Alexander K. Converse ^1* Maryann N. Krasko ^2,3 Denis Michael Rudisch ^2,3,4 Charlie L. Lunaris ⁵ Alex F. Nisbet ^2,3 Maxim S. Slesarev ⁶ John C. Szot ^2,3 Andrew G. Hoerst ^2,3 Glen Leverson ² Catherine L. Callagher ⁷ Michelle Ciucci ^2,5,8

• ¹ Waisman Center, University of Wisconsin-Madison, Madison, United States
• ² Department of Surgery-Division of Otolaryngology, University of Wisconsin-Madison, USA, Madison, United States
• ³ Department of Communication Science and Disorders, University of Wisconsin-Madison, USA, Madison, United States
• ⁴ Institute for Clinical and Translational Research, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, United States
• ⁵ Department of Communication Science and Disorders, University of Northern Colorado, Greeley, USA, Greeley, United States
• ⁶ Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, United States
• ⁷ Department of Neurology, University of Wisconsin-Madison, Madison, United States
• ⁸ Neuroscience Training Program, University of Wisconsin-Madison, Madison, United States

Introduction: Parkinson disease (PD) is a neurodegenerative condition affecting multiple sensorimotor and cognitive systems. The Pink1-/-rat model exhibits vocal, cognitive, and limb use deficits seen in idiopathic PD. We sought to measure glucose metabolism in brain regions in Pink1-/-and wild type (WT) rats, and to associate these to measures of ultrasonic vocalization, cognition, and limb use behavior.Methods: Pink1-/-(n=12) and WT (n=14) rats were imaged by [ 18 F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in a repeated measures design at approximately 10 months of age and six weeks later. Relative regional glucose metabolism was indexed by whole brain normalized FDG uptake, which was calculated for eighteen regions identified a priori for comparison. Behavioral measures included tests of communication via ultrasonic vocalization, cognition with 5-Choice Serial Reaction Time Test (5-CSRTT), and limb use with Cylinder Test and Challenge Beam.Results: Relative glucose metabolism was significantly different in Pink1-/-rats in prelimbic area, striatum, nucleus ambiguus, globus pallidus, and posterior parietal association cortex compared to WT controls. For behavioral measures, Pink1-/-rats demonstrated quieter vocalizations with a restricted frequency range, and they showed increased number of foot-faults and hindlimb steps (shuffling) in limb motor tests. Significant behavior vs. brain correlations included associations of ultrasonic vocalization parameters with glucose metabolism indices in locus coeruleus and substantia nigra.Conclusions: FDG PET reveals abnormalities in relative regional brain glucose metabolism in Pink1-/rats in brain regions that are important to cognition, vocalization, and limb motor control that are also impacted by Parkinson disease. This method may be useful for mechanistic studies of behavioral deficits and therapeutic interventions in translational studies in the Pink1-/-PD model.