Abstract
Blood oxygen level dependent (BOLD) signal in functional magnetic resonance imaging (fMRI) is frequently used as a proxy for underlying neural activity. Although this is a plausible assumption for experiments where a task is performed, it may not hold to the same degree for conditions of fMRI recording in a task-free, “resting” state where neural synaptic events are weak and, hence, neurovascular coupling and endothelial vascular factors become more prominent (Hillman Annu Rev Neurosci 37:161–181, 2014, 10.1146/annurev-neuro-071013-014111). Here we investigated the magnitude of change of BOLD in consecutive samples over the acquisition time period (turnover of BOLD, “TBOLD”) by first-order differencing of single-voxel BOLD time series acquired in 70 areas of the cerebral cortex of 57 cognitively healthy women in a task-free resting state. More specifically, we evaluated (a) the variation of TBOLD among different cortical areas, (b) its dependence on age, and (c) its dependence on the presence (or absence) of the neuroprotective Human Leukocyte Antigen (HLA) gene DRB1*13 (DRB1*13:02 and DRB1*13:01). We found that TBOLD (a) varied substantially by 2.2 × among cortical areas, being highest in parahippocampal and entorhinal areas and lowest in parietal-occipital areas, (b) was significantly reduced in DRB1*13 carriers across cortical areas (from ~ 15% reduction in orbitofrontal cortex to 2% reduction in cuneus), and (c) increased with age in noncarriers of DRB1*13 but decreased with age in DRB1*13 carriers. These findings document significant dependencies of TBOLD on cortical area location, HLA DRB1*13 and age.
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Partial funding for this study was provided by the University of Minnesota (the Anita Kunin Chair in Women's Healthy Brain Aging, the Brain and Genomics Fund, the McKnight Presidential Chair of Cognitive Neuroscience, and the American Legion Brain Sciences Chair). The sponsors had no role in the current study design, analysis or interpretation, or in the writing of this paper. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government.
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APG conceived the research; PC and LMJ contributed to data acquisition; PC extracted the relevant fMRI data; APG and PC contributed to data analysis; LMJ, PC and APG wrote the paper; all authors read, edited and approved the final version of the paper.
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James, L.M., Christova, P. & Georgopoulos, A.P. BOLD turnover in task-free state: variation among brain areas and effects of age and human leukocyte antigen (HLA) DRB1*13. Exp Brain Res 240, 1967–1977 (2022). https://doi.org/10.1007/s00221-022-06382-y
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DOI: https://doi.org/10.1007/s00221-022-06382-y