Limor Avivi-Arber

Face sensorimotor cortex and its neuroplasticity related to orofacial sensorimotor functions

This review describes evidence in subprimates and primates that the face primary somatosensory cortex (face SI) and primary motor cortex (face MI) are involved in sensorimotor integration and control of orofacial motor functions that include semiautomatic movements (e.g., chewing, swallowing) and voluntary movements (e.g., jaw-opening). The review also notes that the neuroplastic capabilities of the face SI and face MI have recently been documented, and may reflect or allow for functional adaptation (or maladaptation) of the orofacial sensorimotor system to an altered oral state or oral motor behaviour. They may contribute to the processes whereby patients undergoing oral rehabilitation can (or cannot) restore the lost orofacial sensorimotor functions. Such understanding is important since pain, injuries to the oral tissues, and alterations to the dental occlusion induced by tooth loss or attrition are common occurrences in humans that may sometimes be accompanied by impaired oral sensorimotor functions. Furthermore, impaired oral sensorimotor functions are common in many neurological disorders, sometimes making the most vital functions of eating, swallowing and speaking difficult and thereby reducing the patients quality of life. It has also been well documented that such negative consequences can be improved following oral rehabilitation as patients adapt, for example, to a new dental prosthesis aimed at restoring function. Therefore, understanding the mechanisms and cortical neuroplastic processes underlying orofacial sensorimotor functions and adaptation is also important for the development of new therapeutic strategies to facilitate recovery of patients suffering from orofacial pain and sensorimotor disorders and improve their quality of life.

Effects of incisor extraction on jaw and tongue motor representations within face sensorimotor cortex of adult rats

Loss of teeth is associated with changes in somatosensory inputs and altered patterns of mastication, but it is unclear whether tooth loss is associated with changes in motor representations within face sensorimotor cortex of rats. We used intracortical microstimulation (ICMS) and recordings of cortically evoked muscle electromyographic (EMG) activities to test whether changes occur in the ICMS‐defined motor representations of the left and right jaw muscles [masseter, anterior digastric (LAD, RAD)] and tongue muscle [genioglossus (GG)] within the cytoarchitectonically defined face primary motor cortex (face‐M1) and adjacent face primary somatosensory cortex (face‐S1) 1 week following extraction of the right mandibular incisor in anesthetized (ketamine‐HCl) adult male Sprague‐Dawley rats. Under local and general anesthesia, an “extraction” group (n = 8) received mucoalveolar bone surgery and extraction of the mandibular right incisor. A “sham‐extraction” group (n = 6) received surgery with no extraction. A “naive” group (n = 6) had neither surgery nor extraction. Data were compared by using mixed‐model repeated‐measures ANOVA. Dental extraction was associated with a significantly increased number of sites within face‐M1 and face‐S1 from which ICMS evoked RAD EMG activities, a lateral shift of the RAD and LAD centers of gravity within face‐M1, shorter onset latencies of ICMS‐evoked GG activities within face‐M1 and face‐S1, and an increased number of sites within face‐M1 from which ICMS simultaneously evoked RAD and GG activities. Our novel findings suggest that dental extraction may be associated with significant neuroplastic changes within the rats face‐M1 and adjacent face‐S1 that may be related to the animals ability to adapt to the altered oral state. J. Comp. Neurol. 518:1030–1045, 2010.

Cortical Orofacial Motor Representation Effect of Diet Consistency

Jaw and tongue motor alterations may occur following changes in food consistency, but whether such changes are associated with re-organization of motor representations within the facial sensorimotor cortex is unclear. We used intracortical microstimulation (ICMS) and recordings of evoked electromyographic responses to determine jaw (anterior digastric) and tongue (genioglossus) motor representations within the histologically defined face primary motor cortex (face-M1) and adjacent somatosensory cortex (face-S1) of rats fed hard (N = 6) or soft (N = 6) diet for 2 to 3 weeks. ICMS evoked jaw and tongue responses from an extensive area within the face-M1 and a smaller area within the face-S1. A significant contralateral predominance was reflected in the number and latency of ICMS-evoked jaw responses (p < 0.05). There were no significant differences between the hard- and soft-diet groups in jaw and tongue motor representations, suggesting that the rat’s ability to adapt to changes in diet consistency may not be associated with significant neuroplasticity of sensorimotor cortex motor outputs.

