Functional but not structural networks of the human laryngeal motor cortex show left hemispheric lateralization during syllable but not breathing production

Abstract

The laryngeal motor cortex (LMC) is indispensible for the vocal motor control of speech and song production. Patients with bilateral lesions in this region are unable to speak and sing, although their nonverbal vocalizations, such as laughter and cry, are preserved. Despite the importance of the LMC in the control of voluntary voice production in humans, the literature describing its connections remains sparse. We used diffusion tensor probabilistic tractography and functional magnetic resonance imaging-based functional connectivity analysis to identify LMC networks controlling two tasks necessary for speech production: voluntary voice as repetition of two different syllables and voluntary breathing as controlled inspiration and expiration. Peaks of activation during all tasks were found in the bilateral ventral primary motor cortex in close proximity to each other. Functional networks of the LMC during voice production but not during controlled breathing showed significant left-hemispheric lateralization (p < 0.0005). However, structural networks of the LMC associated with both voluntary voice production and controlled breathing had bilateral hemispheric organization. Our findings indicate the presence of a common bilateral structural network of the LMC, upon which different functional networks are built to control various voluntary laryngeal tasks. Bilateral organization of functional LMC networks during controlled breathing supports its indispensible role in all types of laryngeal behaviors. Significant left-hemispheric lateralization of functional networks during simple but highly learned voice production suggests the readiness of the LMC network for production of a complex voluntary behavior, such as human speech.

Figure 1.

Schematic illustration of the experimental design in a single subject. The subject fixated at the black cross and listened to the acoustically presented sample task for a 3.6 s period. Acoustic samples were pseudorandomized and presented as syllables /iʔi/, /ihi/, or single voluntary breathing. An arrow then cued the subject to produce the task within a 5 s period, which was followed by a 2 s period of image acquisition. No stimulus was presented for the silent fixation condition, during which the subject silently fixated at the cross and arrow.

Figure 2.

A–C, Group maps of functional activation during production of voluntary voice production as repetition of syllables /iʔi/ (A) and /ihi/ (B) and during voluntary breathing (C). Cortical activation is presented on inflated cortical surfaces; subcortical and cerebellar activation is shown on the series of axial images of a single subject in the standard space (p ≤ 0.05, corrected). The color scale bar represents t-values (14 degrees of freedom). D, Bar graphs depicting the total number of significantly activated voxels in each hemisphere during production of voice (combined syllables /iʔi/ and /ihi/) and controlled breathing. Error bars represent SE. LH, Left hemisphere, RH, right hemisphere. E, Graphs depicting hemispheric LIs of functional activation during voluntary voice production (combined syllables /iʔi/ and /ihi/) and controlled breathing in each subject based on the comparisons between the number of significantly activated voxels in the left and right hemisphere during each task. LI = (number of activated voxels in left hemisphere − number of activated voxels in right hemisphere)/(number of activated voxels in left hemisphere + number of activated voxels in right hemisphere). Values >0 indicate left-hemispheric lateralization; values <0 indicate right-hemispheric lateralization.

Figure 3.

Functional and structural networks of the laryngeal motor cortex associated with production of syllable /iʔi/. Functional connections (A) and probabilistic tractography (B) from both left and right hemispheric seed regions (marked as black circle) are presented on the inflated cortical surfaces; subcortical and cerebellar connections are shown on the series of axial images of a single subject in the standard space (p ≤ 0.05, corrected). For functional networks, color scale bar represents z-values, which reflect the strength of PPI connections, ranging from positive (red-yellow) to negative (light blue-dark blue). For structural networks, color scale bar illustrates the probabilistic distribution of structural connections expressed as the number of subjects (from 1 to 13 subjects) having a pathway pass through a given brain region.

Figure 4.

Functional and structural networks of the laryngeal motor cortex associated with production of syllable /ihi/. Functional connections (A) and probabilistic tractography (B) from both left and right hemispheric seed regions (marked as black circle) are presented on the inflated cortical surfaces; subcortical and cerebellar connections are shown on the series of axial images of a single subject in the standard space (p ≤ 0.05, corrected). For functional networks, color scale bar represents z-values, which reflect the strength of PPI connections, ranging from positive (red-yellow) to negative (light blue-dark blue). For structural networks, color scale bar illustrates the probabilistic distribution of structural connections expressed as the number of subjects (from 1 to 13 subjects) having a pathway pass through a given brain region.

