Brainstem Correlates of a Cold Pressor Test Measured by Ultra-High Field fMRI

Introduction: Modern imaging techniques such as blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) allow the non-invasive and indirect measurement of brain activity. Whether changes in signal intensity can be detected in small brainstem regions during a cold pressor test (CPT) has not been explored thoroughly. The aim of this study was to measure whole brain and brainstem BOLD signal intensity changes in response to a modified CPT. Methods: BOLD fMRI was measured in healthy normotensive participants during a randomized crossover study (modified CPT vs. control test) using ultra-high field 7 Tesla MRI scanner. Data were analyzed using Statistical Parametric Mapping (SPM) in a whole-brain approach, and with a brainstem-specific analysis using the spatially unbiased infra-tentorial template (SUIT) toolbox. Blood pressure (BP) and hormonal responses (norepinephrine and epinephrine levels) were also measured. Paired t-test statistics were used to compare conditions. Results: Eleven participants (six women, mean age 28 ± 8.9 years) were analyzed. Mean arterial BP increased from 83 ± 12 mm Hg to 87 ± 12 mm Hg (p = 0.0009) during the CPT. Whole-brain analysis revealed significant activations linked to the CPT in the right supplementary motor cortex, midcingulate (bilateral) and the right anterior insular cortex. The brainstem-specific analysis showed significant activations in the dorsal medulla. Conclusion: Changes in BOLD fMRI signal intensity in brainstem regions during a CPT can be detected, and show an increased response during a cold stress in healthy volunteers. Consequently, BOLD fMRI at 7T is a promising tool to explore and acquire new insights in the comprehension of neurogenic hypertension.