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Individual differences in haemoglobin concentration influence bold fMRI functional connectivity and its correlation
Phillip G D Ward1, Edwina R Orchard1, Stuart Oldham2
1Monash Biomedical Imaging, Monash University, 770 Blackburn Rd, Melbourne, Victoria 3800, Australia; Turner Institute for Brain and Mental Health, Monash University, Melbourne, Victoria, Australia; Australian Research Council Centre of Excellence for Integrative Brain Function, Melbourne, Victoria, Australia.
Individual differences in hemoglobin levels significantly confound resting-state functional connectivity measures derived from BOLD-fMRI. Controlling for hemoglobin is crucial for reproducible brain connectome and cognition studies.
Area of Science:
- Neuroscience
- Medical Imaging
- Human Physiology
Background:
- Resting-state functional connectivity (rsFC) is commonly measured using Blood-Oxygen-Level-Dependent functional Magnetic Resonance Imaging (BOLD-fMRI).
- The BOLD signal reflects changes in blood oxygenation, influenced by hemoglobin concentration.
- Individual variations in hemoglobin may independently affect BOLD signal-to-noise ratio, potentially confounding rsFC.
Purpose of the Study:
- To investigate if group differences in hemoglobin confound rsFC measures.
- To examine if hemoglobin variability influences the relationship between rsFC and cognitive performance.
- To map the neuroanatomical distribution of hemoglobin's influence on rsFC.
Main Methods:
- Analysis of rsFC in 518 healthy elderly subjects (259 men).
- Median-splitting participants by hemoglobin concentration within each sex group.
- Assessing differences in rsFC, sex-specific effects, and relationships between rsFC and cognitive tests.
Main Results:
- Significant differences in rsFC were found between high and low hemoglobin groups in both men and women.
- Hemoglobin influenced the connectome differently across sexes: widespread increases in males, and parietal/subcortical increases with temporo-parietal decreases in females.
- Despite no cognitive differences between hemoglobin groups, significant differences in connectivity-cognition relationships were observed, particularly in males.
Conclusions:
- Individual hemoglobin variability is a significant confounder in BOLD-fMRI rsFC studies.
- Controlling for hemoglobin is essential for reproducibility in human brain connectome research, especially when comparing groups, sexes, or examining cognition relationships.
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