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Eur Heart J. 2019 Apr 14;40(15):1183-1187. doi: 10.1093/eurheartj/ehz068.

Altered limbic and autonomic processing supports brain-heart axis in Takotsubo syndrome.

Author information

University Heart Center, Department of Cardiology, University Hospital Zurich, Raemistrasse 100, Zurich, Switzerland.
Division Neuropsychology, Department of Psychology, University of Zurich, Binzmuehlestrasse 14, Zurich, Switzerland.
Center for Molecular Cardiology, Schlieren Campus, University of Zurich, Wagistrasse 12, Schlieren, Switzerland.
Royal Brompton and Harefield Hospitals Trust and Imperial College, Cardiology, Sydney Street, London, UK.
University Research Priority Program (URPP), Dynamic of Healthy Aging, University of Zurich, Andreasstrasse 15, Zurich, Switzerland.



Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction often triggered by emotional or physical stress. Severe activation of the sympathetic nervous system with catecholamine release caused by a dysfunctional limbic system has been proposed as a potential mechanism. We hypothesize that brain regions responsible for autonomic integration and/or limbic processing might be involved in the development of TTS. Here, we investigated alterations in resting state functional connectivity in TTS patients compared with healthy controls.


Using brain functional magnetic resonance imaging (fMRI), resting state functional connectivity has been assessed in 15 subjects with TTS and 39 healthy controls. Network-based statistical analyses were conducted to identify subnetworks with altered resting state functional connectivity. Sympathetic and parasympathetic networks have been constructed in addition to the default mode network and whole-brain network. We found parasympathetic- and sympathetic-associated subnetworks both showing reduced resting state functional connectivity in TTS patients compared with controls. Important brain regions constituting parasympathetic- and sympathetic-associated subnetworks included the amygdala, hippocampus, and insula as well as cingulate, parietal, temporal, and cerebellar regions. Additionally, the default mode network as well as limbic regions in the whole-brain analysis demonstrated reduced resting state functional connectivity in TTS, including the hippocampus, parahippocampal, and medial prefrontal regions.


For the first time, we demonstrate hypoconnectivity of central brain regions associated with autonomic functions and regulation of the limbic system in patients with TTS. These findings suggest that autonomic-limbic integration might play an important role in the pathophysiology and contribute to the understanding of TTS.


Sympathetic; Autonomic-limbic integration; Brain–heart connection; Parasympathetic; Resting state fMRI; Takotsubo syndrome

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