Brain activity during rest is characterized by slow (0.01–0.1 Hz) fluctuations of blood oxygenation level-dependent functional magnetic resonance imaging signals. These fluctuations are organized as functional connectivity networks called resting-state networks, anatomically corresponding to specific neuronal circuits. As Parkinson’s disease is mainly characterized by a dysfunction of the sensorimotor pathways, which can be influenced by levodopa administration, the present study investigated the functional connectivity changes within the sensorimotor resting-state network in drug-naïve patients with Parkinson’s disease after acute levodopa administration. Using a double-blind placebo-controlled design, resting-state functional magnetic resonance imaging was carried out in 20 drug-naïve patients with Parkinson’s disease, immediately before and 60 min after, oral administration of either levodopa or placebo. Control resting-state functional magnetic resonance imaging data were recorded in 18 age- and sex-matched healthy volunteers. Independent component analysis was performed to extract resting-state network maps and associated time-course spectral features. At the anatomical level, levodopa enhanced the sensorimotor network functional connectivity in the supplementary motor area, a region where drug-naïve patients with Parkinson’s disease exhibited reduced signal fluctuations compared with untreated patients. At the spectral frequency level, levodopa stimulated these fluctuations in a selective frequency band of the sensorimotor network. The reported effects induced by levodopa on sensorimotor network topological and spectral features confirm that the sensorimotor system is a target of acute levodopa administration in drug-naïve patients with Parkinson’s disease. Moreover, while the regional changes in supplementary motor area reflect the functional improvement in motor function, the rhythm-specific modulation induced by the dopamine precursor discloses a novel aspect of pharmacological stimulation in Parkinson’s disease, adding further insight to the comprehension of levodopa action.

The diagnosis of Parkinson’s disease (PD) remains still clinical; nevertheless, in the last decades, the rapid evolution of advanced MRI techniques has made it possible to detect structural and, increasingly, functional brain changes in patients with PD. Indeed, functional MRI (fMRI) techniques have offered the opportunity to directly measure the brain’s activity and connectivity in patients with PD both in early and complicated stage of the disease. The aims of the following review are (1) to present an overview of recent fMRI reports investigating the activity and connectivity of sensorimotor areas in patients with PD using both task-related and “resting-state” fMRI analysis (2) to elucidate potential pathophysiological mechanisms underlying dyskinetic motor complications in the advanced stage of PD.