Conjunctive coding of letter pairs emerges in segregated human medial temporal lobe neurons during working memory

Abstract

Composing individual memory traces into unified representations is fundamental to encoding of structured relationships and flexible cognition. A central debate in neuroscience concerns the neural mechanisms of these compositions: are these compositions encoded through mixed selectivity, where the same neurons simultaneously represent individual and composed items, or through conjunctive coding within a distinct and specialized neuronal population? Here, we tested these competing hypotheses by recording 996 single units from the medial temporal lobe of 11 epilepsy patients performing a letter-string working memory task. We found neural encoding of both single letters and letter pairs during task related periods, with the latter peaking during the maintenance phase. Crucially, letter pairs were encoded by a sparse subset of neurons that did not show significant selectivity for their constituent letters. This suggests the existence of a segregated population of neurons recruited to compose items independently of single letter neural encoding. These findings provide evidence that the human medial temporal lobe separately encodes compositions within segregated neurons, offering direct neurophysiological support for conjunctive coding at the single-neuron level.