Long‐term neuroplasticity of the face primary motor cortex and adjacent somatosensory cortex induced by tooth loss can be reversed following dental implant replacement in rats

Tooth loss is common, and exploring the neuroplastic capacity of the face primary motor cortex (face‐M1) and adjacent primary somatosensory cortex (face‐S1) is crucial for understanding how subjects adapt to tooth loss and their prosthetic replacement. The aim was to test if functional reorganization of jaw and tongue motor representations in the rat face‐M1 and face‐S1 occurs following tooth extraction, and if subsequent dental implant placement can reverse this neuroplasticity. Rats (n = 22) had the right maxillary molar teeth extracted under local and general anesthesia. One month later, seven rats had dental implant placement into healed extraction sites. Naive rats (n = 8) received no surgical treatment. Intracortical microstimulation (ICMS) and recording of evoked jaw and tongue electromyographic responses were used to define jaw and tongue motor representations at 1 month (n = 8) or 2 months (n = 7) postextraction, 1 month postimplant placement, and at 1–2 months in naive rats. There were no significant differences across study groups in the onset latencies of the ICMS‐evoked responses (P > 0.05), but in comparison with naive rats, tooth extraction caused a significant (P < 0.05) and sustained (1–2 months) decreased number of ICMS‐defined jaw and tongue sites within face‐M1 and ‐S1, and increased thresholds of ICMS‐evoked responses in these sites. Furthermore, dental implant placement reversed the extraction‐induced changes in face‐S1, and in face‐M1 the number of jaw sites even increased as compared to naive rats. These novel findings suggest that face‐M1 and adjacent face‐S1 may play a role in adaptive mechanisms related to tooth loss and their replacement with dental implants. J. Comp. Neurol. 523:2372–2389, 2015.

Dental Occlusal Changes Induce Motor Cortex Neuroplasticity

Modification to the dental occlusion may alter oral sensorimotor functions. Restorative treatments aim to restore sensorimotor functions; however, it is unclear why some patients fail to adapt to the restoration and remain with sensorimotor complaints. The face primary motor cortex (face-M1) is involved in the generation and control of orofacial movements. Altered sensory inputs or motor function can induce face-M1 neuroplasticity. We took advantage of the continuous eruption of the incisors in Sprague-Dawley rats and used intracortical microstimulation (ICMS) to map the jaw and tongue motor representations in face-M1. Specifically, we tested the hypothesis that multiple trimming of the right mandibular incisor, to keep it out of occlusal contacts for 7 d, and subsequent incisor eruption and restoration of occlusal contacts, can alter the ICMS-defined features of jaw and tongue motor representations (i.e., neuroplasticity). On days 1, 3, 5, and 7, the trim and trim-recovered groups had 1 to 2 mm of incisal trimming of the incisor; a sham trim group had buccal surface trimming with no occlusal changes; and a naive group had no treatment. Systematic mapping was performed on day 8 in the naive, trim, and sham trim groups and on day 14 in the trim-recovered group. In the trim group, the tongue onset latency was shorter in the left face-M1 than in the right face-M1 (P < .001). In the trim-recovered group, the number of tongue sites and jaw/tongue overlapping sites was greater in the left face-M1 than in the right face-M1 (P = 0.0032, 0.0016, respectively), and the center of gravity was deeper in the left than in the right face-M1 (P = 0.026). Therefore, incisor trimming and subsequent restoration of occlusal contacts induced face-M1 neuroplasticity, reflected in significant disparities between the left and right face-M1 in some ICMS-defined features of the tongue motor representations. Such neuroplasticity may reflect or contribute to subjects’ ability to adapt their oral sensorimotor functions to an altered dental occlusion.

Neuroplastic changes in the sensorimotor cortex associated with orthodontic tooth movement in rats.

