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Front. Hum. Neurosci. | doi: 10.3389/fnhum.2018.00077

Single Session Low Frequency Left Dorsolateral Prefrontal Transcranial Magnetic Stimulation Changes Neurometabolite Relationships in Healthy Humans

 Nathaniel R. Bridges1*,  Richard A. McKinley1,  Danielle Boeke1,  Matthew S. Sherwood2,  Jason G. Parker3, Lindsey K. McIntire4, Justin M. Nelson4, Catherine Fletchall5,  Natasha Alexander5, Amanda N. McConnell5, Chuck Goodyear4 and Jeremy T. Nelson6
  • 1Air Force Research Laboratory, United States
  • 2Wright State Research Institute, Wright State University, United States
  • 3Kettering Health Network Innovation Center, United States
  • 4Infoscitex Inc., United States
  • 5Grandview Medical Center, Kettering Health Network, United States
  • 6Research Imaging Institute, School of Medicine, University of Texas Health Science Center at San Antonio, United States

Background: Dorsolateral prefrontal cortex (DLPFC) low frequency repetitive transcranial magnetic stimulation (LF-rTMS) has shown promise as a treatment and investigative tool in the medical and research communities. Researchers have made significant progress elucidating DLPFC LF-rTMS effects—primarily in individuals with psychiatric disorders. However, more efforts investigating underlying molecular changes and establishing links to functional and behavioral outcomes in healthy humans are needed.
Objective: We aimed to quantify neuromolecular changes and relate these to functional changes following a single session of DLPFC LF-rTMS in healthy participants.
Methods: 11 participants received sham-controlled neuronavigated 1Hz rTMS to the region most activated by a 7-letter Sternberg task (SWMT) within the left DLPFC. We quantified SWMT performance, functional magnetic resonance activation and proton magnetic resonance spectroscopy neurometabolite measure changes before and after stimulation.
Results: A single LF-rTMS session was not sufficient to change DLPFC neurometabolite levels and these changes did not correlate with DLPFC activation changes. Real rTMS, however, significantly altered neurometabolite correlations (compared to sham rTMS), both with baseline levels and between the metabolites themselves. Additionally, real rTMS was associated with diminished reaction time performance improvements and increased activation within the motor, somatosensory and lateral occipital cortices.
Conclusion: These results show that a single session of LF-rTMS is sufficient to influence metabolite relationships and causes widespread activation in healthy humans. Investigating correlational relationships may provide insight into mechanisms underlying LF-rTMS.

Keywords: Transcranial magnetic stimulation (TMS), dorsolateral prefrontal cortex (DLPFC), Low frequency, Magnetic Resonance Spectroscopy, Sternberg task, healthy subjects

Received: 27 Sep 2017; Accepted: 12 Feb 2018.

Edited by:

Adrian G. Guggisberg, Université de Genève, Switzerland

Reviewed by:

Florian Müller-Dahlhaus, Universität Tübingen, Germany
Jean Schoenen, University of Liège, Belgium
Dario Cazzoli, ARTORG Zentrum für Biomedizinische Technikforschung, Medizinische Fakultät, Universität Bern, Switzerland  

Copyright: © 2018 Bridges, McKinley, Boeke, Sherwood, Parker, McIntire, Nelson, Fletchall, Alexander, McConnell, Goodyear and Nelson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Nathaniel R. Bridges, Air Force Research Laboratory, Bldg 840, 2510 Fifth Street, Wright-Patterson AFB, Dayton, 45433-7951, OH, United States,