The Cerebral Structural and Functional Signatures of Impulse Control Disorder in Parkinson’s Disease (P4.104)

Objective: To assess cortical thickness (CT), white matter (WM) microstructural integrity and resting state (RS) functional connectivity in Parkinson’s disease patients with impulse control disorder (PD-ICD) compared with healthy controls and PD no-ICD cases matched for disease stage and duration, motor impairment, and cognitive status. Background: Compared with PD no-ICD, PD-ICD patients are characterized by more severe psychiatric symptomatology and cerebral structural alterations in the meso-cortico-limbic circuit. However, while comparing these syndromes, patient disease stage, motor impairment, and cognitive status must be taken into account. Methods: This study included 85 PD patients (35 with ICD) and 50 healthy controls. Patient groups were matched for age-of-onset, disease duration, levodopa equivalent dose, Hoehn and Yahr scale score, Unified PD rating scale-III score, and cognitive status. All subjects underwent 3D T1-weighted, diffusion tensor (DT) and RS functional MRI (RS-fMRI). Results: Compared with controls, both patient groups showed a widespread pattern of brain alterations involving the extrapyramidal, pyramidal and associative systems. Compared with PD no-ICD, PD-ICD patients showed more severe neuropsychiatric symptoms, reduced CT of the superior frontal and precentral gyri, and motor and extra-motor WM tract involvement. Relative to PD no-ICD, PD-ICD patients also showed: decreased functional connectivity of the right and left inferior orbitofrontal gyri within the right-fronto-parietal and dorsal-attentive networks, respectively; and increased functional connectivity of the right precentral and postcentral gyri within the sensorimotor network and of the right cerebellum within the cerebellar-associative network. In PD-ICD, WM damage of the genu of the corpus callosum and the right uncinate was associated with ICD duration and severity of depressive symptoms. Conclusions: This study demonstrates a severe involvement of frontal, meso-limbic and motor circuits in PD-ICD patients. A multimodal neuroimaging approach is promising for understanding the mechanisms associated with ICD and for the detection of PD patients at risk to develop ICD.