- Email: [email protected]
Chapter 19 Midbrain and medullary regulation of respiration and vocalization
G . Holstege, R. Bandler and C.B. Saper (Eds.) Progress in Brain Research, Vol. 107 0 1996 Elsevier Science B.V. All rights reserved
CHAPTER 19
Midbrain and medullary regulation of respiration and vocalization Pamela J. Davis’, Shi Ping Zhang2 and Richard Bandler2 ‘National Voice Centre, Faculty of Health Sciences, The University of Sydney, NSW, Australia, and ’Department of Anatomy and Histology, The University of Sydney, NSW, Australia
Introduction Most emotional reactions and behaviors include changes in the breathing pattern and many are also associated with vocalization. There is much evidence that the respiratory changes and vocalization associated with emotional behaviors are dependent on an intact midbrain (Kelly et al., 1946; Adametz and O’Leary, 1959; De Molina and Hunsperger, 1962; Randall, 1964), specifically the lateral part of the caudal two-thirds of the periaqueductal gray matter (PAG) surrounding the aqueduct (Jurgens and Pratt, 1979a; Bandler, 1982, 1988; Larson and Istler, 1986; Davis et al., 1993; Zhang et al., 1994).
Vocalization evoked from the midbrain periaqueductal gray In the freely moving or unanesthetized decerebrate cat stimulation of neurons in the lateral column of the intermediate PAG by microinjections of the excitatory amino acid D,L-homocysteic acid (DLH; WOnmol, 30-200nl) evokes a number of discrete patterns of vocalization including howling, hissing, mewing and growling, as well as tachypnea or respiratory rate changes (Bandler, 1982; Bandler and Carrive, 1988; Davis et al., 1993; Zhang et al., 1994). Two basic types of vocalization are evoked: type A (“voiced”) sounds including howl, mew and growls, and type B sounds
(“unvoiced”) associated with hissing (Zhang et al., 1994). The voiced sounds were associated with activation of the laryngeal thyro-arytenoid and crico-thyroid muscles and inactivity of the posterior crico-arytenoid muscle in the expiratory phase (PCAE),while unvoiced sounds were characterized by excitation of the posterior crico-arytenoid muscle (expiratory phase) and thyro-arytenoid muscles and no significant activation of the crico-thyroid. In addition, stronger expiratory (external oblique, internal oblique and internal intercostal) electromyographic (EMG) increases were associated with voiced sound production, and larger increases in oral muscle activity (genio-glossus and digastric) were associated with unvoiced vocalization. Unvoiced sounds were evoked from PAG sites generally rostra1 (A3.3 level) to sites at which voiced sounds were evoked (P0.2-A2.5 level) (Zhang et al., 1994). Those sites associated with increased breathing rate (tachypneic sites) were distributed more widely throughout the intermediate and caudal PAG (A 3.3-PO.2) and the deep layers of the superior colliculus (see Figs. 9 and 13 in Zhang et al., 1994). Smaller, just-threshold doses of DLH (300 pmol to 3 nmol) injected into the same discrete regions of the lateral PAG also evoked the same patterned activation characteristic of voiced and voiceless vocalization, often with barely audible sound, and also a tachypneic pattern without vocalization (Zhang et al., 1994). Figure 1A illustrates the pat-
316
Fig. 1. Patterns of EMG activity evoked from the lateral column of the intermediate PAG (d2.5). (A) Computer-chart records of integrated EMG activity recorded ipsilateral to 3 DLH microinjection sites at different medio-lateral locations. The lower inset depicts a section of raw EMG record from site 1 showing voiced and unvoiced sound patterns. The tracheal pressure record (TP) signals are calibrated in cmH20. (B) Computer-chart records from a different cat illustrating the effects of 6 DLH microinjections made at different dorso-ventral sites along a micropipette track in the PAG. In all sections the bars on the EMG records correspond to 50 arbitrary units. The location of each injection site is shown in the inset drawing of PAG; calibration bars correspond to 0.5 nun. Adapted from Figs. 10 and 12 in Zhang et al. (1994).
erns evoked from 3 adjacent medio-lateral sites, separated by 500 mm. A 600 pmol dose of DLH injected at site 1 evoked two distinct patterns (voiced and unvoiced) which alternated with each expiration. At site 2, 500 mm lateral to site 1, a 900pmol DLH dose evoked only an unvoiced pattern. The tachypneic pattern (site 3, not illustrated) was characterized by an increase (or recruitment) of PCAE and occasionally an increase in respiratory rate, but no recruitment of other laryngeal and abdominalhntercostal muscles. Figure 1B illustrates, in a different cat, three of the differ-
ent patterns evoked by 3 nmol DLH injections at different dorsoventral sites, also separated by 500 mm. DLH injection at PAG site 1 evoked a tachypneic pattern while at site 2 an unvoiced vocalization pattern associated with a strong excitation of PCAE and genio-glossus muscle was evoked. At sites 3 and 4 (not illustrated), a mixture of voiced and unvoiced sound patterns was evoked while more ventrally at site 5 a pure voiced sound pattern was evoked. Most ventrally at site 6 no effect was observed (not illustrated). At no PAG site were individual muscles ever
3 17
activated. As illustrated in Fig. 1, just-threshold doses of DLH evoked the patterned activation of laryngeal and abdominalhntercostal muscles at all sites tested, whereas smaller doses tested at the same sites (typically 300 pmol) were ineffective for all muscles (Fig. 11 in Zhang et al., 1994). This suggests that the underlying PAG organization takes the form of a representation of muscle patterns, rather than individual muscles. A schematic representation of the characteristic EMG patterns, indicating the differences in onset and amplitude of muscle activity, during voiced and voiceless sound production is provided in Fig. 2. As illustrated in this figure, the abdominal muscles were activated much earlier than the oral muscles for voiced responses, whereas for unvoiced vocalization, the oral muscles increased their activity ahead of the abdominal muscles. Frequently, the inspiratory muscles (diaphragm, posterior cricoarytenoid) were more active prior to each vocalization burst. It may well be that the effects evoked from the PAG by DLH microinjection are dependent on the combination of excitation of distinct sets of output neurons: “respiratory patterning” PAG neurons regulating respiratory rate and depth changes and “vocalization patterning” PAG neu-
””?”’” voiced
1
voice
oral rn inspiratory rn
rons which coordinate the different patterns of muscle activity characteristic of voiced and unvoiced sounds.
Afferent influences on periaqueductal grayevoked respiratory and vocal patterns Davis et al. (1993) showed that the vocalization evoked from PAG can be modified by respiratory afferent discharge. A sustained excitation of laryngeal, intercostal and abdominal muscles was evoked by the combination of PAG excitation and manipulation of the air pressure in the tracheobronchial and pulmonary airways. When the latter was increased and held constant, the duration of an individual PAG-evoked vocalization could be extended, seemingly “indefinitely”. That this reflex effect (Breuer, 1970) was mediated by sensory receptors in the vagus nerve, presumably pulmonary stretch receptor afferents, was established by demonstrating a reversible block of the reflex effect on the crico-thyroid and abdominal muscles by vagal nerve cooling followed by nerve rewarming. Positive pressure/flow stimulation of the upper airways was also effective in modulating the phonatory duration, presumably via slowly adapting laryngeal receptors (Sant’Ambrogio et al., 1983; Hwang et al., 1984). It is possible, then, that lateral PAG output neurons not only directly mediate the motor pattern for vocalization but are also modulated by the afferent input which occurs during that period (Sessle et al., 1981). Summation of the pulmonary vagal, upper airway and other respiratory afferent input (e.g. from chest wall muscle receptors) with the PAG motor output presumably ensures that the vocalization will be coordinated always with the volume of air in the lungs and the ability to generate the subglottic pressure to sustain vocalization. Although there has been no attempt to experimentally manipulate lung pressure during human speech, it does appear that the breathing patterns during speech are coordinated with afferent signals related to lung volume. In a different series of human experiments we examined influences on the expiratory duration of speech (Winkworth et al.,
cI b TA
7 -
100 rns
Fig. 2. Schematic representation of muscle activity during PAG-evoked voiced and unvoiced type vocalization. The profile and amplitude of the various muscle representations correspond to the general pattern observed in averaged EMG activity (genio-glossus GG, digastric DG,diaphragm D, posterior crico-arytenoid PCA, thyro-arytenoid TA, crico-thyroid CT, internal intercostal IIC, internal oblique 10, external oblique EO). Adapted from Fig. 7 in B a n g et al. (1994)
318
1994, 1995). As well as confirming earlier reports that the language structure is dominant in determining when a breath is taken, a novel finding was that the inspiratory depth was strongly associated with the length of the subsequent expiration, even during “natural” spontaneous speech. One possibility is that the respiratory afferent control system described above for PAG-evoked vocalization in the cat is also involved in the regulation of human speech utterance length. Certainly, different expiratory muscle groups are progressively recruited during human speech and singing as lung volume declines (Draper et al., 1959) and it is possible that pulmonary and upper airway stretch-sensitive afferents play a role in regulating not only the duration of the speech breaths, but also the level of expiratory muscle recruitment according to the volume of air in the lungs.
