Human cerebral circuitry related to cardiac control: a neuroimaging meta-analysis
Abstract
Serious arrhythmias often follow stroke, highlighting the important role that the cerebral cortex has in neural regulation of the heart. Neuroimaging studies reveal patterns of activation associated with autonomic cardiovascular responses. Using the activation likelihood estimation, a meta-analysis was performed to identify cortical activation patterns related to heart rate and heart rate variability across studies that used differing stimuli of cardiovascular arousal. Consistent associations with heart rate and heart rate variability were observed in the anterior cingulate, amygdala, insula, and prefrontal cortex, among others. Also, evidence is provided of insular lateralization associated with autonomic cardiac responses. Ann Neurol 2016;79:709-716.
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The more liberal threshold of p < .01 is appropriate for smaller sample sizes.
“The more liberal threshold of p <.01 is appropriate for smaller sample sizes, and has been adopted by previous ALE studies (Di et al., 2017; Falcone & Jerram, 2018; Ruiz Vargas et al., 2016).”
From Bridging phenomenology and neural mechanisms of inner speech: ALE meta-analysis on egocentricity and spontaneity in a dual-mechanistic framework (2023) · cites this paper as Ruiz Vargas et al., 2016
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“Thus, it is plausible to hypothesize that the activity in the AI contributes both to error awareness and to cardiac responses (Ruiz Vargas et al., 2016; Ullsperger et al., 2010).”
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“Simultaneously, degeneration of brain regions that regulate autonomic outflow, such as the amygdala, brainstem, hypothalamus and insular cortex, can impair cardiac control 71,72 .”
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“This involvement of the mid-posterior insula is also supported by neuroimaging meta-analyses, which show activation of both the anterior and posterior insula during autonomic or heart rate variations (Beissner et al., 2013; Ferraro et al., 2022; Ruiz Vargas et al., 2016; Thayer et al., 2012).”
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“…includes brain regions such as the prefrontal cortex, anterior cingulate cortex, insula, amygdala, and deep brain regions such as the pons and medulla oblongata (Agorastos et al., 2023; Arakaki et al., 2023; Matusik et al., 2023; Mulcahy et al., 2019; Ruiz Vargas et al., 2016; Thayer et al., 2009).”
Disrupted Brain Functional Status in Patients with Reversible Cerebral Vasoconstriction Syndrome
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“40,41 Some studies have demonstrated potential connections of left insular damage to speci fi c cardiac disorders with parasympathetic dysfunctions, including Takotsubo cardiomyopathy, 42,43 which is a cardiac disease that potentially shares characteristics with RCVS. 44 Sym-pathetic overactivity is…”
Wounded brain, ailing heart: Central autonomic network disruption in acute stroke
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“Neurophysiological studies also indicate functional lateralization of the insula in the autonomic control of homeostatic processes [65].”
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“The anterior cingulate cortex could well play a pivotal role as it is both involved in trance states (its dorsal portion activity is reduced during hypnosis), and represents one of the key cortical structures of the autonomic central network [24].”
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Colombi, F., Fusi, G., Crepaldi, M., & Rusconi, M. (2026) · Brain Science · doi:10.3390/brainsci16070702 · Cited by 1
“…heart rate variability (HRV) or blood volume pulse (BVP), which are considered (parasympathetic) indices of top-down self-regulation (see, e.g., [95,96]), have already been linked to improved executive functioning [97,98] and better emotional regulation abilities [99,100] and are therefore…”
Fang, Y.-R., Li, T.-Y., Liang, W.-W., Du, Q., Pan, C.-S., & Zhu, Z. (2025) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2025.111673 · Cited by 1 · see citing works
Post-stroke Arrhythmias: Performance of Brain-heart Crosstalk Networks
Liu, L.-X., Wu, B.-Q., & Huang, J.-J. (2025) · Current Cardiology Reviews · doi:10.2174/011573403x363465250407072854 · Cited by 1
“Acute vascular injury in this subregion of the insula may lead to autonomic imbalance and increased sympathetic nervous system function, resulting in myocardial injury [47, 49].”
Bello, M. D., Chang, C., & McIntosh, R. (2024) · Brain and Cognition · doi:10.1016/j.bandc.2024.106134 · Cited by 1 · see citing works
Heart Rate Variability in Insulo-Opercular Epilepsy
Tran, T. P. Y., Pouliot, P., Assi, E. B., Rainville, P., Myers, K., Robert, M., Bouthillier, A., Keezer, M., & Nguyen, D. (2021) · Brain Science · doi:10.3390/brainsci11111505 · Cited by 1 · see citing works
“This was somewhat unexpected, since the insula is known to be part of the central autonomic network [49,50].”
