Lehto Lauri J, Slopsema Julia P, Johnson Matthew D, Shatillo Artem, Teplitzky Benjamin A, Utecht Lynn, Adriany Gregor, Mangia Silvia, Sierra Alejandra, Low Walter C, Gröhn Olli, Michaeli Shalom
Center for Magnetic Resonance Research, Radiology, University of Minnesota, 2021 6th St SE, Minneapolis, MN 55455, USA.
J Neural Eng. 2017 Feb;14(1):016016. doi: 10.1088/1741-2552/aa5238. Epub 2017 Jan 9.
Target selectivity of deep brain stimulation (DBS) therapy is critical, as the precise locus and pattern of the stimulation dictates the degree to which desired treatment responses are achieved and adverse side effects are avoided. There is a clear clinical need to improve DBS technology beyond currently available stimulation steering and shaping approaches. We introduce orientation selective neural stimulation as a concept to increase the specificity of target selection in DBS.
This concept, which involves orienting the electric field along an axonal pathway, was tested in the corpus callosum of the rat brain by freely controlling the direction of the electric field on a plane using a three-electrode bundle, and monitoring the response of the neurons using functional magnetic resonance imaging (fMRI). Computational models were developed to further analyze axonal excitability for varied electric field orientation.
Our results demonstrated that the strongest fMRI response was observed when the electric field was oriented parallel to the axons, while almost no response was detected with the perpendicular orientation of the electric field relative to the primary fiber tract. These results were confirmed by computational models of the experimental paradigm quantifying the activation of radially distributed axons while varying the primary direction of the electric field.
The described strategies identify a new course for selective neuromodulation paradigms in DBS based on axonal fiber orientation.
深部脑刺激（DBS）治疗的靶点选择性至关重要，因为刺激的精确位置和模式决定了实现预期治疗反应以及避免不良副作用的程度。显然临床上需要在现有刺激引导和塑形方法的基础上改进DBS技术。我们引入方向选择性神经刺激这一概念，以提高DBS中靶点选择的特异性。
该概念涉及使电场沿轴突路径定向，通过使用三电极束在平面上自由控制电场方向，并利用功能磁共振成像（fMRI）监测大鼠脑胼胝体中神经元的反应来进行测试。开发了计算模型以进一步分析不同电场方向下的轴突兴奋性。
我们的结果表明，当电场与轴突平行定向时观察到最强的fMRI反应，而当电场相对于主要纤维束垂直定向时几乎检测不到反应。通过量化径向分布轴突的激活同时改变电场主要方向的实验范式计算模型证实了这些结果。
所描述的策略为基于轴突纤维方向的DBS选择性神经调节范式确定了一条新途径。
