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Theta-burst microstimulation in the human entorhinal area improves memory specificity

Titiz, Ali S. and Hill, Michael R. H. and Mankin, Emily A. and Aghajan, Zahra M. and Eliashiv, Dawn and Tchemodanov, Natalia and Maoz, Uri and Stern, John and Tran, Michelle E. and Schuette, Peter and Behnke, Eric and Suthana, Nanthia A. and Fried, Itzhak (2017) Theta-burst microstimulation in the human entorhinal area improves memory specificity. eLife, 6 . Art. No. e29515. ISSN 2050-084X. PMCID PMC5655155. https://resolver.caltech.edu/CaltechAUTHORS:20171030-090445181

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Abstract

The hippocampus is critical for episodic memory, and synaptic changes induced by long-term potentiation (LTP) are thought to underlie memory formation. In rodents, hippocampal LTP may be induced through electrical stimulation of the perforant path. To test whether similar techniques could improve episodic memory in humans, we implemented a microstimulation technique that allowed delivery of low-current electrical stimulation via 100 μm-diameter microelectrodes. As thirteen neurosurgical patients performed a person recognition task, microstimulation was applied in a theta-burst pattern, shown to optimally induce LTP. Microstimulation in the right entorhinal area during learning significantly improved subsequent memory specificity for novel portraits; participants were able both to recognize previously-viewed photos and reject similar lures. These results suggest that microstimulation with physiologic level currents—a radical departure from commonly used deep brain stimulation protocols—is sufficient to modulate human behavior and provides an avenue for refined interrogation of the circuits involved in human memory.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.7554/eLife.29515DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655155/PubMed CentralArticle
ORCID:
AuthorORCID
Mankin, Emily A.0000-0003-2163-913X
Aghajan, Zahra M.0000-0003-4245-3975
Maoz, Uri0000-0002-7899-1241
Fried, Itzhak0000-0002-5962-2678
Additional Information:© 2017 Titiz et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. Received: 12 June 2017; Accepted: 03 October 2017; Published: 24 October 2017. We thank Tony Fields, Kirk Shattuck, Michael Jenkins, and Antonio Campos for technical assistance; Deena Pourshaban, Marianna Holliday, Samantha Briones, Nancy Guerrero, Güldamla Kalender, and Brooke Salaz for general assistance; the IDRE statistical consulting group at UCLA for providing insightful discussions regarding statistical analysis methods, and the participants for volunteering for this study. Funding: This paper was supported by the following grants: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung PBSKP3-124730 to Michael R H Hill. National Institute of Neurological Disorders and Stroke NS084017 to Itzhak Fried. National Institute of Neurological Disorders and Stroke NS058280 to Emily A Mankin, Zahra M Aghajan. A.P. Giannini Foundation Postdoctoral Fellowship to Emily A Mankin. Defense Advanced Research Projects Agency N66001-14-2-4029 to Itzhak Fried. G. Harold and Leila Y. Mathers Charitable Foundation 09212007 to Itzhak Fried. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Competing interests: No competing interests declared. Author Contributions: Formal analysis, Investigation, Writing—original draft, Writing—review and editing. Conceptualization, Software, Funding acquisition, Validation, Investigation, Methodology, Critically reviewed manuscript. Data curation, Software, Formal analysis, Funding acquisition, Validation, Investigation, Visualization, Writing—original draft, Writing—review and editing. Data curation, Formal analysis, Validation, Writing—original draft, Writing—review and editing. Investigation, Methodology, Critically reviewed manuscript. Software, Investigation, Critically reviewed manuscript. Software, Formal analysis, Critically reviewed manuscript. Investigation, Methodology, Critically reviewed manuscript. Data curation, Formal analysis, Investigation, Project administration, Critically reviewed manuscript. Formal analysis, Visualization, Critically reviewed manuscript. Visualization, Methodology, Critically reviewed manuscript. Conceptualization, Supervision, Funding acquisition, Investigation, Methodology, Project administration, Writing—review and editing. Conceptualization, Resources, Supervision, Funding acquisition, Investigation, Methodology, Writing—original draft, Project administration, Writing—review and editing. Ethics: Human subjects: All research was carried out at the UCLA Medical Center and the UCLA Institutional Review Board approved the study protocol (IRB#10-000973). All subjects provided written consent to participate in the study.
Funders:
Funding AgencyGrant Number
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungPBSKP3-124730
NIHNS084017
NIHNS058280
A. P. Giannini FoundationUNSPECIFIED
Defense Advanced Research Projects Agency (DARPA)N66001-14-2-4029
G. Harold and Leila Y. Mathers Charitable Foundation09212007
PubMed Central ID:PMC5655155
Record Number:CaltechAUTHORS:20171030-090445181
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20171030-090445181
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:82768
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:30 Oct 2017 19:57
Last Modified:05 Mar 2020 00:14

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