The periaqueductal gray-nucleus retroambigualisvocalization pathway Holstege (1989; and Chapter 20, this volume) provided anatomical evidence that neurons in the caudal two-thirds of the lateral PAG project to premotor interneuronal pools in the nucleus retroambigualis (NRA) in the caudal ventrolateral medulla. In the same paper, Holstege reported that NRA neurons project not only to intercostal and abdominal spinal motoneuronal pools, but also to the vicinity of more rostrally located laryngeal, pharyngeal and mouth-opening muscle motoneuronal pools. This led to the proposal that the NRA, by regulating motoneuronal pools controlling laryngeal pharyngeal and mouth opening, as well as expiratory muscles, could serve as a “final common pathway” for vocalization. Others have proposed that the PAG pathway to the laryngeal motoneurons in the nucleus ambiguus is dominated by projections to interneurons in the pontine and rostral medullary reticular formation (Jurgens and Pratt, 1979a; Thoms and Jurgens, 1987). To study this question Zhang et al. (1995) examined the laryngeal EMG changes associated
with vocalization evoked from the lateral PAG, before and after a series of medullary transections which eliminated the medulla caudal to the obex, including the NRA. Initially, excitation of cricothyroid, thyro-arytenoid, posterior crico-arytenoid, genio-glossus or digastric was evoked from the PAG after transections made at the spinomedullary junction in each of four similar experiments. When the medullary transection extended to the obex, PAG-evoked activity in crico-thyroid and thyro-arytenoid muscles was effectively abolished, while that for PCAE, genio-glossus and digastric was attenuated. These results indicate that PAG regulates the crico-thyroid and thyroarytenoid muscles via an initial projection to medullary neurons caudal to the obex (presumably in the NRA) which project (directly or indirectly) to crico-thyroid and thyro-arytenoid motoneuronal groups lying rostral to the obex (Holstege, 1989). These muscles are critical in adducting and tensing the vocal folds for sound generation. Further studies demonstrated that activity in the internal intercostal and abdominal muscles, often with vocalization, was evoked by DLH microinjection into NRA. Considered together these data are consistent with the proposal that PAG regulation of expiratory effort, vocal fold adduction and tension, all of which are essential components of sound production, is mediated via a direct projection to the NRA. There was, however, little evidence that NRA neurons were associated with oro-facial modulation of that sound as NRA evoked vocalization was associated neither with mouth opening or closing, lip rounding or spreading, tongue protrusion or curling nor were consistent changes in genio-glossus or digastric activity evoked by DLH injection into the NRA (Zhang et al., 1992, 1995). These findings are not consistent with the suggestion based on earlier anatomical data that NRA efferents include substantial projections to the motor trigeminal, facial and hypoglossal nuclei (Holstege, 1989). Our data, then, indicate that the NRA is a critical locus for PAG output, mediating sound production but not the oro-facial modulation of that sound.
319
Although vocalization, as well as a variety of muscle excitations unaccompanied by vocalization, could be evoked from the rostra1 half of the NRA by the microinjection of DLH, the naturalsounding acoustic characteristics and stereotyped muscle activation associated with PAG-evoked vocalization were never evoked from the NRA. The NRA-evoked muscle patterns included not only a lack of involvement of oro-facial musculature but also a high level of tonic discharge in the crico-thyroid, internal oblique, external oblique, internal intercostal and diaphragm muscles upon which expiratory-phased activation was superimposed (Fig. 4, in Zhang et al., 1995). Quite clearly, then, the NRA contains neurons which are capable of recruiting laryngeal and expiratory muscles in an appropriate manner to produce sound, but in contrast to the PAG, the neural organization (at least, as revealed by the technique of micro injection of DLH) for the integration of “natural sounding” vocalization does not appear to be present. A schematic model summarizing these findings is provided in Fig. 3. Our data suggest that the PAG influences the excitability of laryngeal tensor (crico-thyroid), laryngeal adductor (thyro-arytenoid) and expiratory (external oblique, internal oblique, internal intercostal) muscles indirectly via the NRA. That is, the projection from the PAG to the NRA is concerned with laryngeal tensing, adduction, and forced expiration, which is essential for sound production. In contrast, the PAG regulation of oro-facial activity must be mediated via other pathways, with little, if any, contribution from the NRA. As well, the change in the inspiratory pattern during PAG-evoked vocalization suggests that PAG neurons also project to inspiratory pre-motor neurons (not shown) although these putative pathways have yet to be delineated.
Emotional control of respiration and sound production Most animal species utilize vocalization as an integral part of their emotional repertoire. Vocalization evoked from PAG by DLH microinjection
Fig. 3. Proposed neural pathway for the production of emotional (non-verbal) vocalization. For graphical illustration only a single PAC-NRA output pathway is represented, although there is a bilateral projection from the lateral part of the PAG to the NRA (Holstege, 1989).
appears indistinguishable from spontaneous feline calls (Zhang et al., 1994) and was generally evoked as part of an integrated respiratory, cardiovascular and behavioral response. The sound quality of human speech also reflects the emotional state of the speaker and, like that of vocalization in lower species, is accompanied also by autonomic alterations which may include elevations in blood pressure and heart rate (Abel et al., 1987; Linden, 1987; Freed et al., 1989). Further, the frequency pattern of vocal fold vibration, the voice quality as well as the breathing pattern and its timing (i.e. those voicing parameters which are modulated in the cat by PAG neurons) are factors which have been identified as likely to convey information about the emotional state of the speaker (Scherer and Scherer, 1981; Sundberg, 1987; Sundberg et al., 1995). The PAG region is closely involved in the expression of emotion (Bandler, 1988; Bandler et al.,
320
1991; Holstege, 1991; Bandler and Shipley, 1994) and it is considered a critical part of the emotional motor system (Holstege, 1991; and Chapter 1, this volume). Thus, it is not surprising that PAC neurons when excited by DLH microinjection evoke some of the respiratory and vocal changes associated with such reactions. As vocalization is an intrinsic part of many emotional reactions which are controlled by the PAC this may explain the well known association between emotion and vocal control. In several studies, professional actors have been asked to simulate the effects of various emotional states on speech. With respect to an intermediate neutral tone, the frequency of the laryngeal vibration (voice pitch) was found to be raised in joy or anger and lowered in sorrow (Sedlacek and Sychra, 1963; Williams and Stevens, 1972). Fear was manifested by rapid increases and decreases in pitch (Williams and Stevens, 1972). These simulated data are consistent with live voice recordings obtained from individuals experiencing aircraft tragedies (Williams and Stevens, 1969; Ruiz et al., 1990). Considering the importance of voice pitch in conveying emotional expression, Sundberg et al. (1995) examined singing in which emotional expression is, in part, dictated by the musical score. It was found that differences in the tempo, voice loudness, loudness variation, vibrato, and voice timbre (as reflected by formant frequency) were very important in the perceived emotionality of sung performance. Changes in the pattern of breathing are an integral part of most emotional reactions (von Euler, 1981). Studies of the breathing patterns during spontaneous speech and mood state (McNair et al., 1971) of healthy young women over a 3-week period revealed that each of the six subjects studied showed a significant within-subject association between respiratory speech activity and depressed and anxious mood over this period (Winkworth et al., 1995). From these findings, obtained during everyday conversations and monologues, it is likely that the breathing patterns associated with speech expressing strong emotion would show an even greater effect.
