A Computational Study on the Activation of Neural Transmission in Deep Brain Stimulation

Deep brain stimulation (DBS) is an established treatment for neurodegenerative movement disorders such as Parkinson's disease that mitigates symptoms by overwriting pathological signals from the central nervous system to the motor system. Nearly all computational models of DBS, directly or indirectly, associate clinical improvements with the extent of fiber activation in the vicinity of the stimulating electrode. However, it is not clear how such activation modulates information transmission. Here, we use the exact cable equation for straight or curved axons and show that DBS segregates the signaling pathways into one of the three communicational modes: complete information blockage, uni-, and bi-directional transmission. Furthermore, all these modes respond to the stimulating pulse in an asynchronous but frequency-locked fashion. Asynchrony depends on the geometry of the axon, its placement and orientation, and the stimulation protocol. At the same time, the electrophysiology of the nerve determines frequency-locking. Such a trimodal response challenges the notion of activation as a binary state and studies that correlate it with the DBS outcome. Importantly, our work suggests that a mechanistic understanding of DBS action relies on distinguishing between these three modes of information transmission.