DAT SPECT and Procedural Motor Skills in Parkinson's Disease
Parkinson DiseasePatients with Parkinson's disease (PD) are known to be affected by subtle cognitive impairment early in the disease course, mostly in the executive field. Procedural motor skills, mainly controlled by the basal ganglia associative loop (in particular dorsal caudate nucleus) (Rodriguez-Oroz et al., 2009), have also been studied in patients with PD (Schnider et al., 1995; Muslimovic et al., 2007; Terpening et al., 2013). However, the correlation of dopaminergic 123I-FP-CIT SPECT imaging and cognitive impairment has not been assessed. One reason is the absence of reference values for striatal uptake until recently. Last year, the investigators established local uptake reference values for DAT imaging based on a large cohort of subjects with non-degenerative conditions (Nicastro et al., 2016) and can therefore use these values to precisely assess uptake loss in patients with PD. With the present study, the investigators expect to enroll patients with early PD for whom a 123I-FP-CIT SPECT has been previously performed in the center. Subjects will perform a specific motor task based on mirror-drawing of star-shaped figures. This will be done by inverting the direction of horizontal/vertical computer mouse movements on the screen. Speed and error rates will be assessed for patients as well as healthy control subjects. Correlation with striatal SPECT uptake, especially caudate nucleus uptake, will be analyzed for PD patients. In addition, resting-state EEG will be performed for all subjects. General medication and dopaminergic drugs in particular, whenever used, will not be discontinued. For all subjects enrolled in the study, cognitive and neurological examination will be performed.
Long-term Stability of LFP Recorded From the STN and the Effects of DBS
Parkinson's DiseaseMovement disorders such as Parkinson Disease, dystonia, and tremor are related to abnormalities of part of the brain known as the basal ganglia. Recently, it has been suggested that the basal ganglia works by oscillations (group of neurons cycle between activation/deactivation when stimulated) of electrical signals. A treatment that involves insertion of electrodes in the subthalamic nucleus (STN) for electrical stimulation, known as deep brain stimulation (DBS), is an established treatment for advanced Parkinson's disease. However its mechanism of action is still not completely understood. Currently, DBS utilizes an "open loop" system whereby the stimulation settings are manually adjusted depending on the patients' clinical response. Determine whether the local field potential (LFP) recorded from the STN is stable over a 1.5 year period. Address whether STN LFP is a suitable control signal, and how it should be used to change DBS parameters
Dynamic ASPECTS of Internal PRE-ACTIVATION of Effects Sensors of Voluntary ACTION in PARKINSON's...
Parkinson's DiseaseThe ability to predict sensory effects of people's own motor actions is a key component of Human action realization. Recent studies revealed this anticipation process to be involved in early and late stages of voluntary actions. Nevertheless, the question whether the action-effect anticipation is impacted or not by "motor pathologies", such as the Parkinson's disease, remains unclear. The current study is aimed to clarify this issue by using a subliminal priming paradigm in patients with Parkinson's disease and in matched control participants. Indeed, subliminal primes corresponding to visual action-effects are displayed at different time points before the actions' execution. Results should allow to determine whether or not the action-effect prediction is impaired at different stages of voluntary action in patients with Parkinson's disease.
eOnOff - D1 Extension
Parkinson DiseaseClinical assessments can only offer a snapshot of daily life with Parkinson's Disease, while wearable devices can offer immensely more information that can improve the understanding of this disease. With recent advancements in technology, investigators are now able to use watch-like devices to more effectively measure the symptoms of Parkinson's Disease outside of the doctor's office. The present study is designed to evaluate the usability, applicability, and interpretability of an electronic VA Patient Motor Diary (eON-OFF), MC10 BioStampRC actigraphy sensor, APDM actigraphy sensor and the GENEActiv Watch in persons with Parkinson's Disease. There is no placebo/control group.
Superior Colliculus Activity in Parkinson Disease: a Potential Marker?
Parkinson's DiseaseThe ultimate goal of this project is to evaluate a possible new strategy to diagnose earlier Parkinson's disease, using the superior colliculus as a biomarker. Preliminary data from the investigator's group in a rat model of Parkinson's disease suggest that the superior colliculus, a sensory structure, show an early deficit in visual processing. The investigator's data also suggests that with the evolution of the disease, this structure presents a neuronal re-organisation leading which causes a sensory rebound after the introduction of the treatment. The light responses in the superior colliculus were faster, bigger in amplitude and lasted longer (Rolland et al., 2012). Those results raise an important question about the superior colliculus functional state in Parkinson's patients. If this structure have a similar neuroplasticity, the investigators could hypothesize that the superior colliculus may also present a sensory rebound when introducing the treatment. If this hypothesis is true, the accelerated and amplified light responses of this structure may explain the difficulties felt by the patients to inhibit reflexive saccades induced by the appearance of unexpected visual stimuli. Indeed, the superior colliculus is involved in the orientation of the head and eye toward any sudden changes in our environment (Wurtz and Albano, 1980) and the light responses of this structure are strongly correlated with the speed of the saccade (Marino et al., 2012). Therefore, the investigators want to test if a similar deficit could be observed in the superior colliculus of newly diagnosed PD patients. Data will be compared to matching controls.
