Citation: Tip LM. Breathing patterns in psychopathology and blood oxygen levels - Risk factor for cognitive decline?. J Clin Images Med Case Rep. 2022; 3(5): 1838.

Short commentary

Neuronal brain activity is assumed to be reflected by blood level oxygenation levels, also known as BOLD signal, measured with fMRI. A scan of the literature points to both oxygen and carbon dioxide blood levels effects on BOLD fMRI. The roles of oxygen (O2 ; hypoxia/hypoxemia, hyperoxia) and carbon dioxide (CO2 ; hypocapnia, hypercapnia) in neuronal activity and BOLD signal are complex and still under investigation [1,2]. Inspiration while varying levels of O2 and CO2 in the air have been used to investigate resting state fMRI [3].

Blood oxygenation can be influenced by breathing patterns, which is usually considered as ‘physiological noise’ that needs to be controlled for during fMRI [4,5].

Studying breathing is not straightforward because of its combination of voluntary and automatic processes involved, and factors in respiratory control versus respiratory perception (for a review on neuroimaging and cognitive/emotional processing within brain structures) [6].

Variations in arterial CO2 have an effect on resting state BOLD signal [7]. Breath-holding changes blood levels of CO2 which results in an increase in BOLD-signal [8] while hyperventilating can reduce BOLD signal [9].

CO2 levels are stronger related to BOLD signals than volume of breathing [10]. Furthermore, there can be individual differences in the cerebrovascular effects of CO2 inhalation [11]. This is important information when one wants to measure, and correct for CO2 levels in BOLD fMRI - measuring respiration volume just with a belt around the abdomen would according to this evidence be insufficient for a valid measuring.

Only few researchers have stated that interpretation of respiratory ‘confounders’ in measuring brain activity could be meaningful regarding the experience of emotion [12].

Recent research shows that the experience of different emotions, anxiety and depressive state, have different effects on breathing [13]. Anxiety disorders, and especially panic disorder, are known for the effects on breathing [14,15]. From another view point, there is some indirect evidence of a possible connection of depression and breathing, as serotonin receptors are central respiratory chemoreceptors [16].

Giardino et al [17] conclude in their review, that anxiety can influence cerebral blood flow by its effect on CO2 . In addition, research on breathlessness could contribute to the understanding of the association between affect and breathing patterns [18].

Sighing can be seen as a way to reset breathing irregularities caused by stress or sustained attention [19] and reduces anxious physiological tension [20]. Individual differences in traitnegative affectivity reflect in differences in sighing pattern [21] and there is evidence that sighing is a way to regulate emotions [22,23].

Sighing can also have an effect on the cardiovascular system [24].

So far, breathing patterns and the effects on brain activity or fMRI BOLD signals have mainly been studied in certain medical conditions like asthma/COPD and Obstructive Sleep Apnea (OSA). There is increasing evidence for the role of OSA in cognitive decline because of the resulting intermittent hypoxia in humans [25,26]. In rats, intermittent hypoxia can cause vascular aging [27] and in mice, plaques [28].

If you look at risk factors for the development of dementia more closely, it is visible that some of them have to do with breathing one way or the other: smoking (change in blood O2 and CO2 levels; reduced lung capacity), exercise (lung capacity) and obesity (amongst others due to the physical limitations to breathing, for an overview of respiratory physiology in obesity) [29].

Exercise is assumed to be beneficial to prevent cognitive decline by improving vascular health [30,31].

Normal aging can increase CO2 blood levels as a result of arterial stiffness [32] and has an effect on lung capacity [33], and for this, exercise can be helpful.

It is not clear what the exact effect is of exercise on breathing in cognitive decline. There is some evidence of this add-on effect, as training in breathing can have a positive effect on cognitive decline that exceeds that of exercise training [34].

Another link related to breathing training could come from research on mindfulness, which is known for decreasing symptoms of depression and anxiety. Mindfulness training typically incorporates attention for breathing [35] and can impact on cardiovascular receptivity to stress [36].

A potential effect could be, that by learning to observe without changing behaviour -one of the values taught in mindfulness- this can have an effect on breathing patterns. Some evidence was found for the role of perception of interoceptive cues after mindfulness training in neuronal processing [37].

A review on meditation in the elderly showed that this can be helpful in the prevention of dementia [38].

Conclusion

Anxiety and depression are known risk-factors in the development of dementia. Breathing patterns have an effect on BOLD fMRI and can be caused by affective state or go together with certain psychopathology. Cognitive decline is reflected in decreased BOLD fMRI.

