Developing a hippocampal neural prosthetic to facilitate human memory encoding and recall of stimulus features and categories

Abstract

Objective: Here, we demonstrate the first successful use of static neural stimulation patterns for specific information content. These static patterns were derived by a model that was applied to a subject's own hippocampal spatiotemporal neural codes for memory.

Approach: We constructed a new model of processes by which the hippocampus encodes specific memory items via spatiotemporal firing of neural ensembles that underlie the successful encoding of targeted content into short-term memory. A memory decoding model (MDM) of hippocampal CA3 and CA1 neural firing was computed which derives a stimulation pattern for CA1 and CA3 neurons to be applied during the encoding (sample) phase of a delayed match-to-sample (DMS) human short-term memory task.

Main results: MDM electrical stimulation delivered to the CA1 and CA3 locations in the hippocampus during the sample phase of DMS trials facilitated memory of images from the DMS task during a delayed recognition (DR) task that also included control images that were not from the DMS task. Across all subjects, the stimulated trials exhibited significant changes in performance in 22.4% of patient and category combinations. Changes in performance were a combination of both increased memory performance and decreased memory performance, with increases in performance occurring at almost 2 to 1 relative to decreases in performance. Across patients with impaired memory that received bilateral stimulation, significant changes in over 37.9% of patient and category combinations was seen with the changes in memory performance show a ratio of increased to decreased performance of over 4 to 1. Modification of memory performance was dependent on whether memory function was intact or impaired, and if stimulation was applied bilaterally or unilaterally, with nearly all increase in performance seen in subjects with impaired memory receiving bilateral stimulation.

Significance: These results demonstrate that memory encoding in patients with impaired memory function can be facilitated for specific memory content, which offers a stimulation method for a future implantable neural prosthetic to improve human memory.

Keywords: CA1; CA3; cognition; neurophysiology; nonlinear; prosthetic.

Figure 1

Delayed match to sample (DMS) task performed on a touch screen by patients seated in either the hospital bed or a chair. Trial is started by patient touching a focus ring which causes the sample image to be presented (SP). After patient responds by touching the sample image there is a delay and then the match image is presented (MP). Patient touches one of the images in the match phase to end the trial. During recording sessions, a 4 s window centered on SR is recorded and used for computation of Category-Specific code. During stimulation sessions, a 4 s stimulation is started at SP.

Figure 2

Sample patterns from an individual patient for each of the categories. Unique patterns that were 4 s in length were derived for each subject for every patient using the MDM applied to each patient’s own neural recordings. Each “tick” marks a single stimulation pulse (1 ms duration, 150 μA constant current ~1 V, biphasic, 50 ms per phase) on a channel. As multiple neurons could be isolated on an individual trial during a recording session, the MDM model calculated stimulation patterns by channel and not by neuron. Subsequent stimulation pulses for a given channel occurred no sooner than 50 ms (20 Hz). Note theta-frequency-like clusters (~4 Hz) in some categories.

Figure 3

Diagram of an individual-trial DR screen following DMS stimulation session. Images consist of the sample/match image, one Nonmatch image from the same trial, and one novel image not used in any prior testing. The “familiarity” choices displayed with each image are converted to a numeric ranking (0 = Do not recognize, 5 = Definitely saw) for scoring and analysis.

Figure 4

Heat maps of significant results. Significant results shown between Match Stim vs. NoStim (top row) and NonMatch Stim vs. NoStim (bottom row) per subject and category. Significant results with a decrease in performance are indicated with yellow and orange, and increased performance with blue. Grey indicates no significant difference in performance. Squares with black Xs indicate combinations with too few trials to compute.

Figure 5

Heat maps of significant results. Significant results shown between Match Stim vs. NoStim (top rows) and NonMatch Stim vs. NoStim (bottom rows) per subject and category, broken down by unilateral or bilateral stimulation, and by impaired or intact memory in subjects. Significant results with a decrease in performance are indicated with yellow and orange, and increased performance with blue. Grey indicates no significant difference in performance. Squares with black Xs indicate combinations with too few trials to compute.

Figure 6

(A) Graph of individual patient performance on stimulated and non stimulated trials. DMS performance is for all trials combined and is not an average of performance within categories. (B) Graph showing the relative differences of patient performance between stimulated and non stimulated trials using non stimulated trials as a baseline.

Figure 7

Graph of category performance on stimulated and non stimulated trials. Performance for each category was calculated by combining all trials from all patients and not by averaging the performances of the patients within a category.