Enhancing effects of flavored nutritive stimuli on cortical swallowing network activity

Abstract

A better understanding of the central control of the physiology of deglutition is necessary for devising interventions aimed at correcting pathophysiological conditions of swallowing. Positive modulation of the cortical swallowing network can have clinical ramifications in dysphagia due to central nervous system deficits. Our aim was to determine the effect of nutritive sensory input on the cortical swallowing network. In 14 healthy right-handed volunteers, we utilized a paradigm-driven protocol to quantify the number of activated voxels and their signal intensity within the left hemispheric cortical swallowing network by high-resolution functional MRI (fMRI) during five different swallowing conditions. Swallowing conditions included a dry swallow (saliva) and natural water-, lemon-, popcorn-, and chocolate-flavored liquid swallows. Each flavored liquid was presented simultaneously by its image, scent, and taste in random order and tested over three runs. fMRIs were analyzed in a blinded fashion. Average fMRI blood oxygenation level-dependent signal intensity and number of activated voxels during swallowing concurrent with nutritive gustatory, olfactory, and visual stimulations were significantly increased compared with dry/natural water swallows throughout the cortical swallowing network (P < 0.001 and P < 0.05, respectively). Subregion analysis showed the increased activity for flavored liquids in prefrontal, cingulate gyrus, and sensory/motor cortex, but not in precuneus and insula. Concurrent gustatory, olfactory, and visual nutritive stimulation enhances the activity of the cortical swallowing network. This finding may have clinical implications in management of swallowing disorders due to cortical lesions.

Fig. 1.

Swallow-related cortical activity in cingulate gyrus. A: average percent signal increase in cingulate gyrus. Flavored swallows showed significantly more functional MRI (fMRI) activity than dry/water swallow. We performed ANOVA and Tukey's test for multiple pair-wise comparisons. †P < 0.01 vs. dry swallow (pre). *P < 0.05 vs. water. ‡P < 0.01 vs. dry swallow (post). Values are means ± SE. B: average swallow-related blood oxygenation level-dependent (BOLD) response waveforms across all trials in cingulate gyrus (n = 294). Note considerable differences in magnitude of fMRI activity waveforms for flavor-stimulated swallows compared with dry and water swallows. C: coordinates of peak signal intensity with each flavor within the cingulate gyrus based on the Talairach-Tournoux system. x, y, and z (in mm) represent left, posterior, and superior directions, respectively. Corresponding Z score of peak activity voxel with each flavor is also presented.

Fig. 2.

Swallow-related cortical activity in insula. A: average percent signal increase in insula. Difference between flavored stimuli and dry swallow failed to reach statistical significance. We performed nonparametric Kruskal-Wallis test because of unequal variances among groups. Values are means ± SE. B: average swallow-related BOLD response waveforms across all trials in insula (n = 294). Note differences in the magnitude of fMRI waveforms for the flavor-stimulated swallows; however, these differences did not reach statistical significance. C: coordinates of peak signal intensity with each flavor within insula based on the Talairach-Tournoux system, with x, y, and z as described in Fig. 1 legend. Corresponding Z score of peak activity voxel with each flavor is also presented.

Fig. 3.

Swallow-related cortical activity in prefrontal cortex. A: average percent signal increase in prefrontal cortex. Average fMRI signal intensity for all flavored swallows was significantly different from that for dry/water swallow. We performed ANOVA and Tukey's post test for multiple pair-wise comparisons. †P < 0.001 vs. dry swallow (pre). *P < 0.01 vs. water. ‡P < 0.001 vs. dry swallow (post). Values are means ± SE. B: average swallow-related BOLD response waveform across all trials in prefrontal cortex (n = 294). Note considerable differences in magnitude of fMRI activity waveforms for the flavor-stimulated swallows compared with dry swallow and water. C: coordinates of peak signal intensity with each flavor within prefrontal cortex based on the Talairach-Tournoux system, with x, y, and z as described in Fig. 1 legend. Corresponding Z score of peak activity voxel with each flavor is also presented.

Fig. 4.

Swallow-related cortical activity in sensory/motor cortex. A: average percent signal increase in sensory/motor cortices. Average fMRI signal intensity change for all flavored swallows was significantly different from that for dry/water swallow. We performed ANOVA and Tukey's test for multiple pair-wise comparisons. †P < 0.001 vs. dry swallow (pre). *P < 0.001 vs. water. ‡P < 0.001 vs. dry swallow (post). Values are means ± SE. B: average swallow-related BOLD response waveform across all trials in sensory/motor cortices (n = 294). Note considerable differences in magnitude of fMRI activity waveforms for flavor-stimulated swallows compared with dry swallow and water. C: average percent signal increase in sensory cortex. Average fMRI signal intensity change for all flavored swallows was significantly different from that for dry/water swallow. We performed ANOVA and Tukey's test for multiple pair-wise comparisons. †P < 0.001 vs. dry swallow (pre). *P < 0.001 vs. water. ‡P < 0.001 vs. dry swallow (post). Values are means ± SE. D: average percent signal increase in motor cortex. Average fMRI signal intensity change for all flavored swallows was significantly different from that for dry/water swallow. We performed ANOVA and Tukey's test for multiple pair-wise comparisons. †P < 0.001 vs. dry swallow (pre). *P < 0.001 vs. water. ‡P < 0.001 vs. dry swallow (post). Values are means ± SE. Note more robust swallow-related BOLD response to flavored liquids in motor cortex than sensory cortex (P < 0.01). E: coordinates of peak signal intensity with each flavor within sensory/motor cortex based on Talairach-Tournoux system, with x, y, and z as described in Fig. 1 legend. Corresponding Z score of peak activity voxel with each flavor is also presented.

Fig. 5.

Swallow-related cortical activity in precuneus region. A: average percent signal increase in precuneus. Difference between flavored stimuli and dry swallow failed to reach statistical significance. We performed nonparametric Kruskal-Wallis test because of unequal variances among groups. Values are means ± SE. B: average swallow-related BOLD response waveforms across all trials in precuneus (n = 294). Magnitude of fMRI waveforms for flavor-stimulated swallows did not differ significantly from that for dry swallow. C: coordinates of peak signal intensity with each flavor within precuneus region based on Talairach-Tournoux system, with x, y, and z as described in Fig. 1 legend. Corresponding Z score of peak activity voxel with each flavor is also presented. #Group analysis of water swallows did not show any significant activity within precuneus. Z score within the region is presented only for comparative purposes.

Fig. 6.

Total cortical swallowing network activity. A: activated cortical regions during swallow showing total cortical swallowing network. Significant activity associated with each stimulus throughout cortical swallowing network from medial anterior oblique view of a glass brain (all the activity is seen through the tissue). Note more robust activity with flavor-associated swallows than with saliva or water swallows. B: average percent signal increase in cortical swallowing network. Average fMRI signal intensity change for all flavored swallows was significantly different from that for dry/water swallow. We performed ANOVA and Tukey's test for multiple pair-wise comparisons. †P < 0.001 vs. dry swallow (pre). *P < 0.001 vs. water. ‡P < 0.001 vs. dry swallow (post). Values are means ± SE. C: average swallow-related BOLD response waveform across all trials in cortical swallowing network (n = 294). Magnitude of fMRI activity waveforms for the flavor-stimulated swallows was considerably different from that for dry swallow and water.