The question is, if the link between psychopathology and dementia development could be (partially) explained by the effect of breathing patterns, related to affective state and/or psychopathology.

Individual habitual patterns are expected to especially manifest during resting state. This would be important in the research on dementia prevention as the areas that are active during resting state, are the first to become impaired in the development of dementia.

Future research

Future research may want to focus on how breathing patterns are associated with psychopathological disorders and what the respective effects are on neuronal brain activity and/ or connectivity, measured with BOLD fMRI; what the potential chemical/metabolic effects in the brain are, in regards to breathing patterns and blood oxygenation; and how a) breathing patterns and b) chemical or metabolic effects of breathing play a role in cognitive decline.

References

1. Cardenas DP, Muir ER, Huang S, Boley A, Lodge D, et al. Functional MRI during hyperbaric oxygen: Effects of oxygen on neurovascular coupling and BOLD fMRI signals. NeuroImage. 2015; 119: 382-389.
2. Sheng M, Liu P, Mao D, Ge Y, Lu H. The impact of hyperoxia on brain activity: A resting-state and task-Evoked Electroencephalography (EEG) study. PLOS One. 2017; 12: e0176610.
3. Lajoie I, Tancredi FB, Hoge RD. The impact of inspired oxygen levels on calibrated fMRI measurements of M, OEF and resting CMRO2 using combined hypercapnia and hyperoxia. PLOS One. 2017; 12: e0174932.
4. Auer DP. Spontaneous low-frequency blood oxygenation leveldependent fluctuations and functional connectivity analysis of the ‘resting’ brain. Magnetic Resonance Imaging. 2008; 26: 1055-1064.
5. Birn RM. The role of physiological noise in resting-state functional connectivity. NeuroImage. 2012; 62: 864-870.
6. Evans KC. Cortico-limbic circuitry and the airways: Insights from functional neuroimaging of respiratory afferents and efferent’s. Biological Psychology. 2010; 84: 13-25.
7. Wise RG, Ide K, Poulin MJ, Tracey I. Resting fluctuations in arterial carbon dioxide induce significant frequency variations in BOLD signal. NeuroImage. 2003; 21: 1652-1664.
8. Kastrup A, Li T, Takahashi A, Glover GH, Moseley ME. Functional Magnetic Resonance Imaging of regional cerebral blood oxygenation changes during breath holding. 1998.
9. Weckesser M, Posse S, Olthoff U, Kemna L, Dager S, et al. Functional imaging of the visual cortex with BOLD- contrast MRI: Hyperventilation decreases signal response. Magnetic Resonance in Medicine. 1999; 41: 213-216.
10. Vogt KM, Ibinson JW, Schmalbroek P, Small RH. Comparison between end-tidal CO2 and respiration volume per time for detecting BOLD signal fluctuations during paced hyperventilation. Magnetic Resonance Imaging. 2011; 29: 1186-1194.
11. Fisher JA. The CO2 stimulus for cerebrovascular reactivity: Fixing inspired concentrations vs. targeting end-tidal partial pressures. Journal of Cerebral Blood Flow & Metabolism. 2016; 36: 1004- 1011.
12. Iacovelli V, Hasson U. The relationship between BOLD signal and autonomic nervous system functions: implications for processing of ‘’physiological noise’’. Magnetic Resonance Imaging. 2011; 29: 1338-1345.
13. Vleminx E, Van Diest I, Van de Bergh O. Emotion, sighing and respiratory variability. Psychophysiology. 2015; 52: 657-666.
14. Grassi M, Caldirola D, Di Chiara NV, Riva A, Daccò S, et al. Are respiratory abnormalities specific for panic disorder? A metaanalysis. Neuropsychobiology. 2014; 70: 52-60.
15. Grassi M, Caldirola D, Vanni G, Guerriero G, Piccinni M, et al. Baseline respiratory parameters in panic disorders: A meta-analysis. Journal of Affective Disorders. 2013; 146: 158-173.
16. Teran FA, Massey CA, Richerson GB. Serotonin neurons and central respiratory chemoreception: where are we now? Progress in brain research. 2014; 209: 207-233.
17. Giardino ND, Friedman SD, Dager SR. Anxiety, respiration, and cerebral blood flow: implications for functional brain imaging. Comprehensive Psychiatry. 2007; 48: 103-112.
