DESCRIPTION (provided by applicant): Fecal Incontinence (FI) affects 8-15 % of the US population, predominantly women and elderly, and 45% of nursing home residents. It significantly impairs quality of life and poses a major health care burden. FI is characterized by significant neuromuscular dysfunction of the pelvic floor that includes bilateral lumbo-anorectal and sacro-anorectal neuropathy and sensori-motor dysfunction. This multifactorial etiology suggests that maladaptive neuroplastic changes in the neural innervation of lower gastrointestinal tract could play a significant role in the pathogenesis of FI. A critical barrier o progress in the treatment of FI is the lack of understanding of how treatments affect the core pathophysiological mechanisms of FI and the absence of mechanistically based non-invasive therapies. Our goal is to address the problem of FI by developing therapies that modulate peripheral and central neuronal perturbations and thereby improve visceromotor control and sensori-motor dysfunctions, and to understand the neurobiologic basis of these treatments. Our central hypothesis is that a novel non-invasive treatment, consisting of combined translumbar magnetic stimulation (rTLMS) and transsacral magnetic stimulation (rTSMS), will significantly improve FI by enhancing peripheral and central neural excitability and will provide a multidimensional therapeutic effect by enhancing anal muscle strength, improving stool perception and improving rectal capacity. Our approach is based on our preliminary studies which suggest that repetitive translumbar magnetic stimulation (rTLMS) and transsacral magnetic stimulation (rTSMS) improve anorectal pain and neuropathy and induce central neuroplastic changes. Our objectives are to 1) address the significant gap in our knowledge regarding the peripheral and central neuroenteric axis and how perturbations in the afferent and efferent neural signaling can affect FI; 2) develop a new treatment for FI with repetitive magnetic stimulation and determine the feasibility, safety and optimal frequency setting of rTLMS and rTSMS; 3) determine the mechanistic basis for this neuromodulation therapy; 4) identify if the locus for improvement lies in the afferent or efferent signaling or both. Our expected outcomes include development of new treatment approaches for FI which are mechanistically based, effective, safe, low cost, less invasive, low risk and less dependent on patient compliance. The impact of our project include a new non-invasive treatment modality for FI, a scientific basis for the development of this treatment and improved understanding of the peripheral and central neuroenteric axis in FI.

PUBLIC HEALTH RELEVANCE: Our goal is to address the problem of Fecal Incontinence (FI) by developing therapies that modulate peripheral and central neuronal perturbations and thereby improve visceromotor control and sensori-motor dysfunctions, and to understand the neurobiologic basis of these treatments. Our expected outcomes include development of new treatment approaches for FI which are mechanistically based, effective, safe, low cost, less invasive, low risk and less dependent on patient compliance. The impact of our project include a new non-invasive treatment modality for FI, a scientific basis for the development of this treatment and improved understanding of the peripheral and central neuroenteric axis in FI.