Cranial nerve modulation for treatment-resistant major depressive disorder and temporal lobe epilepsy

Matthew Peter Ward, Purdue University


Vagus nerve stimulation (VNS) is a device-based therapy for treatment-resistant major depressive disorder (MDD) and temporal lobe epilepsy (TLE). Patterned electrical stimulation of the left vagus nerve mediates the therapeutic effects, but the mechanisms remain unclear. The same stimulus yields differential vagal nerve activation across patients, making efficacy comparisons between studies impossible and those within limited. If the effects of VNS are conveyed by nerve fibers activated in response to stimulation, then a more objective method of investigation and therapy is with respect to the type, proportion and rate (or pattern) of nerve fiber activation. This methodology enables comparisons of therapeutic efficacy and biomarker level changes with respect to the biological conduit of the therapy. Furthermore, it opens avenues for closed-loop control of VNS efficacy. An Automated Nerve Control (ANC) System is presented. It autonomously predicts the level of nerve activation in response to any rectangular pulse. In doing so, it analogously derives a customized guide for activating 0-100% of A, B, or C fiber types within a nerve. A feedback signal between the predicted and measured nerve response is used to maintain any level of A, B, or C fiber activation. A single adjustment to the stimulus pulse amplitude or duration, as predicted with the ANC System, yields any desired A, B, or C fiber activation level. Data demonstrating the performance and applications of the ANC System relative to conventional, stimulus-focused methods are presented, with an emphasis on enhancing VNS efficacy in MDD and TLE.




Irazoqui, Purdue University.

Subject Area

Neurosciences|Mental health|Biomedical engineering

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