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

Abstract

Aims 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. Methods and results 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. Conclusion 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.

The Brain-Heart Connection in Takotsubo Syndrome: The Central Nervous System, Sympathetic Nervous System, and Catecholamine Overload

“…Specifically, patients with TTS had a cortex over the limbic region and significantly reduced connectivity in the autonomic nervous system, including the left amygdala, both hippocampi, the left superior temporal pole, and right putamen [47]. Moreover, a recently published study similarly reported reduced functional connectivity in the limbic systems of patients with TTS patients relative to healthy individuals [48]. As noted above, the proportion of individuals with mental disorders was found to be higher among patients with TTS than in a general population.…”

Takotsubo syndrome: between evidence, myths, and misunderstandings

“…In total, 50% of patients with TS suffer from an acute or chronic neurological or psychiatric disease [4], which suggests that the brain may be a critical component during pathogenesis. A recent study showed characteristic activity of brain regions in functional MRI [47], which may be the basis for future research to identify specific changes of regional brain function potentially inducing myocardial stunning. As outlined above, a "humoral" hypothesis postulates that circulating catecholamines, sex hormones, and others finally induce or trigger TS.…”

COVID‑19 related stress exacerbates common physical and mental pathologies and affects treatment (Review)

“…The brain-heart interaction has been long acknowledged as a significant factor for various cardiovascular diseases (15). Overstimulation of the sympathetic nervous system due to physical or emotional stressors has been hypothesized as the underlying cause of myocardial infarction, hypertension, arrythmias and stress induced/Takotsubo cardiomyopathy (15)(16)(17).…”