Pedro M Paz-Alonso1, I Navalpotro-Gomez2,3,4, P Boddy1, R Dacosta-Aguayo2,3, M Delgado-Alvarado2,3,5,6,7, A Quiroga-Varela2,3,8, H Jimenez-Urbieta2,3, M Carreiras1,9, Maria C Rodriguez-Oroz1,3,8,9,10. 1. BCBL. Basque Center on Cognition, Brain and Language, Donostia-San Sebastián, Spain. 2. Neurodegenerative Disorders Area, Biodonostia Health Research Institute, Donostia-San Sebastián, Spain. 3. CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, Madrid, Spain. 4. Servei de Neurologia, Hospital del Mar, Parc de Salut Mar-IMIM, Barcelona, Spain. 5. Neurology Department, Sierrallana Hospital, Torrelavega, Spain. 6. IDIVAL, Valdecilla Biomedical Research Institute, Santander, Spain. 7. Biomedical Research Networking Center for Mental Health (CIBERSAM), Madrid, Spain. 8. Neuroscience Area, Center for Applied Medical Research (CIMA), Universidad de Navarra, Pamplona, Spain. 9. Ikerbasque (Basque Foundation for Science), Bilbao, Spain. 10. Department of Neurology, Clínica Universidad de Navarra, Universidad de Navarra, Pamplona, Spain.
Abstract
BACKGROUND: Impulse control disorders related to alterations in the mesocorticolimbic dopamine network occur in Parkinson's disease (PD). Our objective was to investigate the functional neural substrates of reward processing and inhibitory control in these patients. METHODS: Eighteen PD patients with impulse control disorders, 17 without this complication, and 18 healthy controls performed a version of the Iowa Gambling Task during functional magnetic resonance scanning under 3 conditions: positive, negative, and mixed feedback. Whole-brain contrasts, regions of interest, time courses, functional connectivity analyses, and brain-behavior associations were examined. RESULTS: PD patients with impulse control disorders exhibited hyperactivation in subcortical and cortical regions typically associated with reward processing and inhibitory control compared with their PD and healthy control counterparts. Time-course analyses revealed that only PD patients with impulse control disorders exhibited stronger signal intensity during the initial versus final periods of the negative-feedback condition in bilateral insula, and right ventral striatum. Interestingly, hyperactivation of all the examined right-lateralized frontostriatal areas during negative feedback was positively associated with impulse control disorder severity. Importantly, positive associations between impulse control disorder severity and regional activations in the right insula and right inferior frontal gyrus, but not the right subthalamic nucleus, were mediated by functional connectivity with the right ventral striatum. CONCLUSIONS: During a reward-based task, PD patients with impulse control disorders showed hyperactivation in a right-lateralized network of regions including the subthalamic nucleus that was strongly associated with impulse control disorder severity. In these patients, the right ventral striatum in particular played a critical role in modulating the functional dynamics of right-lateralized inhibitory-control frontal regions when facing penalties.
BACKGROUND: Impulse control disorders related to alterations in the mesocorticolimbic dopamine network occur in Parkinson's disease (PD). Our objective was to investigate the functional neural substrates of reward processing and inhibitory control in these patients. METHODS: Eighteen PDpatients with impulse control disorders, 17 without this complication, and 18 healthy controls performed a version of the Iowa Gambling Task during functional magnetic resonance scanning under 3 conditions: positive, negative, and mixed feedback. Whole-brain contrasts, regions of interest, time courses, functional connectivity analyses, and brain-behavior associations were examined. RESULTS:PDpatients with impulse control disorders exhibited hyperactivation in subcortical and cortical regions typically associated with reward processing and inhibitory control compared with their PD and healthy control counterparts. Time-course analyses revealed that only PDpatients with impulse control disorders exhibited stronger signal intensity during the initial versus final periods of the negative-feedback condition in bilateral insula, and right ventral striatum. Interestingly, hyperactivation of all the examined right-lateralized frontostriatal areas during negative feedback was positively associated with impulse control disorder severity. Importantly, positive associations between impulse control disorder severity and regional activations in the right insula and right inferior frontal gyrus, but not the right subthalamic nucleus, were mediated by functional connectivity with the right ventral striatum. CONCLUSIONS: During a reward-based task, PDpatients with impulse control disorders showed hyperactivation in a right-lateralized network of regions including the subthalamic nucleus that was strongly associated with impulse control disorder severity. In these patients, the right ventral striatum in particular played a critical role in modulating the functional dynamics of right-lateralized inhibitory-control frontal regions when facing penalties.
Authors: Brian N Haagensen; Damian M Herz; David Meder; Kristoffer H Madsen; Annemette Løkkegaard; Hartwig R Siebner Journal: Neuroimage Clin Date: 2020-06-25 Impact factor: 4.881