Quantitative Analysis of Orofacial Development and Median Clefts in Xenopus Laevis

Xenopus has become a useful tool to study the molecular mechanisms underlying orofacial development. However, few quantitative analyses exist to describe the anatomy of this region. In this study we combine traditional facial measurements with geometric morphometrics to describe anatomical changes in the orofacial region during normal and abnormal development. Facial measurements and principal component (PC) analysis indicate that during early tadpole development the face expands primarily in the midface region accounting for the development of the upper jaw and primary palate. The mouth opening correspondingly becomes flatter and wider as it incorporates the jaw elements. A canonical variate analysis of orofacial and mouth opening shape emphasized that changes in the orofacial shape occur gradually. Orofacial anatomy was quantified after altered levels of retinoic acid using all‐trans retinoic acid or an inhibitor of retinoic acid receptors or by injecting antisense oligos targeting RALDH2. Such perturbations resulted in major decreases in the width of the midface and the mouth opening illustrated in facial measurements and a PC analysis. The mouth opening shape also had a gap in the primary palate resulting in a median cleft in the mouth opening that was only illustrated quantitatively in the morphometric analysis. Finally, canonical and discriminant function analysis statistically distinguished the orofacial and mouth opening shape changes among the different modes used to alter retinoic acid signaling levels. By combining quantitative analyses with molecular studies of orofacial development we will be better equipped to understand the complex morphogenetic processes involved in palate development and clefting. Anat Rec, 297:834–855, 2014. © 2014 Wiley Periodicals, Inc.     

Association of orofacial with laryngeal and respiratory motor output during speech

Speech motor coordination most likely involves synaptic coupling among neural systems that innervate orofacial, laryngeal, and respiratory muscles. The nature and strength of coupling of the orofacial with the respiratory and laryngeal systems was studied indirectly by correlating orofacial speeds with fundamental frequency, vocal intensity, and inspiratory volume during speech. Fourteen adult subjects repeated a simple test utterance at varying rates and vocal intensities while recordings were obtained of the acoustic signal and movements of the upper lip, lower lip, tongue, jaw, rib cage, and abdomen. Across subjects and orofacial speed measures (14 subjects x 4 structures), significant correlations were obtained for fundamental frequency in 42 of 56 cases, for intensity in 35 of 56 cases, and for inspiratory volume in 14 of 56 cases. These results suggest that during speech production there is significant neural coupling of orofacial muscle systems with the laryngeal and respiratory systems as they are involved in vocalization. Comparisons across the four orofacial structures revealed higher correlations for the jaw relative to other orofacial structures. This suggests stronger connectivity between neural systems linking the jaw with the laryngeal and respiratory systems. This finding may be relevant to the frame/content theory of speech production, which suggests that the neural circuitry involved in jaw motor control for speech has evolved to form relatively strong linkages with systems involved in vocalization.     

A study on synaptic coupling between single orofacial mechanoreceptors and human masseter muscle

The connection between individual orofacial mechanoreceptive afferents and the motoneurones that innervate jaw muscles is not well established. For example, although electrical and mechanical stimulation of orofacial afferents in bulk evokes responses in the jaw closers, whether similar responses can be evoked in the jaw muscles from the discharge of type identified single orofacial mechanoreceptive afferents is not known. Using tungsten microelectrodes, we have recorded from 28 afferents in the inferior alveolar nerve and 21 afferents in the lingual nerve of human volunteers. We have used discharges of single orofacial afferents as the triggers and the electromyogram (EMG) of the masseter as the source to generate spike-triggered averaged records to illustrate time-based EMG modulation by the nerve discharge. We have then used cross correlation analysis to quantify the coupling. Furthermore, we have also used coherence analysis to study frequency-based relationship between the nerve spike trains and the EMG. The discharge patterns of the skin and mucosa receptors around the lip and the gingiva generated significant modulation in EMGs with a success rate of 40% for both cross correlation and coherence analyses. The discharge patterns of the periodontal mechanoreceptors (PMRs) generated more coupling with a success rate of 70% for cross correlation and about 35% for coherence analyses. Finally, the discharges of the tongue receptors displayed significant coupling with the jaw muscle motoneurones with a success rate of about 40% for both analyses. Significant modulation of the jaw muscles by single orofacial receptors suggests that they play important roles in controlling the jaw muscle activity so that mastication and speech functions are executed successfully.     

