Hemispheric Network Expression in Parkinson’s Disease: Relationship to Dopaminergic Asymmetries

Article type: Research Article

Authors: Tang, Chris C.^{a; 1} | Holtbernd, Florian^{b; c; d; 1} | Ma, Yilong^a | Spetsieris, Phoebe^a | Oh, Alice^a | Fink, Gereon R.^{e; f} | Timmermann, Lars^{f; g} | Eggers, Carsten^{g; h} | Eidelberg, David^{a; *}

Affiliations: [a] Center for Neurosciences, The Feinstein Institutes for Medical Research, Manhasset, NY, USA | [b] RWTH Aachen University, Department of Neurology, Aachen, Germany | [c] JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Juelich Research Centre and RWTH Aachen University, Aachen, Germany | [d] Institute of Neuroscience and Medicine 4 (INM-4), Juelich Research Centre, Juelich, Germany | [e] Department of Neurology, University of Cologne, Cologne, Germany | [f] Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Jülich Research Centre, Jülich, Germany | [g] Department of Neurology, University Hospital of Giessen and Marburg, Marburg, Germany | [h] Center for Mind, Brain and Behavior, Universities Marburg and Giessen, Marburg, Germany

Correspondence: [*] Correspondence to: David Eidelberg, MD, Centre for Neurosciences, The Feinstein Institutes for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA. Tel.: +1 516 562 2498; Fax: +1 516 562 1008; E-mail: [email protected]

Note: [1] These authors contributed equally to the study

Abstract: Background:Parkinson’s disease (PD) is characterized by brain metabolic networks, specifically associated with motor and cognitive manifestations. Few studies have investigated network changes in cerebral hemispheres ipsilateral and contralateral to the clinically more affected body side. Objective:We examined hemispheric network abnormalities and their relationship to striatal dopaminergic deficits in PD patients at different stages. Methods:45 PD patients underwent dual-tracer positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) and 18F-fluorodopa (FDOPA) in a high-resolution PET scanner. In all patients, we computed expression levels for the PD-related motor/cognition metabolic patterns (PDRP/PDCP) as well as putamen/caudate FDOPA uptake values in both hemispheres. Resulting hemispheric measures in the PD group were compared with corresponding healthy control values and assessed across disease stages. Results:Hemispheric PDRP and PDCP expression was significantly elevated contralateral and ipsilateral to the more affected body side in patients with unilateral symptoms (H&Y 1: p < 0.01) and in patients with bilateral limb involvement (H&Y 2-3: p < 0.001; H&Y 4: p < 0.003). Elevations in pattern expression were symmetrical at all disease stages. By contrast, FDOPA uptake in the caudate and putamen was reduced bilaterally (p < 0.002), with lower values on both sides at more advanced disease stages. Hemispheric uptake was asymmetrical in both striatal regions, with lower contralateral values at all disease stages. The magnitude of hemispheric uptake asymmetry was smaller with more advanced disease, reflecting greater change ipsilaterally. Conclusion:Symmetrical network expression in PD represents bilateral functional effects unrelated to nigrostriatal dopaminergic asymmetries.

Keywords: Parkinson’s disease, brain metabolic networks, PET, brain metabolism, dopaminergic function

DOI: 10.3233/JPD-202117

Journal: Journal of Parkinson's Disease, vol. 10, no. 4, pp. 1737-1749, 2020