Possible role of the periaqueductal gray and nucleus retroambigualis in the neural control of mammalian sound production, including human speech The similarity of the laryngeal and respiratory muscle recruitment patterns associated with PAGevoked vocalization, and human vowel and voiceless consonant phonation (Zhang et al., 1994; Davis et al., 1995) leads us to consider that the PAC may well be a crucial brain site for mammalian voice production, not only in the production of emotional or involuntary sounds, but also as a generator of specific respiratory and laryngeal motor patterns essential for human speech and song. Such findings are consistent with the idea that the central neural substrates for the sound production underlying human speech could be built upon components present in phylogenetically lower species. Previously, it has been considered that the neocortical vocal control pathway utilized in speech acts independently of subcortical pathways, including the PAG circuitry, that mediate emotional and reflexive vocalization. The disruption of voluntary vocal expression in Parkinson’s disease and spasmodic dysphonia, but normal “emotional” vocal expression in response to an emotional trigger (Arnold, 1959; Heaver, 1959), is sometimes used to support this claim. We would suggest, instead, a working hypothesis that humans produce speech sounds via the same midbrain PAG circuitry which is fundamentally involved in emotional motor control. Although speech is complex and subject to linguistic control, it is, nonetheless, still a modified form of respiration (von Euler, 1986; Davis et al., 1993). PAG neuronal networks are ideally positioned to integrate the various afferent and efferent systems necessary to produce speech as part of a coordinated respiratory response. Some of the main differences between human speech and emotional vocalization of other species are the human ability to modify the vocal quality and to inhibit sound production when the social situation demands. Such control mechanisms undoubtedly involve higher centers in the forebrain. In this regard it is interesting that recent
321
studies have revealed that the cortical and forebrain inputs to PAG are more substantial and extensive than previously envisaged (Chapter 1 , this volume) (Shipley et al., 1991; Bandler and Shipley, 1994). Although the integrity of cortical limbic structures may be important for social vocalization, evidence in favor of a role for the PAG as a general, all-purpose sound pattern generator are the findings, in several animal species, that all naturalsounding vocalization is critically dependent on the integrity of the PAG. Thus, PAG lesions in experimental animals results in permanent loss of both spontaneous vocalization and vocalization evoked by electrical stimulation at sites either in the forebrain or the caudal brain stem (Jurgens and Pratt, 1979a; Bandler, 1988). In contrast, the quality of species-specific vocalization is not dramatically altered either by forebrain lesions, or even complete removal of the forebrain (Goltz, 1892; Brown, 1915; Bard and Macht, 1958; Woods, 1964; Sutton et al., 1974; Kirzinger and Jiirgens, 1985). Similarly, in humans, both anencephalic infants and hydranencephalic infants (with little or no forebrain, but an intact midbrain) have been reported to vocalize in a manner which is relatively similar to that of normal infants (AndrkThomas et al., 1944; Andrk-Thomas, 1954; Aylward et al., 1978). Observations on infants born without such abnormalities, but at a stage of development when the forebrain is grossly immature (e.g. 22-24 weeks gestation) are also capable of intermittent vocalization (D. Henderson-Smart, pers. commun.). In contrast, although there are relatively few case reports of individuals with specific PAG lesions (Botez and Barbeau, 1971), possibly because the region is adjacent to key brain structures associated with the maintenance of consciousness, mutism has been reported in several cases in which patients have sustained damage to the midbrain including the PAG (Lenneberg, 1962; Botez and Barbeau, 1971; BoczAn et al., 1972; von Cramon, 1981; Cummings et al., 1983). A schematic model of interaction between cortical language structures and the PAG for the neu-
ral control of speech and song, as well as nonverbal sounds (e.g. laughing, crying) is illustrated in Fig. 4. In this figure, we have proposed separate neural pathways for articulation and sound production. This idea is consistent with our finding that the NRA mediates the sound production components of PAG-evoked vocalization, but not the oro-facial modulation of that sound (Zhang et al., 1992, 1995). The articulation of human speech is characterized by very rapid changes in oro-facial muscle activity associated with the production of various consonants and it is likely that the fine control of these movements is achieved via direct projections from the motor cortex to brainstem oro-facial motoneuronal pools. Indeed, there is evidence for a rich human cortico-bulbar pathway for the volun-
Fig. 4. Proposed neural pathway for the production of human speech and song.
322
tary control of oro-facial motoneurons (Kuypers, 1958). It is a general observation that vocal and articulatory speech control may be differentially impaired. For example, a number of emotional reactions are characterized by a complete or partial loss of voice, yet relatively few such reactions are associated with a loss of the ability to articulate, or to whisper (Aronson, 1990). Marshall et al. (1988) describe a case who lost the ability to produce sound but whose language and articulation was intact with an artificial sound source (electronic artificial larynx). The site(s) of neurological damage responsible for this disorder are unclear but the subject underwent a craniotomy for clipping of an aneurysm at the trifurcation of the left middle cerebral artery and had a long history of mild to moderate hydrocephalus with ballooning of the left temporal horn of the left lateral ventricle. In contrast, we suggest that the voluntary motor pathway for the sound production component of speech and song includes higher brain structures which project significantly to the PAG (Jiirgens and von Cramon, 1982; Shipley et al., 1991; Bandler and Shipley, 1994) and excite neuronal networks which coordinate the various muscle patterns for voiced and unvoiced sound production. In this regard it is worth noting the recent figures displaying activation of the PAG by PET imaging of the human brain during speech (Raichle, 1994). Although the specific pathway by which cortical speech and language regions might target specific PAG neuronal networks have not been delineated, there are data to suggest that the anterior cingulate is critically involved (Jurgens and Pratt, 1979b; Jiirgens and von Cramon, 1982). Interestingly, in contrast to the fine motor control of oral structures, such as the tongue, voluntary control of the larynx and palate is relatively poor when sound is not produced, and appears limited to little more than closure of the vocal cords (associated with expiratory apnea) and limited rostro-caudal movements (Lofqvist et al., 1981). However, as soon as a sound is produced, there can be quite exquisite control of the vocal folds to alter the pitch and quality of that sound. This strongly suggests that the voluntary control systems for the larynx must
be tightly linked with neural circuits activating patterned activities such as respiration, vocalization, swallowing and coughing. There are also speech data which support the idea of a separation of laryngeal-respiratory and oro-facial components. Mead and Reid (1988) observed that speakers were only able to interrupt an expiratory airflow at the level of the larynx (“uh-uh-uh”) by synchronous activity in abdominal, intercostal and laryngeal muscles, whereas at the level of the tongue (“t-t-t”), this could be achieved without respiratory synchronization. Lieberman ( 1 99 1, 1994) argues that humans have evolved radical differences in the shape of the tongue, mouth and pharynx from other primates which permit articulatory speech maneuvers and hypothesizes that these anatomical differences are responsible for the evolution of human speech. We add to this proposal the idea that the articulatory differences which are so important for human speech are built upon an existing PAG-NRA neuronal circuitry coordinating sound production. That this circuitry is part of the emotional motor system may serve to explain the emotional quality of all speech and song.
Summary The lateral column of the midbrain periaqueductal gray (PAG) appears to contain the motor pattern generators for various types of vocalization. Further, the motor patterns which can be evoked by PAG neuronal excitation are influenced by afferent control mechanisms linked to the availability of air in the lungs. The PAG has been shown to influence the excitability of laryngeal adductor (thyroarytenoid), tensor (crico-thyroid) and expiratory (internal intercostal, external oblique, internal oblique) muscles indirectly, via the nucleus retroambigualis (NRA) while the PAG control of oro-facial muscles involves a separate pathway that does not appear to include a synapse in the NRA. We propose that neurons in the lateral PAG column could play an important role, not only in the production of emotional vocalization, but also as a generator of specific respiratory and laryngeal
323
motor patterns essential for human speech and song.
Acknowledgements Supported by grants to P.D. from the Australian National Health and Medical Research Council; and to R.B. from the Australian National Health and Medical Research Council and the C. and V. Ramaciotti Foundation.
