I Navalpotro-Gomez1,2, R Dacosta-Aguayo1,2, F Molinet-Dronda3, A Martin-Bastida4, A Botas-Peñin5, H Jimenez-Urbieta1,2, M Delgado-Alvarado1,2,6, B Gago1,2, A Quiroga-Varela1,2,7, Maria C Rodriguez-Oroz8,9,10,11,12. 1. Neurodegenerative Disorders Area, Biodonostia Health Research Institute, San Sebastian, Spain. 2. Network Center for Biomedical Research in Neurodegenerative Diseases, CIBERNED, Madrid, Spain. 3. MicroPET Research Unit, Center for Applied Medical Research, Universidad de Navarra, Pamplona, Spain. 4. Department of Neurology, Clínica Universidad de Navarra, Universidad de Navarra, Pamplona, Spain. 5. Department of Biomedical Engineering, Tecnun, Universidad de Navarra, Pamplona, Spain. 6. Neurology Department, Sierrallana Hospital, Torrelavega, Spain. 7. Neuroscience Area, Center for Applied Medical Research (CIMA), Universidad de Navarra, Pamplona, Spain. 8. Network Center for Biomedical Research in Neurodegenerative Diseases, CIBERNED, Madrid, Spain. mcroroz@unav.es. 9. Department of Neurology, Clínica Universidad de Navarra, Universidad de Navarra, Pamplona, Spain. mcroroz@unav.es. 10. Neuroscience Area, Center for Applied Medical Research (CIMA), Universidad de Navarra, Pamplona, Spain. mcroroz@unav.es. 11. Ikerbasque (Basque Foundation of Science), Bilbao, Spain. mcroroz@unav.es. 12. Basque Center on Cognition, Brain and Language (BCBL), San Sebastian, Spain. mcroroz@unav.es.
Abstract
PURPOSE: Previous studies in patients with Parkinson's disease (PD) and impulse control disorders (ICDs) have produced heterogeneous results regarding striatal dopamine transporter (DaT) binding and activity in the mesocorticolimbic network. Our aim here was to study the relationship between striatal DaT availability and cortical metabolism, as well as motor, behavioural and cognitive features of PD patients with ICD. METHODS: In a group of PD patients with ICD (PD-ICD, n = 16) and 16 matched PD patients without ICD (PD-noICD, n = 16), DaT single-photon emission computed tomography (SPECT) imaging (DaTSCAN) was used to study DaT availability in predefined striatal volumes of interest (VOIs): putamen, caudate nucleus and ventral striatum (VS). In addition, the specific association of striatal DaT binding with cortical limbic and associative metabolic activity was evaluated by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in PD-ICD patients and investigated using statistical parametric mapping (SPM8). Finally, associations between DaT availability and motor, behavioural and cognitive features were assessed. RESULTS: PD-ICD patients had a significantly lower DaT density in the VS than PD-noICD patients, which was inversely associated with ICD severity. Lower DaT availability in the VS was associated with lower FDG uptake in several cortical areas belonging to the limbic and associative circuits, and in other regions involved in reward and inhibition processes (p < 0.0001 uncorrected; k > 50 voxels). No significant results were observed using a higher conservative threshold (p < 0.05; FDR corrected). PD-ICD patients also displayed impairment in interference and attentional Stroop Task execution, and more anxiety, all associated with reduced DaT availability in the VS and caudate nucleus. CONCLUSIONS: ICDs in PD patients are related to reduced DaT binding in the VS, which accounts for dysfunction in a complex cortico-subcortical network that involves areas of the mesolimbic and mesocortical systems, being associated with reward evaluation, salience attribution and inhibitory control processes.
PURPOSE: Previous studies in patients with Parkinson's disease (PD) and impulse control disorders (ICDs) have produced heterogeneous results regarding striatal dopamine transporter (DaT) binding and activity in the mesocorticolimbic network. Our aim here was to study the relationship between striatal DaT availability and cortical metabolism, as well as motor, behavioural and cognitive features of PDpatients with ICD. METHODS: In a group of PDpatients with ICD (PD-ICD, n = 16) and 16 matched PDpatients without ICD (PD-noICD, n = 16), DaT single-photon emission computed tomography (SPECT) imaging (DaTSCAN) was used to study DaT availability in predefined striatal volumes of interest (VOIs): putamen, caudate nucleus and ventral striatum (VS). In addition, the specific association of striatal DaT binding with cortical limbic and associative metabolic activity was evaluated by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in PD-ICDpatients and investigated using statistical parametric mapping (SPM8). Finally, associations between DaT availability and motor, behavioural and cognitive features were assessed. RESULTS:PD-ICDpatients had a significantly lower DaT density in the VS than PD-noICDpatients, which was inversely associated with ICD severity. Lower DaT availability in the VS was associated with lower FDG uptake in several cortical areas belonging to the limbic and associative circuits, and in other regions involved in reward and inhibition processes (p < 0.0001 uncorrected; k > 50 voxels). No significant results were observed using a higher conservative threshold (p < 0.05; FDR corrected). PD-ICDpatients also displayed impairment in interference and attentional Stroop Task execution, and more anxiety, all associated with reduced DaT availability in the VS and caudate nucleus. CONCLUSIONS: ICDs in PDpatients are related to reduced DaT binding in the VS, which accounts for dysfunction in a complex cortico-subcortical network that involves areas of the mesolimbic and mesocortical systems, being associated with reward evaluation, salience attribution and inhibitory control processes.
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