Cholinergic relevant functional reactivity is associated with dopamine responsiveness of tremor in Parkinson’s disease

Tremor in Parkinson’s disease (PD) has distinct responsiveness to dopamine, which is supposed not be exclusively related to dopamine deficiency but has a close relationship with cholinergic system. This phenomenon indicates that cholinergic system may be an important regulatory for distinct dopamine responsiveness of parkinsonian tremor. Through investigating the alterations of cholinergic and dopaminergic network during levodopa administration, we aimed at exploring the mechanisms of differed dopamine responsiveness of parkinsonian tremor. Fifty-two PD patients with tremor were enrolled. MRI scanning, UPDRS III and its sub-symptom scores were collected in OFF and ON status (dopaminergic challenge test). Then, patients were divided into two groups (dopamine-resistant tremor and dopamine-responsive tremor) according to the tremor change rate median score. Dopaminergic and cholinergic network were obtained. LASSO regression was conducted to identify functional connectivity with distinct reactivity during levodopa administration between groups. Afterwards, detailed group comparisons, interaction and correlation analyses were performed. The reactivity of cholinergic connectivity showed the highest possibility to distinguish two groups, especially connectivity of right basal forebrain 123 to right parietal operculum cortex (R.BF123-R.PO). After levodopa administration, connectivity of R.BF123-R.PO was decreased for dopamine-responsive tremor while which remained unchanged for dopamine-resistant tremor. The reactivity of R.BF123-R.PO was negatively correlated with tremor change rate. Reduced cholinergic connectivity to parietal operculum may be an underlying mechanism for the responsive tremor in PD and the distinct cholinergic reactivity of parietal operculum to levodopa may be a core pathophysiology for the differed DA responsiveness of tremor in PD.

Discrimination between parkinsonian tremor and essential tremor using artificial neural network with hybrid features

BACKGROUND: Essential tremor (ET) and the tremor in Parkinson’s disease (PD) are the two most common pathological tremors with a certain overlap in the clinical presentation. OBJECTIVE: The main purpose of this work is to use an artificial neural network to select the best features and to discriminate between the two types of tremors. The features used are of hybrid type obtained from two different algorithms: the statistical signal characterization (SSC) of the signal describing its morphology, and the soft-decision wavelet-decomposition (SDWD) features extracted from the accelerometer and surface EMG signals. METHODS: The SSC method is used to obtain morphology-based features of the spectrum of the accelerometer and two surface EMG signals. The SDWD technique is used in this work to obtain the approximate spectral representation of both accelerometer and the two surface EMG signals. Two sets of data (training and test) are used in this paper. The training set consists of 21 ET subjects and 19 PD subjects, while the test set consists of 20 ET and 20 PD subjects. A neural network of the type feed forward back propagation has been used to combine best SSC features and best SDWD features of the accelerometer and EMG signals. RESULTS: Efficiency result of 92.5% was obtained using best hybrid features. CONCLUSIONS: The artificial neural network has been used successfully to combine two types of features in an automatic discrimination system between PD and ET.

Effect of galanin on severity of tremor in Parkinson's disease

Objective. To study the effect of galanin on the severity of tremor in Parkinson's disease. Materials and methods. A comprehensive examination of 73 patients with Parkinson's disease and 16 apparently healthy individuals (control group) was carried out. We used the clinical-anamnestic method, the Hen-Yar scale of movement disorders in Parkinson's disease (PD), the MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Serum galanin content was determined by enzyme immunoassay. Serum galanin was determined by enzyme-linked immunosorbent assay using an ELISA Kit for Galanin (USA). Statistical processing of the material was carried out using the Statistica 10.0 program. Results. Tremor is one of the main complaints of PD patients. In the main group, the average severity of the disease, subjective and objective manifestations of movement disorders were determined. In patients with PD, a decrease in the quantitative content of blood serum galanin (6.0 [4.3; 10.2] ng / ml) was determined in comparison with the control group (16.9 [9.8; 18.1] ng/ml, p = 0.001). A negative correlation dependence of the galanin content with motor manifestations was revealed in the first (R = 0.8; p = 0, 0001) and second (R = 0.53; p = 0.000002) parts of the MDS-UPDRS, as well as with the severity of resting tremor in the hand (R = 0.81; p = 0.000000) and leg (R = 0.76; p = 0.000001). The dependence of serum galanin on the form of the disease was not obtained in the study. Conclusions. In Parkinson's disease, there is a decrease in the quantitative content of the neuropeptide galanin in the blood serum, which is negatively associated with motor manifestations of the disease and is associated with the severity of parkinsonian tremor.

Increasing Serotonin to Reduce Parkinsonian Tremor

While current dopamine-based drugs seem to be effective for most Parkinson's disease (PD) motor dysfunctions, they produce variable responsiveness for resting tremor. This lack of consistency could be explained by considering recent evidence suggesting that PD resting tremor can be divided into different partially overlapping phenotypes based on the dopamine response. These phenotypes may be associated with different pathophysiological mechanisms produced by a cortical-subcortical network involving even non-dopaminergic areas traditionally not directly related to PD. In this study, we propose a bio-constrained computational model to study the neural mechanisms underlying a possible type of PD tremor: the one mainly involving the serotoninergic system. The simulations run with the model demonstrate that a physiological serotonin increase can partially recover dopamine levels at the early stages of the disease before the manifestation of overt tremor. This result suggests that monitoring serotonin concentration changes could be critical for early diagnosis. The simulations also show the effectiveness of a new pharmacological treatment for tremor that acts on serotonin to recover dopamine levels. This latter result has been validated by reproducing existing data collected with human patients.

Characterisation of Dentatorubrothalamic tract with Diffusion Spectrum Imaging in Patients suffering from Parkinson’s disease

Introduction: Clinical data support that the dentatorubrothalamic tract (DRTT) is an effective target for deep brain stimulation (DBS) in medically refractory tremor. Nevertheless, the achievement of a realistically detailed depiction of DRTT for preoperative direct targeting remains a challenge.Methods: Ten patients with Parkinson’s disease from the Inselspital Bern database were selected. We used diffusion spectrum imaging (DSI) scans for deterministic fiber tracking of the DRTT with the Track Vis software. Thereafter we compared our DSI-characterized DRTT with the existing anatomical data.Results: In 6 out of 10 individuals the full course of DRTT has been in high affiliation/consistency/association/adherence with the anatomical course of DRTT as described in literature.Conclusions: In this study DSI fiber tracking was used to characterize successfully the DRTT anatomical course in its complexity in a quest of the optimal DBS target for parkinsonian tremor. To our knowledge such attempt has not occurred before. Further studies are required to standardize the protocol of DRTT fiber Tracking and to implement it as a valid DBS preoperative planning technique.