title: Non-demented Parkinson's disease patients with apathy show decreased grey matter volume in key executive and reward-related nodes.
abstract: Apathy is a common but poorly understood neuropsychiatric disturbance in Parkinson's disease (PD). In a recent study using event-related brain potentials we demonstrated impaired reward processing and compromised mesocortico-limbic pathways in PD patients with clinical symptoms of apathy. Here we aimed to further investigate the involvement of reward circuits in apathetic PD patients by assessing potential differences in brain structure. Using structural magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) we quantified grey matter volume (GMV) in a sample of 18 non-demented and non-depressed PD patients with apathy, and 18 matched non-apathetic patients. Both groups were equivalent in terms of sociodemographic characteristics, disease stage, cognitive performance and L-Dopa equivalent daily dose. Apathetic patients showed significant GMV loss in cortical and subcortical brain structures. Various clusters of cortical GMV decrease were found in the parietal, lateral prefrontal cortex, and orbitofrontal cortex (OFC). The second largest cluster of GMV loss was located in the left nucleus accumbens (NAcc), a subcortical structure that is a key node of the human reward circuit. Isolated apathy in our sample is explained by the combined GMV loss in regions involved in executive functions, and cortical and subcortical structures of the mesolimbic reward pathway. The correlations observed between apathy and cognition suggests apathy as a marker of more widespread brain degeneration even in a sample of non-demented PD patients.
authors.affiliation: Department of Neurology, Movement Disorders Unit, Hospital de la Santa Creu i Sant Pau Sant Antoni M. Claret 167, Universitat Autònoma de Barcelona, 08025, Barcelona, Spain.|Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain.|Centro Investigación Biomedica en Red-Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Saul
authors.initials: S
authors.lastname: Martinez-Horta
authors.affiliation: Faculty of Medicine, Autonomous University of Barcelona, Barcelona, Spain.
authors.forename: Frederic
authors.initials: F
authors.lastname: Sampedro
authors.affiliation: Department of Neurology, Movement Disorders Unit, Hospital de la Santa Creu i Sant Pau Sant Antoni M. Claret 167, Universitat Autònoma de Barcelona, 08025, Barcelona, Spain.|Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain.|Centro Investigación Biomedica en Red-Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Pagonabarraga
authors.affiliation: Department of Neurology, Movement Disorders Unit, Hospital de la Santa Creu i Sant Pau Sant Antoni M. Claret 167, Universitat Autònoma de Barcelona, 08025, Barcelona, Spain.|Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain.|Centro Investigación Biomedica en Red-Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.|Universitat Oberta de Catalunya (UOC), Barcelona, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Fernandez-Bobadilla
authors.affiliation: Department of Neurology, Movement Disorders Unit, Hospital de la Santa Creu i Sant Pau Sant Antoni M. Claret 167, Universitat Autònoma de Barcelona, 08025, Barcelona, Spain.|Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain.|Centro Investigación Biomedica en Red-Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Marin-Lahoz
authors.affiliation: Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain.|Human Neuropsychopharmacology Group IIB-Sant Pau, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Riba
authors.affiliation: Department of Neurology, Movement Disorders Unit, Hospital de la Santa Creu i Sant Pau Sant Antoni M. Claret 167, Universitat Autònoma de Barcelona, 08025, Barcelona, Spain. jkulisevsky@santpau.cat.|Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain. jkulisevsky@santpau.cat.|Centro Investigación Biomedica en Red-Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain. jkulisevsky@santpau.cat.|Faculty of Medicine, Autonomous University of Barcelona, Barcelona, Spain. jkulisevsky@santpau.cat.|Universitat Oberta de Catalunya (UOC), Barcelona, Spain. jkulisevsky@santpau.cat.
authors.forename: Jaime
authors.initials: J
authors.lastname: Kulisevsky
mesh_terms: D000368:Aged; D057565:Apathy; D001284:Atrophy; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D056344:Executive Function; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging* / Q000473:pathology; D006801:Humans; D007406:Interview, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009042:Motivation; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000473:pathology; D009929:Organ Size; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000473:pathology / Q000523:psychology*; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D012201:Reward; D012959:Socioeconomic Factors
keywords: Apathy; Behavior; MRI; Motivation; Parkinson’s disease; VBM