fMRI study of brain activity elicited by oral parafunctional movements.

Parafunctional masticatory activity, such as the tooth clenching and grinding that is associated with bruxism, is encountered by clinicians in many disciplines, including dentistry, neurology and psychiatry. Despite this, little is known about the neurological basis for these activities. To identify the brain network engaged in such complex oromotor activity, functional magnetic resonance imaging (fMRI) was used to elucidate the brain activation patterns of 20 individuals (10 males and 10 females, mean s.d. age of 26.3+/-4.1 years) with (parafunctional, PFx group, 5M/5F) and without (normal functional, NFx group, 5 M/5F) self-reported parafunctional grinding and clenching habits during clenching and grinding tasks. Subject group classification was based on: (i) self-reported history, (ii) clinical examination, (iii) evaluation of dental casts and (iv) positive responses to the temporomandibular disorder (TMD) History Questionnaire [Dworkinand LeResche, Journal of Craniomandibular Disorders, (1992) 6:301]. While subjects performed these oromotor tasks, each wore a custom-designed oral appliance minimizing head motion during imaging. Mean per cent signal changes showed significant between group differences in motor cortical (supplementary motor area, sensorimotor cortex and rolandic operculum) and subcortical (caudate) regions. Supplementary motor area data suggest that motor planning and initiation, particularly during the act of clenching, are less prominent in individuals with oromotor parafunctional behaviours. The overall extent of activated areas was reduced in subjects with self-reported parafunctional masticatory activity compared with the controls. This study's methodology and findings provide an initial step in understanding the neurological basis of parafunctional masticatory activities that are relevant for therapeutic research applications of temporomandibular joint and muscle disorders and associated comorbidities.

Effects of post-natal serotonin levels on craniofacial complex.

Although the role of serotonin (5-hydroxytryptamine or 5-HT) in pre-natal craniofacial growth and development has been studied, no research has been done on the effects of serotonin on post-natal craniofacial growth and development. The following experimental question was tested: What effect does increasing in vivo serotonin levels adjacent to trigeminal motoneurons have on post-natal craniofacial structures in young, actively growing rats? Forty male Sprague-Dawley rats were divided into 4 experimental groups (10% serotonin microspheres, 15% serotonin microspheres, blank microspheres, sham surgeries) and underwent stereotactic neurosurgery at post-natal day 35; 5 rats of each group were killed at 14 and 21 post-surgical days for data collection. Statistical analyses by mixed-model, 4 x 2 repeated-measures ANOVA, and post hoc Fisher LSD tests revealed significant (P < or = 0.05, 0.01) differences between groups and sides for muscle weight, cranial dimension, and TMJ dimension data. Data described here indicate that significant alterations of post-natal craniofacial structures can be caused by altered in vivo levels of serotonin adjacent to trigeminal motoneurons.

Increased in vivo levels of neurotransmitters to trigeminal motoneurons: effects on craniofacial bone and TMJ.

The results of chronic, in vivo delivery of excitatory and inhibitory neurotransmitter substances upon the craniofacial skeleton are of ongoing interest to clinician and basic scientist alike. Our purpose was to document and compare the effects of biodegradable glycine, glutamate, and thyrotropin-releasing hormone (TRH) microspheres upon the craniofacial skeleton and TMJ of actively growing rats. Glycine, glutamate, TRH, and blank microspheres were stereotactically implanted in proximity to motoneurons within the trigeminal motor nucleus in order to test the following null hypotheses: (1) neurotransmitter microspheres implanted near trigeminal motoneurons of growing rats have no significant effect on the craniofacial skeleton and temporomandibular joints of implanted animals, and (2) there are no significant differences between the relative effects of glutamate, TRH (excitatory to trigeminal motoneurons), and glycine (inhibitory to trigeminal motoneurons) implants upon the craniofacial skeleton and temporomandibular joint. Fifty male Sprague-Dawley rats underwent stereotactic neurosurgery at 35 days; five rats each were killed at 14 and 21 days postoperative for data collection and comparison between glycine-, glutamate-, TRH-, blank-microsphere, and sham-surgery rats. Glycine rats had significantly (P < or = 0.05, 0. 01) smaller implant-side cranial dimensions and mandibular condyles, all glycine rats showed increased gracility of implant-side bones, and deviation of their facial skeleton away from the implant-side; this was in contrast to the generally larger implant-side bony structures in both glutamate and TRH rats. The two null hypotheses were both rejected. Due to their inhibitory and excitatory effects upon trigeminal motoneurons, masticatory muscles, and their neuromuscular generation of biomechanical forces that affect bone, the neurotransmitter substances glycine, glutamate, and TRH appear to play an important role in the growth and development of the mammalian craniofacial skeleton and TMJ.