References Abel, H.H., Mottau, B., KliiBendorf, D. and Koepchen, H.P. (1987) Pattern of different components of the respiratory cycle and autonomic parameters during speech. In: G. Sieck, S . Gandevia and W. Cameron (Eds.), Respiratory Muscles and their Neuromotor Control, Alan R. Liss, New York, pp. 109-1 13. Adametz, J. and O’Leary, J.L. (1959) Experimental mutism resulting from periaqueductal lesions in cats. Neurol. Minneap., 9: 636-642. Andrt-Thomas, J. (1954) Le nouveau-nt normal et l’anenc6phale. Presse Mkd., 62: 885-886. Andrt-Thomas, J., Lepage, F. and Sorrel-Dejerine, M. (1944) Examen anatomo-clinique de deux anenctphales protubtrantiels. Rev. Neurol., 76: 173-193. Arnold, G.E. (1959) Spastic dysphonia: I. Changing interpretation of a persistent affliction. Logos, 2: 3-14. Aronson, A.E. (1990) Clinical Voice Disorders: An Interdisciplinary Approach. 3rd edn., Thieme, New York. Aylward, G.P., Lazzara, A. and Meyer, J. (1978) Behavioral and neurological characteristics of a hydranencephalic infant. Dev. Med. Child Neurol., 20: 21 1-217. Bandler, R. (1982) Induction of rage following microinjections of glutamate into midbrain but not hypothalamus of cats. Neurosci. Lett., 30: 183-188. Bandler, R. (1988) Brain mechanisms of aggression as revealed by electrical and chemical stimulation: suggestion of a central role for the midbrain periaqueductal grey region. In: A. Epstein and A. Morrison (Eds.), Progress in Psychobiology and Physiological Psychology, 13, Academic Press, pp. 67-153. Bandler, R. and Carrive, P. (1988) Integrated defence reaction elicited by excitatory amino acid injection in the midbrain periaqueductal grey region of the unrestrained cat. Brain Res., 439: 95-106. Bandler, R. and Shipley, M.T. (1994) Columnar organization in the midbrain periaqueductal gray: modules for emotional expression? Trends Neurosci., 17: 379-389. Bandler, R., Carrive, P. and Depaulis, A. (1991) Emerging principles of organization of the midbrain periaqueductal
gray matter. In: A. Depaulis and R. Bandler (Eds.), The Midbrain Periaqueductal Gray Matter: Functional, Anatomical and Immunohistochemical Organization, Plenum Press, New York, pp. 1-8. Bard, P. and Macht, M.B. (1958) The behaviour of chronically decerebrate cats. In: G.E.W. Wolstenholme and C.M. O’Connor (Eds.), CIBA Foundation Symposium on Neurological Basis oflehaviour, Churchill, London, pp. 55-75. Bocziin, G., Sorszegi, P. and Kleininger, 0. (1972) Clinical and pathological study of mutism following operations of pinealoma and medulloblastomas. In: J. Hirschberg, Gy. Sztpe and E. Vass-Koviics (Eds.), Papers in Interdisciplinary Speech Research, Akadtmiai Kiad6, Budapest. Botez, M.I. and Barbeau, A. (1971) Role of subcortical structures, and particularly of the thalamus, in the mechanisms of speech and language. Int. J. Neurol., 8: 300-320. Breuer, J. (1970) Self-steering of respiration through the nervus vagus (English translation by Elisabeth Ullman) In: R. Porter (Ed.), Breathing: Hering-Breuer Centenary Symposium, Churchill, London, pp. 365-394. Brown, T.G. (1915) Note on the physiology of the basal ganglia and mid-brain of the anthropoid ape, especially in reference to the act of laughter. J. Physiol. (London), 49: 195-207. Cummings, J.L., Benson, D.F., Houlihan, J.P. and Gosenfeld, L.F. (1983) Mutism: loss of neocortical and limbic vocalization. J. Nervous Mental Dis., 171: 255-259. Davis, P.J., Zhang, S.P. and Bandler, R. (1993) Pulmonary and upper airway afferent influences on the motor pattern of vocalization evoked by excitation of the midbrain periaqueductal gray of the cat. Brain Res., 607,61-80. Davis, P.J., Winkworth, A., Zhang, S.P. and Bandler, R. (1995) The neural control of vocalization: respiratory and emotional influences, J. Voice, in press. De Molina, A.F. and Hunsperger, R.W. (1962) Organization of the subcortical system governing defence and flight reactions in the cat. J. Physiol. (London), 160: 200-213 Draper, M.H., Ladefoged, P. and Whitteridge, D. (1959) Respiratory muscles in speech, J. Speech Hear. Res., 2: 16-27. Freed, C.D., Thomas, S.A., Lynch, J.J., Stein, R. and Friedmann, E. (1989) Blood pressure, heart rate and heart rhythm changes in patients with heart disease during talking. Heart Lung, 18: 17-22. Goltz, F. (1892) The dog without cerebrum. P’ugers Arch., 51: 570-614. Heaver, L. (1959) Spastic dysphonia. 11. Psychiatric considerations. Logos, 2: 15-24. Holstege, G. (1989) An anatomical study on the final common pathway for vocalization in the cat. J. Comp. Neurol., 284: 242-252. Holstege, G. (1991) Descending motor pathways and the spinal motor system. Limbic and non-limbic components. Prog. Brain Res., 87: 307-421. Hwang, J.C., St. John, W.M. and Bartlett, Jr., D. (1984) Re-
324 ceptors responding to changes in upper airway pressure. Respir. Physiol., 55: 355-366. Jiirgens, U. and Pratt, R. (1979a) Role of the periaqueductal grey in vocal expression of emotion. Brain Res., 167: 367378. Jurgens, U. and Pratt, R. (1979b) The cingular vocalization pathway in the squirrel monkey. Exp. Brain Res., 34: 499510. Jurgens, U. and von Cramon, D. (1982) On the role of the anterior cingulate cortex in phonation: a case report. Brain Lung., 15: 234-248. Kelly, A.H., Beaton, L.E. and Magoun, H.W. (1946) A midbrain mechanism for facio-vocal activity. J. Neurophysiol., 9: 181-189. Kirzinger, A. and Jiirgens, U. (1985) The effects of brainstem lesions on vocalization in the squirrel monkey. Brain Res., 358: 150-162. Kuypers, H.G.J.M. (1958) Corticobulbar connections to the pons and lower brain-stem in man. Brain, 81: 364-388. Larson, C.R. and Kistler, M.K. (1986) The relationship of periaqueductal gray neurons to vocalization and laryngeal EMG in the behaving monkey. Exp. Brain Res., 63: 5 9 6 606. Lenneberg, E.H. (1962) Case report: understanding language without ability to speak: a case report. J. Abnormal Social Psychol., 65: 419425 Lieberman, P. (1991) Uniquely Human: The Evolution of Speech, Thought, and Seljless Behavior, Harvard University Press, Cambridge, MA. Lieberman, P. (1994) Human language and human uniqueness. Lung. Commun., 14: 87-95. Linden, W. (1987) A microanalysis of autonomic activity during human speech. Psychosom. Med., 49: 562-578. Lijfqvist, A. Baer, T. and Yoshioka, H. (1981) Scaling of glottal opening. Phonetica, 38: 265-276. Marshall, R.C., Gandour, J. and Windsor, J. (1988) Selective impairment of phonation: a case study. Brain Lang., 35: 3 13-339. McNair, D., Lorr, M. and Droppelman, L. (1971) Profile of Mood States Manual, Educational and Industrial Testing Service, San Diego, CA. Mead, J. and Reid, M.B. (1988) Respiratory muscle activity during repeated airflow interruption. J. Appl. Physiol., 64: 2314-2317. Raichle, M.E. (1994) Visualizing the mind. Sci. Am. 270: 3642. Randall, W. L. (1964) The behaviour of cats (Felis catus) with lesions in the caudal midbrain region. Behuviour, 23: 107139. Ruiz, R., Legros, C. and Guell, A. (1990) Voice analysis to predict the psychological or physical state of a speaker. Aviat. Space Environ. Med., 61: 266-271. Sant’ Ambrogio, G., O.P. Mathew, J.T. Fisher and Sant’Ambrogio, F.B. (1983) Laryngeal receptors responding to
transmural pressure, airflow and local muscle activity. Respir. Physiol., 54: 317-330. Scherer, K.R. and Scherer, U. (1981) Speech behaviour and personality. In: J.K. Darby (Ed.), Speech Evaluation in Psychiatry, Grune and Stratton, New York. Sedlacek, K. and Sychra, A. (1963) Die melodie als faktor des emotionellen ausdrucks. Fol. Phon., 15; 89-98. Sessle, B., Ball, G.J. and Lucier, G.E.(1981) Suppressive influences from periaqueductal gray and nucleus raphe magnus on respiration and related reflex activities and on solitary tract neurons, and effect of naloxone. Brain Res., 216: 145-161. Shipley, M.T., Ennis, M., Rizvi, T.A. and Behbehani, M.M. (199 1) Topographical specificity of forebrain inputs to the midbrain periaqueductal gray: evidence for discrete longitudinal organized input columns. In: A. Depaulis and R. Bandler (Eds.), The Midbrain Periaqueductal Gray Matter: Functional, Anatomical and lmmunohistochemical Organization, Plenum Press, New York, pp. 417-448. Sundberg, J. (1987) Speech, song and emotion. In: J. Sundberg (Ed.),The Science of the Singing Voice, North Illinois Press, DeKalb, IL. Sundberg, J., Iwarsson, J. and Hagegkd, H. (1995) A singer’s expression of emotions in sung performance. In: 0. Fujimura and M. Hirano (Eds.), Vocal Fold Physiology, Singular, San Diego, CA, in press. Sutton, D., Larson, C. and Lindeman, R.C. (1974) Neocortical and limbic lesion effects on primate phonation. Brain Res., 71: 61-75. Thoms, G. and Jurgens, U. (1987) Common input of the cranial motor nuclei involved in phonation in squirrel monkey. Enp. Neurol., 95: 85-99. von Cramon, D. (1981) Traumatic mutism and the subsequent reorganizations of speech functions. Neuropsychologia, 19: 801-805. von Euler, C. (1981) The contribution of sensory inputs to the pattern generation of breathing, Can. J. Physiol. Phurmacol., 59: 700-706. von Euler, C. (1986) Brain stem mechanisms for generation and control of breathing pattern. In: N.S. Cherniack and J.G. Widdicombe (Eds.), Handbook of Physiology, Section 3, The Respiratory System, Vol II, Control of Breathing, American Physiological Society, Bethesda, MD, pp. 1 4 7 . Williams, C.E. and Stevens, K.N. (1969) On determining the emotional state of pilots during flight: an exploratory study. Aerospace Med., 40: 1369-1372. Williams, C.E. and Stevens, K.N. (1972) Emotions and speech: some acoustic correlates. J. Acoust. SOC.Am., 52: 1238-1 250. Winkworth, A.L., Davis, P.J., Adams, R. and Ellis, E. (1994) Variability and consistency in speech breathing during reading: lung volumes, speech intensity, and linguistic factors. J. Speech Hearing Res., 37,535-556. Winkworth, A.L., Davis, P.J., Ellis, E. and Adams, R. (1995)
325 Breath patterns during spontaneous speech. J. Speech Hearing Res., 38: 124-144. Woods, J.W. (1964) Behavior of chronic decerebrate rats. J. Neurophysiol., 27: 635-644. Zhang, S.P., Davis, P.J., Carrive, P. and Bandler, R. (1992) Vocalization and marked pressor effect evoked by excitation of neurons in the nucleus retroambigualis of the cat. Neurusci. Leu.,140: 103-107.
Zhang, S.P.,Davis, P.J., Bandler, R. and Carrive, P. (1994) Brain stem integration of vocalization: role of the midbrain periaqueductal gray. J. Neuruphysiul., 72: 1337-1356. Zhang, S.P., Davis, P.J. and Bandler, R. (1995) Brain stem integration of vocalization: role of the nucleus retroambigualis. J. Neurophysiol., 74: 2500-25 12.
