Gene-expression correlates of the oscillatory signatures supporting human episodic memory encoding

In humans, brain oscillations support critical features of memory formation. However, understanding the molecular mechanisms underlying this activity remains a major challenge. Here, we measured memory-sensitive oscillations using intracranial electroencephalography recordings from the temporal cortex of patients performing an episodic memory task. When these patients subsequently underwent resection, we employed transcriptomics on the temporal cortex to link gene expression with brain oscillations and identified genes correlated with oscillatory signatures of memory formation across six frequency bands. A co-expression analysis isolated oscillatory signature-specific modules associated with neuropsychiatric disorders and ion channel activity, with highly correlated genes exhibiting strong connectivity within these modules. Using single-nucleus transcriptomics, we further revealed that these modules are enriched for specific classes of both excitatory and inhibitory neurons, and immunohistochemistry confirmed expression of highly correlated genes. This unprecedented dataset of patient-specific brain oscillations coupled to genomics unlocks new insights into the genetic mechanisms that support memory encoding.

Automated summary

This study investigated the molecular mechanisms underlying memory formation through analyzing patient-specific brain oscillations and gene expression, revealing correlations between specific genes and oscillatory signatures of memory formation in different frequency bands. The study showed that these genes are associated with neuropsychiatric disorders and ion channel activity, and are enriched in excitatory and inhibitory neurons. The findings provide new insights into the genetic mechanisms that support memory encoding.