Towards understanding rTMS mechanism of action: Stimulation of the DLPFC causes network-specific increase in functional connectivity

Martin Tik; André Hoffmann; Ronald Sladky; Livia Tomova; Allan Hummer; Lucia Navarro de Lara; Henryk Bukowski; Jürgen Pripfl; Bharat Biswal; Claus Lamm; Christian Windischberger

doi:10.1016/j.neuroimage.2017.09.022

Towards understanding rTMS mechanism of action: Stimulation of the DLPFC causes network-specific increase in functional connectivity

Martin Tik
, André Hoffmann
, Ronald Sladky
, Livia Tomova
, Allan Hummer
, Lucia Navarro de Lara
, Henryk Bukowski
, Jürgen Pripfl
, Bharat Biswal
, Claus Lamm
, Christian Windischberger (Corresponding author)

Department of Cognition, Emotion, and Methods in Psychology

Publications: Contribution to journal › Article › Peer Reviewed

Abstract

Transcranial magnetic stimulation (TMS) is a powerful non-invasive technique for the modulation of brain activity. While the precise mechanism of action is still unknown, TMS is applied in cognitive neuroscience to establish causal relationships between stimulation and subsequent changes in cerebral function and behavioral outcome. In addition, TMS is an FDA-approved therapeutic agent in psychiatric disorders, especially major depression. Successful repetitive TMS in such disorders is usually applied over the left dorso-lateral prefrontal cortex (DLPFC) and treatment response mechanism was therefore supposed to be based on modulations in functional networks, particularly the meso-cortico-limbic reward circuit. However, mechanistic evidence for the direct effects of rTMS over DLPFC is sparse. Here we show the specificity and temporal evolution of rTMS effects by comparing connectivity changes within 20 common independent components in a sham-controlled study. Using an unbiased whole-brain resting-state network (RSN) approach, we successfully demonstrate that stimulation of left DLPFC modulates anterior cingulate cortex (ACC) connectivity in one specific meso-cortico-limbic network, while all other networks are neither influenced by rTMS nor by sham treatment. The results of this study show that the neural correlates of TMS treatment response are also traceable in DLPFC stimulation of healthy brains and therefore represent direct effects of the stimulation procedure.

Original language	English
Pages (from-to)	289-296
Number of pages	8
Journal	NeuroImage
Volume	162
Early online date	12 Sept 2017
DOIs	https://doi.org/10.1016/j.neuroimage.2017.09.022
Publication status	Published - 15 Nov 2017

Funding

This research was financially supported by the CREAM project that has been funded by the European Commission under Grant Agreement no 612022 (FP7 ICT 2013-10). This publication reflects the views only of the authors, and the European Commission cannot be held responsible for any use that may be made of the information contained therein. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Additional financial support was supplied by the MMI-CNS research cluster (University of Vienna and Medical University of Vienna, FA103FC001 ) and the Austrian National Bank (OeNB, Anniversary Fund No. 14350 ).

Austrian Fields of Science 2012

301401 Brain research

Keywords

Journal Article
Clinical application
ICA
1000 Functional connectomes project
Resting-state
TMS

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10.1016/j.neuroimage.2017.09.022

Cite this

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title = "Towards understanding rTMS mechanism of action: Stimulation of the DLPFC causes network-specific increase in functional connectivity",

abstract = "Transcranial magnetic stimulation (TMS) is a powerful non-invasive technique for the modulation of brain activity. While the precise mechanism of action is still unknown, TMS is applied in cognitive neuroscience to establish causal relationships between stimulation and subsequent changes in cerebral function and behavioral outcome. In addition, TMS is an FDA-approved therapeutic agent in psychiatric disorders, especially major depression. Successful repetitive TMS in such disorders is usually applied over the left dorso-lateral prefrontal cortex (DLPFC) and treatment response mechanism was therefore supposed to be based on modulations in functional networks, particularly the meso-cortico-limbic reward circuit. However, mechanistic evidence for the direct effects of rTMS over DLPFC is sparse. Here we show the specificity and temporal evolution of rTMS effects by comparing connectivity changes within 20 common independent components in a sham-controlled study. Using an unbiased whole-brain resting-state network (RSN) approach, we successfully demonstrate that stimulation of left DLPFC modulates anterior cingulate cortex (ACC) connectivity in one specific meso-cortico-limbic network, while all other networks are neither influenced by rTMS nor by sham treatment. The results of this study show that the neural correlates of TMS treatment response are also traceable in DLPFC stimulation of healthy brains and therefore represent direct effects of the stimulation procedure.",

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AU - Hummer, Allan

AU - Navarro de Lara, Lucia

AU - Bukowski, Henryk

AU - Pripfl, Jürgen

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AU - Lamm, Claus

AU - Windischberger, Christian

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KW - ICA

KW - 1000 Functional connectomes project

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KW - TMS

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Towards understanding rTMS mechanism of action: Stimulation of the DLPFC causes network-specific increase in functional connectivity

Abstract

Funding

Austrian Fields of Science 2012

Keywords

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