Brain activity has been shown to be influenced by respiratory behavior. Here, we evaluated whether respiration-induced hypo- or hypercapnia may support differentiation between physiological versus pathological respiratory behavior. In particular, we investigated whether systemic physiological measures could predict the brain’s time-frequency hemodynamics after three respiratory challenges (i.e., breath-holding, rebreathing, and hyperventilation) compared to resting-state. Prefrontal hemodynamics were assessed in healthy subjects (N = 27) using functional near-infrared spectroscopy (fNIRS). Systemic physiological measures were assessed in form of heart rate, partial end-tidal carbon dioxide, respiration rate, and saturation of peripheral oxygen. Time-frequency dynamics were quantified using the wavelet transform coherence (i.e., defined here as cortical-systemic coherence). We found that the three respiratory challenges modulated cortical-systemic coherence differently: (1) After rebreathing, cortical-systemic coherence could be predicted from the amplitude of the heart rate (strong negative correlation). (2) After breath-holding, the same observation was made (moderate negative correlation). (3) After hyperventilation, no significant effect was observed. (4) These effects were found only in the frequency range of very low-frequency oscillations. The presented findings highlight a distinct role of rebreathing in predicting cortical-systemic coupling based on heart rate changes, which may represents a measure of affective states in the brain. The applied multimodal assessment of hemodynamic and systemic physiological measures during respiratory challenges may therefore have potential applications in the differentiation between physiological and pathological respiratory behavior.
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Abrams, K., Rassovsky, Y., & Kushner, M. G. (2006). Evidence for respiratory and nonrespiratory subtypes in panic disorder. Depression and Anxiety, 23, 474–481.
Adhikari, A., Topiwala, M. A., & Gordon, J. A. (2010). Synchronized activity between the ventral hippocampus and the medial prefrontal cortex during anxiety. Neuron, 65, 257.
Alexopoulos, D., Christodoulou, J., Toulgaridis, T., Sitafidis, G., Klinaki, A., & Vagenakis, A. (1995). Hemodynamic response to hyperventilation test in healthy volunteers. Clinical Cardiology, 18, 636–641.
Birn, R. M., Smith, M. A., Jones, T. B., & Bandettini, P. A. (2008). The respiration response function: the temporal dynamics of fMRI signal fluctuations related to changes in respiration. NeuroImage, 40, 644–654.
Birn, R. M., Murphy, K., Handwerker, D. A., & Bandettini, P. A. (2009). fMRI in the presence of task-correlated breathing variations. Brain Body Med, 47, 1092–1104.
Boas, D. A., Dale, A. M., & Franceschini, M. A. (2004). Diffuse optical imaging of brain activation: approaches to optimizing image sensitivity, resolution, and accuracy. NeuroImage, 23, S275–S288.
Bright, M. G., & Murphy, K. (2013). Reliable quantification of BOLD fMRI cerebrovascular reactivity despite poor breath-hold performance. NeuroImage, 83, 559–568.
Bright, M. G., & Murphy, K. (2015). Is fMRI “noise” really noise? Resting state nuisance regressors remove variance with network structure. NeuroImage, 114, 158–169.
Chai, X. J., Castañón, A. N., Öngür, D., & Whitfield-Gabrieli, S. (2012). Anticorrelations in resting state networks without global signal regression. NeuroImage, 59, 1420–1428.
Chang, C., & Glover, G. H. (2009). Effects of model-based physiological noise correction on default mode network anti-correlations and correlations. NeuroImage, 47, 1448–1459.
Coryell, W., Noyes, R., & Clancy, J. (1982). Excess mortality in panic disorder. A comparison with primary unipolar depression. Archives of General Psychiatry, 39, 701–703.
Coryell, W., Noyes, R., & House J (1986). Mortality among outpatients with anxiety disorders. The American Journal of Psychiatry, 143, 508–510.
Denollet, J., & Brutsaert, D. L. (1998). Personality, disease severity, and the risk of long-term cardiac events in patients with a decreased ejection fraction after myocardial infarction. Circulation, 97, 167–173.
Eke, M., & McNally, R. J. (1996). Anxiety sensitivity, suffocation fear, trait anxiety, and breath-holding duration as predictors of response to carbon dioxide challenge. Behaviour Research and Therapy, 34, 603–607.
