Diffusion kurtosis imaging in the basal ganglia, as compared with conventional diffusion-tensor imaging, can improve the diagnosis of PD.

IMPORTANCE Currently, diagnosis of Parkinson disease is mainly based on clinical criteria characterized by motor symptoms including bradykinesia, rigidity, resting tremor, and postural instability. Reliable in vivo biomarkers to monitor disease severity and reflect the underlying dopaminergic degeneration are important for future disease-modifying therapy in Parkinson disease. OBJECTIVES To use [ 18 F]9-fluoropropyl-(+)-dihydrotetrabenazine (18 F-DTBZ; [ 18 F]AV-133) positron emission tomography (PET) to explore the characteristics of vesicular monoamine transporter type 2 imaging in patients with Parkinson disease (PD) with different severity levels as well as to investigate its capability in monitoring clinical severity. DESIGN, SETTING, AND PARTICIPANTS Regional uptakes for 18 F-DTBZ PET of different disease stages were measured. Seventeen healthy control participants and 53 patients in 3 groups of mild, moderate, and advanced stages of PD were recruited for 18 F-DTBZ PET scans from the Movement Disorders Clinic in the Chang Gung Memorial Hospital, Taiwan. MAIN OUTCOMES AND MEASURES The severity of disease in patients with PD was quantified by modified Hoehn-Yahr Scale, Unified Parkinson Disease Rating Scale total scores and subscores of posture instability and gait disturbance, tremor, akinesia, and rigidity while not taking medication. Both voxelwise-and volume of interest-based image analyses were performed. The specific uptake ratio (SUR) of each volume of interest and voxel was calculated as (target uptake − reference uptake) / reference uptake using the occipital reference region from magnetic resonance imaging-based spatially normalized 18 F-DTBZ images for each participant. Average SUR images were displayed as 2-dimensional and 3-dimensional to illustrate the image patterns in each group. The nonparametric Kruskal-Wallis test on regional SUR was used for group comparison between healthy control participants and patients with PD at different stages. Quantitative parameters were correlated with severity of disease and disease duration by Spearman correlation. Voxelwise analysis for evaluating dopaminergic neuron decline of different PD stages was performed by SPM5. RESULTS The 2-dimensional and 3-dimensional 18 F-DTBZ PET images demonstrated that the reduction of vesicular monoamine transporter type 2 availability was obviously correlated with the severity of disease in patients with PD. The mean reductions of vesicular monoamine transporter type 2 density for the caudate, putamen, and substantia nigra were 21.50%, 58.20%, and 21.10% for mild PD; 60.75%, 79.49%, and 39.87% for moderate PD; and 63.94%, 83.20%, and 44.00% for advanced PD, respectively. The SURs of bilateral striatal regions exhibited significantly exponential correlations to stage; disease duration; Unified Parkinson Disease Rating Scale motor score; posture instability and gait disturbance; and akinesia, rigidity, and tremor scores. CONCLUSIONS AND RELEVANCE In PD, 18 F-DTBZ PET is a potential imaging biomarker for measuring dopaminergic ...

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A number of experiments in animals have shown that successful induction of plasticity can be abolished if an individually ineffective intervention is given shortly afterwards. Such effects are termed depotentiation/de-depression. These effects contrast with metaplasticity/homeostatic plasticity in which pretreatment of the system with one protocol modulates the response to a second plasticity-inducing protocol. Homeostatic plasticity maintains the balance of plasticity in the nervous system at a stable level whereas depotentiation/de-depression abolishes synaptic plasticity that has just occurred in order to prevent ongoing learning. In the present study, we developed novel protocols to explore the reversal of LTP-and LTD-like effects in healthy conscious humans based on the recently developed theta burst form of repetitive transcranial magnetic stimulation (TBS). The potentiation effect induced by intermittent TBS (iTBS) was completely erased by a short form of continuous TBS (cTBS150) given 1 min after iTBS, whereas the depressive effect of continuous TBS (cTBS) was successfully abolished by a short form of iTBS (iTBS150). The reversal was specific to the nature of the second protocol and was time dependent since it was less effective when the intervention was given 10 min after induction of plasticity. All these features are compatible with those of depotentiation and de-depression demonstrated in animal studies. The development of the present protocols would be helpful to study the physiology of the reversal of plasticity and learning and to probe the abnormal depotentiation/de-depression shown in animal models of neurological diseases (e.g. Parkinson's disease with dyskinesia, dystonia and Huntingon's disease).