Application of high-frequency repetitive transcranial magnetic stimulation to the DLPFC alters human prefrontal-hippocampal functional interaction

Edda Bilek, Axel Schäfer, Elisabeth Ochs, Christine Esslinger, Maria Zangl, Michael M. Plichta, Urs Braun, Peter Kirsch, Thomas G. Schulze, Marcella Rietschel, Andreas Meyer-Lindenberg, Heike Tost

Research output: Contribution to journalArticle

Abstract

Neural plasticity is crucial for understanding the experience-dependent reorganization of brain regulatory circuits and the pathophysiology of schizophrenia. An important circuit-level feature derived from functional magnetic resonance imaging (fMRI) is prefrontal-hippocampal seeded connectivity during working memory, the best established intermediate connectivity phenotype of schizophrenia risk to date. The phenotype is a promising marker for the effects of plasticity-enhancing interventions, such as high-frequency repetitive transcranial magnetic stimulation (rTMS), and can be studied in healthy volunteers in the absence of illness-related confounds, but the relationship to brain plasticity is unexplored. We recruited 39 healthy volunteers to investigate the effects of 5 Hz rTMS on prefrontal-hippocampal coupling during working memory and rest. In a randomized and sham-controlled experiment, neuronavigation-guided rTMS was applied to the right dorsolateral prefrontal cortex (DLPFC), and fMRI and functional connectivity analyses [seeded connectivity and psychophysiological interaction (PPI)] were used as readouts. Moreover, the test-retest reliability of working-memory related connectivity markers was evaluated. rTMS provoked a significant decrease in seeded functional connectivity of the right DLPFC and left hippocampus during working memory that proved to be relatively time-invariant and robust. PPI analyses provided evidence for a nominal effect of rTMS and poor test-retest reliability. No effects on n-back-related activation and DLPFC-hippocampus resting-state connectivity were observed. These data provide the first in vivo evidence for the effects of plasticity induction on human prefrontal-hippocampal network dynamics, offer insights into the biological mechanisms of a well established intermediate phenotype linked to schizophrenia, and underscores the importance of the choice of outcome measures in test-retest designs.

Original languageEnglish (US)
Pages (from-to)7050-7056
Number of pages7
JournalJournal of Neuroscience
Volume33
Issue number16
DOIs
StatePublished - Apr 17 2013
Externally publishedYes

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Transcranial Magnetic Stimulation
Prefrontal Cortex
Short-Term Memory
Schizophrenia
Phenotype
Reproducibility of Results
Hippocampus
Healthy Volunteers
Magnetic Resonance Imaging
Neuronavigation
Neuronal Plasticity
Brain
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Application of high-frequency repetitive transcranial magnetic stimulation to the DLPFC alters human prefrontal-hippocampal functional interaction. / Bilek, Edda; Schäfer, Axel; Ochs, Elisabeth; Esslinger, Christine; Zangl, Maria; Plichta, Michael M.; Braun, Urs; Kirsch, Peter; Schulze, Thomas G.; Rietschel, Marcella; Meyer-Lindenberg, Andreas; Tost, Heike.

In: Journal of Neuroscience, Vol. 33, No. 16, 17.04.2013, p. 7050-7056.

Research output: Contribution to journalArticle

Bilek, E, Schäfer, A, Ochs, E, Esslinger, C, Zangl, M, Plichta, MM, Braun, U, Kirsch, P, Schulze, TG, Rietschel, M, Meyer-Lindenberg, A & Tost, H 2013, 'Application of high-frequency repetitive transcranial magnetic stimulation to the DLPFC alters human prefrontal-hippocampal functional interaction', Journal of Neuroscience, vol. 33, no. 16, pp. 7050-7056. https://doi.org/10.1523/JNEUROSCI.3081-12.2013
Bilek, Edda ; Schäfer, Axel ; Ochs, Elisabeth ; Esslinger, Christine ; Zangl, Maria ; Plichta, Michael M. ; Braun, Urs ; Kirsch, Peter ; Schulze, Thomas G. ; Rietschel, Marcella ; Meyer-Lindenberg, Andreas ; Tost, Heike. / Application of high-frequency repetitive transcranial magnetic stimulation to the DLPFC alters human prefrontal-hippocampal functional interaction. In: Journal of Neuroscience. 2013 ; Vol. 33, No. 16. pp. 7050-7056.
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