Figure 5.

Block diagrams illustrating the organization of functional (I) and structural (II) networks originating from the left and right hemispheric seeds in the laryngeal motor cortex during production of voluntary voice (combined syllables /iʔi/ and /ihi/) (A, C) and controlled breathing (B, D). I, Brain regions in rectangles indicate the regions showing differences in functional networks between voice and breathing production. Regions included in the orange blocks depict positive connections of the laryngeal motor cortex, while the regions in the blue blocks indicate negative connections of the laryngeal motor cortex. II, Color-coded blocks indicate the probability of a tract passage through a given brain region. The scale represents chance of probability (percentage) of the tracts in the region and the number of subjects in whom those tracts were identified. dPreM, Dorsal premotor cortex; vPreM, ventral premotor cortex; vlPFC, ventrolateral prefrontal cortex; dlPFC, dorsolateral prefrontal cortex; Ins, insula; pOp, posterior operculum; AG, angular gyrus; SMG, supramarginal gyrus; vS1/M1, ventral primary sensorimotor cortex; dS1/M1, dorsal primary sensorimotor cortex; aCC, anterior cingulate cortex; mCC, middle cingulate cortex; pCC, posterior cingulate cortex; Put, putamen; Cd, caudate nucleus; Gp, globus pallidus; Thal, thalamus; Cbl, cerebellum.

Figure 6.

Bar graphs depicting the total number of voxels functionally (A–C) and structurally (D–F) connected with the left and right laryngeal motor cortex during voluntary voice production and voluntary breathing. Significant left-right seed-specific hemispheric differences (marked with an asterisk) were found for functional connections of the left laryngeal motor cortex during both types of syllable production, but not during voluntary breathing. Error bars represent SE. G, H, Graphs depicting hemispheric LIs of functional (G) and structural (H) networks during voluntary voice production (i.e., syllables /iʔi/ and /ihi/) and controlled breathing for each subject based on the comparisons between the number of voxels functionally and structurally connected with the left and right seed regions of the laryngeal motor cortex. LI = (number of connected voxels of left seed in left hemisphere − number of connected voxels of right seed in right hemisphere)/(number of connected voxels of left seed in left hemisphere + number of connected voxels of right seed in right hemisphere). Values >0 indicate left-hemispheric lateralization; values <0 indicate right-hemispheric lateralization.

Figure 7.

Functional and structural networks of the laryngeal motor cortex associated with voluntary breathing. Functional connections and probabilistic tractography from both left and right hemispheric seed regions (marked as black circle) are presented on the inflated cortical surfaces; subcortical and cerebellar connections are shown on the series of axial images of a single subject in the standard space (p ≤ 0.05, corrected). For functional networks, color scale bar represents z-values, which reflect the strength of PPI correlations, ranging from positive (red-yellow) to negative (light blue-dark blue). For structural networks, color scale bar illustrates probabilistic distribution of structural connections (e.g., the chance of probability of a pathway passing through a given brain region) ranging from 1 to 13 subjects.

Figure 8.

Post hoc PPI analyses of the contrasted activation during syllable /iʔi/ and syllable /ihi/ productions (A) and voluntary voice production (i.e., syllable /iʔi/) (B) and controlled breathing productions. Significant differences in functional networks of the laryngeal motor cortex between the tasks are shown on the series of sagittal and axial images of a single subject in the standard space (p ≤ 0.05, corrected). Scale bars represent positive (red-yellow) and negative (light blue-dark blue) PPI values (z-score). ACC, Anterior cingulate cortex.

Figure 9.

Group common and distinct functional and structural networks of the laryngeal motor cortex during voluntary voice production (i.e., syllable /iʔi/ production) and voluntary breathing. Functional connections (F) during each task are shown in yellow; structural connections (S) underlying each task are shown in white; overlap between the functional and structural connections (F × S) is shown in red (p ≤ 0.05, corrected).