PT - JOURNAL ARTICLE AU - Michal T. Kucewicz AU - Brent M. Berry AU - Vaclav Kremen AU - Laura R. Miller AU - Fatemeh Khadjevand AU - Youssef Ezzyat AU - Joel M. Stein AU - Paul Wanda AU - Michael R. Sperling AU - Richard Gorniak AU - Kathryn A. Davis AU - Barbara C. Jobst AU - Robert E. Gross AU - Bradley Lega AU - S Matt Stead AU - Daniel S Rizzuto AU - Michael J. Kahana AU - Gregory A. Worrell TI - Electrical Stimulation Modulates High Gamma Activity and Human Memory Performance. AID - 10.1523/ENEURO.0369-17.2018 DP - 2018 Jan 24 TA - eneuro PG - ENEURO.0369-17.2018 4099 - http://www.eneuro.org/content/early/2018/01/24/ENEURO.0369-17.2018.short 4100 - http://www.eneuro.org/content/early/2018/01/24/ENEURO.0369-17.2018.full AB - Direct electrical stimulation of the brain has emerged as a powerful treatment for multiple neurological diseases, and as a potential technique to enhance human cognition. Despite its application in a range of brain disorders, it remains unclear how stimulation of discrete brain areas affects memory performance and the underlying electrophysiological activities. Here, we investigated the effect of direct electrical stimulation in four brain regions known to support declarative memory: hippocampus, parahippocampal neocortex, prefrontal cortex and lateral temporal cortex. Intracranial EEG recordings with stimulation were collected from 22 patients during performance of verbal memory tasks. We found that high gamma (62-118 Hz) activity induced by word presentation was modulated by electrical stimulation. This modulatory effect was greatest for trials with ‘poor’ memory encoding. The high gamma modulation correlated with the behavioral effect of stimulation in a given brain region – it was negative, i.e. the induced high gamma activity was decreased, in the regions where stimulation decreased memory performance, and positive in the lateral temporal cortex where memory enhancement was observed. Our results suggest that the effect of electrical stimulation on high gamma activity induced by word presentation may be a useful biomarker for mapping memory networks and guiding therapeutic brain stimulation.Significance Statement Brain stimulation technologies for memory disorders can be advanced with improved understanding of the physiologic processes modulated by electrical current. In this study, intracranial EEG recordings from epilepsy patients performing memory tasks during direct brain stimulation revealed distinct changes in the induced high gamma activity, particularly on the trials with poor memory encoding. Given that these physiologic changes were correlated with the effect of stimulation on task performance, we propose they may be useful as a biomarker to optimize brain stimulation parameters for memory enhancement. These findings could help accelerate development of brain-machine interface technologies to treat memory and cognitive disorders.