Two different motor systems are needed to generate human speech

Vocalizations such as mews and cries in cats or crying and laughter in humans are examples of expression of emotions. These vocalizations are generated by the emotional motor system, in which the mesencephalic periaqueductal gray (PAG) plays a central role, as demonstrated by the fact that lesions in the PAG lead to complete mutism in cats, monkeys, as well as in humans. The PAG receives strong projections from higher limbic regions and from the anterior cingulate, insula, and orbitofrontal cortical areas. In turn, the PAG has strong access to the caudal medullary nucleus retroambiguus (NRA). The NRA is the only cell group that has direct access to the motoneurons involved in vocalization, i.e., the motoneuronal cell groups innervating soft palate, pharynx, and larynx as well as diaphragm, intercostal, abdominal, and pelvic floor muscles. Together they determine the intraabdominal, intrathoracic, and subglottic pressure, control of which is necessary for generating vocalization. Only humans can speak, because, via the lateral component of the volitional or somatic motor system, they are able to modulate vocalization into words and sentences. For this modulation they use their motor cortex, which, via its corticobulbar fibers, has direct access to the motoneurons innervating the muscles of face, mouth, tongue, larynx, and pharynx. In conclusion, humans generate speech by activating two motor systems. They generate vocalization by activating the prefrontal‐PAG‐NRA‐motoneuronal pathway, and, at the same time, they modulate this vocalization into words and sentences by activating the corticobulbar fibers to the face, mouth, tongue, larynx, and pharynx motoneurons. J. Comp. Neurol. 524:1558–1577, 2016. © 2015 Wiley Periodicals, Inc.

[1]  G. Holstege,et al.  Location of motoneurons innervating soft palate, pharynx and upper esophagus. Anatomical evidence for a possible swallowing center in the pontine reticular formation. An HRP and autoradiographical tracing study. , 1983, Brain, behavior and evolution.

[2]  H. Kuypers Some projections from the peri‐central cortex to the pons and lower brain stem in monkey and chimpanzee , 1958, The Journal of comparative neurology.

[3]  J. Newman Neural circuits underlying crying and cry responding in mammals , 2007, Behavioural Brain Research.

[4]  M. Hirano,et al.  Topographic Arrangement of Motoneurons Innervating the Suprahyoid and Infrahyoid Muscles: A Horseradish Peroxidase Study in Cats , 1983, The Annals of otology, rhinology, and laryngology.

[5]  A. Esposito,et al.  Complete mutism after midbrain periaqueductal gray lesion. , 1999, Neuroreport.

[6]  Jean Massion,et al.  Red nucleus: past and future , 1988, Behavioural Brain Research.

[7]  T. Koga,et al.  Neuronal gagging activity patterns may be generated by neurons in the reticular area dorsomedial to the retrofacial nucleus in dogs , 1997, Experimental Brain Research.

[8]  B. Horwitz,et al.  Laryngeal Motor Cortex and Control of Speech in Humans , 2011, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[9]  R. Bandler,et al.  Excitation of neurones in a restricted portion of the midbrain periaqueductal grey elicits both behavioural and cardiovascular components of the defence reaction in the unanaesthetised decerebrate cat , 1987, Neuroscience Letters.

[10]  E. Taber The cytoarchitecture of the brain stem of the cat. I. Brain stem nuclei of cat , 1961, The Journal of comparative neurology.

[11]  G. Holstege,et al.  The emotional motor system. , 1992, European journal of morphology.

[12]  H. Kuypers Corticobular connexions to the pons and lower brain-stem in man: an anatomical study. , 1958, Brain : a journal of neurology.

[13]  D. G. Lawrence,et al.  Cortical projections to the red nucleus and the brain stem in the Rhesus monkey. , 1967, Brain research.

[14]  G. Holstege Anatomical study of the final common pathway for vocalization in the cat , 1989, The Journal of comparative neurology.

[15]  G. Holstege,et al.  Anatomical evidence for red nucleus projections to motoneuronal cell groups in the spinal cord of the monkey , 1988, Neuroscience Letters.

[16]  G. Holstege,et al.  Amygdaloid projections to the mesencephalon, pons and medulla oblongata in the cat , 1978, Experimental Brain Research.

[17]  H. Schrøder Onuf's nucleus X: A morphological study of a human spinal nucleus , 2004, Anatomy and Embryology.