CHAPTER 19
Midbrain and medullary regulation of respiration and vocalization Pamela J. Davis’, Shi Ping Zhang2 and Richard Bandler2 ‘National Voice Centre, Faculty of Health Sciences, The University of Sydney, NSW, Australia, and ’Department of Anatomy and Histology, The University of Sydney, NSW, Australia
Introduction Most emotional reactions and behaviors include changes in the breathing pattern and many are also associated with vocalization. There is much evidence that the respiratory changes and vocalization associated with emotional behaviors are dependent on an intact midbrain (Kelly et al., 1946; Adametz and O’Leary, 1959; De Molina and Hunsperger, 1962; Randall, 1964), specifically the lateral part of the caudal two-thirds of the periaqueductal gray matter (PAG) surrounding the aqueduct (Jurgens and Pratt, 1979a; Bandler, 1982, 1988; Larson and Istler, 1986; Davis et al., 1993; Zhang et al., 1994).
Vocalization evoked from the midbrain periaqueductal gray In the freely moving or unanesthetized decerebrate cat stimulation of neurons in the lateral column of the intermediate PAG by microinjections of the excitatory amino acid D,L-homocysteic acid (DLH; WOnmol, 30-200nl) evokes a number of discrete patterns of vocalization including howling, hissing, mewing and growling, as well as tachypnea or respiratory rate changes (Bandler, 1982; Bandler and Carrive, 1988; Davis et al., 1993; Zhang et al., 1994). Two basic types of vocalization are evoked: type A (“voiced”) sounds including howl, mew and growls, and type B sounds
(“unvoiced”) associated with hissing (Zhang et al., 1994). The voiced sounds were associated with activation of the laryngeal thyro-arytenoid and crico-thyroid muscles and inactivity of the posterior crico-arytenoid muscle in the expiratory phase (PCAE),while unvoiced sounds were characterized by excitation of the posterior crico-arytenoid muscle (expiratory phase) and thyro-arytenoid muscles and no significant activation of the crico-thyroid. In addition, stronger expiratory (external oblique, internal oblique and internal intercostal) electromyographic (EMG) increases were associated with voiced sound production, and larger increases in oral muscle activity (genio-glossus and digastric) were associated with unvoiced vocalization. Unvoiced sounds were evoked from PAG sites generally rostra1 (A3.3 level) to sites at which voiced sounds were evoked (P0.2-A2.5 level) (Zhang et al., 1994). Those sites associated with increased breathing rate (tachypneic sites) were distributed more widely throughout the intermediate and caudal PAG (A 3.3-PO.2) and the deep layers of the superior colliculus (see Figs. 9 and 13 in Zhang et al., 1994). Smaller, just-threshold doses of DLH (300 pmol to 3 nmol) injected into the same discrete regions of the lateral PAG also evoked the same patterned activation characteristic of voiced and voiceless vocalization, often with barely audible sound, and also a tachypneic pattern without vocalization (Zhang et al., 1994). Figure 1A illustrates the pat-
316
Fig. 1. Patterns of EMG activity evoked from the lateral column of the intermediate PAG (d2.5). (A) Computer-chart records of integrated EMG activity recorded ipsilateral to 3 DLH microinjection sites at different medio-lateral locations. The lower inset depicts a section of raw EMG record from site 1 showing voiced and unvoiced sound patterns. The tracheal pressure record (TP) signals are calibrated in cmH20. (B) Computer-chart records from a different cat illustrating the effects of 6 DLH microinjections made at different dorso-ventral sites along a micropipette track in the PAG. In all sections the bars on the EMG records correspond to 50 arbitrary units. The location of each injection site is shown in the inset drawing of PAG; calibration bars correspond to 0.5 nun. Adapted from Figs. 10 and 12 in Zhang et al. (1994).
erns evoked from 3 adjacent medio-lateral sites, separated by 500 mm. A 600 pmol dose of DLH injected at site 1 evoked two distinct patterns (voiced and unvoiced) which alternated with each expiration. At site 2, 500 mm lateral to site 1, a 900pmol DLH dose evoked only an unvoiced pattern. The tachypneic pattern (site 3, not illustrated) was characterized by an increase (or recruitment) of PCAE and occasionally an increase in respiratory rate, but no recruitment of other laryngeal and abdominalhntercostal muscles. Figure 1B illustrates, in a different cat, three of the differ-
ent patterns evoked by 3 nmol DLH injections at different dorsoventral sites, also separated by 500 mm. DLH injection at PAG site 1 evoked a tachypneic pattern while at site 2 an unvoiced vocalization pattern associated with a strong excitation of PCAE and genio-glossus muscle was evoked. At sites 3 and 4 (not illustrated), a mixture of voiced and unvoiced sound patterns was evoked while more ventrally at site 5 a pure voiced sound pattern was evoked. Most ventrally at site 6 no effect was observed (not illustrated). At no PAG site were individual muscles ever
3 17
activated. As illustrated in Fig. 1, just-threshold doses of DLH evoked the patterned activation of laryngeal and abdominalhntercostal muscles at all sites tested, whereas smaller doses tested at the same sites (typically 300 pmol) were ineffective for all muscles (Fig. 11 in Zhang et al., 1994). This suggests that the underlying PAG organization takes the form of a representation of muscle patterns, rather than individual muscles. A schematic representation of the characteristic EMG patterns, indicating the differences in onset and amplitude of muscle activity, during voiced and voiceless sound production is provided in Fig. 2. As illustrated in this figure, the abdominal muscles were activated much earlier than the oral muscles for voiced responses, whereas for unvoiced vocalization, the oral muscles increased their activity ahead of the abdominal muscles. Frequently, the inspiratory muscles (diaphragm, posterior cricoarytenoid) were more active prior to each vocalization burst. It may well be that the effects evoked from the PAG by DLH microinjection are dependent on the combination of excitation of distinct sets of output neurons: “respiratory patterning” PAG neurons regulating respiratory rate and depth changes and “vocalization patterning” PAG neu-
””?”’” voiced
1
voice
oral rn inspiratory rn
rons which coordinate the different patterns of muscle activity characteristic of voiced and unvoiced sounds.
Afferent influences on periaqueductal grayevoked respiratory and vocal patterns Davis et al. (1993) showed that the vocalization evoked from PAG can be modified by respiratory afferent discharge. A sustained excitation of laryngeal, intercostal and abdominal muscles was evoked by the combination of PAG excitation and manipulation of the air pressure in the tracheobronchial and pulmonary airways. When the latter was increased and held constant, the duration of an individual PAG-evoked vocalization could be extended, seemingly “indefinitely”. That this reflex effect (Breuer, 1970) was mediated by sensory receptors in the vagus nerve, presumably pulmonary stretch receptor afferents, was established by demonstrating a reversible block of the reflex effect on the crico-thyroid and abdominal muscles by vagal nerve cooling followed by nerve rewarming. Positive pressure/flow stimulation of the upper airways was also effective in modulating the phonatory duration, presumably via slowly adapting laryngeal receptors (Sant’Ambrogio et al., 1983; Hwang et al., 1984). It is possible, then, that lateral PAG output neurons not only directly mediate the motor pattern for vocalization but are also modulated by the afferent input which occurs during that period (Sessle et al., 1981). Summation of the pulmonary vagal, upper airway and other respiratory afferent input (e.g. from chest wall muscle receptors) with the PAG motor output presumably ensures that the vocalization will be coordinated always with the volume of air in the lungs and the ability to generate the subglottic pressure to sustain vocalization. Although there has been no attempt to experimentally manipulate lung pressure during human speech, it does appear that the breathing patterns during speech are coordinated with afferent signals related to lung volume. In a different series of human experiments we examined influences on the expiratory duration of speech (Winkworth et al.,
cI b TA
7 -
100 rns
Fig. 2. Schematic representation of muscle activity during PAG-evoked voiced and unvoiced type vocalization. The profile and amplitude of the various muscle representations correspond to the general pattern observed in averaged EMG activity (genio-glossus GG, digastric DG,diaphragm D, posterior crico-arytenoid PCA, thyro-arytenoid TA, crico-thyroid CT, internal intercostal IIC, internal oblique 10, external oblique EO). Adapted from Fig. 7 in B a n g et al. (1994)
318
1994, 1995). As well as confirming earlier reports that the language structure is dominant in determining when a breath is taken, a novel finding was that the inspiratory depth was strongly associated with the length of the subsequent expiration, even during “natural” spontaneous speech. One possibility is that the respiratory afferent control system described above for PAG-evoked vocalization in the cat is also involved in the regulation of human speech utterance length. Certainly, different expiratory muscle groups are progressively recruited during human speech and singing as lung volume declines (Draper et al., 1959) and it is possible that pulmonary and upper airway stretch-sensitive afferents play a role in regulating not only the duration of the speech breaths, but also the level of expiratory muscle recruitment according to the volume of air in the lungs.
