Specific responses of human hippocampal neurons are associated with better memory

Abstract

A population of human hippocampal neurons has shown responses to individual concepts (e.g., Jennifer Aniston) that generalize to different instances of the concept. However, recordings from the rodent hippocampus suggest an important function of these neurons is their ability to discriminate overlapping representations, or pattern separate, a process that may facilitate discrimination of similar events for successful memory. In the current study, we explored whether human hippocampal neurons can also demonstrate the ability to discriminate between overlapping representations and whether this selectivity could be directly related to memory performance. We show that among medial temporal lobe (MTL) neurons, certain populations of neurons are selective for a previously studied (target) image in that they show a significant decrease in firing rate to very similar (lure) images. We found that a greater proportion of these neurons can be found in the hippocampus compared with other MTL regions, and that memory for individual items is correlated to the degree of selectivity of hippocampal neurons responsive to those items. Moreover, a greater proportion of hippocampal neurons showed selective firing for target images in good compared with poor performers, with overall memory performance correlated with hippocampal selectivity. In contrast, selectivity in other MTL regions was not associated with memory performance. These findings show that a substantial proportion of human hippocampal neurons encode specific memories that support the discrimination of overlapping representations. These results also provide previously unidentified evidence consistent with a unique role of the human hippocampus in orthogonalization of representations in declarative memory.

Keywords: discrimination; hippocampus; invariance; memory; selectivity.

Fig. 1.

Subjects learned (encoding) and recognized (recognition) photographs of famous faces. During the encoding block, subjects saw 10 photographs of 10 famous individuals in random order and were instructed to learn the photographs. During the recognition block, subjects saw previously learned (target) photographs and novel (lure and foil) photographs and were asked whether they had seen the photograph before by pressing one of two buttons. (Top) Image courtesy of Bob McNeely (The White House). (Bottom, Left to Right) Images courtesy of ©ImageCollect.com/Alpha-Globe Photos, Inc.; US Department of Defense and Eric Draper; Bob McNeely (The White House); and ©ImageCollect.com photographers James Colburn/ipol/Globe Photos, Inc. and acepixs.

Fig. 2.

(A) Shown is percentage correct for recognition of the target image averaged across 40 sessions from 25 patients (n = 40) split into low and high performers. (B) Shown is the memory performance for lure images as measured by the discrimination index score (p(“New”|Lure) – p(“New”|Target)). A discrimination index score of 1 would be the maximal possible score, indicating high performance on the memory task. Lure 1 = most similar and lure 3 = least similar to the target photograph.

Fig. 3.

Example single-unit responses. An example of a target-selective unit in the CA3 and dentate gyrus (CA3DG) (A) and subiculum (B) in a high performer, which significantly increases in firing rate (Hertz) to the target image much more so than to the lure and foil images during retrieval. (C and D) Shown is an example of a target-responsive unit in CA3DG in a low performer, which significantly increases in firing rate similarly to both the target and lure image. Images courtesy of (A, Left to Right) ©ImageCollect.com photographers Ken Babolcsay-Ipol/Globe Photo, StarMaxWorldwide, Acepixs, Roger Harvey-Globe Photos, Byron Purvis/AdMedia; (B, Left to Right) Bob McNeely (The White House); ©ImageCollect.com photographers Alpha-Globe Photos Inc., James Colburn/ipol/Globe Photos Inc., and acepixs; US Department of Defense and Eric Draper; (C, Left to Right) ©ImageCollect.com photographers Jonathan Alcorn/ZUMA Press, Paul Skipper/glob Ephotos Inc., Ken Babolcsay/Ipol/Globe Photos Inc., Donald Sanders-Globe Photos Inc., Christopher Little/cbs; (D, Left to Right) ©ImageCollect.com photographers Rick Mackler Rangefinder-Globe Photos Inc., StarMaxWorldwide, s_bukley, Nina Prommer-Globe Photos Inc., Clinton H. Wallace/ipol/Globe Photos Inc.

Fig. 4.

(A) Shown is the percentage of target-responsive units that significantly increased in firing rate to the target image only (target-selective) and not to lure or foil images. We found more target-selective units within the hippocampus [CA3, and dentate gyrus (CA3DG) and subiculum] in high compared with low performers. No significant differences were found in the proportion of target-selective units in high compared with low performers in the ERC, PHC, or amygdala. (B) Shown is the significant correlation between memory performance (discrimination index score) and the percentage reduction in average firing rate from the target to the most similar lure (Lure 1) in the hippocampus (combined CA3DG and subiculum). Each data point reflects the firing rate reduction from target to lure 1 averaged across all target responsive units within a given subject.