Orthodontic tooth movement (OTM) causes transient pain and changes in the dental occlusion that may lead to altered somatosensory inputs and patterns of mastication. This study used intracortical microstimulation (ICMS) and electromyographic (EMG) recordings to test whether neuroplastic changes occur in the ICMS‐defined motor representations of left and right anterior digastric (LAD, RAD), masseter, buccinator, and genioglossus (GG) muscles within the rats face primary motor cortex (face‐M1) and adjacent face primary somatosensory cortex (face‐S1) during OTM. Analyses included any changes in the number of ICMS sites representing these muscles and in the onset latencies of ICMS‐evoked responses in the muscles. Sprague–Dawley rats were divided into experimental (E), sham (S), and naive (N) groups; OTM was induced in the E group. Statistical analyses involved a mixed model repeated‐measures analysis of variance (MMRM ANOVA). OTM resulted in significant neuroplastic changes in the number of positive sites in the E group for LAD, RAD, and GG muscles in face‐M1 and face‐S1 at days 1, 7, and 28 of continuous orthodontic force application, and in the number of sites in face‐M1 from which ICMS could simultaneously evoke EMG responses in different combinations of LAD, RAD, and GG muscles. However, the onset latencies of ICMS‐evoked responses were not significantly different between groups or between face‐M1 and face‐S1. The neuroplastic changes documented in this study may reflect adaptive sensorimotor changes in response to the altered environment in the oral cavity induced by OTM. J. Comp. Neurol. 523:1548–1568, 2015.

Jaw sensorimotor control in healthy adults and effects of ageing

The oro-facial sensorimotor system is a unique system significantly distinguished from the spinal sensorimotor system. The jaw muscles are involved in mastication, swallowing and articulatory speech movements and their integration with respiration. These sensorimotor functions are vital for sustaining life and necessitate complex neuromuscular processing to provide for exquisite sensorimotor control of numerous oro-facial muscles. The function of the jaw muscles in relation to sensorimotor control of these movements may be subject to ageing-related declines. This review will focus on peripheral, brainstem and higher brain centre mechanisms involved in reflex regulation and sensorimotor coordination and control of jaw muscles in healthy adults. It will outline the limited literature bearing on age-related declines in jaw sensorimotor functions and control including reduced biting forces and increased risk of impaired chewing, speaking and swallowing. The mechanisms underlying these alterations include age-related degenerative changes within the peripheral neuromuscular system and in brain regions involved in the generation and control of jaw movements. In the light of the vital role of jaw sensorimotor functions in sustaining life, normal ageing involves compensatory mechanisms that utilise the neuroplastic capacity of the brain and the recruitment of additional brain regions involved in sensorimotor performance and closely associated functions (e.g. cognition and memory). However, these regions are themselves susceptible to detrimental age-related changes. Thus, better understanding of the peripheral and central mechanisms underlying age-related sensorimotor impairment is crucial for developing improved treatment approaches to prevent or cure impaired jaw sensorimotor functions and to thereby improve health and quality of life.

Widespread Volumetric Brain Changes following Tooth Loss in Female Mice

Tooth loss is associated with altered sensory, motor, cognitive and emotional functions. These changes vary highly in the population and are accompanied by structural and functional changes in brain regions mediating these functions. It is unclear to what extent this variability in behavior and function is caused by genetic and/or environmental determinants and which brain regions undergo structural plasticity that mediates these changes. Thus, the overall goal of our research program is to identify genetic variants that control structural and functional plasticity following tooth loss. As a step toward this goal, here our aim was to determine whether structural magnetic resonance imaging (sMRI) is sensitive to detect quantifiable volumetric differences in the brains of mice of different genetic background receiving tooth extraction or sham operation. We used 67 adult female mice of 7 strains, comprising the A/J (A) and C57BL/6J (B) strains and a randomly selected sample of 5 of the 23 AXB-BXA strains (AXB1, AXB4, AXB24, BXA14, BXA24) that were produced from the A and B parental mice by recombinations and inbreeding. This panel of 25 inbred strains of genetically diverse inbred strains of mice is used for mapping chromosomal intervals throughout the genome that harbor candidate genes controlling the phenotypic variance of any trait under study. Under general anesthesia, 39 mice received extraction of 3 right maxillary molar teeth and 28 mice received sham operation. On post-extraction day 21, post-mortem whole-brain high-resolution sMRI was used to quantify the volume of 160 brain regions. Compared to sham operation, tooth extraction was associated with a significantly reduced regional and voxel-wise volumes of cortical brain regions involved in processing somatosensory, motor, cognitive and emotional functions, and increased volumes in subcortical sensorimotor and temporal limbic forebrain regions including the amygdala. Additionally, comparison of the 10 BXA14 and 21 BXA24 mice revealed significant volumetric differences between the two strains in several brain regions. These findings highlight the utility of high-resolution sMRI for studying tooth loss-induced structural brain plasticity in mice, and provide a foundation for further phenotyping structural brain changes following tooth loss in the full AXB-BXA panel to facilitate mapping genes that control brain plasticity following orofacial injury.