[18]  J. D. Boyd,et al.  Cytoarchitecture of the Human Brain Stem , 1955 .

[19]  F. Wallois,et al.  C-Fos-like immunoreactivity in the cat brainstem evoked by sneeze-inducing air puff stimulation of the nasal mucosa , 1995, Brain Research.

[20]  J. O'leary,et al.  Experimental mutism resulting from periaqueductal lesions in cats , 1959, Neurology.

[21]  P. Mason Chapter 15 Descending pain modulation as a component of homeostasis. , 2006, Handbook of clinical neurology.

[22]  U. Jürgens Neural pathways underlying vocal control , 2002, Neuroscience & Biobehavioral Reviews.

[23]  N. Mizuno,et al.  Localization of motoneurons innervating perineal muscles: a HRP study in cat , 1978, Brain Research.

[24]  M. Botez,et al.  Role of subcortical structures, and particularly of the thalamus, in the mechanisms of speech and language. A review. , 1971, International journal of neurology.

[25]  R. Bandler,et al.  Vocalization and marked pressor effect evoked from the region of the nucleus retroambigualis in the caudal ventrolateral medulla of the cat , 1992, Neuroscience Letters.

[26]  G. Holstege,et al.  The anatomy of brain stem pathways to the spinal cord in cat. A labeled amino acid tracing study. , 1982, Progress in brain research.

[27]  K. Fukui,et al.  Nucleus ambiguus motoneurons innervating the canine intrinsic laryngeal muscles by the fluorescent labeling technique , 1984, Experimental Neurology.

[28]  A Barnet,et al.  Visual and auditory function in an hydranencephalic infant. , 1966, Brain research.

[29]  Katherine A. Houpt,et al.  Differences between vocalization evoked by social stimuli in feral cats and house cats , 2011, Behavioural Processes.

[30]  U. Jürgens,et al.  The neural control of vocalization in mammals: a review. , 2009, Journal of voice : official journal of the Voice Foundation.

[31]  H. Magoun,et al.  A midbrain mechanism for facio-vocal activity. , 1946, Journal of neurophysiology.

[32]  Gert Holstege,et al.  Emotional innervation of facial musculature , 2002, Movement disorders : official journal of the Movement Disorder Society.

[33]  On Certain Dissociations of Consciousness Levels within the Syndrome of Akynetic Mutism; pp. 38–48 , 1961 .

[34]  U. Jürgens,et al.  The anterior cingulate cortex and the phonatory control in monkey and man , 1983, Neuroscience & Biobehavioral Reviews.

[35]  H. Ralston,et al.  Monosynaptic projections from the lateral periaqueductal gray to the nucleus retroambiguus in the rhesus monkey: Implications for vocalization and reproductive behavior , 2000, The Journal of comparative neurology.

[36]  H. Kuypers,et al.  An anatomical analysis of cortico-bulbar connexions to the pons and lower brain stem in the cat. , 1958, Journal of anatomy.

[37]  U. Jürgens,et al.  Cortical lesion effects and vocalization in the squirrel monkey , 1982, Brain Research.

[38]  Roger N. Lemon,et al.  Cortical projections to the red nucleus and the brain stem in the rhesus monkey , 2016, Brain Research.

[39]  R. Hunsperger,et al.  Affective behaviour by electrical stimulation in the forebain and brain stem of the cat. , 1967, Progress in brain research.

[40]  G. Holstege Some anatomical observations on the projections from the hypothalamus to brainstem and spinal cord: An HRP and autoradiographic tracing study in the cat , 1987, The Journal of comparative neurology.

[41]  R. Bandler,et al.  Integrated defence reaction elicited by excitatory amino acid microinjection in the midbrain periaqueductal grey region of the unrestrained cat , 1988, Brain Research.

[42]  Shenmin Zhang,et al.  Brain stem integration of vocalization: role of the midbrain periaqueductal gray. , 1994, Journal of neurophysiology.

[43]  F. Skultety Experimental mutism in dogs. , 1962, Archives of neurology.

[44]  G. Holstege,et al.  Ultrastructural evidence for direct monosynaptic rubrospinal connections to motoneurons in Macaca mulatta , 1988, Neuroscience Letters.

[45]  G. Holstege The periaqueductal gray controls brainstem emotional motor systems including respiration. , 2014, Progress in brain research.

[46]  G. Holstege Descending motor pathways and the spinal motor system: limbic and non-limbic components. , 1991, Progress in brain research.

