129 research outputs found

    STN activity recorded in vitro:Dissociated cell cultures

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    In PD, because of the loss of the dopaminergic nigrostriatal connection, the basal ganglia neurons, including the STN, fire by low-frequency oscillatory bursts and fire in synchrony. Under normal conditions, the basal ganglia neurons fire irregularly. The reciprocal pallido-subthalamic connection can be mimicked in vitro and is capable of burst firing. This pattern can be influenced by co-cultures of striatum and cortex (Plenz and Kitai 1999). The observed bursting activity was unaccompanied by synchronous activity in STN slice preparations after the addition of glutamate, dopamine, GABA, or muscarine receptor agonists and/or antagonists. Therefore, synchrony of STN activity in the parkinsonian state is dependent on its extrinsic connections (Wilson et al. 2004). Dissociation of central nervous system areas of P1 (day 1 postnatal) rat pups makes it possible to culture these neurons in a chemically defined medium (Heida 2003). By placing these cultures on MEAs, their spontaneous electrical activity can be recorded. By using polyethylenimine as substrate, a seemingly monolayered network can be created in culture on the MEA (see Rutten et al. 2001 for an overview).</p

    Selective stimulation of the subthalamic nucleus

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    Parkinson's disease (PD) is the second most common neurodegenerative disorder. In 2008, about 30.000 PD patients were registered at hospitals in the Netherlands. The number of PD patients is expected to increase by 47% from 2005 to 2025. PD is characterized by several motor related symptoms including tremor, bradykinesia, i.e. reduced movement speed and amplitude, hypokinesia, i.e. poverty of movement, episodes of freezing, impaired balance and postural control, dyskinesia, i.e. overactivity of muscles, rigidity, and adaptive responses. In the initial stage, PD is usually treated with Levodopa. This treatment is often very effective, but the efficacy of levodopa drops with time. The disease progressively becomes more severe and therefore it becomes increasingly difficult to treat in advanced stages. Surgical treatment in PD is usually employed when the patient responds well to medication, but experiences motor fluctuations and intolerable side effects as a result of high dosages

    Technological advances in deep brain stimulation: Towards an adaptive therapy

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    Parkinson's disease (PD) is neurodegenerative movement disorder and a treatment method called deep brain stimulation (DBS) may considerably reduce the patient’s motor symptoms. The clinical procedure involves the implantation of a DBS lead, consisting of multiple electrode contacts, through which continuous high frequency (around 130 Hz) electric pulses are delivered in the brain. In this thesis, I presented the research which had the goal to improve current DBS technology, focusing on bringing the conventional DBS system a step closer to adaptive DBS, a personalized DBS therapy. The chapters in this thesis can be seen as individual building blocks for such an adaptive DBS system. After the general introduction, the first two chapters, two novel DBS lead designs are studied in a computational model. The model showed that both studied leads were able to exploit the novel distribution of the electrode contacts to shape and steer the stimulation field to activate more neurons in the chosen target compared to the conventional lead, and to counteract lead displacement. In the fourth chapter, an inverse current source density (CSD) method is applied on local field potentials (LFP) measured in a rat model. The pattern of CSD sources can act as a landmark within the STN to locate the potential stimulation target. The fifth and final chapter described the last building block of the DBS system. We introduced an inertial sensors and force sensor based measurement system, which can record hand kinematics and joint stiffness of PD patients. A system which can act as a feedback signal in an adaptive DBS system

    Measuring activity of the subthalamic nucleus in acute slices using multi electrode arrays

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    The symptoms of Parkinson’s disease (a.o.: tremor, rigidity) can be suppressed by electrical stimulation of the basal ganglia. The most common target nucleus of this so called Deep Brain Stimulation (DBS) is the subthalamic nucleus (STN). Good clinical results are obtained by the application of pulses of 200 �?�s, 1-3 V amplitude at a constant rate of about 130 Hz. However, the mechanism(s) responsible for the clinical improvements are not yet elucidated. The use of acute brain slices as a model is widely used, despite the inevitable loss of many connections. Accurate (i.e. subthreshold) measurements of single neuron and multiple neuron (up to ~3, for practical reasons) membrane potentials are obtained by patch-clamp technique. We propose to use arrays of microelectrodes in slice recordings of STN. We present here our first results

    Exposing Neuronal Cells to Electric Fields

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