Prolonged seizure suppression by a single implantable polymeric-TRH microdisk preparation.

Thyrotropin-releasing hormone (TRH; Protirelin) is an endogenous neuropeptide known to have anticonvulsant effects in several seizure models and in intractable epileptic patients. Like most neuropeptides, its duration of action may be limited by a lack of sustained site-specific bioavailability. To attempt to provide long-term delivery, we attached TRH to a biodegradable polyanhydride copolymer as a sustained-release carrier. Utilizing the rat kindling model of temporal lobe epilepsy, a single TRH microdisk implanted stereotaxically into the seizure focus (amygdala) significantly suppressed kindling expression when assessed by the number of stimulations required to reach each behavioral stage and to become fully kindled (8.63 +/- 0.92 vs. 16.17 +/- 1.37; Mean +/- S.E.M.). Two indices of seizure severity, afterdischarge duration (Mean +/- S.E.M., sec.) (stimulated amygdala [87.40 +/- 5.47 vs. 51.80 +/- 15.65] and unstimulated amygdala [89.60 +/- 5.55 vs. 48.67 +/- 15.8] and clonus duration (71.2 +/- 5.94 vs. 29.40 +/- 8.87; Mean +/- S.E.M., sec.), were also significantly reduced by a single polymeric-TRH implant. Fifty days after initiation of the study a significant reduction in clonus duration (53.90 +/- 3.27 vs. 40.09 +/- 4.14) still remained in the TRH-implanted groups. This report is the first to provide evidence in support of in situ microdisk pharmacotherapy for potential neuropeptide delivery in intractable epilepsy and possibly other neurological disorders.

Oxidative capacity of rat masseter muscle after implantation of thyrotropin-releasing hormone microspheres in proximity to trigeminal motoneurones.

Earlier work has shown that two important consequences of implanting thyrotropin-releasing hormone (TRH) microspheres near motoneurones within the trigeminal motor nucleus of actively growing rats are increased muscle mass and a darkening of the implant-side masticatory muscles. These phenomena have been associated with altered neuromuscular activity patterns and biomechanical forces that directly influence craniofacial growth and development. Now, whether the implantation of TRH microspheres in proximity to trigeminal motoneurones would affect the oxidative capacity of the implant-side masseter muscles was investigated. Cytochrome C oxidase (COX) assays were carried out for both implant- and non-implant-side masseters of TRH (n = 5) and blank microsphere (n = 6) Sprague-Dawley rats after stereotactic surgery at 35 days of age. Analyses of both groups at 14 days post-implantation revealed that the COX activity levels of implant-side masseters in TRH-implanted rats was significantly (P< or =0.05) greater than that of non-implant-side masseters; rats implanted with blank microsphere exhibited no significant difference between implant- and non-implant-side masseter COX activity levels. The stated null hypothesis was therefore rejected. These data suggest that TRH implants in proximity to trigeminal motoneurones effect increased oxidative capacity of the masseter muscle as measured by COX activity.

Craniofacial and TMJ effects after glutamate and TRH microsphere implantation in proximity to trigeminal motoneurons of growing rats.