Fox, M., Zhang, D., Snyder, A., & Raichle, M. (2009). The global signal and observed anticorrelated Resting state brain networks. Journal of Neurophysiology, 101, 3270–3283.
Funane, T., Atsumori, H., Katura, T., Obata, A. N., Sato, H., Tanikawa, Y., Okada, E., & Kiguchi, M. (2014). Quantitative evaluation of deep and shallow tissue layers’ contribution to fNIRS signal using multi-distance optodes and independent component analysis. Neuroimage, 85, 150–165.
Gagnon, L., Yücel, M. A., Dehaes, M., Cooper, R. J., Perdue, K. L., Selb, J., Huppert, T. J., Hoge, R. D., & Boas, D. A. (2012). Quantification of the cortical contribution to the NIRS signal over the motor cortex using concurrent NIRS-fMRI measurements. NeuroImage, 59, 3933–3940.
Germon, T. J., Evans, P. D., Barnett, N. J., Wall, P., Manara, A. R., & Nelson, R. J. (1999). Cerebral near infrared spectroscopy: emitter-detector separation must be increased. British Journal of Anaesthesia, 82, 831–837.
Golestani, A. M., Chang, C., Kwinta, J. B., Khatamian, Y. B., & Jean Chen, J. (2015). Mapping the end-tidal CO2 response function in the resting-state BOLD fMRI signal: spatial specificity, test–retest reliability and effect of fMRI sampling rate. NeuroImage, 104, 266–277.
Gorman, J. M., Browne, S. T., Papp, L. A., Martinez, J., Welkowitz, L., Coplan, J. D., Goetz, R. R., Kent, J., & Klein, D. F. (1997). Effect of Antipanic Treatment on Response to Carbon Dioxide. Biological Psychiatry, 42, 982–991.
Grinsted, A., Moore, J., & Jevrejeva, S. (2004). Application of the cross wavelet transform and wavelet coherence to geophysical time series. Nonlinear Processes in Geophysics, 11, 561–566.
Grubb, R., Raichle, M., Eichling, J., & Ter-Pogossian, M. (1974). The effects of changes in PaCO2 cerebral blood volume, blood flow, and vascular mean transit time. Stroke, 5, 630–639.
Haines, A. P., Imeson, J. D., & Meade, T. W. (1987). Phobic anxiety and ischaemic heart disease. BMJ, 295, 297–299.
Haines, A., Cooper, J., & Meade, T. W. (2001). Psychological characteristics and fatal ischaemic heart disease. Heart, 85, 385–389.
Holper, L., Wolf, M., & Tobler, P. N. (2014a). Comparison of functional near-infrared spectroscopy and electrodermal activity in assessing objective versus subjective risk during risky financial decisions. NeuroImage, 84, 833–842.
Holper, L., Scholkmann, F., & Wolf, M. (2014b). The relationship between sympathetic nervous activity and cerebral Hemodynamics and oxygenation: A study using skin conductance measurement and functional near-infrared spectroscopy. Behavioural Brain Research, 270, 95–107.
Holper L, Scholkmann F, Seifritz E (2015). Time-frequency dynamics of the sum of intra- and extracerebral hemodynamic functional connectivity during resting-state and respiratory challenges assessed by multimodal functional near-infrared spectroscopy. NeuroImage, 120, 481–492.
Homma, I., & Masaoka, Y. (2008). Breathing rhythms and emotions. Experimental Physiology, 93, 1011–1021.
Kastrup, A., Li, T.-Q., Takahashi, A., Glover, G. H., & Moseley, M. E. (1998). Functional magnetic resonance imaging of regional cerebral blood oxygenation changes during breath holding. Stroke, 29, 2641–2645.
Kastrup, A., Krüger, G., Glover, G. H., & Moseley, M. E. (1999). Assessment of cerebral oxidative metabolism with breath holding and fMRI. Magnetic Resonance in Medicine, 42, 608–611.
Kawachi, I., Colditz, G. A., Ascherio, A., Rimm, E. B., Giovannucci, E., Stampfer, M. J., & Willett, W. C. (1994a). Prospective study of phobic anxiety and risk of coronary heart disease in men. Circulation, 89, 1992–1997.
