Increased bradykinesia in Parkinson’s disease with increased movement complexity: elbow flexion-extension movements

The present research investigates factors contributing to bradykinesia in the control of simple and complex voluntary limb movement in Parkinson’s disease (PD) patients. The functional scheme of the basal ganglia (BG)–thalamocortical circuit was described by a mathematical model based on the mean firing rates of BG nuclei. PD was simulated as a reduction in dopamine levels, and a loss of functional segregation between two competing motor modules. In order to compare model simulations with performed movements, flexion and extension at the elbow joint is taken as a test case. Results indicated that loss of segregation contributed to bradykinesia due to interference between competing modules and a reduced ability to suppress unwanted movements. Additionally, excessive neurotransmitter depletion is predicted as a possible mechanism for the increased difficulty in performing complex movements. The simulation results showed that the model is in qualitative agreement with the results from movement experiments on PD patients and healthy subjects. Furthermore, based on changes in the firing rate of BG nuclei, the model demonstrated that the effective mechanism of Deep Brain Stimulation (DBS) in STN may result from stimulation induced inhibition of STN, partial synaptic failure of efferent projections, or excitation of inhibitory afferent axons even though the underlying methods of action may be quite different for the different mechanisms

A Long-Term Monitor Including Activity Classification for Motor Assessment in Parkinson’s Disease Patients

Tremor and bradykinesia are two prominent features of Parkinson's disease (PD). This paper presents the PD monitor, a measurement system using accelerometry to quantify tremor and bradykinesia. A correlation analysis of the physician's scores and the PD monitor demonstrated that the system accurately measured the severity of tremor and bradykinesia whilts assessing a broad spectrum of aspects related to both symptoms. In conclusion the PD monitor can be used for a detailed evaluation of the PD monitor symptoms in order to optimize treatment

The teratogenic effects of hypervitaminosis A on the formation of the neural tube

Contains fulltext : mmubn000001_02665198x.pdf (publisher's version ) (Open Access)Promotores : H. Lammers en J. Langman[X], 99 p

Parkinsonian movements in model and experiment

Parkinson's disease (PD) is known to originate from a degeneration of dopaminergic neurons in the substania nigra. One of the most debilitating aspects of PD is the inability to initiate and execute voluntary movements (bradykinesia and akinesia). PD patients are particularly impaired in the performance of complex movements, e.g. simultaneous and sequiential motor tasks... The goal of the current research is to develop a methematical model of the functional scheme of the 'motor' basal ganglia-thalamocortical circuit. In addition, an experimental study is set up to investigate movements performed by PD patients, and the effectiveness of DBS.\u

Effectiveness of deep brain stimulation in subthalamic nucleus in Parkinson’s disease – a somatotopic organisation

Deep Brain Stimulation (DBS) in subthalamic nucleus (STN) has substantially improved the suppression of symptoms in Parkinson's disease (PD). However, a quantitative understanding of the high-frequency stimulation opn the neuronal elements surrounding the electrode and the resulting effects for the different symptoms for upper and lower extremities is missing. The aim of the study is to investigate if there is a somatotopic organisation of the STN

Deep Brain Stimulation - the challenges ahead

Parkinson’s disease (PD) is characterized by progressive loss of dopamine neurons in the pars compacta of the substantia nigra, which results in reduced activity in the thalamus. Clinically effective deep brain stimulation (DBS) has been achieved with electrode contacts in the anterior- dorsal subthalamic nucleus (STN), globus pallidus internus (GPi) and ventral intermediate nucleus (Vim). Stimulation parameters (monopolar cathodic; 1-5 V amplitude; 60-200 μs pulse duration; 120-180 Hz frequency) have been established primarily by trial and error. Although DBS has substantially improved the suppression of symptoms in PD-patients: an average reduction of akinesia (42%), rigidity (49%), tremor (27%), the mechanism of DBS is still unclear and side- effects may occur (e.g. ocular deviation, hypophonia, speech disturbances). There is a lack of quantitative understanding of the influence of high-frequency stimulation on the neuronal elements surrounding the electrode and the neuronal systems involved

Modelling motor cortex stimulation for chronic pain control. electrical potential field, activating functions and responses of simple nerve fibre models

This computer modelling study on motor cortex stimulation (MCS) introduced a motor cortex model, developed to calculate the imposed electrical potential field characteristics and the initial response of simple fibre models to stimulation of the precentral gyrus by an epidural electrode, as applied in the treatment of chronic, intractable pain. The model consisted of two parts: a three-dimensional volume conductor based on tissue conductivities and human anatomical data, in which the stimulation-induced potential field was computed, and myelinated nerve fibre models allowing the calculation of their response to this field. A simple afferent fibre branch and three simple efferent fibres leaving the cortex at different positions in the precentral gyrus were implemented. It was shown that the thickness of the cerebrospinal fluid (CSF) layer between the dura mater and the cortex below the stimulating electrode substantially affected the distribution of the electrical potential field in the precentral gyrus and thus the threshold stimulus for motor responses and the therapeutic stimulation amplitude. When the CSF thickness was increased from 0 to 2.5 mm, the load impedance decreased by 28%, and the stimulation amplitude increased by 6.6 V for each millimetre of CSF. Owing to the large anode-cathode distance (10 mm centre-to-centre) in MCS, the cathodal fields in mono- and bipolar stimulation were almost identical. Calculation of activating functions and fibre responses showed that only nerve fibres with a directional component parallel to the electrode surface were excitable by a cathode, whereas fibres perpendicular to the electrode surface were excitable under an anode