Abstract
Introduction: Brainstem nuclei govern the arterial baroreflex, which is crucial for heart rate and blood pressure control. Yet, brainstem function is difficult to explore in living humans and is therefore mostly studied using animal models or postmortem human anatomy studies. We developed a methodology to identify brainstem nuclei involved in baroreflex cardiovascular control in humans by combining pharmacological baroreflex testing with functional magnetic resonance imaging.Materials and Methods: In 11 healthy men, we applied eight repeated intravenous phenylephrine bolus doses of 25 and 75 μg followed by a saline flush using a remote-controlled injector during multiband functional magnetic resonance imaging (fMRI) acquisition of the whole brain including the brainstem. Continuous finger arterial blood pressure, respiration, and electrocardiogram (ECG) were monitored. fMRI data were preprocessed with a brainstem-specific pipeline and analyzed with a general linear model (GLM) to identify brainstem nuclei involved in central integration of the baroreceptor input.Results: Phenylephrine elicited a pressor response followed by a baroreflex-mediated lengthening of the RR interval (25 μg: 197 ± 15 ms; 75 μg: 221 ± 33 ms). By combining fMRI responses during both phenylephrine doses, we identified significant signal changes in the nucleus tractus solitarii (t = 5.97), caudal ventrolateral medulla (t = 4.59), rostral ventrolateral medulla (t = 7.11), nucleus ambiguus (t = 5.6), nucleus raphe obscurus (t = 6.45), and several other brainstem nuclei [p < 0.0005 family-wise error (few)-corr.].Conclusion: Pharmacological baroreflex testing during fMRI allows characterizing central baroreflex regulation at the level of the brainstem in humans. Baroreflex-mediated activation and deactivation patterns are consistent with previous investigations in animal models. The methodology has the potential to elucidate human physiology and mechanisms of autonomic cardiovascular disease.
Highlights
Brainstem nuclei govern the arterial baroreflex, which is crucial for heart rate and blood pressure control
Cardiovascular control centers in the brainstem govern arterial baroreflexes, which are important for human blood pressure buffering (Jordan et al, 2002) and long-term blood pressure control (Bisognano et al, 2011)
Blood pressure traces deteriorated toward the end of the experiment in six of 11 subjects
Summary
Brainstem nuclei govern the arterial baroreflex, which is crucial for heart rate and blood pressure control. Projections to the cVLM and from there to the rVLM adjust efferent sympathetic traffic (Dampney, 1994; Dampney et al, 2002) Damage to these brainstem nuclei results in profound abnormalities in human blood pressure control. Brainstem fMRI has previously been validated for several applications including trigeminal pain research (Schulte et al, 2016), resting state connectivity measurement
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