Motor Control of Masticatory Muscles

This chapter focuses on the brainstem and higher brain center mechanisms involved in the execution, initiation, reflex regulation, and sensorimotor coordination of the masticatory musculature. A brief overview is given of masticatory musculoskeletal biomechanics, but other chapters may be consulted for general aspects of biomechanics related to motor control and for the structural and functional features of this musculature and its motor units and muscle fibers and sensory innervation. Mastication is a complex motor function that involves the simultaneous bilateral coordinated activation and/or inactivation of the jaw, tongue and face muscles. Jaw opening occurs by downward traction of the mandible by the anterior belly of the digastric muscle and the mylohyoid muscle and anterior traction of the condyles by the lateral pterygoid muscle. Jaw closing occurs by activation of the masseter, temporalis, and medial pterygoid muscles. Jaw protrusion requires activation of the lateral pterygoid, the anterior fibers of the temporalis and the superficial masseter muscles, and jaw retrusion is brought about by activation of the posterior fibers of the temporalis muscles. During mastication, the tongue muscles (e.g., genioglossus—tongue protrusion; hyoglossus—tongue depression; styloglossus—tongue retrusion; palatoglossus—tongue elevation) assist in maneuvering the food bolus from side to side, and the lip muscles (e.g., orbicularis oris—perioral sphincter, zygomaticus major—elevation and retraction of the modiolus) and cheek muscles (buccinators—retraction of the modiolus), along with the tongue muscles, assist in maintaining the food bolus within the mouth on the occlusal table (Dubner et al. 1978; Lang 1995; Miles et al. 2004).

Sagittal Plane Kinematics of the Jaw and Hyolingual Apparatus During Swallowing in Macaca mulatta

Studies of mechanisms of feeding behavior are important in a society where aging- and disease-related feeding disorders are increasingly prevalent. It is important to evaluate the clinical relevance of animal models of the disease and the control. Our present study quantifies macaque hyolingual and jaw kinematics around swallowing cycles to determine the extent to which macaque swallowing resembles that of humans. One female and one male adult Macaca mulatta were trained to feed in a primate chair. Videofluoroscopy was used to record kinematics in a sagittal view during natural feeding on solid food, and the kinematics of the hyoid bone, thyroid cartilage, mandibular jaw, and anterior-, middle-, and posterior-tongue. Jaw gape cycles were defined by consecutive maximum gapes, and the kinematics of the swallow cycles were compared with those of the two consecutive non-swallow cycles preceding and succeeding the swallow cycles. Although there are size differences between macaques and humans, and macaques have shorter durations of jaw gape cycles and hyoid and thyroid upward movements, there are several important similarities between our macaque data and human data reported in the literature: (1) The durations of jaw gape cycles during swallow cycles are longer than those of non-swallow cycles as a result of an increased duration of the jaw-opening phase; (2) Hyoid and thyroid upward movement is linked with a posterior tongue movement and is faster during swallow than non-swallow cycles; (3) Tongue elevation propagates from anterior to posterior during swallow and non-swallow cycles. These findings suggest that macaques can be a useful experimental model for human swallowing studies.