Central Autonomic Mechanisms Involved in the Control of Laryngeal Activity and Vocalization

Abstract

In humans, speech is a complex process that requires the coordinated involvement of various components of the phonatory system, which are monitored by the central nervous system. The larynx in particular plays a crucial role, as it enables the vocal folds to meet and converts the exhaled air from our lungs into audible sounds. Voice production requires precise and sustained exhalation, which generates an air pressure/flow that creates the pressure in the glottis required for voice production. Voluntary vocal production begins in the laryngeal motor cortex (LMC), a structure found in all mammals, although the specific location in the cortex varies in humans. The LMC interfaces with various structures of the central autonomic network associated with cardiorespiratory regulation to allow the perfect coordination between breathing and vocalization. The main subcortical structure involved in this relationship is the mesencephalic periaqueductal grey matter (PAG). The PAG is the perfect link to the autonomic pontomedullary structures such as the parabrachial complex (PBc), the Kölliker-Fuse nucleus (KF), the nucleus tractus solitarius (NTS), and the nucleus retroambiguus (nRA), which modulate cardiovascular autonomic function activity in the vasomotor centers and respiratory activity at the level of the generators of the laryngeal-respiratory motor patterns that are essential for vocalization. These cores of autonomic structures are not only involved in the generation and modulation of cardiorespiratory responses to various stressors but also help to shape the cardiorespiratory motor patterns that are important for vocal production. Clinical studies show increased activity in the central circuits responsible for vocalization in certain speech disorders, such as spasmodic dysphonia because of laryngeal dystonia.

Keywords: central nervous system; laryngeal dystonia; laryngeal motoneurons; laryngeal motor cortex; nucleus ambiguous; nucleus retroambiguus; parabrachial complex; periacueductal gray matter; speech; vocal emission.

Figure 1

Diagram of the main mesencephalic and pontomedullary regions involved in cardiorespiratory and laryngeal control. Periaqueductal grey matter (PAG) modulates the ongoing activity in the pontomedullary respiratory circuits in response to behavioral and cognitive information; the pontine respiratory group (PRG) includes the Kölliker–Fuse nucleus (KF) and medial parabrachial (mPB) and it is involved in the control of the switch off between inspiration and expiration; the dorsal respiratory group (DRG) includes the nucleus of the solitary tract (NTS), it receives sensory information from the lungs and chemoreceptors and it is involved in the control of inspiration; the ventral respiratory group (VRG) includes the pre–Bötzinger complex (Pre–BötC) involved in the generation of rhythmic breathing, the Bötzinger complex (BötC) with expiratory neurons, the retrotrapezoid nucleus and parafacial respiratory group (RTN/pFRG) with chemosensitive neurons, the nucleus ambiguous (nA) where the laryngeal motoneurons are located, the rostral ventral respiratory group (rVRG) with inspiratory neurons, and the caudal ventral respiratory group (cVRG) with expiratory neurons. The A5 region, rostro–ventro–lateral medulla (RVLM), and caudal–ventral–lateral medulla (CVLM) are regions that are involved in cardiovascular control.

Figure 2

Extracellular recordings of three putative cells recorded from the A5 region. (a) Silent neuron (upper trace, four superimposed sweeps). The lower trace shows constant latency responses (four superimposed sweeps) to the dlPAG stimulation. (b) Spontaneously active cell (upper trace, five superimposed sweeps). The lower trace shows excitations with short latency responses from dlPAG stimulation (five superimposed sweeps). Instantaneous respiratory rate (upper trace, rpm), respiratory flow (mL/s), pleural pressure (cmH₂O), instantaneous heart rate (bpm), and blood pressure (mmHg) in a spontaneously breathing rat showing the cardiorespiratory response evoked on dlPAG stimulation (c) before the microinjection of muscimol in the A5 region (50 nL over 5 s) and (d) after the microinjection of muscimol in the A5 region (50 nL over 5 s). Black line shows the onset of the dlPAG electrical stimulation (5 s). Authors’ figure modified from [32].

Figure 3

Laryngeal and respiratory responses to (a) electrical stimulation in the mPB (b) electrical stimulation in the lPB and (c) glutamate microinjection in the A5 region. Phrenic nerve discharge, respiratory airflow, pleural pressure, subglottic pressure, and integrated phrenic nerve discharge show an expiratory facilitatory response with an increase in subglottic pressure during electrical stimulation (20 μA, 0.4 ms pulses, 50 Hz for 5 s) in the medial parabrachial nucleus, an inspiratory facilitatory response with a decrease in subglottic pressure during electrical stimulation (10 μA, 0.4 ms pulses, 50 Hz for 5 s) in the lateral parabrachial nucleus, and an expiratory facilitatory response with an increase in subglottic pressure during a glutamate injection (10 nL over 5 s) in the A5 region. The arrow shows the onset of the injection. Authors’ figure modified from [33].