[47]  G. Holstege,et al.  Nucleus retroambiguus projections to the periaqueductal gray in the cat , 2002, The Journal of comparative neurology.

[48]  S. C. Wang,et al.  Localization of the central vocalization mechanism in the brain stem of the cat. , 1962, Experimental neurology.

[49]  Erich Seifritz,et al.  Differential sex-independent amygdala response to infant crying and laughing in parents versus nonparents , 2003, Biological Psychiatry.

[50]  U. Jürgens,et al.  Projections of the ventrolateral pontine vocalization area in the squirrel monkey , 2006, Experimental Brain Research.

[51]  K. Fiedler,et al.  Insular cortex activity and the evocation of laughter , 2016, The Journal of comparative neurology.

[52]  R. Morecraft,et al.  Cortical innervation of the hypoglossal nucleus in the non‐human primate (Macaca mulatta) , 2014, The Journal of comparative neurology.

[53]  G. Holstege,et al.  The somatic motor system. , 1996, Progress in brain research.

[54]  K. Saleem,et al.  Complementary circuits connecting the orbital and medial prefrontal networks with the temporal, insular, and opercular cortex in the macaque monkey , 2008, The Journal of comparative neurology.

[55]  N. Lanerolle,et al.  Functional Neural Pathways for Vocalization in the Domestic Cat , 1988 .

[56]  G. Holstege,et al.  Direct projections from the nucleus retroambiguus to cricothyroid motoneurons in the cat , 2002, Neuroscience Letters.

[57]  Elise Wattendorf,et al.  Exploration of the neural correlates of ticklish laughter by functional magnetic resonance imaging. , 2013, Cerebral cortex.

[58]  J. Jakuš,et al.  Multifunctional ventral respiratory group: bulbospinal expiratory neurons play a role in pudendal discharge during vomiting. , 1995, Journal of the autonomic nervous system.

[59]  B. Cohen,et al.  Vertical glaze paralysis and the rostral interstitial nucleus of the medial longitudinal fasciculus. , 1982, Brain : a journal of neurology.

[60]  G. Holstege,et al.  Propiospinal projections from the ventral and lateral funiculi to the motoneurons in the lumbosacral cord of the cat. , 1971, Brain research.

[61]  J. Buchwald,et al.  Voiced calls evoked by hypothalamic stimulation in the cat , 2004, Experimental Brain Research.

[62]  G. Holstege,et al.  Afferent projections to pharynx and soft palate motoneurons: A light and electron microscopical tracing study in the cat , 2005, The Journal of comparative neurology.

[63]  Vocalization in the squirrel monkey (Saimiri sciureus) elicited by brain stimulation , 2004, Experimental Brain Research.

[64]  Richard S. J. Frackowiak,et al.  Noun and verb retrieval by normal subjects. Studies with PET. , 1996, Brain : a journal of neurology.

[65]  Gert Holstege,et al.  Motor organization of positive and negative emotional vocalization in the cat midbrain periaqueductal gray , 2016, The Journal of comparative neurology.

[66]  J. Holstege,et al.  Distribution of dopamine immunoreactivity in the rat, cat, and monkey spinal cord , 1996, The Journal of comparative neurology.

[67]  Steffen R. Hage,et al.  Comparative analyses of speech and language converge on birds , 2014, Behavioral and Brain Sciences.

[68]  G. P. Pal,et al.  Location of the phrenic nucleus in the human spinal cord , 1999, Journal of anatomy.

[69]  J. Robinson The lower urinary tract. , 1982, British journal of clinical pharmacology.

[70]  J. Feldman,et al.  Differential innervation of protruder and retractor muscles of the tongue in rat , 1995, The Journal of comparative neurology.

[71]  G. Holstege,et al.  Projections from the rostral mesencephalic reticular formation to the spinal cord , 2004, Experimental Brain Research.

[72]  M. Hirano,et al.  Arrangement of motoneurons innervating the intrinsic laryngeal muscles of cats as demonstrated by horseradish peroxidase. , 1982, Acta oto-laryngologica.

[73]  E. Merrill,et al.  The lateral respiratory neurones of the medulla: their associations with nucleus ambiguus, nucleus retroambigualis, the spinal accessory nucleus and the spinal cord. , 1970, Brain research.