The tongue as a factor in craniofacial growth. 4. Results of animal experiments

Post-natal craniofacial growth in the miniature pig MIN-LEWE is influenced by the tongue in various ways. Periodic and locally differentiated intensive craniofacial growth explains why the tongue has a measurable effect on jaw growth only at certain times. This is the situation in animals glossectomized at an age of 12 weeks. Shortening of the tongue in miniature pigs aged six weeks resulted in no measurable changes in the jaw after a prolonged post-surgical interval (23 weeks), which indicates that the capacity of the orofacial system during post-natal development is considerable.     

Voluntary control of human jaw stiffness

Recent studies of human arm movement have suggested that the control of stiffness may be important both for maintaining stability and for achieving differences in movement accuracy. In the present study, we have examined the voluntary control of postural stiffness in 3D in the human jaw. The goal is to address the possible role of stiffness control in both stabilizing the jaw and in achieving the differential precision requirements of speech sounds. We previously showed that patterns of kinematic variability in speech are systematically related to the stiffness of the jaw. If the nervous system uses stiffness control as a means to regulate kinematic variation in speech, it should also be possible to show that subjects can voluntarily modify jaw stiffness. Using a robotic device, a series of force pulses was applied to the jaw to elicit changes in stiffness to resist displacement. Three orthogonal directions and three magnitudes of forces were tested. In all conditions, subjects increased the magnitude of jaw stiffness to resist the effects of the applied forces. Apart from the horizontal direction, greater increases in stiffness were observed when larger forces were applied. Moreover, subjects differentially increased jaw stiffness along a vertical axis to counteract disturbances in this direction. The observed changes in the magnitude of stiffness in different directions suggest an ability to control the pattern of stiffness of the jaw. The results are interpreted as evidence that jaw stiffness can be adjusted voluntarily, and thus may play a role in stabilizing the jaw and in controlling movement variation in the orofacial system.     

The tongue as a factor in craniofacial growth. 2. The influence of the width dimension of the lower jaw

The role played by the tongue in orofacial growth is also indicated by the reduced width of the lower jaw. In miniature pigs MINI-LEWE that were partially glossectomized at an age of 12 weeks lateral growth of the whole lower jaw was reduced after eight months. In animals that had been glossectomized at an age of six weeks lateral growth of the lower jaw was reduced in the region of the 1st deciduous molars and the canines right months after glossectomy.     

Demystifying ritual abuse - insights by self-identified victims and health care professionals

ABSTRACT

Empirical evidence on organized and ritual child sexual abuse (ORA), that is, organized child sexual abuse with an ideological framework, is rare and definitions of the term “ritual” are often vague or inhomogeneous. The aim of the current study is to analyze contents, purposes and acts of violence in ORA.

In a project of the Independent Inquiry into Child Sexual Abuse in Germany, 165 adults who identified themselves as ORA victims as well as 174 health care professionals who supported ORA victims were recruited via various sources and completed anonymous online surveys.

Both samples report experiences with ideological frameworks in organized child sexual abuse contexts at the same ratio (88%). Ideologies are mostly perceived as a means to facilitate violent acts (e.g. commercial sexual exploitation). Positive correlations between the manifestation of ideologies and all violent acts suggest that organized and ritual perpetrator groups use the same violent strategies, but ritual or ideological groups, in which perpetrators are more often family members, use them to a greater extent.

A modified narrative of “ritual abuse” as a (pseudo-)ideological, domestic and more violent subtype of organized child sexual abuse could enhance the credibility and visibility of ORA in science as well as in society.     