Idiopathic Parkinson's Progression and Dopamine Transporter SPECT
Parkinson DiseaseDaTscanTM Ioflupane I123, a radiopharmaceutical will be used as an adjunct diagnostic tool in combination with single photon emission computed tomography (SPECT) to evaluate striatal dopamine transporter (DAT) distribution in patients with idiopathic Parkinson's disease. Patients will be monitored twice - once at baseline, and again after 1 year - to identify potential biomarkers for progression of Parkinson's disease.
Predictive Factors of Short/Long-term Outcome and Complications of Bilateral DBS in PD
Parkinson DiseaseThe purpose and main objective of this study is the research of pre-operative and operative predictive factors of short-term (1-year) and long-term (15-years) improvement of quality of life, motor and non-motor symptoms in Parkinson's disease patients who have undergone to bilateral Subthalamic Nucleus Deep Brain Stimulation. The hypothesis of the study is that the definition of pre-operative and operative predictive factors could be able to improve the pre-operative prognostic accuracy of outcome and complications after surgery, allowing also a better selection of the most suitable candidates for bilateral Subthalamic Nucleus Deep Brain Stimulation. For example, we can suppose that an older age at surgery, elevated axial score, a less preoperative dopa-responsiveness, the presence of mild executive dysfunction at surgery or an unfavourable social status, could negatively influence the short and long term surgery outcome
Quantification of Cerebral Cholinergic Function in Parkinson´s Disease by Means of Nuclear Medicine...
Parkinson´s DiseaseAcetylcholine1 moreParkinson´s disease is based on a Lewy body degeneration of cerebral and extracerebral neurons. This Lewy body degeneration includes cerebral cholinergic neurons besides dopaminergic neurons. In previous studies the investigators found that some clinical parkinsonian symptoms - primarily hypokinesia and rigidity - significantly correlate with the dopaminergic nigrostriatal degeneration which was quantified by dopamine transporter imaging. In contrast to that, resting or postural parkinsonian tremor does not correlate with the dopaminergic nigrostriatal degeneration. Obviously further cerebral changes - for instance possible changes / degeneration of cerebral cholinergic neurons - contribute to parkinsonian tremor. In this study the investigators apply cerebral 5-IA-85380-SPECT to quantify the local density of cerebral nicotinergic cholinergic receptors in patients with Parkinson´s disease. The investigators will correlate the results of cerebral 5-IA-85380-SPECT with the clinical parkinsonian main symptoms hypokinesia, rigidity and primarily resting and postural tremor. In particular, it is of interest whether changes of cerebral cholinergic neurons are involved in the generation of parkinsonian tremor.
Executive, Activities of Daily Living, and Cholinergic Functions in Parkinson's Disease
Parkinson's DiseaseThis research study will evaluate functions of memory, thinking, behavior, and daily life activities and how these relate to the measurement of certain chemicals (acetylcholine and dopamine) in the brain using an imaging procedure called positron emission tomography (PET). You may know that in Alzheimer's dementia (dementia is a disease where persons become forgetful and confused), a reduction in the amount of acetylcholine, a "neurotransmitter" substance (a chemical messenger that nerve cells need to communicate with each other), may be responsible for some of the memory and behavioral changes. At the present time, the investigators have no clear information on the levels of acetylcholine in the brain of patients with Parkinson's disease who also have memory or behavioral changes.
Phosphorylation of ERK1/2 in Patients With Parkinson's Disease
Parkinson DiseaseLevodopa-induced dyskinesia severely limits the use of levodopa in Parkinson's disease and constitutes a debilitating complication of dopaminergic treatment in late stage. Among several neurobiological mechanisms identified so far, the investigators have established in experimental models the key role of D1 receptor hypersensitivity and a"Ras-ERK" signalling pathway. As the very same dopamine receptor machinery and the Ras-ERK pathway are present in blood lymphocytes, the investigators wish to test the hypothesis that the level of ERK phosphorylation in lymphocytes is a biomarker of levodopa-induced dyskinesia in Parkinson's Disease. The study will be performed in dyskinetic levodopa-treated patients and non-Parkinson's Disease controls. Blood sampling "off" and "on" levodopa treatment (1 hour post-dose), as well as clinical data collection will be done during a scheduled pre-op work-up (deep brain stimulation). Subsequently, suspended lymphocytes from blood samples will be immunolabelled using an anti-pERK antibody and mean fluorescence intensity and percent of labelled lymphocytes will be assessed by flow cytometry. Additionally, plasma and urine samples will be collected "on" et "off" for dosage of dopamine. The motor effect of levodopa will be assessed through UPRSIII rating scale and eye movement (saccades) speed by non-invasive oculometric recordings.