Ultra-high field functional brainstem imaging of nuclei responsible for blood pressure control
Presented During:
Friday, June 27, 2025: 11:30 AM - 12:45 PM
Brisbane Convention & Exhibition Centre
Room:
M1 & M2 (Mezzanine Level)
Poster No:
1752
Submission Type:
Abstract Submission
Authors:
Rebecca Glarin1, Donggyu Rim2, Luke Henderson3, Vaughan Macefield2
Institutions:
1University of Melbourne, Melbourne, Victoria, 2Monash University, Melbourne, Victoria, 3University of Sydney, Sydney, New South Wales
First Author:
Co-Author(s):
Introduction:
Muscle sympathetic nerve activity (MSNA) is composed of bursts of action potentials generated by muscle vasoconstrictor neurones that supply arterioles in skeletal muscles. MSNA is tightly coupled to the cardiac cycle via the arterial baroreflex, and by controlling blood flow to muscle, contributes importantly to the beat-to-beat regulation of blood pressure through variations in arteriolar diameter. MSNA originates within a nucleus of the brainstem - the rostral ventrolateral medulla (RVLM). Using MSNA-coupled functional MRI (fMRI) (Macefield, 2010) - in which we record MSNA and perform fMRI simultaneously, we can exploit the higher spatial resolution and signal-to-noise found at ultra-high field 7 Tesla. We aim to functionally identify the brainstem nuclei responsible for generating sympathetic drive using high-resolution 7T fMRI coupled with direct recordings of MSNA
Methods:
Recording: A tungsten microelectrode was inserted into a muscle fascicle of the left common peroneal nerve at the knee of 10 healthy subjects (7M/3F, mean age 26± 3) (Hagbarth,1968) Neural activity was amplified (gain 20000, bandpass 0.3-5.0 kHz) using an MR-compatible low-noise headstage (NeuroAmpEX, ADInstruments) and spontaneous bursts of MSNA identified and measured using analysis software (LabChart).
Imaging: Blood Oxygen Level Dependent (BOLD) gradient echo, echo-planar images (EPI) were collected in a 4s ON, 4s OFF (210 volumes) sparse-sampling protocol throughout the brainstem. Imaging was acquired on a 7T Magnetom Plus (Siemens, Germany) with a 1Tx/32Rx head coil (Nova Medical Inc., USA). EPI consisted of TR=4000ms; TE=20ms; flip angle=45; field of view=22.2 cm; voxel size=1mm isotropic, imaged in the axial plane, perpendicular to the long axis of the brainstem. A sagittal whole brain 3D T1 scan was acquired for fMRI co-registration, TR=5000ms, TE=3.1ms, flip angle 4/5, 0.75mm isotropic.
Analysis: Preprocessing and statistical analysis were performed using SPM12 (Wellcome Trust Centre for Neuroimaging, London); linear detrending and spatial smoothing (1 mm) were applied. The Spatially Unbiased Infratentorial Template (SUIT), (Diedrichsen, 2006) was used to isolate the brainstem and cerebellum on the fMRI and T1 and aligned to MNI space. The MSNA data acquired during the 4 s OFF period were divided into 4x1s epochs. The first analysis model coupled the occurrence of a burst of MSNA in each epoch with the equivalent epoch in the BOLD signal, 4s later to account for neural conduction and haemodynamic delays (Figure 1). The second model was designed to correlate the amplitude of a MSNA burst with the BOLD signal in the corresponding epoch.
Imaging: Blood Oxygen Level Dependent (BOLD) gradient echo, echo-planar images (EPI) were collected in a 4s ON, 4s OFF (210 volumes) sparse-sampling protocol throughout the brainstem. Imaging was acquired on a 7T Magnetom Plus (Siemens, Germany) with a 1Tx/32Rx head coil (Nova Medical Inc., USA). EPI consisted of TR=4000ms; TE=20ms; flip angle=45; field of view=22.2 cm; voxel size=1mm isotropic, imaged in the axial plane, perpendicular to the long axis of the brainstem. A sagittal whole brain 3D T1 scan was acquired for fMRI co-registration, TR=5000ms, TE=3.1ms, flip angle 4/5, 0.75mm isotropic.
Analysis: Preprocessing and statistical analysis were performed using SPM12 (Wellcome Trust Centre for Neuroimaging, London); linear detrending and spatial smoothing (1 mm) were applied. The Spatially Unbiased Infratentorial Template (SUIT), (Diedrichsen, 2006) was used to isolate the brainstem and cerebellum on the fMRI and T1 and aligned to MNI space. The MSNA data acquired during the 4 s OFF period were divided into 4x1s epochs. The first analysis model coupled the occurrence of a burst of MSNA in each epoch with the equivalent epoch in the BOLD signal, 4s later to account for neural conduction and haemodynamic delays (Figure 1). The second model was designed to correlate the amplitude of a MSNA burst with the BOLD signal in the corresponding epoch.
Results:
Fluctuations in BOLD signal intensity covaried with fluctuations in the occurrence and amplitude of the concurrently recorded bursts of MSNA. A group-level analysis identified increases in MSNA-coupled BOLD signal intensity in RVLM, raphe obscurus (RO), periaqueductal grey (PAG), cuneiform nucleus (CN) and dorsal motor nucleus of the vagus (DMV) when coupled with burst occurrence (uncorrected p<0.001). Analysis of the burst amplitude found a decrease in BOLD signal in nucleus tractus solitarius (NTS) and caudal ventrolateral medulla (CVLM) and an increase in the CN (uncorrected p<0.005) (Figure 2).
Conclusions:
Using Ultra-High Field MSNA-coupled fMRI we have shown that spontaneous bursts of MSNA covary with spontaneous increases in BOLD signal intensity, with burst incidence being coupled to fluctuations in signal intensity within RVLM, RO, PAG, CN and DMV. Conversely, burst amplitude was coupled to fluctuations in signal intensity in NTS, CVLM and CN. The improved signal-to-noise and higher spatial resolution available at 7T provide highly specific imaging of small nuclei responsible for generating sympathetic drive. This is the first study in humans to identify that different nuclei within the brainstem are responsible for controlling the occurrence of a burst and the strength of a burst, as predicted by Kienbaum et al (2001).
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Anatomy and Functional Systems 2
Subcortical Structures 1
Keywords:
Autonomics
Brainstem
FUNCTIONAL MRI
HIGH FIELD MR
Peripheral Nerve
Sub-Cortical
1|2Indicates the priority used for review
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Provide references using APA citation style.
Hagbarth, K. E., & Vallbo, A. B. (1968). Pulse and respiratory grouping of sympathetic impulses in human muscle-nerves. Acta Physiol Scand, 74(1), 96-108. doi:10.1111/j.1748-1716.1968.tb04218.x
Kienbaum, P., Karlssonn, T., Sverrisdottir, Y. B., Elam, M., & Wallin, B. G. (2001). Two sites for modulation of human sympathetic activity by arterial baroreceptors? J Physiol, 531(Pt 3), 861-869. doi:10.1111/j.1469-7793.2001.0861h.x
Macefield, V. G., & Henderson, L. A. (2010). Real-time imaging of the medullary circuitry involved in the generation of spontaneous muscle sympathetic nerve activity in awake subjects. Hum Brain Mapp, 31(4), 539-549. doi:10.1002/hbm.20885