Impaired Functional Connectivity of Sensorimotor Network Predicts Recovery in Drug-Induced Parkinsonism

Abstract

Objective: In a substantial portion of patients with drug-induced parkinsonism (DIP), parkinsonism may persist for long periods after discontinuation of offending drugs, suggesting subtle underlying neurodegeneration. We hypothesized that patients with DIP have impaired functional connectivity (FC) of brain networks, which may determine the reversibility of parkinsonism.

Methods: In this case-control study, we consecutively recruited 60 patients with DIP and 32 healthy controls. We used independent component analysis and dual regression of functional magnetic resonance imaging data to identify seven resting-state networks and compared FC of the networks between the DIP and control groups. Among regions where the two groups showed a significant difference in the FC with sensorimotor network, we compared the FC between patients who had completely recovered (n = 21) and those who had partially recovered (n = 39) within 3 months of cessation of the offending drugs.

Results: Patients with DIP had decreased FC between the sensorimotor network and widespread brain regions, when compared to healthy controls. FC in the prefrontal regions was negatively correlated with parkinsonian motor score. Patients who partially recovered had a significantly lower FC in the prefrontal and cerebellar regions than those who recovered completely, providing a useful predictor of recovery status.

Conclusions: Patients with DIP had decreased FC of the sensorimotor network, which correlated with the severity of parkinsonism and predicted the recovery status after cessation of offending drugs. Impaired FC of the sensorimotor network can be used as a biomarker to evaluate the severity and prognosis of DIP.