PT  - JOURNAL ARTICLE
AU  - Edda Bilek
AU  - Axel Schäfer
AU  - Elisabeth Ochs
AU  - Christine Esslinger
AU  - Maria Zangl
AU  - Michael M. Plichta
AU  - Urs Braun
AU  - Peter Kirsch
AU  - Thomas G. Schulze
AU  - Marcella Rietschel
AU  - Andreas Meyer-Lindenberg
AU  - Heike Tost
TI  - Application of High-Frequency Repetitive Transcranial Magnetic Stimulation to the DLPFC Alters Human Prefrontal–Hippocampal Functional Interaction
AID  - 10.1523/JNEUROSCI.3081-12.2013
DP  - 2013 Apr 17
TA  - The Journal of Neuroscience
PG  - 7050--7056
VI  - 33
IP  - 16
4099  - http://www.jneurosci.org/content/33/16/7050.short
4100  - http://www.jneurosci.org/content/33/16/7050.full
SO  - J. Neurosci.2013 Apr 17; 33
AB  - 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.