By Lucie Wilson, a first-year PhD student at Sheffield Hallam University and registered adult nurse.
Project background
We understand that most individuals are exposed to ambient levels of carbon monoxide (CO) every day, for example, due to the burning of fossil fuels or transport emissions. Additional factors such as tobacco smoking also increase an individual’s exposure to CO dramatically.
Despite the government detailing an acceptable level of atmospheric CO to be around 6-9 parts per million, far lesser levels of CO have been linked with diseases such as heart disease and stroke.
Vascular disease remains a prominent contributing factor in the development of neurological impairment, and recent works have identified causal relationships between low-level CO exposure and dementia diagnosis, though research remains limited and mostly observational in nature.
Numerous studies focus on the impacts of acute, high levels of CO on human populations, noting that this exposure often results in serious injury or death. CO is a colourless, odourless, and tasteless gas, and haemoglobin’s affinity for CO over oxygen ensures that CO inhalation remains one of the major causes of poisonings around the world.
Despite this, our knowledge of the impact of low-level CO on humans, particularly from a cognitive perspective, remains largely unexplored.
A recent study showed how functional Magnetic Resonance Imaging (fMRI) could be used to assess how brain activation was affected by low-level CO inhalation (Bendell et al, 2020).This study identified reduced blood flow in multiple brain regions in healthy volunteers after their exhaled CO levels were increased by only 3ppm. A specific technique was employed here, termed Blood Oxygen Level Dependent (BOLD) fMRI.
This is a method commonly used in fMRI that relies on differences in brain blood flow, to identify areas of high and low activity in the brain. Essentially an active part of the brain will require more oxygenated blood, and so this influx can be picked up with BOLD imaging.
This is because oxygenated blood has different magnetic properties to that of deoxygenated blood and so will demonstrate a different fMRI signal, compared to brain regions that are less active. This means that BOLD fMRI signal can be caused either by neuronal activation, by changes in brain blood flow, or by both.
The Study
Raw fMRI scan data were analyzed to understand how cognitive function may have been impacted by low-level CO exposure.
Healthy young adults were recruited to receive a small amount of CO mixed with air, via a one-way breathing circuit, to increase their exhaled CO levels by around 3ppm. Whilst in the scanner, participants performed a basic reaction time task to test their cognitive function.
The task consisted of the volunteer pressing a button with their right hand as fast as they could when a flashing dot appeared on the screen. Their reaction times were recorded, and fMRI images were captured using the BOLD method.
Findings
All participants demonstrated a significant increase in their exhaled CO levels following CO inhalation, compared to an air only control intervention. They also exhibited slower reaction times after CO inhalation.
Calculating their average brain activation revealed consistent activation across the cerebellum and motor cortex both after breathing CO and breathing air. This demonstrated that the participants all performed the task in the same way.
Both the cerebellum and motor cortex play an important role in movement execution and coordination, and so were likely activated because participants were pushing the button to respond in the reaction time task. Of all the brain scans, the scan after CO inhalation had the lowest amount of activation in both these regions, compared to air control brain scans.
At group level, a statistically significant reduction in BOLD signal was identified after CO inhalation in the middle and superior temporal gyrus brain regions. Temporal gyri have lots of different functions within the brain but are commonly involved with visual perception and so may have been triggered in the reaction time task by visually processing the dot flashes within the scanner.
Research has found that the temporal lobe can be particularly at-risk following CO toxicity, and other studies have linked impairments in the middle temporal gyrus to both autism and Alzheimer’s disease.
Summary
The findings of this research suggest that exposure to a relatively low amount of CO (raising exhaled CO levels by only 3ppm) was sufficient to cause not only changes in brain activation, but also in cognitive task performance. With this technique, we cannot tell for certain if CO affected the neuronal activation linked to the task, the associated brain blood flow, or both.
As the only thing different between these scans was the CO inhalation, it is highly likely that this change in neuronal activation and/or brain blood flow was linked to CO. This does pose the question of how ambient CO pollution may be affecting our neurovascular health and highlights the need for further study.
Next steps
The results of this data have informed the next steps in my PhD project where I will be recruiting more participants to undergo both fMRI and transcranial doppler ultrasound (TCD) scans, to investigate how low-level CO inhalation may affect both vascular (as can be measured with TCD) and neurological responses.
Participants’ exhaled CO levels will be increased by around 3ppm to align with previous work. I will also be utilising blood sample analysis to start to explore what biological mechanisms may be underpinning my imaging findings. It is my hope that this work will help us better understand what CO does to our brains.
References
Bendell, C., Moosavi, S. H. and Herigstad, M., (2019). Low-level carbon monoxide exposure affects BOLD fMRI response. Journal of Cerebral Blood Flow & Metabolism. 40(11). Pp. 2215-2224.
Chen, H-L., Chen, P-C., Lu, C-H., Hsu, N-W., Chou, K-H., Lin, C-P., Wu, R-W., Li, S-H., Cheng, Y-F. and Lin, W-C., (2013). Structural and cognitive deficits in chronic carbon monoxide intoxication: a voxel-based morphometry study. BMC Neurology. 13(129).
Dong, Q-Y., Li, T-R., Jiang, X-Y., Wang, X-N., Han, Y. and Jiang, J-H., (2021). Glucose metabolism in the right middle temporal gyrus could be a potential biomarker for subjective cognitive decline: a study of a Han population. Alzheimer’s Research & Therapy. 13(74).
Lo, C-P., Chen, S-Y., Lee, K-W., Chen, W-L., Chen, C-Y., Hsueh, C-J. and Huang, G-S., (2007). Brain Injury After Acute Carbon Monoxide Poisoning: Early and Late Complications. AJR. 189. Pp. 205-211.