Altering stimulus timing via fast rhythmic sensory stimulation induces STDP-like recall performance in human episodic...

Episodic memory provides humans with the ability to mentally travel back to the past,¹ where experiences typically involve associations between multimodal information. Forming a memory of the association is thought to be dependent on modification of synaptic connectivity.^2,3 Animal studies suggest that the strength of synaptic modification depends on spike timing between pre- and post-synaptic neurons on the order of tens of milliseconds, which is termed "spike-timing-dependent plasticity" (STDP).⁴ Evidence found in human in vitro studies suggests different temporal scales in long-term potentiation (LTP) and depression (LTD), compared with the critical time window of STDP in animals.^5,6 In the healthy human brain, STDP-like effects have been shown in the motor cortex, visual perception, and face identity recognition.^{7,8,9,10,11,12,13} However, evidence in human episodic memory is lacking. We investigated this using rhythmic sensory stimulation to drive visual and auditory cortices at 37.5 Hz with four phase offsets. Visual relative to auditory cued recall accuracy was significantly enhanced in the 90° condition when the visual stimulus led at the shortest delay (6.67 ms). This pattern was reversed in the 270° condition when the auditory stimulus led at the shortest delay. Within cue modality, recall was enhanced when a stimulus of the corresponding modality led the shortest delay (6.67 ms) compared with the longest delay (20 ms). Our findings provide evidence for STDP in human episodic memory, which builds an important bridge from in vitro studies in animals to human memory behavior.