Basic Science Program
Relating deficits to pathology in models of Parkinson Disease: The pathology of Parkinson disease is complex, and the pathogenesis underlying cranial sensorimotor behaviors, such as voice and swallowing deficits, are virtually unknown. Further, the onset of these deficits may occur in the preclinical periods. To address these issues in the basic science laboratory, we employ neurotoxin and genetic rat and mouse models of Parkinson diseases and test the onset and progression of vocalization, tongue use, chewing, functional swallowing, olfaction, forelimb use, and gait deficits. Our primary goals are to relate these behavioral deficits to the complex pathology of PD in order to improve behavioral, pharmacologic and surgical interventions.
Role of norepinephrine: Standard treatments of PD target the primary disease pathology of nigrostriatal dopamine depletion, typically leading to improvements in motor deficits. However, these treatments do not achieve similar results with respect to cranial sensorimotor deficits affecting speech and swallowing. This suggests that PD affects speech and swallowing via a different mechanism. The neuropathology in Parkinson disease involves significant degeneration of noradrenergic (norepinephrine) neurons in the locus coeruleus in addition to loss of nigrostriatal dopamine. Our goal is to characterize the role of norepinephrine in communicative and ingestive behaviors and how this is affected by noradrenergic neuron loss during PD progression.
Photomicrographs of insoluble aSyn inclusions (anti-aSyn immunolabel (dark, aggregated protein)) in coronal brain sections containing PAG , SN, LC, and AMBin WT (A-D), PINK1 +/- (E-H) and PINK1
/ (I-L). Scale bar in the lower right of panel A is 0.1mm, bright field magnification is 20X.
PD as a whole body disease: Recent evidence shows that Parkinson disease affects not only the central nervous system, but also affects autonomic function and peripheral nerves and muscles. Our research efforts are aimed at determining the timing and progression of pathology in peripheral nerves and muscles that affect communication and ingestive behaviors.
Clinical Science Program
High Resolution Manometry: This collaboration with Timothy McCulloch, MD, FACS explores developing and implementing this clinical tool that can detect subtle changes to swallow physiology. Swallowing is a critical life function that must be performed safely to ensure adequate nutrition and avoid airway compromise; failure can lead to life threatening complications. Complex pressures are generated during the swallow and directly measuring these pressures along with X-ray video images of the swallow can provide a great deal of information for diagnosing and treating swallowing problems. This line of research develops and tests a new method of analyzing, displaying and classifying multiple pressures and images generated during the swallow to allow physicians and speech language pathologists to improve the accuracy of diagnosis and management of swallowing disorders.
High-resolution manometry (HRM) images depicting pressure profiles of typical (left and center) and dysphasic (right) swallows. At far right is a 3D HRM image, which is captured using pressure sensors extending in six directions from a three-dimensional catheter. This technique can allow for more precise diagnosis of a patient’s swallowing issues.