**Abstract**

Speech is a complex process that requires the coordination of multiple structures of the phonatory system regulated by the central nervous system. Specifically, the larynx is the key point necessary for the vocal folds to come into contact to convert the air that comes out of our lungs into sound. Vocal emission involves the genesis of a precise and prolonged expiration that provides an adequate pressure/air flow component to generate a subglottic pressure compatible with vocalization. The starting point for voluntary vocal production is the laryngeal motor cortex (LMC), a common structure in mammals, although the specific location within the cortex differs in humans. LCM projects to the periaqueductal gray matter (PGM), which leads to pontomedullary structures to locate the generators of laryngeal-respiratory motor patterns, necessary for vocal emission. All these regions present a high expression of FOXP2 transcription factor, necessary for brain and lung development that is closely related to vocalization. These central structures have in common that not only convey cardiorespiratory responses to environmental stress but also support vocalization. At clinical level, recent studies show that central circuits responsible for vocalization present an overactivity in certain speech disorders such as spasmodic dysphonia due to laryngeal dystonia.

**Keywords:** central nervous system, laryngeal motor cortex, laryngeal motoneurons, periacueductal gray matter, FOXP2, vocal emission, speech, laryngeal dystonia

### **1. Introduction**

Central control of vocalization involves the activation of different interrelated brain structures in complex networks. Vocalization in mammals depends on a network originating in the laryngeal motor cortex, which projects to the mesencephalic Periaqueductal Gray Matter (PAG). The PAG modifies the activity of all pontomedullary structures responsible of generating all the laryngeal-respiratory motor patterns, necessary for vocal emission. These pontomedullary generators control the pattern and intensity of activation of respiratory, laryngeal, oropharyngeal, and craniofacial motor neurons [1].

Vocal emission involves the genesis of a precise and prolonged expiration that provides an adequate pressure/air flow component to generate a subglottic pressure compatible with vocalization. The nucleus ambiguus (nA), where laryngeal motor neurons are concentrated, is mainly responsible for this. All these regions present a high expression of the FOXP2 factor. FOXP2 is a transcription factor necessary for brain and lung development that is closely related to vocalization. Throughout the evolution of the human species, synaptic connectivity and plasticity in the circuits of the basal ganglia were increased, improving motor control and human cognitive and linguistic abilities [2].

Vocal fold abduction and adduction are known to be accomplished by two distinct populations of motor neurons located within the caudal third of the nA. It can be divided into three main parts: the compact formation (with motor neurons that innervate the esophagus), the semi-compact formation (with motor neurons that innervate the pharynx and the cricothyroid muscle of the larynx innervated by the superior laryngeal nerve) and the sparse formation (with motor neurons that innervate the laryngeal muscles except the cricothyroid) [3].

In previous work by our research group, the activity of the laryngeal motor neurons of nA and the reflex mechanisms involved in respiratory laryngeal responses have been characterized, suggesting that the parabrachial complex (PBc) and the A5 region (A5) have a role in modifying the activity of laryngeal motoneurones localized in the nA and accordingly the striated laryngeal muscles of the upper airway [4, 5] (**Figure 1**). Pontomedullary respiratory nuclei: PBc, A5, the nucleus of the solitary tract (NTS), nA and retroambiguous nuclei (nRA), paraambiguous (nPA) and retrofacial (nRF) integrate inputs from central and peripheral receptors and from superior structures to produce changes in the basic respiratory rhythm (eupnea). These changes are a prerequisite for survival (for example, tachypnea associated with the defense reaction, which increases the supply of oxygen preparing to fight or defend, or the response of gasping reset in the event of intense anxiety with respiratory alkalosis). But these changes in respiration are also necessary to maintain a constant

#### **Figure 1.**

*Laryngeal and respiratory responses to electrical stimulation in the medial (a) and lateral (b) parabrachial nucleus and (c) to glutamate microinjection in the A5 region. Phrenic nerve discharge, respiratory airflow, pleural pressure, subglottic pressure and integrated phrenic nerve discharge showing an expiratory facilitatory response with an increase of subglottic pressure during electrical stimulation (20 mA, 0.4-ms pulses, 50 Hz for 5 s) in the medial parabrachial nucleus, an inspiratory facilitatory response with the decrease of subglottic pressure during electrical stimulation (10 mA, 0.4-ms pulses, 50 Hz for 5 s) in the lateral parabrachial nucleus and an expiratory facilitatory response with an increase of subglottic pressure during a glutamate injection (10 nl over 5 s) in the A5 region. The arrow shows the onset of injection.*

expiratory flow that allows vocalization. It is known that Periaqueductal Gray Matter (PAG) is a key point in coordinating the efferent activity from limbic, corticoprefrontal and cingulate afferents, modifying the activity of all these mesencephalicpontomedullary nuclei [2].
