Exploiting pallidal plasticity for stimulation in Parkinson's disease

TY - JOUR

T1 - Exploiting pallidal plasticity for stimulation in Parkinson's disease

AU - Lourens, Marcel A J

AU - Schwab, Bettina C

AU - Nirody, Jasmine A

AU - Meijer, Hil G E

AU - van Gils, Stephan A

PY - 2015/4

Y1 - 2015/4

N2 - 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.APPROACH: 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.MAIN 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.SIGNIFICANCE: 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.

AB - 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.APPROACH: 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.MAIN 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.SIGNIFICANCE: 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.

KW - Computer Simulation

KW - Deep Brain Stimulation/methods

KW - Globus Pallidus/physiopathology

KW - Humans

KW - Models, Neurological

KW - Nerve Net/physiopathology

KW - Neuronal Plasticity

KW - Parkinson Disease/physiopathology

KW - Therapy, Computer-Assisted/methods

U2 - 10.1088/1741-2560/12/2/026005

DO - 10.1088/1741-2560/12/2/026005

M3 - SCORING: Journal article

C2 - 25650741

VL - 12

SP - 026005

JO - J NEURAL ENG

JF - J NEURAL ENG

SN - 1741-2560

IS - 2

ER -