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Published in: Clinical Research in Cardiology 9/2020

Open Access 01-09-2020 | Original Paper

Functional neuroimaging in the acute phase of Takotsubo syndrome: volumetric and functional changes of the right insular cortex

Authors: Wolfgang Dichtl, Noora Tuovinen, Fabian Barbieri, Agne Adukauskaite, Thomas Senoner, Andrea Rubatscher, Florian Hintringer, Christian Siedentopf, Axel Bauer, Elke R. Gizewski, Ruth Steiger

Published in: Clinical Research in Cardiology | Issue 9/2020

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Abstract

Background

A brain–heart interaction has been proposed in Takotsubo syndrome (TTS). Structural changes in the limbic system and hypoconnectivity between certain brain areas in the chronic phase of the disease have been reported, but little is known concerning functional neuroimaging in the acute phase. We hypothesized anatomical and functional changes in the central nervous system and investigated whole-brain volumetric and functional connectivity alterations in the acute phase TTS patients compared to controls.

Methods

Anatomical and resting-state functional magnetic resonance imaging were performed in postmenopausal females: thirteen in the acute TTS phase and thirteen healthy controls without evidence of coronary artery disease. Voxel-based morphometry and graph theoretical analysis were applied to identify anatomical and functional differences between patients and controls.

Results

Significantly lower gray matter volumes were found in TTS patients in the right middle frontal gyrus (p = 0.004) and right subcallosal cortex (p = 0.009) compared to healthy controls. When lower threshold was applied, volumetric changes were noted in the right insular cortex (p = 0.0113), the right paracingulate cortex (p = 0.012), left amygdala (p = 0.018), left central opercular cortex (p = 0.017), right (p = 0.013) and left thalamus (p = 0.017), and left cerebral cortex (p = 0.017). Graph analysis revealed significantly (p < 0.01) lower functional connectivity in TTS patients compared to healthy controls, particularly in the connections originating from the right insular cortex, temporal lobes, and precuneus.

Conclusion

In the acute phase of TTS volumetric changes in frontal regions and the central autonomic network (i.e. insula, anterior cingulate cortex, and amygdala) were noted. In particular, the right insula, associated with sympathetic autonomic tone, had both volumetric and functional changes.