18. Wan L, Van Diest I, De Peuter S, Bogaerts K, Van de Woestijne K, et al. Breathlessness rating type influences respiratory behavior during hypercapnia in the rebreathing test. Journal of Psychosomatic Research. 2008; 65: 501-504.
19. Vlemincx E, Van Diest I, Van den Bergh O. A sigh following sustained attention and mental stress: Effects on respiratory variability. Physiology and Behavior. 2012; 107: 1-6.
20. Vleminx E, Van Diest I, Van den bergh O. A sigh of relief or a sigh to relieve: The psychological and physiological relief effect of deep breaths. Psychology & Behaviour. 2016; 165: 127-135.
21. Wuyts R, Vleminx E, Bogaerts K, Van Diest I, Van Den Bergh O. Sigh rate and respiratory variability during normal breathing and the role of negative affectivity. International Journal of Psychophysiology. 2011; 82: 175-179.
22. Vlemincx E, Abelson JL, Lehrer PM, Davenport PW, Van Diest I, et al. Respiratory variability and sighing: A psychophysiological reset hypothesis. Biological Psychology. 2013; 93: 24-32.
23. Vleminx E, Meulders M, Abelson JL. Sigh rate during emotional transitions: More evidence for a sigh of relief. Biological Psychology. 2017; 125: 163-172.
24. Vaschillo EG, Vaschillo B, Buckma JF, Nguyen-Louie T, Heiss S, et al. The effects of sighing on the cardiovascular system. Biologial Psychology. 2015; 106; 86-95.
25. Lavie L. Oxidative stress in obstructive sleep apnea and intermittent hypoxia - Revisited - The bad ugly and good: implications to the heart and brain. Sleep Medicine Reviews. 2015; 20: 27-45.
26. Zhu X, Zhao Y. Sleep-disordered breathing and the risk of cognitive decline: a meta-analysis of 19,940 participants. Sleep Breath. 2017.
27. Docio I, Olea E, Gallego-Martín T, Prieto-Lloret J, Rigual R, et al. Rats exposure to chronic intermittent hypoxia mimics aging effects on carotoid body and vascular responses. Conference Paper. September 2016; Conference: Jornadas de Formación CIBERES. 2017.
28. Daulatzai MA. Death by a thousand cuts in Alzheimer’s disease: Hypoxia - The Prodrome. Neurotoxicity Research. 2013; 24: 216- 243.
29. Parameswaran K, Todd DC, Soth M. Altered respiratory physiology in obesity. Canadian Respiratory Journal. 2006; 13: 203-210.
30. Tarumi T, Zhang R. Cerebral hemodynamics of the aging brain: risk of Alzheimer disease and benefit of aerobic exercise. Frontiers in Physiology. 2014; 5: 1-6.
31. Schiattarella GG, Perrino C, Magliulo F, Carbone A, Bruno AG, et al. Physical activity in the prevention of peripheral artery disease in the elderly. Frontiers in Physiology. 2014; 5: 1-6.
32. Flück D, Beaudin AE, Steinback CD, Kumarpillai G, Shobha N, et al. Effects of aging on the associations between cerebrovascular responses to visual stimulation, hypercapnia and arterial stiffness. Frontiers in Physiology, Integrative Physiology. 2014; 49: 1-12.
33. Skloot GS. The effects of aging on lung structure and function. Clinics in Geriatric Medicine. 2017; 33: 447-457.
34. Ferreira L, Tanaka K, Ferreira Santos-Galduróz R, Carlos J, Galduróz F. Respiratory training as strategy to prevent cognitive decline in aging: a randomized controlled trial. Clinical Interventions in aging. 2015; 10: 593-603.
35. Dickenson J, Berkman ET, Arch J, Lieberman MD. Neural correlates of focused attention during a brief mindfulness induction. SCAN. 2013; 8: 40-47.
36. Demarzo MP, Montero-Marin J, Stein Ph K, Cebolla A, Provinciale JG, et al. Mindfulness may both moderate and mediate the effect of physical fitness on cardiovascular responses to stress: a speculative hypothesis. Frontiers in Physiology, Clinical and Translational Physiology. 2014; 105: 1-8.
37. Haase L, May AC, Falahpour M, Isakovic S, Simmons AN, et al. A pilot study investigating changes in neural processing after mindfulness training in elite athletes. Frontiers in behavioural Neuroscience. 2015; 229: 1-12.
38. Khalsa DS. Stress, meditation, and Alzheimer’s disease prevention: Where the evidence stands. Journal of Alzheimer’s disease. 2015; 48: 1-12.