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Project

Functional map of spinal cord stimulation

Funder: Craig H Neilsen Foundation

Funding period
USD 600 K
Funding amount
Abstract
Multiple techniques are now available for improvement of motor function following spinal cord injury (SCI). One of the most promising is electrical stimulation of the spinal cord. A major challenge for this approach, however, is inconsistency of its effects on the injured cord. In this proposal, we investigate the mechanisms of this inconsistency and determine whether pharmacological treatment directed at these mechanisms can restore more normal and consistent responses. Recent technical develops have allowed direct stimulation of the surface of the cord using sub-dural electrodes in humans. We thus focus on direct stimulation of the dorsal surface of the spinal cord. This direct dorsal electrical stimulation (DDES) allows precise determination of whether the relationship between electrode location and muscle activation is consistent, without the shunting effect of the CSF to spread the stimulation current. All experiments are carried out in the decerebrate cat preparation, in three different states: cord intact and after both acute and chronic spinal cord injury. This preparation has the important advantage of allowing spinal circuits to respond to electrical stimulation without being suppressed by anesthesia, thus providing a functionally relevant platform for evaluating the map between stimulus locations and muscle activations. Equally important, the reticulospinal axons that release the monoamines 5HT and NE are highly active. Our guiding concept is that distorted and inconsistent responses to electrical stimulation emerge in SCI because the interneuronal circuits that normally process and focus sensory inflow have become severely disorganized due to damage to their descending control systems. Substantial restoration of this control following SCI may be possible via drugs that mimic the actions of serotonin (5HT) and norepinephrine (NE) on the dorsal horn. These monoamines are released by reticulospinal axons and normally exert potent presynaptic inhibition on sensory inflow. We thus propose three Aims: 1) to create a map of relations between DDES and motor output, with the cord intact; 2) to determine whether the map loses its specificity following spinal cord injury, both acute and chronic; and 3) to determine whether a more normal, consistent map can be achieved by administration of monoaminergic drugs that act to restore appropriate filtering of sensory input. The results that would emerge from these proposed studies would identify a primary mechanism of distortion and inconsistency of effects of electrical stimulation of the cord following spinal cord injury, as well as provide a strategy to ameliorate these deficits. Taken together, these proposed studies would provide a solid mechanistic foundation for developing improved electrical stimulation therapies for SCI. (CHN: SCIRTS chn:wdg)
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System

Categories
  • FOR (ANZSRC)

    1109 Neurosciences

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC

    Neurosciences

  • RCDC

    Rehabilitation

  • RCDC

    Spinal Cord Injury

  • RCDC

    Neurodegenerative

  • HRCS HC

    Neurological

  • HRCS RAC

    2.1 Biological and endogenous factors

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science