The periaqueductal gray-nucleus retroambigualisvocalization pathway Holstege (1989; and Chapter 20, this volume) provided anatomical evidence that neurons in the caudal two-thirds of the lateral PAG project to premotor interneuronal pools in the nucleus retroambigualis (NRA) in the caudal ventrolateral medulla. In the same paper, Holstege reported that NRA neurons project not only to intercostal and abdominal spinal motoneuronal pools, but also to the vicinity of more rostrally located laryngeal, pharyngeal and mouth-opening muscle motoneuronal pools. This led to the proposal that the NRA, by regulating motoneuronal pools controlling laryngeal pharyngeal and mouth opening, as well as expiratory muscles, could serve as a “final common pathway” for vocalization. Others have proposed that the PAG pathway to the laryngeal motoneurons in the nucleus ambiguus is dominated by projections to interneurons in the pontine and rostral medullary reticular formation (Jurgens and Pratt, 1979a; Thoms and Jurgens, 1987). To study this question Zhang et al. (1995) examined the laryngeal EMG changes associated
with vocalization evoked from the lateral PAG, before and after a series of medullary transections which eliminated the medulla caudal to the obex, including the NRA. Initially, excitation of cricothyroid, thyro-arytenoid, posterior crico-arytenoid, genio-glossus or digastric was evoked from the PAG after transections made at the spinomedullary junction in each of four similar experiments. When the medullary transection extended to the obex, PAG-evoked activity in crico-thyroid and thyro-arytenoid muscles was effectively abolished, while that for PCAE, genio-glossus and digastric was attenuated. These results indicate that PAG regulates the crico-thyroid and thyroarytenoid muscles via an initial projection to medullary neurons caudal to the obex (presumably in the NRA) which project (directly or indirectly) to crico-thyroid and thyro-arytenoid motoneuronal groups lying rostral to the obex (Holstege, 1989). These muscles are critical in adducting and tensing the vocal folds for sound generation. Further studies demonstrated that activity in the internal intercostal and abdominal muscles, often with vocalization, was evoked by DLH microinjection into NRA. Considered together these data are consistent with the proposal that PAG regulation of expiratory effort, vocal fold adduction and tension, all of which are essential components of sound production, is mediated via a direct projection to the NRA. There was, however, little evidence that NRA neurons were associated with oro-facial modulation of that sound as NRA evoked vocalization was associated neither with mouth opening or closing, lip rounding or spreading, tongue protrusion or curling nor were consistent changes in genio-glossus or digastric activity evoked by DLH injection into the NRA (Zhang et al., 1992, 1995). These findings are not consistent with the suggestion based on earlier anatomical data that NRA efferents include substantial projections to the motor trigeminal, facial and hypoglossal nuclei (Holstege, 1989). Our data, then, indicate that the NRA is a critical locus for PAG output, mediating sound production but not the oro-facial modulation of that sound.
319
Although vocalization, as well as a variety of muscle excitations unaccompanied by vocalization, could be evoked from the rostra1 half of the NRA by the microinjection of DLH, the naturalsounding acoustic characteristics and stereotyped muscle activation associated with PAG-evoked vocalization were never evoked from the NRA. The NRA-evoked muscle patterns included not only a lack of involvement of oro-facial musculature but also a high level of tonic discharge in the crico-thyroid, internal oblique, external oblique, internal intercostal and diaphragm muscles upon which expiratory-phased activation was superimposed (Fig. 4, in Zhang et al., 1995). Quite clearly, then, the NRA contains neurons which are capable of recruiting laryngeal and expiratory muscles in an appropriate manner to produce sound, but in contrast to the PAG, the neural organization (at least, as revealed by the technique of micro injection of DLH) for the integration of “natural sounding” vocalization does not appear to be present. A schematic model summarizing these findings is provided in Fig. 3. Our data suggest that the PAG influences the excitability of laryngeal tensor (crico-thyroid), laryngeal adductor (thyro-arytenoid) and expiratory (external oblique, internal oblique, internal intercostal) muscles indirectly via the NRA. That is, the projection from the PAG to the NRA is concerned with laryngeal tensing, adduction, and forced expiration, which is essential for sound production. In contrast, the PAG regulation of oro-facial activity must be mediated via other pathways, with little, if any, contribution from the NRA. As well, the change in the inspiratory pattern during PAG-evoked vocalization suggests that PAG neurons also project to inspiratory pre-motor neurons (not shown) although these putative pathways have yet to be delineated.
Emotional control of respiration and sound production Most animal species utilize vocalization as an integral part of their emotional repertoire. Vocalization evoked from PAG by DLH microinjection
Fig. 3. Proposed neural pathway for the production of emotional (non-verbal) vocalization. For graphical illustration only a single PAC-NRA output pathway is represented, although there is a bilateral projection from the lateral part of the PAG to the NRA (Holstege, 1989).
appears indistinguishable from spontaneous feline calls (Zhang et al., 1994) and was generally evoked as part of an integrated respiratory, cardiovascular and behavioral response. The sound quality of human speech also reflects the emotional state of the speaker and, like that of vocalization in lower species, is accompanied also by autonomic alterations which may include elevations in blood pressure and heart rate (Abel et al., 1987; Linden, 1987; Freed et al., 1989). Further, the frequency pattern of vocal fold vibration, the voice quality as well as the breathing pattern and its timing (i.e. those voicing parameters which are modulated in the cat by PAG neurons) are factors which have been identified as likely to convey information about the emotional state of the speaker (Scherer and Scherer, 1981; Sundberg, 1987; Sundberg et al., 1995). The PAG region is closely involved in the expression of emotion (Bandler, 1988; Bandler et al.,
320
1991; Holstege, 1991; Bandler and Shipley, 1994) and it is considered a critical part of the emotional motor system (Holstege, 1991; and Chapter 1, this volume). Thus, it is not surprising that PAC neurons when excited by DLH microinjection evoke some of the respiratory and vocal changes associated with such reactions. As vocalization is an intrinsic part of many emotional reactions which are controlled by the PAC this may explain the well known association between emotion and vocal control. In several studies, professional actors have been asked to simulate the effects of various emotional states on speech. With respect to an intermediate neutral tone, the frequency of the laryngeal vibration (voice pitch) was found to be raised in joy or anger and lowered in sorrow (Sedlacek and Sychra, 1963; Williams and Stevens, 1972). Fear was manifested by rapid increases and decreases in pitch (Williams and Stevens, 1972). These simulated data are consistent with live voice recordings obtained from individuals experiencing aircraft tragedies (Williams and Stevens, 1969; Ruiz et al., 1990). Considering the importance of voice pitch in conveying emotional expression, Sundberg et al. (1995) examined singing in which emotional expression is, in part, dictated by the musical score. It was found that differences in the tempo, voice loudness, loudness variation, vibrato, and voice timbre (as reflected by formant frequency) were very important in the perceived emotionality of sung performance. Changes in the pattern of breathing are an integral part of most emotional reactions (von Euler, 1981). Studies of the breathing patterns during spontaneous speech and mood state (McNair et al., 1971) of healthy young women over a 3-week period revealed that each of the six subjects studied showed a significant within-subject association between respiratory speech activity and depressed and anxious mood over this period (Winkworth et al., 1995). From these findings, obtained during everyday conversations and monologues, it is likely that the breathing patterns associated with speech expressing strong emotion would show an even greater effect.
