Functional MRI Reveals Locomotion-Control Neural Circuits in Human Brainstem

Abstract

The cuneiform nucleus (CN) and the pedunculopontine nucleus (PPN) in the midbrain control coordinated locomotion in vertebrates, but whether similar mechanisms exist in humans remain to be elucidated. Using functional magnetic resonance imaging, we found that simulated gait evoked activations in the CN, PPN, and other brainstem regions in humans. Brain networks were constructed for each condition using functional connectivity. Bilateral CN–PPN and the four pons–medulla regions constituted two separate modules under all motor conditions, presenting two brainstem functional units for locomotion control. Outside- and inside-brainstem nodes were connected more densely although the links between the two groups were sparse. Functional connectivity and network analysis revealed the role of brainstem circuits in dual-task walking and walking automaticity. Together, our findings indicate that the CN, PPN, and other brainstem regions participate in locomotion control in humans.

Brainstem fMRI

“…On the other hand, no smoothing or using small kernels may not well enable inter-subject consistency, which also reduces sensitivity. For example, compared to a 3 or 4 mm-kernel, smoothing with a 5 mm-kernel resulted in larger task-evoked activations in the brainstem [18]. No smoothing also resulted in more dispersed activation clusters in cortical areas and therefore appeared to be less sensitive in comparison with smoothing with a 6 mm-kernel [31].…”

“…The FieldMap toolbox calculates an unwrapped field map with collected field maps during data acquisition, converts the created field map to the voxel displacement map, and then unwarps geometrically distorted BOLD-fMRI images. This method or similar tools are helpful but can hardly achieve a satisfactory correction for the ventral part of the pons (Figure 1) [18]. [18] are presented.…”

“…This method or similar tools are helpful but can hardly achieve a satisfactory correction for the ventral part of the pons (Figure 1) [18]. [18] are presented. The ventral pons appears to be "dark" in fMRI images because of susceptibility-induced loss of BOLD signals after correction with field maps.…”

“…Brainstem masks are therefore used to prevent impacts driven by noise from the interface between the brainstem and surrounding tissues. The masked analysis has been applied successfully to resting-state brainstem fMRI data [29] and then used to analyze taskinduced activations in the brainstem [18]. These brainstem masks are manually delineated on the basis of mean BOLD images, whereas a CSF mask can be automatically generated to extract nuisance regressors for the aCompCor-based method.…”

“…The CN controls high-speed locomotion whereas the PPN mediates slow/exploratory locomotion in vertebrates [37,38]. Localizing individual nuclei, e.g., the CN or the PPN on the basis of a histochemically defined atlas [25] has also been reported [18]. With higher magnetic susceptibility, iron-rich structures including the red nucleus and substantia nigra can be defined by using quantitative susceptibility mapping [39].…”