Fritzie Arce-McShane, PhD - US grants

PROJECT SUMMARY There is a fundamental gap in understanding the cortical representations and integration of tactile and proprio- ceptive sensations accompanying bodily movements in general and oromotor behavior in particular. This repre- sents an important problem because until it is understood, the mechanisms underlying orofacial pain, sensorimo- tor impairments, and sensorimotor integration will remain largely incomprehensible. The goal of the proposed research is to dissociate the cortical representations of touch and proprioception during natural feeding behavior by using an innovative sequence of nerve blocks together with multi-electrode array recordings and 3D tracking of tongue and jaw movements in non-human primates. The tongue is a unique structure for investigating this because it is in constant motion and assumes various postures when touching other oral structures (e.g., teeth, palate, and gingiva) during feeding. More importantly, the tactile and proprioceptive afferent fibers innervating the tongue enter the central nervous system separately in trigeminal (lingual nerve branch) and hypoglossal cranial nerves, respectively. Such unique anatomy enables experimental dissociation of touch and propriocep- tion. The central hypothesis is that tongue posture and contact with other oral structures are reflected in the proprioception- and tactile-related responses of neurons in the primary somatosensory (SIo) and primary motor (MIo) areas of the orofacial sensorimotor cortex (OSMcx). This hypothesis will be tested by pursuing three spe- cific aims: (1) determine how information about tongue posture and contact with other oral structures is encoded in MIo and SIo during natural feeding by eliminating tactile stimuli to the tongue and surrounding oral structures through sequential nerve blocks to the maxillary and mandibular sensory branches of the trigeminal nerve, (2) dissociate the neurons? motor response from a proprioceptive response by using intracortical microstimulation (ICMS) to evoke muscle twitches while tactile inputs to the tongue and other oral structures are blocked, and (3) characterize the functional connectivity between tactile- and proprioceptive-related regions in OSMcx by spectral coherence analysis and by the effects of low-intensity ICMS of a tactile region on a proprioceptive one and vice versa. The proposed research uses an innovative approach that leverages the unique sensory innervation of the oral region by different cranial nerves and integrates the simultaneous neural recording and tracking of the tongue and jaw movements in 3D. The proposed research is significant because it will bridge the results of decades of research on cortical representation of oral somatosensation and on the biomechanics of tongue/jaw movements during oromotor behavior, thus filling an important gap in the field. The knowledge gained from this work will lay the groundwork for future studies on oral somatosensation, pain mechanisms, and sensorimotor integration. Ultimately such knowledge has the potential to inform the development of strategies for treatment of sensory impairments associated with dental implants, trigeminal neuralgia, temporomandibular disorders, orofa- cial pain, and for the restoration of sensory feedback for use in brain-machine interface.

PROJECT SUMMARY Many age-related oral health problems, such as masticatory dysfunction, dysphagia, periodontal disease, and tooth loss have been associated with Alzheimer?s disease (AD). How cortical and biomechanical changes in oromotor behavior contribute to the onset and progression of AD and age-related dementias (ARD) are widely unknown. This is largely because of a fundamental gap in understanding the neuromechanical processes, at the level of large-scale activity of single neurons and neuronal networks, that underlie healthy aging. This represents an important problem because until they are understood, the cortical mechanisms underlying pathological aging in AD/ARD will remain largely incomprehensible. The goal of the proposed research is to investigate changes in the orofacial sensorimotor-cognitive neuronal network that underlie healthy age-related sensorimotor changes and how these cortical correlates are affected by absent sensory inputs to oral structures and by the presence of AD-like impairments (?pathological aging?) in old rhesus macaques. The central hypothesis is that differential patterns of the dynamics of large-scale neural activity and connectivity in the orofacial sensorimotor cortex (OSMcx) and the ventrolateral frontal cortex (VLFcx) will help disambiguate healthy and pathological aging. This hypothesis will be tested by pursuing three specific aims: (1) to identify the neuronal correlates of healthy age- related changes in feeding behavior, (2) to identify changes in cortical representations of oral somatosensation following sensory nerve block, and (3) to identify changes in neuronal responses and cortical interactions in OSMcx-VLFcx networks following drug-induced AD-like impairments. Thus, we can evaluate and compare the added burden of sensory loss and AD-like impairments on aging. The proposed research uses an innovative approach that leverages the unique sensory innervation of the oral region by different cranial nerves and the use of a pharmacological model to induce AD-like impairments in old rhesus macaques. We will record cortical activity from multiple chronically implanted microelectrode arrays in OSMcx-VLFcx simultaneously with 3D tracking of tongue and jaw kinematics using biplanar videoradiography and the XROMM workflow (X-ray Reconstruction of Moving Morphology) while young and old subjects engage in natural feeding behavior. The proposed research is significant for (1) defining cortical, biomechanical, and immunohistological profiles of healthy and pathological aging, (2) determining potential contributing factors to the onset and progression of AD, and (3) identifying cortical regions that are vulnerable to AD. Using old rhesus macaques has direct translational value to evaluate potential avenues for pharmacological or cortical therapies for AD. The knowledge gained from the proposed study has important implications for earlier identification of individuals with chronic oral health issues who may be at risk for developing AD or ARDs. It may also inform the development of more effective interventions focused on enhancing oral health outcomes in this group and thus preventing the onset or allaying the progression of AD or ARD.