The sequelae of sustained, in vivo delivery of two important neurotransmitter substances, glutamate and thyrotropin-releasing hormone (TRH), upon craniofacial growth and development have previously not been investigated. Our purpose was to document and compare the relative effects of glutamate and TRH microspheres stereotactically placed in proximity to trigeminal motoneurons within the trigeminal motor nucleus. The following null hypotheses were tested: (1) TRH microspheres in proximity to trigeminal motoneurons have no significant effect upon the craniofacial skeleton, and (2) there are no significant differences between the relative effects of chronic, long-term delivery of glutamate and TRH upon the neuromusculoskeletal system of growing rats. Forty male Sprague-Dawley rats were divided into 4 experimental groups (glutamate microspheres, TRH microspheres, blank microspheres, sham surgeries) and underwent stereotactic neurosurgery at 35 days; 5 rats of each group were killed at 14 and 21 days for data collection. Histology revealed that implants were clustered in the pontine reticular formation, close to the ventrolateral tegmental nucleus. Both glutamate and TRH rats had implant-side deviation of their facial skeleton and snout regions; 4 x 2 ANOVA and post hoc t-tests revealed significant (P < or = 0.05, 0.01) differences between groups and sides for motoneuron count, muscle weight, and osteometric data. TRH rats also demonstrated larger implant-side TMJ discs and mandibular fossae in comparison with the other groups. The stated null hypotheses were therefore rejected.

Characterization of brux-like movements in the laboratory rat by optoelectronic mandibular tracking and electromyographic techniques.

High-resolution optoelectronic mandibular tracking and fine-wire electromyographic (EMG) data from the anterior temporalis muscles of laboratory rats (Rattus norvegicus) were collected during mastication (chewing) and bruxing/thegosis (grinding sharpening of teeth) in order to test for task-related activity patterns of the anterior temporalis. Analyses of the collected data revealed that masticatory and bruxing/thegosis cycles displayed significantly different patterns of movement trajectories, displacement, duration, velocity, and acceleration in all three spatial dimensions (frontal vertical, frontal horizontal and sagittal horizontal). Activity patterns in the anterior temporalis during masticatory and bruxing/thegosis behaviours were also significantly different from each other. High-resolution analyses revealed that the masticatory cycle had both opening-burst and closing-burst phasic patterns of anterior temporalis activity while the bruxing/thegosis cycle displayed only opening-burst phasic patterns. The opening- and closing-burst attributes of anterior temporalis phasic activity patterns in relation to physiological centric occlusion also revealed significant differences between masticatory and bruxing/thegosis behaviours. These data demonstrate that the anterior temporalis muscle of the laboratory rat does indeed display task-related activity patterns depending upon the manifested oral behaviour. The task-related shifts of EMG patterns in the anterior temporalis between masticatory bruxing/thegosis behaviours in the same animal suggests a complex neurophysiological substrate that coordinates the three-dimensional expression of phasic activity patterns in the muscle. The radically different nature of masticatory and bruxing/thegosis cycles and their associated EMG patterns in the anterior temporalis suggest the possible existence of a bruxing/thegosis pattern generator in addition to the masticatory one. Careful, high-resolution analyses of these rat behaviours by combined optoelectronic/EMG techniques suggest that the rat model for human bruxism may prove useful in future studies.

Organization and nucleotide sequence of the rat T cell receptor beta-chain complex.

We have characterized four overlapping genomic clones containing the DA rat TCR C beta complex, which span a total of 23 kb and bear two closely related complexes of gene segments. The D beta 1-J beta 1-C beta 1 and the D beta 2-J beta 2-C beta 2 complexes each contain a single diversity segment, six joining segments and four exons that encode the C region. All gene segments appear to be functional except J beta 2.5, which has a 5-bp frame-shifting deletion. This organizational pattern is identical to that of the mouse, and the homologous rat and mouse coding regions share about 92% nucleotide sequence identity. Our sequence comparisons indicate that a localized gene correction event has homogenized the sequences of the first exons of C beta 1 and C beta 2 in the evolutionary time since rats and mice became separate species. We have identified three repetitive elements, each flanked by short direct repeats, present in the region "brain-specific" identifier (ID) sequences, another is a truncated member of the LINE I class of repetitive elements, and the third is a member of the Alu type 2 family. The insertion of at least two, and probably all, of these elements has occurred since the time of rat/mouse divergence. We have identified a substantial number of "cryptic" rearrangement signals (heptamer/nonamer) in the C beta locus, which match the consensus sequence as well or better than authentic signals, and may represent sites of nonfunctional rearrangements.

