Intrinsic brain functional connectivity predicts treatment-related motor complications in early Parkinson’s disease patients

• Published in: Journal of neurology Vol. 271; no. 2; pp. 826 - 834
• Main Authors: De Micco, Rosa, Di Nardo, Federica, Siciliano, Mattia, Silvestro, Marcello, Russo, Antonio, Cirillo, Mario, Tedeschi, Gioacchino, Esposito, Fabrizio, Tessitore, Alessandro
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2024; Springer Nature B.V
• Subjects: Brain; Brain - diagnostic imaging; Brain Mapping - methods; Clinical trials; Dopamine; Dopamine receptors; Frontal gyrus; Humans; Magnetic Resonance Imaging - methods; Medicine; Medicine & Public Health; Movement disorders; Neural networks; Neurodegeneration; Neurodegenerative diseases; Neurology; Neuroradiology; Neurosciences; Original Communication; Parkinson Disease - complications; Parkinson Disease - diagnostic imaging; Parkinson Disease - drug therapy; Parkinson's disease; Patients; Sensorimotor system; Drug-naïve; Treatment-related complications; MRI; Parkinson’s disease; Resting-state connectivity
• ISSN: 0340-5354; 1432-1459; 1432-1459
• DOI: 10.1007/s00415-023-12020-6

Background Treatment-related motor complications may develop progressively over the course of Parkinson’s disease (PD). Objective We investigated intrinsic brain networks functional connectivity (FC) at baseline in a cohort of early PD patients which successively developed treatment-related motor complications over 4 years. Methods Baseline MRI images of 88 drug-naïve PD patients and 20 healthy controls were analyzed. After the baseline assessments, all PD patients were prescribed with dopaminergic treatment and yearly clinically re-assessed. At the 4-year follow-up, 36 patients have developed treatment-related motor complications (PD-Compl) whereas 52 had not (PD-no-Compl). Single-subject and group-level independent component analyses were used to investigate FC changes within the major large-scale resting-state networks at baseline. A multivariate Cox regression model was used to explore baseline predictors of treatment-related motor complications at 4-year follow-up. Results At baseline, an increased FC in the right middle frontal gyrus within the frontoparietal network as well as a decreased connectivity in the left cuneus within the default-mode network were detected in PD-Compl compared with PD-no-Compl. PD-Compl patients showed a preserved sensorimotor FC compared to controls. FC differences were found to be independent predictors of treatment-related motor complications over time. Conclusion Our findings demonstrated that specific FC differences may characterize drug-naïve PD patients more prone to develop treatment-related complications. These findings may reflect the presence of an intrinsic vulnerability across frontal and prefrontal circuits, which may be potentially targeted as a future biomarker in clinical trials.