[74]  John D. Newman,et al.  Effects of tegmental lesions on the isolation call of squirrel monkeys , 1982, Brain Research.

[75]  G. Holstege Anatomical evidence for an ipsilateral rubrospinal pathway and for direct rubrospinal projections to motoneurons in the cat , 1987, Neuroscience Letters.

[76]  J. Abbs,et al.  Musculotopic organization of the facial motor nucleus in macaca fascicularis: A morphometric and retrograde tracing study with cholera toxin B‐HRP , 1990, The Journal of comparative neurology.

[77]  G. Rikard-Bell,et al.  Localization of phrenic motor nucleus in the cat and rabbit studied with horseradish peroxidase , 1980, Brain Research.

[78]  L. Heimer,et al.  Two methods for selective silver impregnation of degenerating axons and their synaptic endings in the central nervous system. , 1967, Brain research.

[79]  H. Ralston,et al.  Monosynaptic projections from the nucleus retroambiguus to motoneurons supplying the abdominal wall, axial, hindlimb, and pelvic floor muscles in the female rhesus monkey , 2000, The Journal of comparative neurology.

[80]  R. Provine Laughter as a scientific problem: An adventure in sidewalk neuroscience , 2016, The Journal of comparative neurology.

[81]  G. Holstege,et al.  Dorsal mesencephalic projections to pons, medulla, and spinal cord in the cat: Limbic and non‐limbic components , 1992, The Journal of comparative neurology.

[82]  G. Holstege,et al.  Pontine and medullary projections to the nucleus retroambiguus: A wheat germ agglutinin‐horseradish peroxidase and autoradiographic tracing study in the cat , 1996, The Journal of comparative neurology.

[83]  V. Vanderhorst,et al.  Organization of lumbosacral motoneuronal cell groups innervating hindlimb, pelvic floor, and axial muscles in the cat , 1997, The Journal of comparative neurology.

[84]  U. Jürgens Localization of a pontine vocalization-controlling area. , 2000, The Journal of the Acoustical Society of America.

[85]  W J H NAUTA,et al.  Silver impregnation of degenerating axon terminals in the central nervous system: (1) Technic. (2) Chemical notes. , 1951, Stain technology.

[86]  G. Holstege,et al.  Location of external anal sphincter motoneurons in the sacral cord of the female domestic pig , 1996, Neuroscience Letters.

[87]  H. Kuypers,et al.  Anatomy of the Descending Pathways , 2011 .

[88]  G. Holstege,et al.  Midbrain and medullary control of postinspiratory activity of the crural and costal diaphragm in vivo. , 2011, Journal of neurophysiology.

[89]  Diethelm W. Richter,et al.  Mechanisms of respiratory rhythm generation , 1992, Current Opinion in Neurobiology.

[90]  R. Bandler,et al.  Brain stem integration of vocalization: role of the nucleus retroambigualis. , 1995, Journal of neurophysiology.

[91]  Y. Ohta,et al.  Sneeze-evoking region within the brainstem , 1990, Brain Research.

[92]  C L Ludlow,et al.  Functional neuroanatomy of human vocalization: an H215O PET study. , 2005, Cerebral cortex.

[93]  Steven M. Barlow,et al.  Central pattern generators for orofacial movements and speech , 2010 .

[94]  G. Holstege,et al.  Descending projections from the nucleus retroambiguus to the iliopsoas motoneuronal cell groups in the female golden hamster: Possible role in reproductive behavior , 1999, The Journal of comparative neurology.

[95]  E J Auerbach,et al.  Activity in the paracingulate and cingulate sulci during word generation: an fMRI study of functional anatomy. , 1999, Cerebral cortex.

[96]  G. Holstege,et al.  The organization of the bulbar fibre connections to the trigeminal, facial and hypoglossal motor nuclei. II. An autoradiographic tracing study in cat. , 1977, Brain : a journal of neurology.

[97]  H. Kuypers CORTICOBULBAR CONNEXIONS TO THE PONS AND LOWER BRAIN-STEM IN MAN , 1958 .

[98]  S. Brudzyński,et al.  Handbook of mammalian vocalization : an integrative neuroscience approach , 2010 .

[99]  Steffen R. Hage Chapter 8.2 - Localization of the central pattern generator for vocalization , 2010 .

[100]  A. Bianchi,et al.  Differential Brainstem Fos-Like Immunoreactivity after Laryngeal-Induced Coughing and Its Reduction by Codeine , 1997, The Journal of Neuroscience.

