High-resolution fMRI detects neuromodulation of individual brainstem nuclei by electrical tongue stimulation in balance-impaired individuals

Abstract

High-resolution functional magnetic resonance imaging (fMRI) can be used to precisely identify blood oxygen level dependent (BOLD) activation of small structures within the brainstem not accessible with standard fMRI. A previous study identified a region within the pons exhibiting sustained neuromodulation due to electrical tongue stimulation, but was unable to precisely identify the neuronal structure involved. For this study, high-resolution images of neural activity induced by optic flow were acquired in nine healthy controls and nine individuals with balance dysfunction before and after information-free tongue stimulation. Subjects viewed optic flow videos to activate the structures of interest. Sub-millimeter in-plane voxels of structures within the posterior fossa were acquired using a restricted field of view. Whole-brain functional imaging verified that global activation patterns due to optic flow were consistent with previous studies. Optic flow activated the visual association cortices, the vestibular nuclei, and the superior colliculus, as well as multiple regions within the cerebellum. The anterior cingulate cortex showed decreased activity after stimulation, while a region within the pons had increased post-stimulation activity. These observations suggest the pontine region is the trigeminal nucleus and that tongue stimulation interfaces with the balance-processing network within the pons. This high-resolution imaging allows detection of activity within individual brainstem nuclei not possible using standard resolution imaging.

Figure 1

A comparison of standard-resolution (A-C) and high-resolution functional MR imaging (D-F). A,D) Slice locations. B,E) Raw T2*-BOLD images. C,F) Single-subject activation of the superior colliculus in response to optic flow. The large voxels of the standard-resolution image are larger than the nuclei themselves. The voxels of the high-resolution image are much smaller than individual nuclei.

Figure 2

Scores from the sensory organization tests (SOTs) before and after CN-NINM stimulation. The dashed line shows the cutoff for impairment as defined by the test. One subject was not able to complete the pre-stimulation testing and is therefore not included. Pre – balance subjects before stimulation. Post – balance-impaired subjects after stimulation.

Figure 3

Significant clusters in the stan-res data from the two-way ANOVA. This analysis compared balance-impaired subjects before stimulation (Pre) to after stimulation (Post). OF shows activity attributable to the effects of optic flow while OF × Stim indicates regions where optic flow-related processing changed after stimulation. No clusters reached significance for the effect of stimulation alone (Stim). Images are thresholded at α ≤ 0.005. Only clusters with a volume greater than 1144 μl are displayed. All Z values are in MNI coordinates.

Figure 4

Significant clusters from the one- and two-sample t-tests showing the effect of optic flow. The first three columns show activity due to optic flow in each group separately while the last two columns show intergroup comparisons (Pre>Nor shows differences between balance-impaired subjects before stimulation to healthy controls, Post>Nor shows differences between balance-impaired subjects after stimulation to healthy controls). Images are thresholded at α ≤ 0.005. Only clusters with a volume greater than 1144 μl are displayed. All Z values are in MNI coordinates.

Figure 5

Significant clusters within the brainstem and cerebellum from the high-res data in the two-way ANOVA. This analysis compared balance-impaired subjects before stimulation (Pre) to after stimulation (Post). OF shows activity attributable to the effects of optic flow while OF × Stim indicates regions where optic flow-related processing changed after stimulation. No clusters reached significance for the effect of stimulation alone (Stim). In the top two rows, the left column shows significant clusters while the right column shows axial diagrams of the brainstem at the approximate axial location (Duvernoy 1995). The image in the lower left shows significant clusters within the cerebellum. The labeled structures in the diagrams are the most likely nuclei of the activation clusters. Images are thresholded at α ≤ 0.005. Only clusters with a volume greater than 20 μl are displayed. All Z values are in MNI coordinates. The dashed line outlines the brainstem. (Abbreviations: TN, trigeminal nucleus; VC, vestibular nuclei complex; R/L/V/D, right/left/ventral/dorsal)