Kawachi, I., Sparrow, D., Vokonas, P. S., & Weiss, S. T. (1994b). Symptoms of anxiety and risk of coronary heart disease. The Normative Aging Study. Circulation, 90, 2225–2229.
Keller, C. J., Bickel, S., Honey, C. J., Groppe, D. M., Entz, L., Craddock, R. C., Lado, F. A., Kelly, C., Milham, M., & Mehta, A. D. (2013). Neurophysiological investigation of spontaneous correlated and anticorrelated fluctuations of the BOLD signal. The Journal of Neuroscience, 33, 6333–6342.
Kim, D.-K., Lee, K.-M., Kim, J., Whang, M.-C., & Kang, S. W. (2013a). Dynamic correlations between heart and brain rhythm during autogenic meditation. Frontiers in Human Neuroscience, 7, 414.
Kim, D.-K., Rhee, J.-H., & Kang, S. W. (2013b). Reorganization of the brain and heart rhythm during autogenic meditation. Frontiers in Integrative Neuroscience, 7, 109.
Kirilina, E., Jelzow, A., Heine, A., Niessing, M., Wabnitz, H., Brühl, R., Ittermann, B., Jacobs, A., & Tachtsidis, I. (2012a). The physiological origin of task-evoked systemic artefacts in functional near infrared spectroscopy. NeuroImage, 61, 70–81.
Kirilina, E., Jelzow, A., Heine, A., Niessing, M., Wabnitz, H., Brühl, R., Ittermann, B., Jacobs, A. M., & Tachtsidis, I. (2012b). The physiological origin of task-evoked systemic artefacts in functional near infrared spectroscopy. NeuroImage, 61, 70–81.
Kiviniemi V, Remes J, Starck T, Nikkinen J, Haapea M, Silven O, Tervonen O (2009): Mapping Transient Hyperventilation Induced Alterations with Estimates of the Multi-Scale Dynamics of BOLD Signal. Front Neuroinformatics 3.
Kox, M., van Eijk, L. T., Zwaag, J., van den Wildenberg, J., Sweep, F. C. G. J., van der Hoeven, J. G., & Pickkers, P. (2014). Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans. Proceedings of the National Academy of Sciences, 111, 7379–7384.
Laszlo, G., Clark, T. J. H., Pope, H., & Campbell, E. J. M. (1971). Differences between alveolar and arterial pCO2 during rebreathing experiments in resting human subjects. Respiration Physiology, 12, 36–52.
Lemaître, F., Bernier, F., Petit, I., Renard, N., Gardette, B., & Joulia, F. (2005). Heart rate responses during a breath-holding competition in well-trained divers. International Journal of Sports Medicine, 26, 409–413.
Lesting, J., Narayanan, R., Kluge, C., Sangha, S., Seidenbecher, T., & Pape (2011). Patterns of coupled theta activity in amygdala-hippocampal-prefrontal cortical circuits during fear extinction. PloS One, 6, e21714.
Likhtik, E., Stujenske, J. M., A Topiwala, M., AZ, H., & JA, G. (2014). Prefrontal entrainment of amygdala activity signals safety in learned fear and innate anxiety. Nature Neuroscience, 17, 106–113.
Maddock, R. J., & Carter, C. S. (1991). Hyperventilation-induced panic attacks in panic disorder with agoraphobia. Biological Psychiatry, 29, 843–854.
Mastrovito, D. (2013). Interactions between resting-state and task-evoked brain activity suggest a different approach to fMRI analysis. The Journal of Neuroscience, 33, 12912–12914.
Nardi, A. E., Valença, A. M., Lopes, F. L., Nascimento, I., Mezzasalma, M. A., & Zin, W. A. (2004). Clinical features of panic patients sensitive to hyperventilation or breath-holding methods for inducing panic attacks. Brazilian Journal of Medical and Biological Research, 37, 251–257.
Nardi, A. E., Valença, A. M., Mezzasalma, M. A., Levy, S. P., Lopes, F. L., Nascimento, I., Freire, R. C., Veras, A. B., & Zin, W. A. (2006). Comparison between hyperventilation and breath-holding in panic disorder: patients responsive and non-responsive to both tests. Psychiatry Research, 142, 201–208.
