EN
Direct electrical stimulation of the human brain can elicit sensory and motor perceptions as well as recall of memories. Stimulating higher order asso‑ ciation areas of the lateral temporal cortex in par‑ ticular has been reported to activate visual and au‑ ditory memory representations of past experiences. We hypothesized that this effect could be utilized to modulate memory processing. Recent attempts at memory enhancement in the human brain have focused on the hippocampus and other mesial tem‑ poral lobe structures, with a few reports of memo‑ ry improvement in small studies of individual brain regions that have not been reproduced. We investi‑ gated the effect of stimulation in four brain regions thought to support declarative memory: hippocam‑ pus, parahippocampal neocortex, prefrontal cortex and temporal cortex. A classic verbal memory task was used to assess the effect of bipolar 50 Hz stimu‑ lation during encoding of word lists on subsequent free recall in human patients implanted with in‑ tracranial electrodes. We found enhanced recall of words from lists with electrical stimulation in the lateral temporal cortex, but not in the other three brain regions tested. This selective enhancement was observed on the level of individual subjects, sub‑ jects stimulated in the temporal cortex, and across the four brain regions studied. In effect, more words were remembered with than without stimulation in the lateral temporal cortex. Stimulation targets in the other brain regions had a negative effect on memory compared to targets in the temporal cortex. These differential behavioral effects were paralleled by modulation of neural activities in the high gam‑ ma frequency band (60‑120 Hz) during memory en‑ coding. These activities were proposed to reflect co‑ ordinated firing of neuronal assemblies – the hypo‑ thetical neural substrate for engrams. We conclude that electrical stimulation in specific brain areas can modulate neural processes induced during encoding of word engrams and enhance their recall. Gamma frequency activities provide a useful biomarker to map memory engrams and guide human brain stim‑ ulation.