This three-year PhD project has been devised to provide stakeholders (neurologists, ophthalmologists and other healthcare professionals, scientists, carbon monoxide (CO) industries and policy professionals) with clinically important information on the effects of low-level exposure to CO on the brain; information that they can immediately make use of within their own professions.
The study will identify and measure the effects of low-level CO exposures on the highly sensitive nerves of the brain and eyes in healthy volunteers. As the exposure dose will be low, the participants will not display explicit symptoms associated with CO exposure.
Exposure concentrations will be around the lower levels relevant to typical UK indoor exposures and below the World Health Organization (WHO)1 guideline doses. By measuring the effects of CO on the light response of the eye, in combination with changes in blood flow to the brain and neuropsychological performance (e.g. memory, learning, information processing and reaction times), the study will provide relevant information to CO stakeholders to facilitate action or further investigation as required by each sector.
The experimental methods used will be:
- Chromodynamic Pupillometry (CDP)
- BOLD functional Magnetic Resonance Imaging (BOLD fMRI)
- Transcranial Doppler ultrasound (TCD)
- CANTAB cognitive testing
The use of these techniques will enable physiological changes to be identified and provide data to assist with analysis and evaluation of the changes.
The work will be carried out at the University of Hertfordshire using CDP, TCD and CANTAB cognitive testing, and replicate studies at Sheffield Hallam University including BOLD fMRI.
CDP assesses fluctuations in the size of the pupil of the eye that correlate with subtle physiological changes within the nervous system. Detecting the pattern of fluctuations that relate to the changes in response to CO is the first step in developing a new, sensitive diagnostic indicator.
TCD is a sensitive method to quantify changes in blood flow to the brain and changes in the size (enlargement) of the blood vessels in the brain, both of which occur with exposure to CO.
BOLD fMRI is sensitive to changes in neurological response and previous, comparative studies using lower levels of CO will be analysed alongside the results from this project to provide greater insight regarding the results obtained.
The use of CANTAB cognitive testing on three separate occasions (baseline, post exposure and follow-up) in all volunteers will enrich our understanding of the pre-symptomatic neurocognitive effects of exposure to CO.
It will establish whether the physiological changes detected using the other diagnostic methods are also expressed by changes in cognitive function. This will help establish what the neurological changes mean for the immediate cognitive functioning of the volunteer. The follow-up phase will confirm the expected reversibility of any neurocognitive changes expressed during the study.
The data will be analysed and discussed in relation to scientific, medical and indoor environmental understanding of CO exposure. The implications that the results might have for low level exposures will make a significant contribution to our understanding of how CO affects the brain and will help improve future treatments and, importantly, provide a rapid, non-invasive and reliable diagnostic indicator of CO exposure.
This work will therefore inform the future development of:
- Improved treatment guidance, neurocognitive awareness and educational campaigns for clinicians
- Evidence to underpin the use of a state-of-the-art ophthalmic diagnostic method not currently used in the diagnosis of CO
- Improved guidelines, protocols, training and intervention strategies to enable government and the gas and alarm industry to ensure health protection
It is expected that the quality of the data gathered will quickly enable progress in the development of a smartphone ‘app’ to perform self-assessments by a wide range of users, enabling rapid clinical diagnosis and treatment.