Graphic abstract

Literature
1.
go back to reference Porto I, Della Bona R, Leo A, Proietti M, Pieroni M, Caltagirone C et al (2013) Stress cardiomyopathy (takotsubo) triggered by nervous system diseases: a systematic review of the reported cases. Int J Cardiol 167:2441–2448CrossRef Porto I, Della Bona R, Leo A, Proietti M, Pieroni M, Caltagirone C et al (2013) Stress cardiomyopathy (takotsubo) triggered by nervous system diseases: a systematic review of the reported cases. Int J Cardiol 167:2441–2448CrossRef
2.
go back to reference Templin C, Ghadri J, Bataiosu DR, Dieckmann J, Jaguszewski M, Sarcon A et al (2015) Clinical characteristics, diagnosis and outcome of Takotsubo cardiomyopathy—results from the International Takotsubo Registry (InterTAK Registry). N Engl J Med 373:929–938CrossRef Templin C, Ghadri J, Bataiosu DR, Dieckmann J, Jaguszewski M, Sarcon A et al (2015) Clinical characteristics, diagnosis and outcome of Takotsubo cardiomyopathy—results from the International Takotsubo Registry (InterTAK Registry). N Engl J Med 373:929–938CrossRef
3.
go back to reference Ay H, Koroshetz WJ, Benner T, Vangel MG, Melinosky C, Arsava EM et al (2006) Neuroanatomic correlates of stroke-related myocardial injury. Neurology 66:1325–1329CrossRef Ay H, Koroshetz WJ, Benner T, Vangel MG, Melinosky C, Arsava EM et al (2006) Neuroanatomic correlates of stroke-related myocardial injury. Neurology 66:1325–1329CrossRef
4.
go back to reference Nagai M, Dote K, Kato M, Sasaki S, Oda N, Kagawa E et al (2017) The insular cortex and takotsubo cardiomyopathy. Curr Pharm Des 23:879–888CrossRef Nagai M, Dote K, Kato M, Sasaki S, Oda N, Kagawa E et al (2017) The insular cortex and takotsubo cardiomyopathy. Curr Pharm Des 23:879–888CrossRef
5.
go back to reference Van Dijk KR, Hedden T, Venkataraman A, Evans KC, Lazar SW, Buckner RL (2010) Intrinsic functional connectivity as a tool for human connections: theory, properties, and optimization. J Neurophysiol 103:297–321CrossRef Van Dijk KR, Hedden T, Venkataraman A, Evans KC, Lazar SW, Buckner RL (2010) Intrinsic functional connectivity as a tool for human connections: theory, properties, and optimization. J Neurophysiol 103:297–321CrossRef
6.
go back to reference Rubinov M, Sporns O (2010) Complex network measures of brain connectivity: uses and interpretations. Neuroimage 52:1059–1069CrossRef Rubinov M, Sporns O (2010) Complex network measures of brain connectivity: uses and interpretations. Neuroimage 52:1059–1069CrossRef
7.
go back to reference Suzuki H, Matsumoto Y, Kaneta T, Sugimura K, Takahashi J, Fukumoto Y et al (2013) Evidence for brain activation in patients with takotsubo cardiomyopathy. Circ J 78:256–258PubMed Suzuki H, Matsumoto Y, Kaneta T, Sugimura K, Takahashi J, Fukumoto Y et al (2013) Evidence for brain activation in patients with takotsubo cardiomyopathy. Circ J 78:256–258PubMed
8.
go back to reference Pereira VH, Marques P, Magalhães R, Português J, Calvo L, Cerqueira JJ et al (2016) Central autonomic nervous system response to autonomic challenges is altered in patients with a previous episode of Takotsubo cardiomyopathy. Eur Heart J Acute Cardiovasc Care 5:152–163CrossRef Pereira VH, Marques P, Magalhães R, Português J, Calvo L, Cerqueira JJ et al (2016) Central autonomic nervous system response to autonomic challenges is altered in patients with a previous episode of Takotsubo cardiomyopathy. Eur Heart J Acute Cardiovasc Care 5:152–163CrossRef
9.
go back to reference Sabisz A, Treder N, Fijalkowska M, Sieminski J, Fijalkowska P, Naumczyk R et al (2016) Brain resting state functional magnetic resonance imaging in patients with takotsubo cardiomyopathy an inseparable pair of brain and heart. Int J Cardiol 224:376–381CrossRef Sabisz A, Treder N, Fijalkowska M, Sieminski J, Fijalkowska P, Naumczyk R et al (2016) Brain resting state functional magnetic resonance imaging in patients with takotsubo cardiomyopathy an inseparable pair of brain and heart. Int J Cardiol 224:376–381CrossRef
10.
go back to reference Templin C, Hänggi J, Klein C, Topka MS, Hiestand T, Levinson RA et al (2019) Altered limbic and autonomic processing supports brain-heart axis in Takotsubo syndrome. Eur Heart J 40:1183–1187CrossRef Templin C, Hänggi J, Klein C, Topka MS, Hiestand T, Levinson RA et al (2019) Altered limbic and autonomic processing supports brain-heart axis in Takotsubo syndrome. Eur Heart J 40:1183–1187CrossRef
11.
go back to reference Hiestand T, Hänggi J, Klein C, Topka MS, Jaguszewski M, Ghadri JR et al (2018) Takotsubo syndrome associated with structural brain alterations of the limbic system. J Am Coll Cardiol 71:809–811CrossRef Hiestand T, Hänggi J, Klein C, Topka MS, Jaguszewski M, Ghadri JR et al (2018) Takotsubo syndrome associated with structural brain alterations of the limbic system. J Am Coll Cardiol 71:809–811CrossRef