Differential involvement of cyclase- versus non-cyclase-coupled D1-like dopamine receptors in orofacial movement topography in mice: Studies with SKF 83822

Though orofacial movements are fundamental motor patterns that are known to be regulated critically by D₁-like dopamine receptors, these processes remain poorly understood. This uncertainty is heightened by evidence for putative D₁-like receptors that are linked not only to adenylyl cyclase (AC) but also to phospholipase C (PLC). Using a new method, we have characterised four topographies of orofacial movement in the mouse using the novel D₁-like agonist SKF 83822, which stimulates AC but not PLC. These were compared with responses to SKF 83959, which stimulates PLC but not AC. Also, effects were characterised using the D₁-like antagonist SCH 23390 and the D₂-like antagonist YM 09151-2. SKF 83822 induced vertical jaw movements with incisor chattering but inhibited horizontal jaw movements; there was little effect on tongue protrusions. Vertical jaw movements induced by SKF 83822 were inhibited by SCH 23390 but uninfluenced by YM 09151-2, while YM 09151-2 released horizontal jaw movements; thus, D₁-like agonist-induced, AC-mediated vertical jaw movements constitute a ‘pure’ D₁-like-dependent process that does not involve D₁-like:D₂-like interactions, while horizontal jaw movements involve oppositional interactions. Orofacial movements in mice appear to consist of at least four phenomenologically dissociable topographies that are mechanistically distinct. They are regulated differentially by AC- and/or PLC-dependent processes and these processes involve distinct D₁-like:D₂-like interactions.     

Spontaneous facial motility in infancy: a 3D kinematic analysis

Early spontaneous orofacial movements have rarely been studied experimentally, though the motor experiences gained from these behaviors may influence the development of motor skills emerging for speech. This investigation quantitatively describes developmental changes in silent, spontaneous lip and jaw movements from 1 to 12 months of age using optically based 3D motion capture technology. Twenty-nine typically developing infants at five ages (1, 5, 7, 9, and 12 months) were studied cross-sectionally. Infants exhibited spontaneous facial movements at all ages studied. Several age-related changes were detected in lip and jaw kinematics: the occurrence of spontaneous movements increased, movement speed increased, the duration of movement epochs decreased and movement coupling among different facial regions increased. Additionally, evidence for stereotypic movements was not strong. The present findings suggest that, during the first year of life, early spontaneous facial movements undergo significant developmental change in the direction of skill development for speech.     

Rocker jaw: Global context for a Polynesian characteristic

Our goal is to describe the global distribution of the “rocker jaw” variant in human populations. Rocker jaw refers to mandibles that lack the antegonial notch, making them unstable on a flat surface. Data were collected by C.G. Turner II on 9,207 individuals from Asia, Europe, the Pacific, and the Americas, and by J.D. Irish on 3,526 individuals from North and South Africa. With a focus on Polynesia, where the trait is most common, frequencies are presented for subdivisions of Oceania, Australasia, Eurasia, the Americas, and Africa. While the rocker jaw is a Polynesian characteristic, the trait is found throughout the world. Within major geographic regions, there are interesting contrasts, for example, (a) the similarity of Jomon and Ainu and their difference from modern Japanese; (b) Aleuts and Northwest Coast Indians are similar and both are distinct from the Inuit and other Native Americans; and (c) North and Sub-Saharan Africans show a regional difference that parallels genetic and dental distinctions. Skeletons in South America that exhibit the rocker jaw have been interpreted as Polynesian voyagers who ventured to the west coast of South America. The rarity of rocker jaw in South American natives supports this view. The rocker jaw can be attributed to the unique basicranium morphology and large upper facial height of Polynesians, which highlights the integrated growth of a functional module (i.e., mastication) of the craniofacial complex. The unusually high frequency of the trait in Polynesians is a product of both function and founder effect/genetic drift.     

