INTRODUCTION: The medial temporal lobe (MTL) contains neurons responding selectively to abstract concepts. Two subtypes exist: image-selective, responding only to visual stimuli, and concept-selective (multimodal) neurons, activating for the same concept regardless of modality. Persistent Activity (PA) —sustained elevated firing during retention is considered the primary working memory maintenance mechanism in the MTL.

AIM(S): To compare activity of image-selective and concept-selective MTL neurons across all phases of a modified Sternberg task, identifying which type exhibits Persistent Activity during memory retention.

METHOD(S): Single-unit recordings were obtained from 19 epilepsy patients with Behnke-Fried depth electrodes across three clinical centers. Patients encoded an image, maintained it across two 2.5-second retention periods separated by a distractor, then performed recognition. Neurons were classified using the ZETA test; firing rates were z-scored relative to baseline. Mixed ANOVA and t-tests were applied.

RESULTS: 17 image-selective and 8 concept-selective neurons were analyzed. Concept-selective neurons responded more strongly during encoding (1.20 vs. 0.61 Hz; p = 0.003). In the first retention period, only concept-selective neurons showed significant PA — elevated firing for the preferred stimulus and below-baseline suppression otherwise (p = 0.001). No significant PA emerged in the second retention period. Response latencies were comparable (~490 ms).

CONCLUSIONS: PA in the MTL is specific to concept-selective neurons. The bidirectional modulation suggests these cells actively maintain working memory content, possibly through the phonological loop. Excluding image-selective neurons from PA analyses may improve interpretive precision in future research.

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