidal cell layer, and the CA1 pyramidal cell layer. CA1 pyramids project the subiculum (SUB), and from the subiculum to cortical and subcortical sites, ultimately for long-term memory storage.
Fig. 3
Fig. 3
Conceptual representation of a hippocampal prosthesis for the human. The biomimetic MIMO model implemented in VLSI performs the same nonlinear transformation as a damaged portion of hippocampus (red “X”). The VLSI device is connected “up-stream” and “down-stream” from the damaged hippocampal area through multi-site electrode arrays.
Fig. 4
Fig. 4
MIMO model for hippocampal CA3-CA1 population dynamics. (A) Schematic diagram of spike train propagation from hippocampal CA3 region to hippocampal CA1 region. (B) MIMO model as a series of MISO models. (C) Structure of a MISO model.
Fig. 5
Fig. 5
MISO model and MIMO prediction. (A) 24-input MISO model of hippocampal CA3-CA1. r1 are the single-pulse response functions; k2s are the paired-pulse response functions for the same input neurons. k2x are the cross-kernels for pairs of neurons. This particular MISO model has six r1, six r2x, and one k2x. (B) Comparison of actual and predicted spatio-temporal patterns of CA1 spikes. Top: Actual spatio-temporal pattern; Bottom: Spatio-temporal pattern predicted by a MIMO model.
Fig. 6
Fig. 6
Summary of the MIMO modeling results. Left: Normalized KS-statistics are reduced by the MISO models. Right top: Comparison of distributions of normalized KS-statistics with and without MISO models. Right bottom: Distributions of normalized KS-statistics with various numbers of recorded CA3 units in the datasets.
Fig. 7
Fig. 7
Cognitive prosthesis reversal of MK801-induced impairment of hippocampal memory encoding using electrical stimulation of CA1 electrodes with MIMO model-predicted spatio-temporal pulse train patterns. Intra-hippocampal infusion of the glutamatergic NMDA channel blocker MK801 (37.5 μg/h; 1.5 mg/ml, 0.25 μl/h) delivered for 14 days suppressed MIMO derived ensemble firing in CA1 and CA3. CA1 spatio-temporal patterns used for recovering memory loss were “strong” patterns derived from previous DNMS trials (see text), and were delivered bilaterally to the same CA1 locations when the sample response occurred to the sample stimulus. Bottom: Mean % correct (±SEM) performance (n = 5 animals) summed over all conditions, including vehicle-infusion (control) without stimulation, MK801 infusion (MK801) without stimulation, and MK801 infusion with the CA1 stimulation (substitute) patterns (MK801 + Stim).
Fig. 8
Fig. 8
VLSI design of the hippocampal prosthesis. (A) Functional block diagram of the hippocampal prosthesis shows the parallel front-end signal processing for each probe. This architecture simplifies the processing and the separate channels that result in spike events make the design more robust and more reliable. (B) Block diagram of the MIMO model computational logic showing the finite state machine control for the Laguerre generator (Lag Gen) and the response generator and the interface to the coefficient memory. The simplified kernel computation and the final stimulation output are shown in the lower half of the figure.
Fig. 9
Fig. 9
Die photo of the Hippocampal Prosthesis VLSI fabricated in National Semiconductor Corporation’s 180-nm CMOS process with labels on the major functional elements MPLNA (Micro-Power Low-Noise Amplifier) and ADC, the Coefficient Memory and the STIM (Charge Metering Stimulation Outputs). The unlabeled areas surrounding these functional elements are “metal fill” to ensure uniformity of processing and are available if needed for additional circuitry.
See this image and copyright information in PMC

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References

    1. Berger TW, Orr WB. Hippocampectomy selectively disrupts discrimination reversal conditioning of the rabbit nictitating membrane response. Behav Brain Res. 1983 Apr;8:49–68. - PubMed
    1. Eichenbaum H, Fagan A, Mathews P, Cohen NJ. Hippocampal system dysfunction and odor discrimination learning in rats: Impairment or facilitation depending on representational demands. Behav Neurosci. 1988 Jun;102:331–9. - PubMed
    1. Milner B. Memory and The Medial Temporal Regions of the Brain. In: Pribram KH, Broadbent DE, editors. Biology of Memory. New York: Academic; 1970. pp. 29–50.
    1. Squire LR, Zola-Morgan S. The medial temporal lobe memory system. Science. 1991 Sep;253:1380–6. - PubMed
    1. Carey ME. Analysis of wounds incurred by U.S. army seventh corps personnel treated in corps hospitals during operation desert storm. J Trauma. 1996 Mar;40:S165–9. - PubMed

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