Effect of occlusal appliance wear on chewing in persons with Down syndrome

The effects of Down syndrome (DS) include orofacial dysmorphology with neuro-motor difficulties and inter-maxillary discrepancy. It is unclear whether improving the inter-arch relationship would suffice to overcome feeding difficulties in persons with DS. This randomized, double-blind, placebo-controlled crossover study is a first step in evaluating the impact of wearing an orthetic intra-oral appliance on chewing variables in 8 subjects with DS (4 males and 4 females; mean age: 27.6+/-6.1 years). The primary chewing variables were measured through video and electromyographic (EMG) recordings. Secondary variables were (i) modifications in oral health status using the oral assessment for Down syndrome (OADS) questionnaire, (ii) number of inter-arch contacting units (ICUs), (iii) subjects' compliance in wearing the appliance and (iv) subjects' preference between placebo and occlusal appliances. The simultaneous use of EMG and video recordings revealed the presence of lower jaw movements not corresponding to EMG activities in the masticatory muscles. Compared with the pre-treatment situation, wearing an occlusal appliance decreased chewing frequency and increased masticatory time. It is not known whether these changes were indicative of an improvement or a worsening of masticatory function. Persons with DS did not fully adapt to changes in food hardness. A large inter-subject variability was noted, but pre-treatment individual values were not predictive of appliance effect. The maintenance of the number of ICUs obtained at the first installation of appliance and the responses to OADS and satisfaction questionnaires suggested that patients felt more comfortable and that jaw and tongue protrusion were reduced with the appliance.     

Neural activities in the substantia nigra modulated by stimulation of the orofacial motor cortex and rhythmical jaw movements in the rat

Neurons related to jaw movements in the substantia nigra pars reticulata were explored by examining changes in their neural activities in response to electrical stimulation of the orofacial sensorimotor cortex and during rhythmical jaw movements induced by mechanical stimulation applied to the oral cavity in the rat. Out of 80 neurons tested, 59 showed changes in their firing patterns of activities in response to the electrical stimulation of the cortex. The responding neurons were mainly located in the dorsolateral part of the substantia nigra pars reticulata. The substantia nigra pars reticulata neurons showing responses were classified into the following five types according to their response patterns: (1) an inhibition preceded by an early excitation and followed by a late excitation (n = 26), (2) an inhibition preceded by an early excitation but not followed by a late excitation (n = 7), (3) an inhibition not preceded by an early excitation but followed by a late excitation (n = 2), (4) an inhibition without early or late excitations (n = 7) and (5) an excitation without an inhibition (n = 17). Out of 18 neurons responding to the cortical stimulation, 11 (61.1%) increased or decreased their neural activities during rhythmical jaw movements. Some of these neurons had a projection to the lateral part of the superior colliculus (n = 5) and/or to the parvicellular reticular formation (n = 2). These results provide first neurophysiological evidence for neurons in the dorsolateral part of the substantia nigra pars reticulata with inputs from and outputs to the areas related to jaw movements. These neurons may participate in the control of jaw movements in the rat.     

Velocity curves of human arm and speech movements

Summary The velocity curves of human arm and speech movements were examined as a function of amplitude and rate in both continuous and discrete movement tasks. Evidence for invariance under scalar transformation was assessed and a quantitative measure of the form of the curve was used to provide information on the implicit cost function in the production of voluntary movement. Arm, tongue and jaw movements were studied separately. The velocity curves of tongue and jaw movement were found to differ in form as a function of movement duration but were similar for movements of different amplitude. In contrast, the velocity curves for elbow movements were similar in form over differences in both amplitude and duration. Thus, the curves of arm movement, but not those of tongue or jaw movement, were geometrically equivalent in form. Measurements of the ratio of maximum to average velocity in arm movement were compared with the theoretical values calculated for a number of criterion functions. For continuous movements, the data corresponded best to values computed for the minimum energy criterion; for discrete movement, values were in the range of those predicted for the minimum jerk and best stiffness criteria. The source of a rate dependent asymmetry in the form of the velocity curve of speech movements was assessed in a control study in which subjects produced simple raising and lowering movements of the jaw without talking. The velocity curves of the non-speech control gesture were similar in form to those of jaw movement in speech. These data, in combination with similar findings for human jaw movement in mastication, suggest that the asymmetry is not a direct consequence of the requirements of the task. The biomechanics and neural control of the orofacial system may be possible sources of this effect.     

