Accentuated Paralimbic and Reduced Mesolimbic D2/3-Impulsivity Associations in Parkinson's Disease

• DOI: 10.1523/jneurosci.1037-23.2023
• Publication Date: 2023-10-18T17:50:55Z
• Authors: Adam J. Stark; Alexander K. Song; Kalen J. Petersen; Kaitlyn R. Hay; Ya-Chen Lin; Paula Trujillo; Hakmook Kang; Jenna M. Collazzo; Manus J. Donahue; David H. Zald; Daniel O. Claassen
• Keywords: Barratt Impulsiveness Scale; Orbitofrontal cortex; Ventral striatum

Impulsivity is a behavioral trait that elevated in many neuropsychiatric disorders. Parkinson's disease (PD) patients can exhibit specific pattern of reward-seeking impulsive-compulsive behaviors (ICBs), as well more subtle changes to generalized impulsivity. Prior studies healthy controls (HCs) suggest impulsivity regulated by D 2/3 autoreceptors mesocorticolimbic circuits. While altered binding noted ICB + PD patients, there limited prior assessment the impulsivity–D relationship PD, and no direct comparison with patterns HCs. We examined 54 (36 M; 18 F) 31 sex- age-matched HC (21 10 subjects using [ F]fallypride, high-affinity receptor ligand, measure striatal extrastriatal nondisplaceable potential (BP ND ). Subcortical cortical exclusively used ROI or exploratory-voxelwise methods, respectively. All completed Barratt Impulsiveness Scale, analyses indicated negative between BP ventral striatum amygdala HCs but not PD. By contrast, voxelwise methods demonstrated positive correlation frontal olfactocentric-paralimbic cortex Subscale analysis also highlighted different aspects impulsivity, significant interactions group motor striatum, attentional paralimbic cortex. These results dopamine functioning distinct regions circuit influence relative importance regional functions shifting neuropharmacological context SIGNIFICANCE STATEMENT The biological determinants have broad clinical relevance, from addiction neurodegenerative Here, we address biomolecular distinctions disease. This first study evaluate large cohort concurrent F]fallypride PET, method allows quantification D2/3 receptors throughout network. demonstrate widespread differences impulsivity–dopamine relationship, including (1) loss subcortical relationships present brain (2) emergence new limbic area. illustrates mechanisms regulation while suggesting compensatory response target for future investigation.