BackgroundRen, Z.-H., Ruan, Y.-J., Zhao, Q.-B., Zhang, W., Lai, L.-Z., & Jiang, G.-R. (2017) · doi:10.3724/sp.j.1041.2017.01302 · Cited by 1
Structural covariance of the salience network associated with heart rate variability
Wei, L.-Q., & Wu, G.-R. (2020) · Brain Imaging and Behavior · doi:10.1007/s11682-020-00298-3
Sullivan, S. G. B., Sliwka, M., Drake, E. D., & Perez, T. M. (2026) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2026.1984309
Guo, K.-L., Guo, W., Wang, Z.-H., Li, H.-X., Ouyang, L., Pu, J.-F., Li, H.-Y., & Tang, Q. (2026) · Clinical Autonomic Research · doi:10.1007/s10286-026-01252-x
Tomasi, J., Tiwari, A., Zai, C., Zai, G., Richter, M., Sanches, M., Lachman, R., Gaspar, C., Cella, M., Greer, B., et al. (2026) · Journal of Affective Disorders · doi:10.1016/j.jad.2026.122508
Distinct brain systems support afferent and efferent autonomic activity
Min, J., Liu, G., Dahl, M., Lee, T.-H., Nashiro, K., Yoo, H., Cho, C., Bogdan, P., Chang, C., Lehrer, P., et al. (2026) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsag054
“Even so, positive correlations in our efferent regions (e.g. the anterior insula, thalamus, and dorsal ACC) were robustly seen in prior studies involving task scans and HRV (Ruiz Vargas et al .”
InfluentialDistinct Brain Systems Support Afferent and Efferent Autonomic ActivityPreprint
Min, J., Liu, G., Dahl, M., Lee, T.-H., Nashiro, K., Yoo, H., Cho, C., Bogdan, P., Chang, C., Lehrer, P., et al. (2026) · bioRxiv · doi:10.64898/2026.06.03.729710
“The fMRI studies investigating brain areas associated with afferent or efferent autonomic signals converge on a few common regions (e.g., insula and ACC; Beissner et al., 2013; Critchley, 2005; Oppenheimer and Cechetto, 2016; Ruiz Vargas et al., 2016).”
InfluentialAnterior cingulate activity is associated with autonomic reactivity to experimentally induced pain.
Chouchou, F., Peyron, R., & Fauchon, C. (2026) · Neurophysiologie clinique · doi:10.1016/j.neucli.2026.103169
Tang, X.-W., Ren, N., Cao, Z.-J., Yu, Z., Han, X., Cai, W.-Q., Yang, Y., Lu, L.-S., Maisedi, M., Sun, Z., et al. (2025) · Acta Neurologica Belgica · doi:10.1007/s13760-025-02971-0
“Emerging evidence indicates that functional interactions between the heart autonomic regulation and the central ner - vous system (CNS), known as the central autonomic network (CAN), are involved in conscious processes [ 13 – 16 ].”
Parameswaran, S., & Balasubramanian, V. (2025) · Behavioural Brain Research · doi:10.1016/j.bbr.2025.115792
Passively Viewing Social Bonding Cues Decreases Vagally Mediated Heart Rate Variability
Araújo, C. R. V., Souza, F. C. D. O., Lacerda, K., Rosário, N. S. A., de Souza, P. D., Sanchez, T. A., Mocaiber, I., & Souza, G. G. (2025) · Evolutionary Psychological Science · doi:10.1007/s40806-025-00429-3
“Importantly, vmHRV represents an index of how the autonomic nervous system is modulated by the activity of both cortical and subcortical brain regions (Ruiz Vargas et al., 2016; Thayer et al., 2012).”
A Case of Complete Resolution of Repeated Syncope Attacks After a Right-Sided Carotid Endarterectomy
Mizukami, S., Hashiguchi, A., Sasaki, K., Moroki, K., & Tokuda, H. (2024) · Cureus · doi:10.7759/cureus.63567
“Consistent associations with heart rate and heart rate variability have been reported in the anterior cingulate, amygdala, insular, and prefrontal cortex, but of great interest is the report that lateralization of the insular cortex is associated with autonomic cardiac responses [4,6,7].”
BackgroundReproducible biomarkers: Leveraging nonlinear descriptors in the face of non-ergodicityPreprint
Mangalam, M., Sadri, A., Hayano, J., Watanabe, E., Kiyono, K., & Kelty-Stephen, D. G. (2023) · arXiv.org · doi:10.48550/arxiv.2305.06954
Heart rate variability and depression
Fráguas, R., & de Souza, B. F. (2021) · The Neuroscience of Depression · doi:10.1016/b978-0-12-817933-8.00038-4
- Authors
- Ruiz Vargas, E., Sörös, P., Shoemaker, J. K., & Hachinski, V.
- Affiliations
- Ivey Business School Western University London Ontario Canada
- University of Lübeck (DE)
- Western University (CA)
- Corresponding author
- Shoemaker, J. Kevin
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2016-04-05
- Volume
- 79
- Issue
- 5
- Pages
- 709-716
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2298525988
- Cited by
- 94
- References
- 41
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 8 · 2023: 8 · 2022: 12 · 2021: 13 · 2020: 12 · 2019: 7 · 2018: 8 · 2017: 5
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Scholarship@Western (Western University) (submittedVersion)
- Funders
- Canadian Space Agency
- Canadian Institutes of Health Research Team Grant in Exercise, Mobility, and Neural Health
- Premier's Discovery Award in the Life Sciences and Medicine
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- cardiac regulation, cerebral cortex, heart rate, heart rate variability, anterior cingulate cortex, amygdala, insula, prefrontal cortex
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