12.
go back to reference Ghadri JR, Wittstein IS, Prasad A, Sharkey S, Dote K, Akashi YJ et al (2018) International expert consensus document on takotsubo syndrome (part I): clinical characteristics, diagnostic criteria, and pathophysiology. Eur Heart J 39:2032–2046CrossRef Ghadri JR, Wittstein IS, Prasad A, Sharkey S, Dote K, Akashi YJ et al (2018) International expert consensus document on takotsubo syndrome (part I): clinical characteristics, diagnostic criteria, and pathophysiology. Eur Heart J 39:2032–2046CrossRef
13.
go back to reference Ghadri JR, Wittstein IS, Prasad A, Sharkey S, Dote K, Akashi YJ et al (2018) International expert consensus document on takotsubo syndrome (part II): diagnostic workup, outcome, and management. Eur Heart J 39:2047–2062CrossRef Ghadri JR, Wittstein IS, Prasad A, Sharkey S, Dote K, Akashi YJ et al (2018) International expert consensus document on takotsubo syndrome (part II): diagnostic workup, outcome, and management. Eur Heart J 39:2047–2062CrossRef
14.
go back to reference Stiermaier T, Santoro F, Graf T, Guastafierro F, Tarantino N, De Gennaro L et al (2018) Prognostic value of N-terminal pro-B-type natriuretic peptide in takotsubo syndrome. Clin Res Cardiol 107:597–606CrossRef Stiermaier T, Santoro F, Graf T, Guastafierro F, Tarantino N, De Gennaro L et al (2018) Prognostic value of N-terminal pro-B-type natriuretic peptide in takotsubo syndrome. Clin Res Cardiol 107:597–606CrossRef
15.
go back to reference Good CD, Johnsrude IS, Ashburner J, Henson RN, Friston KJ, Frackowiak RS (2001) A voxel-based morphometric study of ageing in 465 normal adult human brains. NeuroImage 14:21–36CrossRef Good CD, Johnsrude IS, Ashburner J, Henson RN, Friston KJ, Frackowiak RS (2001) A voxel-based morphometric study of ageing in 465 normal adult human brains. NeuroImage 14:21–36CrossRef
16.
go back to reference Jenkinson M, Beckmann CF, Behrens TE, Woolrich MW, Smith SM (2012) FSL. NeuroImage 62:782–790CrossRef Jenkinson M, Beckmann CF, Behrens TE, Woolrich MW, Smith SM (2012) FSL. NeuroImage 62:782–790CrossRef
17.
go back to reference Dagli MS, Ingeholm JE, Haxby JV (1999) Localization of cardiac-induced signal change in fMRI. NeuroImage 9:407–415CrossRef Dagli MS, Ingeholm JE, Haxby JV (1999) Localization of cardiac-induced signal change in fMRI. NeuroImage 9:407–415CrossRef
18.
go back to reference Windischberger C, Langenberger H, Sycha T (2002) On the origin of respiratory artifacts in BOLD-EPI of the human brain. Magn Reson Imaging 20:575–582CrossRef Windischberger C, Langenberger H, Sycha T (2002) On the origin of respiratory artifacts in BOLD-EPI of the human brain. Magn Reson Imaging 20:575–582CrossRef
19.
go back to reference Joliot M, Jobard G, Naveau M, Delcroix N, Petit L, Zago L et al (2015) AICHA: an atlas of intrinsic connectivity of homotopic areas. J Neurosci Methods 254:46–59CrossRef Joliot M, Jobard G, Naveau M, Delcroix N, Petit L, Zago L et al (2015) AICHA: an atlas of intrinsic connectivity of homotopic areas. J Neurosci Methods 254:46–59CrossRef
20.
go back to reference Zalesky A, Fornito A, Bullmore ET (2010) Network-based statistic: identifying differences in brain networks. NeuroImage 53:1197–1207CrossRef Zalesky A, Fornito A, Bullmore ET (2010) Network-based statistic: identifying differences in brain networks. NeuroImage 53:1197–1207CrossRef
21.
go back to reference Colivicchi F, Bassi A, Santini M, Caltagirone C (2004) Cardiac autonomic derangement and arrhythmias in right-sided stroke with insular involvement. Stroke 35:2094–2098CrossRef Colivicchi F, Bassi A, Santini M, Caltagirone C (2004) Cardiac autonomic derangement and arrhythmias in right-sided stroke with insular involvement. Stroke 35:2094–2098CrossRef
22.
go back to reference Yoshimura S, Toyoda K, Ohara T, Nagasawa H, Ohtani N, Kuwashiro T et al (2008) Takotsubo cardiomyopathy in acute ischemic stroke. Ann Neurol 64:547–554CrossRef Yoshimura S, Toyoda K, Ohara T, Nagasawa H, Ohtani N, Kuwashiro T et al (2008) Takotsubo cardiomyopathy in acute ischemic stroke. Ann Neurol 64:547–554CrossRef
23.
go back to reference Pasquini M, Laurent C, Kroumova M, Masse I, Deplanque D, Leclerc X et al (2006) Insular infarcts and electrocardiographic changes at admission: results of the prognostic of insular cerebral infarcts study (PRINCESS). J Neurol 253:618–624CrossRef Pasquini M, Laurent C, Kroumova M, Masse I, Deplanque D, Leclerc X et al (2006) Insular infarcts and electrocardiographic changes at admission: results of the prognostic of insular cerebral infarcts study (PRINCESS). J Neurol 253:618–624CrossRef
