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Session: Neurophysiology: Biological Neural Networks
Session starts: Thursday 24 January, 10:40
Presentation starts: 11:10
Room: Lamoraalzaal

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K. J. van Dijk (University of Twente)
D. G.M. Zwartjes (University of Twente)
M.L.F. Janssen (Maastricht University)
A. Benazzouz (University of Bordeaux)
Y. Temel (Maastricht University)
V. Visser-Vandewalle (University of Cologne)
Tjitske Heida (University of Twente)
Peter Veltink (University of Twente)

Abstract:
ABSTRACT Parkinson’s disease is an age-related neurodegenerative disorder and is characterized by gradual deterioration of motor symptoms. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is now widely used in neurosurgical therapy, because it markedly improves the Parkinson’s disease symptoms. Tracing studies have shown that the STN is segregated into multiple functional areas. We hypothesize that DBS should be targeted in the area responsible for motor function to reduce unwanted side effects and improve the positive DBS effects. Therefore, we are interested in localization of the functional areas of the STN. In our study, we determine the functional distribution of the synaptic inputs within the STN of anesthetized rats. To identify the functional areas, we stimulate the cortex, namely the motor cortex (MC) and cingulate gyrus (CG), and measure the subthalamic response. In this response signal, we can distinguish unit activity and the local field potential (LFP). Unit activity reflects the action potentials generated by neurons, while the LFP is a consequence of synchronized synaptic activity [1]. In other words, the unit activity is a measure of the output of a single neuron and the LFP the input of the underlying neuronal population. By carefully measuring the LFP response on 320 different points, within and around the STN, we are able to reconstruct the current source density (CSD) in the STN and surrounding volume. The CSD is used to track the sinks and sources of the neuronal input [2]. Cortical neuronal input from MC and CG are conveyed to the STN through two different pathways. The monosynaptic pathway directly enters the STN, while the polysynaptic pathway first passes through the striatum and globus pallidus (GP) before entering the STN. Previous electrophysiological studies have shown a typical multiphasic response in the STN after cortical stimulation, i.e. two excitatory periods, which are interrupted by a brief inhibition, and are followed by a long inhibitory period. Part of this cortically evoked response is explained by the influence of the different pathways [3]. CSD analysis of our recorded LFP data showed that the input from the MC and GP were locally distributed in the STN. The sink corresponding to the excitatory MC input was located medial to the source corresponding to the inhibitory GP input. Furthermore, the CSD analysis showed a strong local source evoking the long inhibitory period after MC and CG stimulation. These sources did not show a distinct separation of the functional areas in the STN, because both the MC and CG stimulation evoked the source on the same location. Although we did not see a distinct separation of the functional areas in the late response, the method in this study was well able to discriminate the sources and sinks evoked through the monosynaptic and polysynaptic pathway after MC stimulation. Therefore, in the future this is a potential approach to improve the localization of the STN motor area during DBS electrode placing in humans. REFERENCES [1] Buzsáki, G., 2004. Large-scale recording of neuronal ensembles, Nature Neuroscience, 7, pp.446–451. [2] Łęski, S. et al., 2007. Inverse current-source density method in 3D: reconstruction fidelity, boundary effects, and influence of distant sources. Neuroinformatics, 5(4), pp.207–22. [3] Magill, P.J. et al., 2004. Synchronous unit activity and local field potentials evoked in the subthalamic nucleus by cortical stimulation. Journal of neurophysiology, 92(2), pp.700–14.