Abstracts

Rationale: Episodic memories allow us to remember not only that we have seen an item before (familiarity) but also provide a subjective impression of how sure we are that we have seen an item before (confidence). The neuronal mechanisms of confidence judgment about one's own memories are poorly understood. The medial temporal lobe (MTL) plays an important role in both the estimation of memory strength as well as visual categorization, but how these processes interact is unclear. Methods: We recorded single neurons in the MTL of patients implanted with depth electrodes for the purpose of localizing epileptic seizures. Patients viewed a sequence of 100 images, 50 of which were novel and 50 of which they had seen before. Patients rated each image as new/old on a 1-6 confidence scale. Single neuron responses were quantified with a Receiver Operating Characteristics (ROC) analysis. The area under the curve (AUC) of the ROC was used as the principal metric. We further analyzed all recorded neurons together to quantify neuronal dynamics. For this population analysis, we performed a regression analysis to estimate the effect size (ω²) and to quantify how much of the neuronal variance could be attributed to visual category and/or familiarity. Results: We recorded in total 1193 neurons from the hippocampus and amygdala from 28 patients in 46 sessions. 95 (8%) of units differentiated new from old stimuli (NO neurons) and their AUC was larger for images remembered with high compared to low subjective confidence (0.68±0.05 vs. 0.63±0.05, p<0.001). This indicates that the neuronal response contained more information when memories were retrieved with high confidence. A separate group of 134 (11%) neurons differentiated the visual category (such as animal, person, or car) of the displayed stimuli. There was no significant overlap between the two groups. Category neurons only explain variance due to visual category but not familiarity (peak ω² 2.36% vs 0.57%, respectively; p < 0.001), and vice versa (peak ω² 0.65% vs. 5.87%, respectively; p < 0.01). The effect size of visual category peaked ~400ms before that for memory (new/old). Conclusions: Only the familiarity-related effect size was modulated by subjective memory strength. The memory signal was ~3 times more informative (mutual information) when retrieval occurred with high compared vs. low confidence. We conclude that NO and category neurons are two distinct functional neuronal populations in the human MTL. Together, these two groups of neurons represent the fundamental attributes of memory: visual category ("what") and familiarity ("new/old"). These findings provide new insights into the neural mechanisms of memory retrieval.