Nasrallah, F. A., Yeow, L. Y., Biswal, B., & Chuang, K.-H. (2015). Dependence of BOLD signal fluctuation on arterial blood CO2 and O2: implication for resting-state functional connectivity. NeuroImage, 117, 29–39.
Nikulin, V. V., Fedele, T., Mehnert, J., Lipp, A., Noack, C., Steinbrink, J., & Curio, G. (2014). Monochromatic Ultra-slow (~ 0.1 Hz) oscillations in the human electroencephalogram and their relation to Hemodynamics. NeuroImage, 97, 71–80.
Obrig, H., Neufang, M., Wenzel, R., Kohl, M., Steinbrink, J., Einhäupl, K., & Villringer, A. (2000). Spontaneous low frequency oscillations of cerebral hemodynamics and metabolism in human adults. NeuroImage, 12, 623–639.
Putman, P. (2011). Resting state EEG delta–beta coherence in relation to anxiety, behavioral inhibition, and selective attentional processing of threatening stimuli. International Journal of Psychophysiology, 80, 63–68.
Rapee, R. M., Brown, T. A., Antony, M. M., & Barlow, D. H. (1992). Response to hyperventilation and inhalation of 5.5 % carbon dioxide-enriched air across the DSM-III—R anxiety disorders. Journal of Abnormal Psychology, 101, 538–552.
Rassovsky, Y., Kushner, M. G., Schwarze, N. J., & Wangensteen, O. D. (2000). Psychological and physiological predictors of response to carbon dioxide challenge in individuals with panic disorder. Journal of Abnormal Psychology, 109, 616–623.
Roth WT, Wilhelm FH, Trabert W (1998): Voluntary Breath Holding in Panic and Generalized Anxiety Disorders. Psychosomatic Medicine, 60, 671–679.
Scholkmann, F., Gerber, U., Wolf, M., & Wolf, U. (2013a). End-tidal CO2: An important parameter for a correct interpretation in functional brain studies using speech tasks. NeuroImage, 66, 71–79.
Scholkmann, F., Wolf, M., & Wolf, U. (2013b). The effect of inner speech on arterial CO2, cerebral hemodynamics and oxygenation - A functional NIRS study. advances in experimental medicine and biology. Advances in Experimental Medicine and Biology, 789, 81–87.
Scholkmann, F., Kleiser, S., Metz, A. J., Zimmermann, R., Mata Pavia, J., Wolf, U., & Wolf, M. (2014a). A review on continuous wave functional near-infrared spectroscopy and imaging instrumentation and methodology. NeuroImage, 85, 6–27.
Scholkmann, F., Klein, S., Gerber, U., Wolf, M., & Wolf, U. (2014b). Cerebral hemodynamic and oxygenation changes induced by inner and heard speech: a study combining functional near-infrared spectroscopy and capnography. Journal of Biomedical Optics, 19, 017002.
Soladoye A, Owoyele B, Olatunji L, Adelusi S (2003): Cardiovascular responses to breath-holding with or without face immersion in young adults. Bioscience Research Communications, 15, 59–63.
Stäubli, M., Vogel, F., Bärtsch, P., Flückiger, G., & Ziegler, W. H. (1994). Hyperventilation-induced changes of blood cell counts depend on hypocapnia. European Journal of Applied Physiology, 69, 402–407.
Sullivan, G. M., Kent, J. M., Kleber, M., Martinez, J. M., Yeragani, V. K., & Gorman, J. M. (2004). Effects of hyperventilation on heart rate and QT variability in panic disorder pre- and post-treatment. Psychiatry Research, 125, 29–39.
Tachtsidis, I., & Papaioannou, A. (2013). Investigation of frontal lobe activation with fNIRS and systemic changes during video gaming. Advances in Experimental Medicine and Biology, 789, 89–95.
Tachtsidis, I., Leung, T., Devoto, L., Delpy, D., & Elwell, C. (2008a). Measurement of frontal lobe functional activation and related systemic effects: a near-infrared spectroscopy investigation. Advances in Experimental Medicine and Biology, 614, 397–403.
Tachtsidis, I., Leung, T., Tisdall, M., Devendra, P., Smith, M., Delpy, D., & Elwell, C. (2008b). Investigation of frontal cortex, motor cortex and systemic haemodynamic changes during anagram solving. Advances in Experimental Medicine and Biology, 614, 21–28.