[101]  G. Holstege,et al.  Propriobulbar fibre connections to the trigeminal, facial and hypoglossal motor nuclei. I. An anterograde degeneration study in the cat. , 1977, Brain : a journal of neurology.

[102]  G. Holstege,et al.  Infralimbic cortex projects to all parts of the pontine and medullary lateral tegmental field in cat , 2006, The European journal of neuroscience.

[103]  U. Jürgens,et al.  Reinforcing concomitants of electrically elicited vocalizations , 1976, Experimental Brain Research.

[104]  U. Ju¨rgens,et al.  On the elicitability of vocalization from the cortical larynx area , 1974 .

[105]  T. Koga,et al.  The central pattern generator for vomiting may exist in the reticular area dorsomedial to the retrofacial nucleus in dogs , 1998, Experimental Brain Research.

[106]  U. Jürgens,et al.  Role of the periaqueductal grey in vocal expression of emotion , 1979, Brain Research.

[107]  B L Baxter,et al.  Comparison of the behavioral effects of electrical or chemical stimulation applied at the same brain loci. , 1967, Experimental neurology.

[108]  J. Price,et al.  Prefrontal cortical projections to longitudinal columns in the midbrain periaqueductal gray in Macaque monkeys , 1998, The Journal of comparative neurology.

[109]  U. Jürgens,et al.  On the elicitability of vocalization from the cortical larynx area. , 1974, Brain research.

[110]  Gert Holstege,et al.  The Midbrain Periaqueductal Gray Control of Respiration , 2008, The Journal of Neuroscience.

[111]  G. Paxinos,et al.  Atlas of the human brain stem , 1995 .

[112]  G. Holstege,et al.  The Nucleus Retroambiguus Control of Respiration , 2009, The Journal of Neuroscience.

[113]  Gert Holstege,et al.  Chapter 1 The emotional motor system , 1996 .

[114]  Edward F Chang,et al.  A probabilistic map of the human ventral sensorimotor cortex using electrical stimulation. , 2015, Journal of neurosurgery.

[115]  Nielsen Jm,et al.  Instincts and emotions in an anencephalic monster. , 1949 .

[116]  B. Nail,et al.  On the location and size of laryngeal motoneurons in the cat and rabbit , 1984, The Journal of comparative neurology.

[117]  R E Myers,et al.  COMPARATIVE NEUROLOGY OF VOCALIZATION AND SPEECH: PROOF OF A DICHOTOMY , 1976, Annals of the New York Academy of Sciences.

[118]  V. Vanderhorst,et al.  Estrogen Induces Axonal Outgrowth in the Nucleus Retroambiguus–Lumbosacral Motoneuronal Pathway in the Adult Female Cat , 1997, The Journal of Neuroscience.

[119]  G. Holstege,et al.  Supraspinal control of motoneurons innervating the striated muscles of the pelvic floor including urethral and anal sphincters in the cat. , 1987, Brain : a journal of neurology.

[120]  G. Holstege,et al.  Brainstem-spinal cord projections in the cat, related to control of head and axial movements. , 1988, Reviews of oculomotor research.

[121]  G. Holstege,et al.  Ultrastructural evidence for direct excitatory retroambiguus projections to cutaneous trunci and abdominal external oblique muscle motoneurons in the cat , 2006, Brain Research Bulletin.

[122]  A. L. Berman The brain stem of the cat : a cytoarchitectonic atlas with stereotaxic coordinates , 1968 .

[123]  G. Holstege,et al.  Spinal cord location of the motoneurons innervating the abdominal, cutaneous maximus, latissimus dorsi and longissimus dorsi muscles in the cat , 1987, Experimental Brain Research.

[124]  G. Holstege,et al.  Projections of the bed nucleus of the stria terminalis to the mesencephalon, pons, and medulla oblongata in the cat , 2004, Experimental Brain Research.

[125]  G. Holstege,et al.  The periaqueductal gray in the cat projects to lamina VIII and the medial part of lamina VII throughout the length of the spinal cord , 1994, Experimental Brain Research.

[126]  T. Hökfelt,et al.  Locus coeruleus neurons in the rat containing neuropeptide Y, tyrosine hydroxylase or galanin and their efferent projections to the spinal cord, cerebral cortex and hypothalamus , 1988, Neuroscience.