Effects of lesions to the trigeminal motor nucleus on temporomandibular disc morphology.

Stereotaxic surgery was performed on the trigeminal motor nuclei (TMNu) of 47 actively growing rats in order to test the effects of neuromuscular alterations on TMJ disc morphology. Lesioned animals received a small electrolytic lesion to their left-side TMNu, while shams had their TMNu stimulated without an actual lesion being produced. Both lesioned and sham-lesioned animals demonstrated significant (P less than 0.05; P less than 0.01) morphological alterations of their discs 28, 56, and 84 days postoperatively. Data indicated that (i) TMNu lesions do indeed affect disc morphology, and (ii) even subtle damage to trigeminal motoneurones can influence TMJ disc morphology. It is therefore suggested that at least some TMJ disease processes have a neuromuscular basis.

Craniofacial alterations following electrolytic lesions of the trigeminal motor nucleus in actively growing rats.

The objective of this study was to define further the role of the trigeminal motor nucleus (TMNu) in the postnatal ontogeny of the mammalian craniofacial skeleton. To that end, 42 male Sprague-Dawley rats underwent stereotaxic surgery at 40 days of age; 21 received small electrolytic lesions to their left-side TMNu (lesioned group) while 21 had TMNu stimulation with no actual electrolytic lesion produced (sham group). Seven rats from each group were killed at 28, 56, and 84 days postoperative to analyze trigeminal motoneuron (TMNe) count, masticatory muscle weight, and osteological growth vector data. At all three time periods, lesioned animals showed significant differences 1) between the surgery and nonsurgery sides, and 2) from sham animals. However, sham animals also demonstrated significant between-side differences for medial pterygoid muscle weight (56 days), mandibular height (28 and 56 days), and mandibular length data (84 days); these data suggested that even relatively slight damage to TMNe can create morphological changes within the craniofacial complex. Snout deviation in a lesioned rat towards the opposite side from all other lesioned animals was correlated with unique damage to its pontine reticular formation; this suggested that the observed morphological alterations of the craniofacial complex may have been due not only to TMNu damage, but also to changed expressions of the masticatory central pattern generator (CPG). Morphological alterations of the craniofacial skeleton resulting from lesions to the TMNu were likely due to changed neuromuscular activity patterns of the masticatory muscles and their biomechanical effects upon bone.

Differences in tooth wear as an indicator of changes in jaw movement in the guinea pig Cavia porcellus.

Patterns of tooth wear have frequently been used to make inferences about jaw movements and tooth use in modern and extinct mammals. However, there has been relatively little experimental work to define the limits of usefulness of tooth wear studies. In the present study, electrolytic lesions in the left trigeminal motor nucleus of five guinea pigs resulted in significant changes of jaw movement. Scanning electron microscopy revealed significant differences in tooth wear between the lesion and non-lesion sides of these animals. Control animals showed no significant differences in tooth wear between right and left sides. The differences in tooth wear in the experimental animals were readily interpretable in terms of the induced changes in jaw movement.

Loci and characteristics of EMG silent periods during masticatory mandibular movements in rats.

Frontal plane mandibular movements and the associated superficial masseter EMG signals of six 39-day-old rats were simultaneously recorded and digitized at a rate of 1 kHz by the optoelectronic method in order to investigate the loci and attributes of masseteric silent periods during mastication of hard (pellets) and soft (slurry) food items. The marked silent periods, defined as cessations of EMG activity during the slow-close (SC) phase of single chewing cycles, were analyzed for their (1) onset and offset durations relative to physiological centric occlusion (PCO), (2) frontal vertical (FV) and frontal horizontal (FH) loci relative to PCO, and (3) FV and FH velocities and accelerations of masticatory mandibular movements in relation to PCO. The start (SSP) and end (ESP) of silent period loci relative to PCO moved superiorly as sequences of pellet mastication progressed. All silent period attributes during slurry consumption were significantly different (p less than or equal to 0.01) from pellet attributes: Slurry SSP and ESP loci were closer to PCO than were pellet loci; durations of silent period loci during pellet mastication were more variable than were slurry durations. FV distance and velocity values for pellets were greater than with pellets. Although FV velocities during both pellet and slurry mastication decreased at ESP relative to SSP values, their FH velocities at ESP actually increased relative to SSP velocities. Loci attributes of EMG silent periods appeared largely dependent on the consistency of the food item being masticated.

