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Modelling the activation of neuronal populations during deep brain stimulation

Background

Deep brain stimulation (DBS) has become an increasingly used clinical therapy for several neurological conditions [1]. However, it is currently impossible to directly measure the distribution of the stimulus in the patient's brain surrounding the implanted electrode, and as a result computational models in the form of finite element models coupled to axon cable models for predicting the volume of tissue activated have proved useful for visualizing stimulation effects. The use of such unconnected axon models, however, relies on the debatable assumption that the excitation of efferent fibres is the functional effect of DBS. quantifying the VTA using anatomically accurate neuronal models as an alternative can provide further clues about the mechanism of DBS.

Methods

For this study, we focused in projection neurons in the subthalamic nucleus (STN), a common target for the treatment of Parkinson's disease. used results from a finite element electric field model [24] which provided the extracellular potential as a stimulus for a range of multicompartment models, starting with myelinated axons [5] and followed by the subthalamic projection neurons of increasing complexity [6].

Results

Our results show that the estimation of the volume of tissue activated is strongly dependent on the type of neuronal model coupled to the FEM results. In response to a 1 V amplitude extracellular pulse, unconnected myelinated axon models up to 4.5 mm away from the electrode fire action potentials at the same frequency as the stimulus. However, for the same stimulus, none of the model STN cells fired at the stimulus frequency, and only cells within 1 mm of the electrode fired at all.

Discussion

In agreement with previous work [5], the prediction of the VTA using cable models of unconnected axons and defining activation as generating action potentials in a 1:1 ratio with the stimulus frequency, provided a convenient way of comparing stimulation parameters. However, the responses of the subthalamic projection neurons, with more complex morphologies and membrane dynamics provide more detailed information about the possible mechanisms underlying the observed improvement in patients' symptoms.

References

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Acknowledgements

This study was supported by a grant from the Medical Research Council of the UK (Grant ID: 78512).

Author information

Correspondence to Nada Yousif.

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Keywords

  • Deep Brain Stimulation
  • Neuronal Model
  • Stimulus Frequency
  • Myelinated Axon
  • Generate Action Potential