Possible role of the periaqueductal gray and nucleus retroambigualis in the neural control of mammalian sound production, including human speech The similarity of the laryngeal and respiratory muscle recruitment patterns associated with PAGevoked vocalization, and human vowel and voiceless consonant phonation (Zhang et al., 1994; Davis et al., 1995) leads us to consider that the PAC may well be a crucial brain site for mammalian voice production, not only in the production of emotional or involuntary sounds, but also as a generator of specific respiratory and laryngeal motor patterns essential for human speech and song. Such findings are consistent with the idea that the central neural substrates for the sound production underlying human speech could be built upon components present in phylogenetically lower species. Previously, it has been considered that the neocortical vocal control pathway utilized in speech acts independently of subcortical pathways, including the PAG circuitry, that mediate emotional and reflexive vocalization. The disruption of voluntary vocal expression in Parkinson’s disease and spasmodic dysphonia, but normal “emotional” vocal expression in response to an emotional trigger (Arnold, 1959; Heaver, 1959), is sometimes used to support this claim. We would suggest, instead, a working hypothesis that humans produce speech sounds via the same midbrain PAG circuitry which is fundamentally involved in emotional motor control. Although speech is complex and subject to linguistic control, it is, nonetheless, still a modified form of respiration (von Euler, 1986; Davis et al., 1993). PAG neuronal networks are ideally positioned to integrate the various afferent and efferent systems necessary to produce speech as part of a coordinated respiratory response. Some of the main differences between human speech and emotional vocalization of other species are the human ability to modify the vocal quality and to inhibit sound production when the social situation demands. Such control mechanisms undoubtedly involve higher centers in the forebrain. In this regard it is interesting that recent
321
studies have revealed that the cortical and forebrain inputs to PAG are more substantial and extensive than previously envisaged (Chapter 1 , this volume) (Shipley et al., 1991; Bandler and Shipley, 1994). Although the integrity of cortical limbic structures may be important for social vocalization, evidence in favor of a role for the PAG as a general, all-purpose sound pattern generator are the findings, in several animal species, that all naturalsounding vocalization is critically dependent on the integrity of the PAG. Thus, PAG lesions in experimental animals results in permanent loss of both spontaneous vocalization and vocalization evoked by electrical stimulation at sites either in the forebrain or the caudal brain stem (Jurgens and Pratt, 1979a; Bandler, 1988). In contrast, the quality of species-specific vocalization is not dramatically altered either by forebrain lesions, or even complete removal of the forebrain (Goltz, 1892; Brown, 1915; Bard and Macht, 1958; Woods, 1964; Sutton et al., 1974; Kirzinger and Jiirgens, 1985). Similarly, in humans, both anencephalic infants and hydranencephalic infants (with little or no forebrain, but an intact midbrain) have been reported to vocalize in a manner which is relatively similar to that of normal infants (AndrkThomas et al., 1944; Andrk-Thomas, 1954; Aylward et al., 1978). Observations on infants born without such abnormalities, but at a stage of development when the forebrain is grossly immature (e.g. 22-24 weeks gestation) are also capable of intermittent vocalization (D. Henderson-Smart, pers. commun.). In contrast, although there are relatively few case reports of individuals with specific PAG lesions (Botez and Barbeau, 1971), possibly because the region is adjacent to key brain structures associated with the maintenance of consciousness, mutism has been reported in several cases in which patients have sustained damage to the midbrain including the PAG (Lenneberg, 1962; Botez and Barbeau, 1971; BoczAn et al., 1972; von Cramon, 1981; Cummings et al., 1983). A schematic model of interaction between cortical language structures and the PAG for the neu-
ral control of speech and song, as well as nonverbal sounds (e.g. laughing, crying) is illustrated in Fig. 4. In this figure, we have proposed separate neural pathways for articulation and sound production. This idea is consistent with our finding that the NRA mediates the sound production components of PAG-evoked vocalization, but not the oro-facial modulation of that sound (Zhang et al., 1992, 1995). The articulation of human speech is characterized by very rapid changes in oro-facial muscle activity associated with the production of various consonants and it is likely that the fine control of these movements is achieved via direct projections from the motor cortex to brainstem oro-facial motoneuronal pools. Indeed, there is evidence for a rich human cortico-bulbar pathway for the volun-
Fig. 4. Proposed neural pathway for the production of human speech and song.
322
tary control of oro-facial motoneurons (Kuypers, 1958). It is a general observation that vocal and articulatory speech control may be differentially impaired. For example, a number of emotional reactions are characterized by a complete or partial loss of voice, yet relatively few such reactions are associated with a loss of the ability to articulate, or to whisper (Aronson, 1990). Marshall et al. (1988) describe a case who lost the ability to produce sound but whose language and articulation was intact with an artificial sound source (electronic artificial larynx). The site(s) of neurological damage responsible for this disorder are unclear but the subject underwent a craniotomy for clipping of an aneurysm at the trifurcation of the left middle cerebral artery and had a long history of mild to moderate hydrocephalus with ballooning of the left temporal horn of the left lateral ventricle. In contrast, we suggest that the voluntary motor pathway for the sound production component of speech and song includes higher brain structures which project significantly to the PAG (Jiirgens and von Cramon, 1982; Shipley et al., 1991; Bandler and Shipley, 1994) and excite neuronal networks which coordinate the various muscle patterns for voiced and unvoiced sound production. In this regard it is worth noting the recent figures displaying activation of the PAG by PET imaging of the human brain during speech (Raichle, 1994). Although the specific pathway by which cortical speech and language regions might target specific PAG neuronal networks have not been delineated, there are data to suggest that the anterior cingulate is critically involved (Jurgens and Pratt, 1979b; Jiirgens and von Cramon, 1982). Interestingly, in contrast to the fine motor control of oral structures, such as the tongue, voluntary control of the larynx and palate is relatively poor when sound is not produced, and appears limited to little more than closure of the vocal cords (associated with expiratory apnea) and limited rostro-caudal movements (Lofqvist et al., 1981). However, as soon as a sound is produced, there can be quite exquisite control of the vocal folds to alter the pitch and quality of that sound. This strongly suggests that the voluntary control systems for the larynx must
be tightly linked with neural circuits activating patterned activities such as respiration, vocalization, swallowing and coughing. There are also speech data which support the idea of a separation of laryngeal-respiratory and oro-facial components. Mead and Reid (1988) observed that speakers were only able to interrupt an expiratory airflow at the level of the larynx (“uh-uh-uh”) by synchronous activity in abdominal, intercostal and laryngeal muscles, whereas at the level of the tongue (“t-t-t”), this could be achieved without respiratory synchronization. Lieberman ( 1 99 1, 1994) argues that humans have evolved radical differences in the shape of the tongue, mouth and pharynx from other primates which permit articulatory speech maneuvers and hypothesizes that these anatomical differences are responsible for the evolution of human speech. We add to this proposal the idea that the articulatory differences which are so important for human speech are built upon an existing PAG-NRA neuronal circuitry coordinating sound production. That this circuitry is part of the emotional motor system may serve to explain the emotional quality of all speech and song.
Summary The lateral column of the midbrain periaqueductal gray (PAG) appears to contain the motor pattern generators for various types of vocalization. Further, the motor patterns which can be evoked by PAG neuronal excitation are influenced by afferent control mechanisms linked to the availability of air in the lungs. The PAG has been shown to influence the excitability of laryngeal adductor (thyroarytenoid), tensor (crico-thyroid) and expiratory (internal intercostal, external oblique, internal oblique) muscles indirectly, via the nucleus retroambigualis (NRA) while the PAG control of oro-facial muscles involves a separate pathway that does not appear to include a synapse in the NRA. We propose that neurons in the lateral PAG column could play an important role, not only in the production of emotional vocalization, but also as a generator of specific respiratory and laryngeal
323
motor patterns essential for human speech and song.
Acknowledgements Supported by grants to P.D. from the Australian National Health and Medical Research Council; and to R.B. from the Australian National Health and Medical Research Council and the C. and V. Ramaciotti Foundation.