Task-related behaviour of motor units in the human temporalis muscle

Muscle activity patterns in some complex human jaw muscles appear to be task sensitive. However, it is presently uncertain how changes in motor task affect motor unit (MU) behaviour in the human temporalis muscle. In this study, activity was recorded from 40 MUs in the anterior region of the muscle. The lowest sustainable firing frequency (LSFF) was reached by slow increases and decreases in firing rate, then firing was maintained at the lowest possible rate without significant pauses. An array of consecutive interspike intervals (ISI) were sampled digitally and used to measure the LSFF for each task associated with the MU. In a controlled paradigm, MU reflex inhibition was measured during the performance of different tasks. Single electrical pulses of non-noxious intensity were delivered to the gingiva near the maxillary canine tooth. During continuous MU firing at a controlled firing frequency of 10 Hz, series of pulses were delivered with increasing delays, after preselected spikes. The MUs fired continuously during the performance of 1–4 postural and tooth-contact tasks. There were significant differences in LSFFs between tasks in those MUs associated with multiple tasks. In the reflex study, all MUs were inhibited, but the magnitude of the inhibition was highly task dependent. Thus, both LSFF and reflex inhibition of temporalis MUs appear to vary with the motor task and are sensitive to the position of the jaw and the direction and location of tooth contact along the tooth row. This behaviour most likely reflects task-related changes in output from orofacial and muscle afferents.     

Encoding of jaw movements by central trigeminal neurons with cutaneous receptive fields

Neurons with orofacial cutaneous receptive fields that responded to jaw movements were recorded in the trigeminal subnucleus interpolaris of the cat. Movement-related neuronal activity was identified by imposing passive ramp and hold stretches of the jaw at four different rates. Thirty-nine neurons with hair (26), skin (9), or convergent (4) receptive fields were studied. Thalamic projection neurons were identified by antidromic stimulation of the ventroposteromedial nucleus of the thalamus. The receptive fields of movement-related hair units included multiple hairs located mainly around the angle of the jaw and chin. The receptive fields of movement-related skin units were smaller than those of hair units and they were located primarily around the angle of the mouth. The convergent units had more than one receptive field that usually included hair or skin. All of the hair units were activated both during opening and closing jaw movements. They typically responded with short bursts of action potentials. Four units with skin receptive fields exhibited similar responses. The five skin units that did not show bursting activity included two that were active during both opening and closing of the jaw, two that were active only during opening, and one that was tonically active during maintained open position. All of the convergent units showed biphasic responses, and three responded with bursts. The maximum discharge rate, the mean discharge rate (mean bursting rate for units with bursting responses), and the total number of spikes per movement were measured. Statistical analysis was performed on these variables to assess functional properties of each unit. The results were used to classify units as velocity, speed, direction, or transient motion detectors. Thirty-three percent of the neurons were trigeminothalamic neurons.     

Correlation of orofacial speeds with voice acoustic measures in the fluent speech of persons who stutter

Stuttering is often viewed as a problem in coordinating the movements of different muscle systems involved in speech production. From this perspective, it is logical that efforts be made to quantify and compare the strength of neural coupling between muscle systems in persons who stutter (PS) and those who do not stutter (NS). This problem was addressed by correlating the speeds of different orofacial structures with vowel fundamental frequency (F0) and intensity as subjects produced fluent repetitions of a simple nonsense phrase at habitual, high, and low intensity levels. It is assumed that resulting correlations indirectly reflect the strength of neural coupling between particular orofacial structures and the respiratory-laryngeal system. An electromagnetic system was employed to record movements of the upper lip, lower lip, tongue, and jaw in 43 NS and 39 PS. The acoustic speech signal was recorded and used to obtain measures of vowel F0 and intensity. For each subject, correlation measures were obtained relating peak orofacial speeds to F0 and intensity. Correlations were significantly reduced in PS compared to NS for the lower lip and tongue, although the magnitude of these group differences covaried with the correlation levels relating F0 and intensity. It is suggested that the group difference in correlation pattern reflects a reduced strength of neural coupling of the lower lip and tongue systems to the respiratory-laryngeal system in PS. Consideration is given to how this may contribute to temporal discoordination and stuttering.     

