Functional connectivity of PAG with core limbic system and laryngeal cortico-motor structures during human phonation

Abstract

Previous studies in animals and humans suggest the periaqueductal grey region (PAG) is a final integration station between the brain and laryngeal musculature during phonation. To date, a limited number of functional magnetic neuroimaging (fMRI) studies have examined the functional connectivity of the PAG during volitional human phonation. An event-related, stimulus-induced, volitional movement paradigm was used to examine neural activity during sustained vocalization in neurologically healthy adults and was compared to controlled exhalation through the nose. The contrast of vocalization greater than controlled expiration revealed activation of bilateral auditory cortex, dorsal and ventral laryngeal motor areas (dLMA and vLMA) (p < 0.05, corrected), and suggested activation of the cerbellum, insula, dorsomedial prefrontal cortex (dmPFC), amygdala, and PAG. The functionally defined PAG cluster was used as a seed region for psychophysiological interaction analysis (PPI) to identify regions with greater functional connectivity with PAG during volitional vocalization, while the above functionally defined amygdala cluster was used in an ROI PPI analysis. Whole-brain results revealed increased functional connectivity of the PAG with left vLMA during voicing, relative to controlled expiration, while trend-level evidence was observed for increased PAG/amygdala coupling during voicing (p = 0.07, uncorrected). Diffusion tensor imaging (DTI) analysis confirmed structural connectivity between PAG and vLMA. The present study sheds further light on neural mechanisms of volitional vocalization that include multiple inputs from both limbic and motor structures to PAG. Future studies should include investigation of how these neural mechanisms are affected in individuals with voice disorders during volitional vocalization.