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

Striatal C-PE2I appears to show greater sensitivity for detecting differences in motor severity than F-dopa. Furthermore, dopamine transporter decline is closely associated with motor progression over time, whereas no such relationship was found with aromatic l-amino acid decarboxylase. C-PE2I may be more effective for evaluating the efficacy of neuroprotective treatments in PD. © 2017 International Parkinson and Movement Disorder Society.

Parkinson’s disease is characterized by the progressive loss of pigmented dopaminergic neurons in the substantia nigra and associated striatal deafferentation. Neuromelanin content is thought to reflect the loss of pigmented neurons, but available data characterizing its relationship with striatal dopaminergic integrity are not comprehensive or consistent, and predominantly involve heterogeneous samples. In this cross-sectional study, we used neuromelanin-sensitive MRI and the highly specific dopamine transporter PET radioligand, 11C-PE2I, to assess the association between neuromelanin-containing cell levels in the substantia nigra pars compacta and nigrostriatal terminal density in vivo, in 30 patients with bilateral Parkinson’s disease. Fifteen healthy control subjects also underwent neuromelanin-sensitive imaging. We used a novel approach taking into account the anatomical and functional subdivision of substantia nigra into dorsal and ventral tiers and striatal nuclei into pre- and post-commissural subregions, in accordance with previous animal and post-mortem studies, and consider the clinically asymmetric disease presentation. In vivo, Parkinson’s disease subjects displayed reduced neuromelanin levels in the ventral (−30 ± 28%) and dorsal tiers (−21 ± 24%) as compared to the control group [F(1,43) = 11.95, P = 0.001]. Within the Parkinson’s disease group, nigral pigmentation was lower in the ventral tier as compared to the dorsal tier [F(1,29) = 36.19, P < 0.001] and lower in the clinically-defined most affected side [F(1,29) = 4.85, P = 0.036]. Similarly, lower dopamine transporter density was observed in the ventral tier [F(1,29) = 76.39, P < 0.001] and clinically-defined most affected side [F(1,29) = 4.21, P = 0.049]. Despite similar patterns, regression analysis showed no significant association between nigral pigmentation and nigral dopamine transporter density. However, for the clinically-defined most affected side, significant relationships were observed between pigmentation of the ventral nigral tier with striatal dopamine transporter binding in pre-commissural and post-commissural striatal subregions known to receive nigrostriatal projections from this tier, while the dorsal tier correlated with striatal projection sites in the pre-commissural striatum (P < 0.05, Benjamini-Hochberg corrected). In contrast, there were no statistically significant relationships between these two measures in the clinically-defined least affected side. These findings provide important insights into the topography of nigrostriatal neurodegeneration in Parkinson’s disease, indicating that the characteristics of disease progression may fundamentally differ across hemispheres and support post-mortem data showing asynchrony in the loss of neuromelanin-containing versus tyrosine hydroxylase positive nigral cells.

Increased nigral iron accumulation in PD appears to be stratified according to disease motor severity and correlates with symptoms related to dopaminergic neurodegeneration. This semi-quantitative in vivo iron assessment could prove useful for objectively monitoring PD progression, especially in clinical trials concerning iron chelation therapies.

Highlights DAT-specific radioligands and PET is one measure of nigrostriatal dopaminergic integrity. Basal ganglia functional connectivity can differentiate patients with PD from healthy controls. Striatal functional connectivity is dependent on the integrity of dopaminergic system. Basal ganglia functional connectivity is compromised by the dopaminergic pathology of PD.

To date, little is known about how neurodegeneration and neuroinflammation propagate in Huntington’s disease (HD). Unfortunately, no treatment is available to cure or reverse the progressive decline of function caused by the disease, thus considering HD a fatal disease. Mutation gene carriers typically remain asymptomatic for many years although alterations in the basal ganglia and cortex occur early on in mutant HD gene–carriers. Positron Emission Tomography (PET) is a functional imaging technique of nuclear medicine which enables in vivo visualization of numerous biological molecules expressed in several human tissues. Brain PET is most powerful to study in vivo neuronal and glial cells function as well as cerebral blood flow in a plethora of neurodegenerative disorders including Parkinson’s disease, Alzheimer’s and HD. In absence of HD–specific biomarkers for monitoring disease progression, previous PET studies in HD were merely focused on the study of dopaminergic terminals, cerebral blood flow and glucose metabolism in manifest and premanifest HD–gene carriers. More recently, research interest has been exploring novel PET targets in HD including the state of phosphodiesterse expression and the role of activated microglia. Hence, a better understanding of the HD pathogenesis mechanisms may lead to the development of targeted therapies. PET imaging follow–up studies with novel selective PET radiotracers such as 11C-IMA–107 and 11C-PBR28 may provide insight on disease progression and identify prognostic biomarkers, elucidate the underlying HD pathology and assess novel pharmaceutical agents and over time.

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