Modulation of Motoneuronal Firing Behavior After Spinal Cord Injury Using Intraspinal Microstimulation Current Pulses: A Modeling Study

摘要

We simulated the effects of delivering focal electrical stimuli to the central nervous system to modulate the firing rate of neurons and alleviate motor disorders. Application of these stimuli to the spinal cord to reduce the increased excitability of motoneurons and resulting spasticity after spinal cord injury (SCI) was examined by means of a morphologically detailed computer model of a spinal motoneuron. High-frequency sinusoidal and rectangular pulses as well as biphasic charge-balanced and charge-imbalanced pulses were examined. Our results suggest that suprathreshold high-frequency sinusoidal or rectangular current pulses could inactivate the Na+ channels in the soma and initial segment, and block action potentials from propagating through the axon. Subthreshold biphasic charge-imbalanced pulses reduced the motoneuronal firing rate significantly (up to approximately 25% reduction). The reduction in firing rate was achieved through stimulation-induced hyperpolarization generated in the first node of Ranvier. Because of their low net DC current, these pulses could be tolerated safely by the tissue. To deliver charge-imbalanced pulses with the lowest net DC current and induce the largest reduction in motoneuronal firing rate, we studied the effect of various charge-imbalanced pulse parameters. Short pulse durations were found to induce the largest reduction in firing rate for the same net DC level. Subthreshold high-frequency sinusoidal and rectangular current pulses and low-frequency biphasic charge-balanced pulses, on the other hand, were ineffective in reducing the motoneuronal firing rate. In conclusion, the proposed electrical stimulation paradigms could provide potential rehabilitation interventions for suppressing the excitability of neurons to reduce the severity of motor disorders after injury to the central nervous system.