Chemokine CXCL13 activates p38 MAPK in the trigeminal ganglion after infraorbital nerve injury

Recent data demonstrated that chemokine CXCL13 mediates neuroinflammation and contributes to the maintenance of neuropathic pain after nerve injury in the spinal cord. Pro-nociceptive chemokines activate mitogen-activated protein kinases (MAPKs) which are potential signaling pathways contributing to the nociceptive behavior in inflammatory or neuropathic pain. However, whether activation of p38 and JNK MAPK signaling pathway in the trigeminal ganglion (TG) are involved in CXCL13 and its receptor CXCR5-mediated orofacial pain has not yet been clarified. Here, we show that the unilateral partial infraorbital nerve ligation (pIONL) induced a profound orofacial pain in wild-type (WT) mice. Western blot results showed that pIONL induced p38 but not JNK activation in the TG of WT mice. However, the orofacial pain induced by pIONL was alleviated in Cxcr5 ^?/? mice, and the activation of p38 was also abrogated in Cxcr5 ^?/? mice. Furthermore, intra-TG injection of CXCL13 evoked mechanical hypersensitivity and increased p-p38 expression in WT mice. But CXCL13 had no effect on pain behavior or p-p38 expression in Cxcr5 ^?/? mice. Finally, pretreatment with p38 inhibitor, SB203580, attenuated the pIONL-induced mechanical allodynia and decreased the mRNA expression of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the TG. Taken together, our data suggest that CXCL13 acts on CXCR5 to increase p38 activation and further contributes to the pathogenesis of orofacial neuropathic pain.     

Electromyographic analysis of the ingestion and rejection of sapid stimuli in the rat

Previous behavior studies (Grill & Norgren, 1978) demonstrated that gustatory stimuli produce stereotyped orofacial movements that constitute the observable concomitants of ingestion and rejection. For further clarification of the relation between these orofacial movements (the buccal phase of ingestion) and the act of swallowing (the pharyngeal phase), electromyographic responses to intraoral sapid stimulation were recorded from a subset of orofacial and pharyngeal muscles in a freely moving chronic preparation. Activity in a jaw opening muscle (anterior digastric), a facial muscle (zygomatic), tongue protruder (genioglossus), tongue retractor (styloglossus), and a pharyngeal constrictor used in swallowing (thyropharyngeus) differentiated between ingestive sequences to water (W), sucrose (S), and NaCl (N) and a rejection response elicited by quinine monohydrochloride (Q). Ingestion responses to W, S, and N consisted of rhythmic alterations between genioglossus and styloglossus activity (intraoral licks) accompanied by episodic bursts of pharyngeal constrictor activity (swallowing). Both bout duration and the number of swallows increased at higher concentrations of S and N. In contrast, Q stimulation elicited a rejection response, characterized by several licks and followed by long duration contractions of the zygomatic and anterior digastric muscles (gapes). During gapes, styloglossus activity rather than genioglossus activity was simultaneous with that of the anterior digastric. At higher concentrations of Q, the latency to gape decreased and the latency to swallow increased. The earliest components of the response to S, N, or Q were virtually indistinguishable from one another, results suggesting that tactile (fluid) stimulation initiates the ingestive sequence and that gustatory stimuli modulate this ongoing activity.     

Atherosclerosis in Indians and lipoprotein (a)

Indians, both immigrant or native, are predisposed to develop a cluster of risk factors, and consequently are more prone to manifest CAD as compared to several other ethnic groups. Lipid profile in them is not characterised by hypercholesterolemia, instead the atherogenic profile is denoted by high TG and low HDL-c levels. Lp(a), is a recently discovered important independent and inheritable risk factor for atherosclerosis. It plays an important role in atherogenesis, and acts as a prothrombotic agent as well. Levels of Lp(a) are significantly higher in Indians subjects as well as their offsprings. Thus, Lp(a) is likely to have substantial role in development of early and extensive atherosclerosis in Indians. It is essential to include Lp(a) in battery of tests for evaluation of coronary risk especially in Indians. Further studies shall unravel the full ramifications of adverse effects of this lipoprotein.