Caffeine's effects on cerebrovascular reactivity and coupling between cerebral blood flow and oxygen metabolism
Open accessAbstract
The blood-oxygenation-level-dependent (BOLD) signal is dependent on multiple physiological factors such as cerebral blood flow (CBF), local oxygen metabolism (CMRO(2)) and cerebral blood volume (CBV). Since caffeine affects both CBF and neural activity, its effects on BOLD remain controversial. The calibrated BOLD approach is an excellent tool to study caffeine because it combines CBF and BOLD measures to estimate changes in CMRO(2). The present study used the calibrated BOLD approach with 5% CO(2) to determine if a 2.5 mg/kg intravenous injection of caffeine changes the coupling between CBF and CMRO(2) during motor and visual tasks. The results show that caffeine decreases n, the CBF:CMRO(2) coupling ratio, from 2.58 to 2.33 in motor (p=0.006) and from 2.45 to 2.23 in visual (p=0.002) areas respectively. The current study also demonstrated that caffeine does not alter cerebrovascular reactivity to CO(2). These results highlight the importance of the calibrated BOLD approach in improving interpretation of the BOLD signal in the presence of substances like caffeine.
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Caffeine reduces cerebral blood velocity and cerebral blood flow (CBF), as assessed by a number of different techniques.
“Caffeine has been shown to reduce cerebral blood velocity and CBF assessed using a number of different techniques (Chen and Parrish 2009b; Hasse et al. 2005; Kennedy and Haskell 2011; Laurienti et al. 2003; Mathew and Wilson 1991; Rack-Gomer et al. 2009).”
From A Double-Blind, Placebo-Controlled Study Evaluating the Effects of Caffeine and L-Theanine Both Alone and in Combination on Cerebral Blood Flow, Cognition and Mood (2015) · cites this paper as Chen and Parrish 2009b
The Discussion (page not supplied) reports that caffeine reduced resting-state CBF by 26% ± 8% in this study and notes similar findings from earlier ASL and PET studies. It mentions a Doppler study of blood velocity, but only to report unchanged reactivity to CO2 after caffeine; it does not establish a reduction in blood velocity. (LLM, conf=0.85)
Experimental — accuracy not yet measuredData from calibrated BOLD fMRI studies suggest that the increase in deoxy-Hb is indicative of neural activation.
“Data from calibrated (to hypercapnia) BOLD fMRI studies showing that a high single dose of caffeine (~200 mg+), administered to habitual consumers, reduces blood flow but increases oxygen consumption in response to task/stimulation, suggest that this increase in deoxy-Hb is indicative of neural activation”
From A Double-Blind, Placebo-Controlled Study Evaluating the Effects of Caffeine and L-Theanine Both Alone and in Combination on Cerebral Blood Flow, Cognition and Mood (2015) · cites this paper as Chen and Parrish 2009b
The Results (page unavailable) report that caffeine increased task-related oxygen consumption relative to blood-flow change. But the Discussion attributes the observed increase in baseline deoxyhemoglobin primarily to reduced resting blood flow; it treats increased neuronal firing as only one possible explanation for altered coupling and says the calibrated BOLD model cannot establish the mechanism. Thus the paper does not establish that the deoxyhemoglobin increase indicates neural activation. (LLM, conf=0.87)
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“A linear dose relationship has been observed between reductions in CBF and caffeine following doses of 1, 2.5 and 5mg/kg caffeine (Chen and Parrish 2009a).”
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- Authors
- Chen, Y., & Parrish, T. B.
- Affiliations
- Northwestern University (US)
- Corresponding author
- Parrish, Todd B.
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2009-02
- Volume
- 44
- Issue
- 3
- Pages
- 647-652
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC2654762
- OpenAlex
- W2019526570
- Cited by
- 100
- References
- 36
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2023: 1 · 2022: 5 · 2021: 2 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 5 · 2016: 7 · 2015: 14 · 2014: 6 · 2013: 9 · 2012: 14
- FWCI
- 4.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Biomedical Imaging and Bioengineering (R01EB002449)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- caffeine, cerebrovascular reactivity, cerebral blood flow, cerebral oxygen consumption, BOLD signal, CO2 reactivity, motor tasks, visual task, cerebral blood volume
- MeSH terms
- Adult, Central Nervous System Stimulants, Blood Flow Velocity, Caffeine, Cerebral Cortex, Cerebrovascular Circulation, Dose-Response Relationship, Drug, Female, Humans, Magnetic Resonance Imaging, Male, Oxygen Consumption
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