Daniel O Claassen1, Adam J Stark1, Charis A Spears1, Kalen J Petersen1, Nelleke C van Wouwe1, Robert M Kessler2, David H Zald3,4, Manus J Donahue1,5,3. 1. Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, USA. 2. Radiology, University of Alabama at Birmingham, Birmingham, Alabama, USA. 3. Psychiatry, Vanderbilt University Medical Center, Nashville, Tennessee, USA. 4. Psychology, Vanderbilt University, Nashville, Tennessee, USA. 5. Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Abstract
BACKGROUND: PD patients treated with dopamine therapy can develop maladaptive impulsive and compulsive behaviors, manifesting as repetitive participation in reward-driven activities. This behavioral phenotype implicates aberrant mesocorticolimbic network function, a concept supported by past literature. However, no study has investigated the acute hemodynamic response to dopamine agonists in this subpopulation. OBJECTIVES: We tested the hypothesis that dopamine agonists differentially alter mesocortical and mesolimbic network activity in patients with impulsive-compulsive behaviors. METHODS: Dopamine agonist effects on neuronal metabolism were quantified using arterial-spin-labeling MRI measures of cerebral blood flow in the on-dopamine agonist and off-dopamine states. The within-subject design included 34 PD patients, 17 with active impulsive compulsive behavior symptoms, matched for age, sex, disease duration, and PD severity. RESULTS: Patients with impulsive-compulsive behaviors have a significant increase in ventral striatal cerebral blood flow in response to dopamine agonists. Across all patients, ventral striatal cerebral blood flow on-dopamine agonist is significantly correlated with impulsive-compulsive behavior severity (Questionnaire for Impulsive Compulsive Disorders in Parkinson's Disease- Rating Scale). Voxel-wise analysis of dopamine agonist-induced cerebral blood flow revealed group differences in mesocortical (ventromedial prefrontal cortex; insular cortex), mesolimbic (ventral striatum), and midbrain (SN; periaqueductal gray) regions. CONCLUSIONS: These results indicate that dopamine agonist therapy can augment mesocorticolimbic and striato-nigro-striatal network activity in patients susceptible to impulsive-compulsive behaviors. Our findings reinforce a wider literature linking studies of maladaptive behaviors to mesocorticolimbic networks and extend our understanding of biological mechanisms of impulsive compulsive behaviors in PD.
BACKGROUND:PDpatients treated with dopamine therapy can develop maladaptive impulsive and compulsive behaviors, manifesting as repetitive participation in reward-driven activities. This behavioral phenotype implicates aberrant mesocorticolimbic network function, a concept supported by past literature. However, no study has investigated the acute hemodynamic response to dopamine agonists in this subpopulation. OBJECTIVES: We tested the hypothesis that dopamine agonists differentially alter mesocortical and mesolimbic network activity in patients with impulsive-compulsive behaviors. METHODS:Dopamine agonist effects on neuronal metabolism were quantified using arterial-spin-labeling MRI measures of cerebral blood flow in the on-dopamine agonist and off-dopamine states. The within-subject design included 34 PDpatients, 17 with active impulsive compulsive behavior symptoms, matched for age, sex, disease duration, and PD severity. RESULTS:Patients with impulsive-compulsive behaviors have a significant increase in ventral striatal cerebral blood flow in response to dopamine agonists. Across all patients, ventral striatal cerebral blood flow on-dopamine agonist is significantly correlated with impulsive-compulsive behavior severity (Questionnaire for Impulsive Compulsive Disorders in Parkinson's Disease- Rating Scale). Voxel-wise analysis of dopamine agonist-induced cerebral blood flow revealed group differences in mesocortical (ventromedial prefrontal cortex; insular cortex), mesolimbic (ventral striatum), and midbrain (SN; periaqueductal gray) regions. CONCLUSIONS: These results indicate that dopamine agonist therapy can augment mesocorticolimbic and striato-nigro-striatal network activity in patients susceptible to impulsive-compulsive behaviors. Our findings reinforce a wider literature linking studies of maladaptive behaviors to mesocorticolimbic networks and extend our understanding of biological mechanisms of impulsive compulsive behaviors in PD.
Authors: Stephen M Smith; Mark Jenkinson; Mark W Woolrich; Christian F Beckmann; Timothy E J Behrens; Heidi Johansen-Berg; Peter R Bannister; Marilena De Luca; Ivana Drobnjak; David E Flitney; Rami K Niazy; James Saunders; John Vickers; Yongyue Zhang; Nicola De Stefano; J Michael Brady; Paul M Matthews Journal: Neuroimage Date: 2004 Impact factor: 6.556
Authors: Erik S Musiek; Yufen Chen; Marc Korczykowski; Babak Saboury; Patricia M Martinez; Janet S Reddin; Abass Alavi; Daniel Y Kimberg; David A Wolk; Per Julin; Andrew B Newberg; Steven E Arnold; John A Detre Journal: Alzheimers Dement Date: 2011-10-21 Impact factor: 21.566
Authors: Kevin J Black; Tamara Hershey; Jonathan M Koller; Tom O Videen; Mark A Mintun; Joseph L Price; Joel S Perlmutter Journal: Proc Natl Acad Sci U S A Date: 2002-12-13 Impact factor: 11.205
Authors: Kalen Petersen; Nelleke Van Wouwe; Adam Stark; Ya-Chen Lin; Hakmook Kang; Paula Trujillo-Diaz; Robert Kessler; David Zald; Manus J Donahue; Daniel O Claassen Journal: Hum Brain Mapp Date: 2017-10-31 Impact factor: 5.038
Authors: Paula Trujillo; Nelleke C van Wouwe; Ya-Chen Lin; Adam J Stark; Kalen J Petersen; Hakmook Kang; David H Zald; Manus J Donahue; Daniel O Claassen Journal: Cortex Date: 2019-01-29 Impact factor: 4.027
Authors: Paula M C Donahue; Rachelle Crescenzi; Chelsea Lee; Maria Garza; Niral J Patel; Kalen J Petersen; Manus J Donahue Journal: Breast Cancer Res Treat Date: 2020-06-29 Impact factor: 4.872
Authors: Alice Martini; Denise Dal Lago; Nicola M J Edelstyn; James A Grange; Stefano Tamburin Journal: Front Neurol Date: 2018-08-28 Impact factor: 4.003