24.
go back to reference Gassanov N, Le MT, Caglayan E, Hellmich M, Erdmann E, Er F (2018) Novel ECG-based scoring tool for prediction of takotsubo syndrome. Clin Res Cardiol 108:68–73CrossRef Gassanov N, Le MT, Caglayan E, Hellmich M, Erdmann E, Er F (2018) Novel ECG-based scoring tool for prediction of takotsubo syndrome. Clin Res Cardiol 108:68–73CrossRef
25.
go back to reference Oppenheimer S (2006) Cerebrogenic cardiac arrhythmias: cortical lateralization and clinical significance. Clin Auton Res 16:6–11CrossRef Oppenheimer S (2006) Cerebrogenic cardiac arrhythmias: cortical lateralization and clinical significance. Clin Auton Res 16:6–11CrossRef
26.
go back to reference Silva AR, Magalhães R, Arantes C, Moreira PS, Rodrigues M, Marques P et al (2019) Brain functional connectivity is altered in patients with Takotsubo syndrome. Sci Rep 9:4187CrossRef Silva AR, Magalhães R, Arantes C, Moreira PS, Rodrigues M, Marques P et al (2019) Brain functional connectivity is altered in patients with Takotsubo syndrome. Sci Rep 9:4187CrossRef
27.
go back to reference Baur V, Hänggi J, Langer N, Jäncke L (2013) Resting-state functional and structural connectivity within an insula-amygdala route specifically index state and trait anxiety. Biol Psychiatry 73:85–92CrossRef Baur V, Hänggi J, Langer N, Jäncke L (2013) Resting-state functional and structural connectivity within an insula-amygdala route specifically index state and trait anxiety. Biol Psychiatry 73:85–92CrossRef
28.
go back to reference Vaccaro A, Despas F, Delmas C, Lairez O, Lambert E, Lambert G et al (2014) Direct evidences for sympathetic hyperactivity and baroreflex impairment in Tako Tsubo cardiopathy. PLoS ONE ONE 9:e93278CrossRef Vaccaro A, Despas F, Delmas C, Lairez O, Lambert E, Lambert G et al (2014) Direct evidences for sympathetic hyperactivity and baroreflex impairment in Tako Tsubo cardiopathy. PLoS ONE ONE 9:e93278CrossRef
29.
go back to reference Liu X, Chen X, Zheng W, Xia M, Han Y, Song H et al (2018) Altered functional connectivity of insular subregions in Alzheimer's disease. Front Aging Neurosci 10:107–119CrossRef Liu X, Chen X, Zheng W, Xia M, Han Y, Song H et al (2018) Altered functional connectivity of insular subregions in Alzheimer's disease. Front Aging Neurosci 10:107–119CrossRef
30.
go back to reference Klein C, Hiestand T, Ghadri JR, Templin C, Jäncke L, Hänggi J (2017) Takotsubo syndrome—predictable from brain imaging data. Sci Rep 7:5434CrossRef Klein C, Hiestand T, Ghadri JR, Templin C, Jäncke L, Hänggi J (2017) Takotsubo syndrome—predictable from brain imaging data. Sci Rep 7:5434CrossRef
31.
go back to reference Thayer JF, Lane RD (2009) Claude Bernard and the heart-brain connection: further elaboration of a model of neurovisceral integration. Neurosci Biobehav Rev 33:81–88CrossRef Thayer JF, Lane RD (2009) Claude Bernard and the heart-brain connection: further elaboration of a model of neurovisceral integration. Neurosci Biobehav Rev 33:81–88CrossRef
32.
go back to reference Wager TD, Waugh CE, Linquist M, Noll DC, Fredrickson BL, Taylor SF (2009) Brain mediators of cardiovascular responses to social threat: part I: reciprocal dorsal and ventral sub-regions of the medial prefrontal cortex and heart-rate reactivity. Neuroimage 47:821–835CrossRef Wager TD, Waugh CE, Linquist M, Noll DC, Fredrickson BL, Taylor SF (2009) Brain mediators of cardiovascular responses to social threat: part I: reciprocal dorsal and ventral sub-regions of the medial prefrontal cortex and heart-rate reactivity. Neuroimage 47:821–835CrossRef
33.
go back to reference Olson CR, Colby CL (2013) The organization of cognition. In: Kandel ER, Schwartz JH, Jessell TM (eds) Principles of neural science, 5th edn. McGraw Hill Medical, New York, pp 402–409 Olson CR, Colby CL (2013) The organization of cognition. In: Kandel ER, Schwartz JH, Jessell TM (eds) Principles of neural science, 5th edn. McGraw Hill Medical, New York, pp 402–409
Metadata
Title
Functional neuroimaging in the acute phase of Takotsubo syndrome: volumetric and functional changes of the right insular cortex
Authors
Wolfgang Dichtl
Noora Tuovinen
Fabian Barbieri
Agne Adukauskaite
Thomas Senoner
Andrea Rubatscher
Florian Hintringer
Christian Siedentopf
Axel Bauer
Elke R. Gizewski
Ruth Steiger
Publication date
01-09-2020
Publisher
Springer Berlin Heidelberg
Published in
Clinical Research in Cardiology / Issue 9/2020
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-020-01602-3

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