Craniofacial sequelae of lesions to facial and trigeminal motor nuclei in growing rats.

Unilateral electrolytic lesions were made in the left-side facial motor nucleus (FMNu) of six Sprague-Dawley rats at 35 days of age in order to correlate craniofacial sequelae with changed motoneuron function. Experimental and control rats were killed at 22, 32, 42, and 52 days postoperatively to provide muscle weight, brain histology, and dry skull preparations for analyses. Dissection, muscle weight, motoneuron count, and osteometric data revealed that lesion-side facial and masticatory muscles were affected by the lesions. Paired t-tests indicated that significant differences existed between weights of experimental lesion- and nonlesion-side anterior digastric, temporalis, masseteric complex, and medial pterygoid muscles, numbers of facial and trigeminal motoneurons, and several skeletal dimensions of the skull. Basi-cranial dimensions of experimental animals were least affected by the lesion, whereas zygomatic arch, dorsal facial region, and mandibular condyle dimensions were most affected. Statistical analyses also detected significant differences between experimental and control groups for several skeletal dimensions of the skull. Data indicated that damage to the trigeminal motor nucleus (TMNu) was secondary to the primary lesion in the FMNu. Motoneurons within the facial and trigeminal neuromuscular complexes (FNC and TNC) play an important role in craniofacial growth and development.

Three-dimensional movement analysis of lateral pterygoid electromyographic activity during mastication in the rat.

Simultaneous recordings of mandibular movement in three dimensions (frontal, horizontal and sagittal plane), and lateral pterygoid electromyographic (EMG) data during mastication of pellets and slurry, were collected from 5 rats by the opto-electronic mandibular tracking (OMT) method and computerized digital-processing of the EMG wave-forms. The microcomputer analyses allowed determination of frontal-, horizontal- and sagittal-plane movement displacements and velocities for whole chew cycles and, during lateral pterygoid activity, opening burst (OB) and closing burst (CB) latencies. There were significant (p less than or equal to 0.01) differences between duration, displacement and velocity data from slurry and pellet chew cycles. OB latencies were significantly (p less than or equal to 0.01) longer than CB, and OB displacements started significantly (p less than or equal to 0.01) farther from minimal gape than CB ones. Working-side OB activity occurred as the mandible moved inferiorly, laterally and posteriorly; working-side CB activity occurred as the mandible moved superiorly, medially and anteriorly. A secondary peak of OB activity, coinciding with anterior sagittal translation during the last third of mandibular depression, was detected; this may represent independent activity of the rat superior lateral pterygoid effecting anterior translation of the mandibular-joint disc and capsule. Rat lateral pterygoid activity has the same basic, bimodal pattern (active during both mandibular depression and elevation) as is found in humans.

Opto-electronic analyses of masticatory mandibular movements and velocities in the rat.

