See Postuma (doi:) for a scientific commentary on this article. Idiopathic REM sleep behaviour disorder (RBD) is associated with frequent conversion to Parkinson’s disease. Rolinski et al. show that resting-state fMRI differentiates cases of RBD and Parkinson’s disease from controls with high sensitivity (96%) and specificity (74–78%). Basal ganglia network connectivity may reveal future Parkinson’s disease before motor symptom onset.

Objective: To investigate whether a serotonin-to-dopamine terminal ratio is related to the appearance of dyskinesias in patients with Parkinson disease (PD).Methods: Twenty-eight patients with idiopathic PD (17 with levodopa-induced dyskinesias [LIDs], 11 without dyskinesias) and 12 age-matched healthy controls were studied with PET and 5[11 C]-3-amino-4-(2-dimethylaminomethylphenyl-sulfanyl)-benzonitrile ( 11 C-DASB) and with SPECT and [ 123 I]N-w-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl)nortropane ( 123 I-ioflupane), which are in vivo specific markers of the serotonin and dopamine transporters' availability, respectively. We have employed a simplified reference tissue model for the quantification of 11 C-DASB, whereas a semiquantification approach was used for 123 I-ioflupane data. We calculated 11 C-DASB binding to 123 I-ioflupane uptake ratios for the caudate and the putamen.Results: Patients with PD showed striatal decreases in 11 C-DASB binding potential (p , 0.01) and in 123 I-ioflupane mean uptake (p , 0.001) compared to controls. The mean 11 C-DASB binding to 123 I-ioflupane uptake ratio in the putamen was 0.779 (increased by 75.8% of the controls' mean) for the nondyskinetic group and 0.901 (increased by 103.4% of the controls' mean) for the patients with dyskinesias. There was a statistically significant difference (p , 0.001) in 11 C-DASB binding to 123 I-ioflupane uptake ratio in the putamen between the group of patients with and without dyskinesias. Higher 11 C-DASB to 123 I-ioflupane binding ratios correlated with longer disease duration for the 28 patients with PD (r 5 0.52; p , 0.01).Conclusions: Serotonin-to-dopamine transporter binding ratio increases as PD progresses and patients experience LIDs. Our findings suggest that, when the dopaminergic innervation in the striatum is critically low, the serotonergic system plays an important role in development of LIDs. Studies in the animal model of Parkinson disease (PD)1 as well as in humans 2-4 have indicated that degeneration of dopaminergic presynaptic terminals in the striatum is critical in the development of L-dopa-induced dyskinesias (LIDs). Due to the progressive degeneration, striatal dopaminergic terminals lose their dopamine storage capacity and the ability to maintain a stable dopamine release rate in the synapse. 5 Serotonergic terminals have been found capable of converting exogenous levodopa into dopamine, store it in synaptic vesicles, and release it in an activity-dependent manner. [6][7][8][9] The above studies propose that serotonergic terminals in the degenerating striatum are responsible for mishandling exogenous levodopa and exacerbating dyskinesia in the animal model 10-12 and PD.13 Accordingly, the presence of dyskinesia could be a reflection of serotonergic over