title: Exploiting pallidal plasticity for stimulation in Parkinson's disease.
abstract: OBJECTIVE
  Continuous application of high-frequency deep brain stimulation (DBS) often effectively reduces motor symptoms of Parkinson's disease patients. While there is a growing need for more effective and less traumatic stimulation, the exact mechanism of DBS is still unknown. Here, we present a methodology to exploit the plasticity of GABAergic synapses inside the external globus pallidus (GPe) for the optimization of DBS.
  
  
  METHODS
  Assuming the existence of spike-timing-dependent plasticity (STDP) at GABAergic GPe-GPe synapses, we simulate neural activity in a network model of the subthalamic nucleus and GPe. In particular, we test different DBS protocols in our model and quantify their influence on neural synchrony.
  
  
  RESULTS
  In an exemplary set of biologically plausible model parameters, we show that STDP in the GPe has a direct influence on neural activity and especially the stability of firing patterns. STDP stabilizes both uncorrelated firing in the healthy state and correlated firing in the parkinsonian state. Alternative stimulation protocols such as coordinated reset stimulation can clearly profit from the stabilizing effect of STDP. These results are widely independent of the STDP learning rule.
  
  
  CONCLUSIONS
  Once the model settings, e.g., connection architectures, have been described experimentally, our model can be adjusted and directly applied in the development of novel stimulation protocols. More efficient stimulation leads to both minimization of side effects and savings in battery power.
authors: MIRA: Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, 7500 AE, The Netherlands.
authors: Marcel A J
authors: MA
authors: Lourens
authors: Bettina C
authors: BC
authors: Schwab
authors: Jasmine A
authors: JA
authors: Nirody
authors: Hil G E
authors: HG
authors: Meijer
authors: Stephan A
authors: SA
authors: van Gils
mesh_terms: D003198:Computer Simulation; D046690:Deep Brain Stimulation / Q000379:methods*; D005917:Globus Pallidus / Q000503:physiopathology*; D006801:Humans; D008959:Models, Neurological; D009415:Nerve Net / Q000503:physiopathology; D009473:Neuronal Plasticity; D010300:Parkinson Disease / Q000503:physiopathology* / Q000628:therapy*; D013813:Therapy, Computer-Assisted / Q000379:methods