The genomic underpinnings of oscillatory biomarkers supporting successful memory encoding in humans

Abstract

In humans, brain oscillations are thought to support critical features of memory formation such as coordination of activity across regions, consolidation, and temporal ordering of events. However, understanding the molecular mechanisms underlining this activity in humans remains a major challenge. Here, we measured memory-sensitive oscillations using direct intracranial electroencephalography recordings from the temporal cortex of patients performing an episodic memory task. By then employing transcriptomics on the resected tissue from the same patients, we linked gene expression with brain oscillations, identifying genes correlated with oscillatory signatures of memory formation across six frequency bands. A co-expression analysis isolated biomarker-specific modules associated with neuropsychiatric disorders as well as ion channel activity. Using single-nuclei transcriptomic data from this resected tissue, we further revealed that biomarker-specific modules are enriched for both excitatory and inhibitory neurons. This unprecedented dataset of patient-specific brain oscillations coupled to genomics unlocks new insights into the genetic mechanisms that support memory encoding. By linking brain expression of these genes to oscillatory patterns, our data help overcome limitations of phenotypic methods to uncover genetic links to memory performance.