References Abel, H.H., Mottau, B., KliiBendorf, D. and Koepchen, H.P. (1987) Pattern of different components of the respiratory cycle and autonomic parameters during speech. In: G. Sieck, S . Gandevia and W. Cameron (Eds.), Respiratory Muscles and their Neuromotor Control, Alan R. Liss, New York, pp. 109-1 13. Adametz, J. and O’Leary, J.L. (1959) Experimental mutism resulting from periaqueductal lesions in cats. Neurol. Minneap., 9: 636-642. Andrt-Thomas, J. (1954) Le nouveau-nt normal et l’anenc6phale. Presse Mkd., 62: 885-886. Andrt-Thomas, J., Lepage, F. and Sorrel-Dejerine, M. (1944) Examen anatomo-clinique de deux anenctphales protubtrantiels. Rev. Neurol., 76: 173-193. Arnold, G.E. (1959) Spastic dysphonia: I. Changing interpretation of a persistent affliction. Logos, 2: 3-14. Aronson, A.E. (1990) Clinical Voice Disorders: An Interdisciplinary Approach. 3rd edn., Thieme, New York. Aylward, G.P., Lazzara, A. and Meyer, J. (1978) Behavioral and neurological characteristics of a hydranencephalic infant. Dev. Med. Child Neurol., 20: 21 1-217. Bandler, R. (1982) Induction of rage following microinjections of glutamate into midbrain but not hypothalamus of cats. Neurosci. Lett., 30: 183-188. Bandler, R. (1988) Brain mechanisms of aggression as revealed by electrical and chemical stimulation: suggestion of a central role for the midbrain periaqueductal grey region. In: A. Epstein and A. Morrison (Eds.), Progress in Psychobiology and Physiological Psychology, 13, Academic Press, pp. 67-153. Bandler, R. and Carrive, P. (1988) Integrated defence reaction elicited by excitatory amino acid injection in the midbrain periaqueductal grey region of the unrestrained cat. Brain Res., 439: 95-106. Bandler, R. and Shipley, M.T. (1994) Columnar organization in the midbrain periaqueductal gray: modules for emotional expression? Trends Neurosci., 17: 379-389. Bandler, R., Carrive, P. and Depaulis, A. (1991) Emerging principles of organization of the midbrain periaqueductal
gray matter. In: A. Depaulis and R. Bandler (Eds.), The Midbrain Periaqueductal Gray Matter: Functional, Anatomical and Immunohistochemical Organization, Plenum Press, New York, pp. 1-8. Bard, P. and Macht, M.B. (1958) The behaviour of chronically decerebrate cats. In: G.E.W. Wolstenholme and C.M. O’Connor (Eds.), CIBA Foundation Symposium on Neurological Basis oflehaviour, Churchill, London, pp. 55-75. Bocziin, G., Sorszegi, P. and Kleininger, 0. (1972) Clinical and pathological study of mutism following operations of pinealoma and medulloblastomas. In: J. Hirschberg, Gy. Sztpe and E. Vass-Koviics (Eds.), Papers in Interdisciplinary Speech Research, Akadtmiai Kiad6, Budapest. Botez, M.I. and Barbeau, A. (1971) Role of subcortical structures, and particularly of the thalamus, in the mechanisms of speech and language. Int. J. Neurol., 8: 300-320. Breuer, J. (1970) Self-steering of respiration through the nervus vagus (English translation by Elisabeth Ullman) In: R. Porter (Ed.), Breathing: Hering-Breuer Centenary Symposium, Churchill, London, pp. 365-394. Brown, T.G. (1915) Note on the physiology of the basal ganglia and mid-brain of the anthropoid ape, especially in reference to the act of laughter. J. Physiol. (London), 49: 195-207. Cummings, J.L., Benson, D.F., Houlihan, J.P. and Gosenfeld, L.F. (1983) Mutism: loss of neocortical and limbic vocalization. J. Nervous Mental Dis., 171: 255-259. Davis, P.J., Zhang, S.P. and Bandler, R. (1993) Pulmonary and upper airway afferent influences on the motor pattern of vocalization evoked by excitation of the midbrain periaqueductal gray of the cat. Brain Res., 607,61-80. Davis, P.J., Winkworth, A., Zhang, S.P. and Bandler, R. (1995) The neural control of vocalization: respiratory and emotional influences, J. Voice, in press. De Molina, A.F. and Hunsperger, R.W. (1962) Organization of the subcortical system governing defence and flight reactions in the cat. J. Physiol. (London), 160: 200-213 Draper, M.H., Ladefoged, P. and Whitteridge, D. (1959) Respiratory muscles in speech, J. Speech Hear. Res., 2: 16-27. Freed, C.D., Thomas, S.A., Lynch, J.J., Stein, R. and Friedmann, E. (1989) Blood pressure, heart rate and heart rhythm changes in patients with heart disease during talking. Heart Lung, 18: 17-22. Goltz, F. (1892) The dog without cerebrum. P’ugers Arch., 51: 570-614. Heaver, L. (1959) Spastic dysphonia. 11. Psychiatric considerations. Logos, 2: 15-24. Holstege, G. (1989) An anatomical study on the final common pathway for vocalization in the cat. J. Comp. Neurol., 284: 242-252. Holstege, G. (1991) Descending motor pathways and the spinal motor system. Limbic and non-limbic components. Prog. Brain Res., 87: 307-421. Hwang, J.C., St. John, W.M. and Bartlett, Jr., D. (1984) Re-
324 ceptors responding to changes in upper airway pressure. Respir. Physiol., 55: 355-366. Jiirgens, U. and Pratt, R. (1979a) Role of the periaqueductal grey in vocal expression of emotion. Brain Res., 167: 367378. Jurgens, U. and Pratt, R. (1979b) The cingular vocalization pathway in the squirrel monkey. Exp. Brain Res., 34: 499510. Jurgens, U. and von Cramon, D. (1982) On the role of the anterior cingulate cortex in phonation: a case report. Brain Lung., 15: 234-248. Kelly, A.H., Beaton, L.E. and Magoun, H.W. (1946) A midbrain mechanism for facio-vocal activity. J. Neurophysiol., 9: 181-189. Kirzinger, A. and Jiirgens, U. (1985) The effects of brainstem lesions on vocalization in the squirrel monkey. Brain Res., 358: 150-162. Kuypers, H.G.J.M. (1958) Corticobulbar connections to the pons and lower brain-stem in man. Brain, 81: 364-388. Larson, C.R. and Kistler, M.K. (1986) The relationship of periaqueductal gray neurons to vocalization and laryngeal EMG in the behaving monkey. Exp. Brain Res., 63: 5 9 6 606. Lenneberg, E.H. (1962) Case report: understanding language without ability to speak: a case report. J. Abnormal Social Psychol., 65: 419425 Lieberman, P. (1991) Uniquely Human: The Evolution of Speech, Thought, and Seljless Behavior, Harvard University Press, Cambridge, MA. Lieberman, P. (1994) Human language and human uniqueness. Lung. Commun., 14: 87-95. Linden, W. (1987) A microanalysis of autonomic activity during human speech. Psychosom. Med., 49: 562-578. Lijfqvist, A. Baer, T. and Yoshioka, H. (1981) Scaling of glottal opening. Phonetica, 38: 265-276. Marshall, R.C., Gandour, J. and Windsor, J. (1988) Selective impairment of phonation: a case study. Brain Lang., 35: 3 13-339. McNair, D., Lorr, M. and Droppelman, L. (1971) Profile of Mood States Manual, Educational and Industrial Testing Service, San Diego, CA. Mead, J. and Reid, M.B. (1988) Respiratory muscle activity during repeated airflow interruption. J. Appl. Physiol., 64: 2314-2317. Raichle, M.E. (1994) Visualizing the mind. Sci. Am. 270: 3642. Randall, W. L. (1964) The behaviour of cats (Felis catus) with lesions in the caudal midbrain region. Behuviour, 23: 107139. Ruiz, R., Legros, C. and Guell, A. (1990) Voice analysis to predict the psychological or physical state of a speaker. Aviat. Space Environ. Med., 61: 266-271. Sant’ Ambrogio, G., O.P. Mathew, J.T. Fisher and Sant’Ambrogio, F.B. (1983) Laryngeal receptors responding to
transmural pressure, airflow and local muscle activity. Respir. Physiol., 54: 317-330. Scherer, K.R. and Scherer, U. (1981) Speech behaviour and personality. In: J.K. Darby (Ed.), Speech Evaluation in Psychiatry, Grune and Stratton, New York. Sedlacek, K. and Sychra, A. (1963) Die melodie als faktor des emotionellen ausdrucks. Fol. Phon., 15; 89-98. Sessle, B., Ball, G.J. and Lucier, G.E.(1981) Suppressive influences from periaqueductal gray and nucleus raphe magnus on respiration and related reflex activities and on solitary tract neurons, and effect of naloxone. Brain Res., 216: 145-161. Shipley, M.T., Ennis, M., Rizvi, T.A. and Behbehani, M.M. (199 1) Topographical specificity of forebrain inputs to the midbrain periaqueductal gray: evidence for discrete longitudinal organized input columns. In: A. Depaulis and R. Bandler (Eds.), The Midbrain Periaqueductal Gray Matter: Functional, Anatomical and lmmunohistochemical Organization, Plenum Press, New York, pp. 417-448. Sundberg, J. (1987) Speech, song and emotion. In: J. Sundberg (Ed.),The Science of the Singing Voice, North Illinois Press, DeKalb, IL. Sundberg, J., Iwarsson, J. and Hagegkd, H. (1995) A singer’s expression of emotions in sung performance. In: 0. Fujimura and M. Hirano (Eds.), Vocal Fold Physiology, Singular, San Diego, CA, in press. Sutton, D., Larson, C. and Lindeman, R.C. (1974) Neocortical and limbic lesion effects on primate phonation. Brain Res., 71: 61-75. Thoms, G. and Jurgens, U. (1987) Common input of the cranial motor nuclei involved in phonation in squirrel monkey. Enp. Neurol., 95: 85-99. von Cramon, D. (1981) Traumatic mutism and the subsequent reorganizations of speech functions. Neuropsychologia, 19: 801-805. von Euler, C. (1981) The contribution of sensory inputs to the pattern generation of breathing, Can. J. Physiol. Phurmacol., 59: 700-706. von Euler, C. (1986) Brain stem mechanisms for generation and control of breathing pattern. In: N.S. Cherniack and J.G. Widdicombe (Eds.), Handbook of Physiology, Section 3, The Respiratory System, Vol II, Control of Breathing, American Physiological Society, Bethesda, MD, pp. 1 4 7 . Williams, C.E. and Stevens, K.N. (1969) On determining the emotional state of pilots during flight: an exploratory study. Aerospace Med., 40: 1369-1372. Williams, C.E. and Stevens, K.N. (1972) Emotions and speech: some acoustic correlates. J. Acoust. SOC.Am., 52: 1238-1 250. Winkworth, A.L., Davis, P.J., Adams, R. and Ellis, E. (1994) Variability and consistency in speech breathing during reading: lung volumes, speech intensity, and linguistic factors. J. Speech Hearing Res., 37,535-556. Winkworth, A.L., Davis, P.J., Ellis, E. and Adams, R. (1995)
325 Breath patterns during spontaneous speech. J. Speech Hearing Res., 38: 124-144. Woods, J.W. (1964) Behavior of chronic decerebrate rats. J. Neurophysiol., 27: 635-644. Zhang, S.P., Davis, P.J., Carrive, P. and Bandler, R. (1992) Vocalization and marked pressor effect evoked by excitation of neurons in the nucleus retroambigualis of the cat. Neurusci. Leu.,140: 103-107.
Zhang, S.P.,Davis, P.J., Bandler, R. and Carrive, P. (1994) Brain stem integration of vocalization: role of the midbrain periaqueductal gray. J. Neuruphysiul., 72: 1337-1356. Zhang, S.P., Davis, P.J. and Bandler, R. (1995) Brain stem integration of vocalization: role of the nucleus retroambigualis. J. Neurophysiol., 74: 2500-25 12.