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Published on: July 9, 2016
Mitochondria and Cognition: An [18F]BCPP-EF Positron Emission Tomography Study of Mitochondrial Complex I Levels and
Ekaterina Shatalina1, Thomas Whitehurst2, Ellis Chika Onwordi3
1Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Medical Research Council Laboratory of Medical Science, Imperial College London, London, United Kingdom.
Background:
Mitochondrial complex I is the largest enzyme complex in the respiratory chain and can be noninvasively measured using [18F]BCPP-EF positron emission tomography (PET). Neurological conditions associated with mitochondria complex I pathology are also associated with altered blood oxygen level-dependent (BOLD) response and impairments in cognition. In this study, we aimed to investigate the relationship between mitochondrial complex I levels, cognitive function, and associated neural activity during task switching in healthy humans.
Methods:
Cognitively healthy adults (N = 23) underwent [18F]BCPP-EF PET scans and functional magnetic resonance imaging (fMRI) while performing a task-switching exercise. Task performance metrics included switch cost and switching accuracy. Data were analyzed using linear mixed-effects models and partial least squares regression (PLS-R).
Results:
We found significant positive associations between [18F]BCPP-EF volume of distribution (VT) and the task-switching fMRI response (β = 3.351, SE = 1.01, z = 3.249, p = .001). Positive Pearson's correlations between [18F]BCPP-EF VT and the fMRI response were observed in the dorsolateral prefrontal cortex (r = 0.61, p = .0019), insula (r = 0.46, p = .0264), parietal precuneus (r = 0.51, p = .0139), and anterior cingulate cortex (r = 0.45, p = .0293). [18F]BCPP-EF VT across task-relevant regions was associated with task switching accuracy (PLS-R, R2 = 0.48, root mean square error [RMSE] = 0.154, p = .011) and with switch cost (PLS-R, R2 = 0.38, RMSE = 0.07, p = .048).
Conclusions:
Higher mitochondrial complex I levels may underlie an individual's ability to exhibit a stronger BOLD response during task switching and are associated with better task-switching performance. This provides the first evidence linking the BOLD response with mitochondrial complex I and suggests a possible biological mechanism for the aberrant BOLD response in conditions associated with mitochondrial complex I dysfunction that should be tested in future studies.
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