Abstract
IntroductionModern 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.MethodsBOLD 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.ResultsEleven 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.ConclusionChanges 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.
Highlights
Modern imaging techniques such as blood oxygen level-dependent (BOLD) functional magnetic resonance imaging allow the non-invasive and indirect measurement of brain activity
Increased sympathetic tone is associated with the initiation and maintenance of many forms of hypertension (Esler and Kaye, 2000; Guyenet, 2006; Fisher and Paton, 2012), and there is growing evidence that the sympathetic tone is regulated by a network of neuronal populations in the brainstem, the spinal cord and the hypothalamus (Sved et al, 2003; Guyenet, 2006)
Several crucial areas in the medulla in the brainstem contribute to the cardiovascular control, such as the rostral ventrolateral medullar (RVLM), the caudal ventrolateral medulla (CVLM) and the nucleus of the solitary tract (NTS) (Guyenet, 2006)
Summary
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. Several crucial areas in the medulla in the brainstem contribute to the cardiovascular control, such as the rostral ventrolateral medullar (RVLM), the caudal ventrolateral medulla (CVLM) and the nucleus of the solitary tract (NTS) (Guyenet, 2006) Together these areas play key roles in the baroreceptor reflex, which is a powerful negative feedback reflex to control cardiovascular function, in addition to having specific, independent contributions to the cardiovascular control (Sved et al, 2000, 2003). Careful physiological investigations in animals show that the baroreceptor sensory nerves from the carotid bodies and the aortic arch project to the NTS resulting in an increased activity of the NTS neurons in response to increases in blood pressure These excitatory neurons of the NTS increase the activity of the CVLM of which the inhibitory neurons project to the RVLM. The increased activity of the inhibitory neurons causes an inhibition of the tonically active sympathoexcitatory neurons in the RVLM and a decrease in sympathetic outflow to blood vessels (Sved et al, 2003; Dampney, 2016)
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