Tachtsidis, I., Leung, T., Chopra, A., Koh, P., Reid, C., & Elwell, C. (2009a). False positives in functional nearinfrared topography. Advances in Experimental Medicine and Biology, 645, 307–314.
Tachtsidis, I., Leung, T., Chopra, A., Koh, P., Reid, C., & Elwell, C. (2009b). False positives In functional nearinfrared topography. Advances in Experimental Medicine and Biology, 645, 307–314.
Takahashi, T., Takikawa, Y., Kawagoe, R., Shibuya, S., Iwano, T., & Kitazawa, S. (2011). Influence of skin blood flow on near-infrared spectroscopy signals measured on the forehead during a verbal fluency task. NeuroImage, 57, 991–1002.
Thomas, S. A., Friedmann, E., Wimbush, F., & Schron, E. (1997). Psychological factors and survival in the cardiac arrhythmia suppression trial (CAST): a reexamination. American Journal of Critical Care, 6, 116–126.
Thomason, M. E., Burrows, B. E., Gabrieli, J. D. E., & Glover, G. H. (2005). Breath holding reveals differences in fMRI BOLD signal in children and adults. NeuroImage, 25, 824–837.
Tong, Y., Hocke, L. M., Fan, X., Janes, A., & Frederick, B. (2015). Can apparent resting state connectivity arise from systemic fluctuations? Frontiers in Human Neuroscience, 9.
Torrence, C., & Compo, G. (1998). A practical guide to wavelet analysis. Bulletin of the American Meteorological Society, 79, 61–78.
Trajkovic I, Scholkmann F, Wolf M (2011): Estimating and validating the interbeat intervals of the heart using near-infrared spectroscopy on the human forehead. Journal of Biomedical Optics, 16, 087002.
van den Hout, M., Boek, C., van der Molen, G., Jansen, A., & Griez, E. (1988). Rebreathing to cope with hyperventilation: experimental tests of the paper bag method. Journal of Behavioral Medicine, 11, 303–310.
Weissman, M. M., Markowitz, J. S., Ouellette, R., Greenwald, S., & Kahn, J. P. (1990). Panic disorder and cardiovascular/cerebrovascular problems: results from a community survey. The American Journal of Psychiatry, 147, 1504–1508.
Woods, S., Charney, D., Loke, J., Goodman, W., Redmond, D., & Heninger, G. (1986). Carbon dioxide sensitivity in panic anxiety: ventilatory and anxiogenic response to carbon dioxide in healthy subjects and patients with panic anxiety before and after alprazolam treatment. Archives of General Psychiatry, 43, 900–909.
Xia, M., Wang, J., & He, Y. (2013). BrainNet viewer: A network visualization tool for human brain connectomics. PloS One, 8, e68910.
Xu Y, Graber H, Barbour R (2014): nirsLAB: A Computing Environment for fNIRS Neuroimaging Data Analysis. Biomedical Optics 2014, OSA Technical Digest (online) (Optical Society of America, 2014), paper BM3A.1
Zhao, H., Tanikawa, Y., Gao, F., Onodera, Y., Sassaroli, A., Tanaka, K., & Yamada, Y. (2002). Maps of optical differential pathlength factor of human adult forehead, somatosensory motor and occipital regions at multi-wavelengths in NIR. Physics in Medicine and Biology, 47, 2075–2093.
This work was funded by the academic career program Filling the Gap (Grant number FTG-1415-007), University of Zurich.
Conflict of Interest
Author LH declares that she has no conflict of interest. Author FS declares that he has no conflict of interest. Author ES declares that he has no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the ethics committee of the Canton Zurich and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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Holper, L., Scholkmann, F. & Seifritz, E. Prefrontal hemodynamic after-effects caused by rebreathing may predict affective states – A multimodal functional near-infrared spectroscopy study. Brain Imaging and Behavior 11, 461–472 (2017). https://doi.org/10.1007/s11682-016-9527-4
- Respiratory challenge
- Time-frequency dynamics
- Cortical-systemic coherence
- Functional near-infrared spectroscopy
- Heart rate
- Partial pressure of carbon dioxide