1. Model-based analysis of the acute effects of transcutaneous magnetic spinal cord stimulation on micturition after spinal cord injury in humans.
- Author
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Fardadi, Mahshid, Leiter, J. C., Lu, Daniel C., and Iwasaki, Tetsuya
- Subjects
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INTERNEURONS , *SPINAL cord , *SPINAL cord injuries , *URINATION , *NEURAL circuitry , *LUMBAR vertebrae - Abstract
Aim: After spinal cord injuries (SCIs), patients may develop either detrusor-sphincter dyssynergia (DSD) or urinary incontinence, depending on the level of the spinal injury. DSD and incontinence reflect the loss of coordinated neural control among the detrusor muscle, which increases bladder pressure to facilitate urination, and urethral sphincters and pelvic floor muscles, which control the bladder outlet to restrict or permit bladder emptying. Transcutaneous magnetic stimulation (TMS) applied to the spinal cord after SCI reduced DSD and incontinence. We defined, within a mathematical model, the minimum neuronal elements necessary to replicate neurogenic dysfunction of the bladder after a SCI and incorporated into this model the minimum additional neurophysiological features sufficient to replicate the improvements in bladder function associated with lumbar TMS of the spine in patients with SCI. Methods: We created a computational model of the neural circuit of micturition based on Hodgkin-Huxley equations that replicated normal bladder function. We added interneurons and increased network complexity to reproduce dysfunctional micturition after SCI, and we increased the density and complexity of interactions of both inhibitory and excitatory lumbar spinal interneurons responsive to TMS to provide a more diverse set of spinal responses to intrinsic and extrinsic activation of spinal interneurons that remains after SCI. Results: The model reproduced the re-emergence of a spinal voiding reflex after SCI. When we investigated the effect of monophasic and biphasic TMS at two frequencies applied at or below T10, the model replicated the improved coordination between detrusor and external urethral sphincter activity that has been observed clinically: low-frequency TMS (1 Hz) within the model normalized control of voiding after SCI, whereas high-frequency TMS (30 Hz) enhanced urine storage. Conclusion: Neuroplasticity and increased complexity of interactions among lumbar interneurons, beyond what is necessary to simulate normal bladder function, must be present in order to replicate the effects of SCI on control of micturition, and both neuronal and network modifications of lumbar interneurons are essential to understand the mechanisms whereby TMS reduced bladder dysfunction after SCI. Author summary: We developed a computer model using Hodgkin-Huxley representations of spinal interneurons to simulate normal bladder control, dysfunctional control of micturition after SCI, and clinically observed bladder responses to transcutaneous magnetic stimulation (TMS) of the lumbar spine. We incorporated an infantile spinal voiding reflex by adding lumbar interneurons to make a spinal voiding reflex possible and modified descending control of these neurons to inhibit the infantile reflex in normal adults. After SCI, the descending inhibition of the spinal voiding reflex is lost, and the spinal voiding reflex re-emerges. To make the lumbar spine response to TMS, it was necessary to add two excitatory interneurons and one inhibitory neuron in the lumbar spine: these neurons manifested frequency-specific responses to TMS. Based on the dynamical properties of the inhibitory and excitatory neurons responding to TMS, low frequency TMS (1 Hz) permitted the action of the re-emergent spinal voiding reflex to coordinate bladder contraction and urethral relaxation so that effective bladder emptying was re-established during TMS. Higher frequency TMS contracted the urethral sphincter and prevented simulated leaking and incontinence. Greater lumbar interneuronal complexity, consistent with animal experiments, is required to simulate bladder responses to SCI and TMS. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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