High-speed, high-resolution data (frontal plane) were collected from 6 Sprague-Dawley rats by opto-electronic mandibular tracking (OMT), followed by microcomputer analysis of individual chew cycles. Mastication comprised rapidly alternating, unilateral cycles with variable degrees of lateral translation. There was no evidence of bilateral mastication (simultaneous chewing on both left and right sides). Analysis revealed significant (p less than or equal to 0.01) differences between whole-cycle, slow-open (SO) phase, fast-open (FO) phase, fast-close (FC) phase, and slow-close (SC) phase duration, height, width, and velocity during mastication of standardized foods (pellets and slurry). Regression analysis between millimetres of vertical/horizontal movement (Y) and vertical/horizontal velocity (X) revealed differences during these mastications. Whole-cycle and SO-phase regression equations had the greatest disparity between pellet and slurry chewing for both vertical and horizontal movements. Correlation coefficient analysis between movement and velocity data indicated that (1) vertical correlations were smaller than horizontal ones, (2) slurry correlations were greater than pellet ones except for whole cycles, (3) FO phase had the largest movement/velocity correlation during both pellet and slurry mastication, and, that (4) SC phase had the smallest movement/velocity correlation. Vertical and horizontal movements during pellet FC phase were significantly (p less than or equal to 0.01) greater than slurry ones; both vertical and horizontal movements during pellet SC phase were significantly (p less than or equal to 0.01) less than slurry ones. This phase-isostasy was also detected during vertical movements in SO and FO phases.(ABSTRACT TRUNCATED AT 250 WORDS)

Masticatory movements and EMG activity following electrolytic lesions of the trigeminal motor nucleus in growing guinea pigs.

Unilateral electrolytic lesions were produced in the left trigeminal motor nucleus (TMN) of six guinea pigs at 49 days of age. Masticatory mandibular movement and EMG data were collected prior to lesioning and at 4 and 12 days postlesion. After the animals were killed 60 days postlesion, dissection and maceration revealed muscular atrophy and craniofacial asymmetries on the lesion side. Analyses of prelesion and postlesion mandibular movement and EMG data indicated significant (p less than 0.05; p less than 0.01) changes in chew cycle durations, dimensions, and EMG activity patterns. Shifts in EMG durations of working- and balancing-side muscles were strongly related to most of the observed skeletal asymmetries. Data indicated that muscular paresis and altered neuromuscular activity can effect skeletal changes in the mammalian craniofacial complex; total muscular paralysis is not a prerequisite for profound morphologic changes. Altered manifestation of masticatory central pattern generators within the central nervous system may also account for variations in craniofacial form and function.

Mandibular movement and muscle activity during mastication in the guinea pig (Cavia porcellus).

Optoelectronic analysis of mandibular movement and electromyography (EMG) of masticatory muscles in Cavia porcellus indicate bilateral, unilateral, and gnawing cycles. During bilateral and unilateral cycles, the mandibular tip moves forward, lateral, and down during the lingual phase of the power stroke to bring the teeth into occlusion. EMG activity is generally asymmetric, with the exception of activity of the temporalis muscle during bilateral cycles. During gnawing cycles, the mandible moves in an anteroposterior direction that is opposite that during bilateral and unilateral chew cycles. Bilateral and unilateral cycles of pellets were significantly longer than carrot. With the exception of the width of bilateral cycles, the magnitude of cycle width, length, and height during the mastication of carrots was greater than that during the mastication of pellets. Significant differences exist between EMG durations during mastication of pellets and carrots. The lateral pterygoid displays continuous activity during gnawing cycles. Significant differences also exist in the duration of EMG activity between the working and balancing side during all three cycle types. High level of activity of balancing side temporalis and anterior belly of digastric (ABD) during bilateral cycles occurs during rotation and depression of the mandible during the power stroke. The temporalis apparently provides a "braking" or compensatory role during closing and power strokes. Differences between Cavia masticatory patterns and those shown by Rattus and Mesocricetus are apparently due to differences in dental morphology, occlusal relationships, and, possibly, the poorly developed temporalis in Cavia. The large number and wide diversity of rodent groups afford students of mammalian mastication an opportunity to investigate and compare different masticatory specializations.

Cerebellar ablation and mastication in the guinea pig (Cavia porcellus).

The jaw movements of 3 subadult guinea pigs were recorded before and after cerebellar ablation with the aid of an optoelectronic tracking system. Despite overall ataxia of the animals' body and limbs, masticatory patterns were essentially normal. The major effects of cerebellar ablation upon Cavia mastication were a statistically significant (P < 0.01) increase in chew cycle duration and a decrease in chew duration variability.