Functional map of spinal cord stimulation

Project: Research project

Description

State your hypotheses and project Aim(s). (Fellows should briefly describe the training opportunity.)

Electrical stimulation has emerged as a potentially powerful therapeutic approach for spinal cord injury (SCI) [1]. A major challenge for this approach, however, is inconsistency of effects with respect to the state of the spinal cord: intact vs injured. In this proposal, we investigate the mechanisms of this inconsistency and determine whether pharmacological treatment directed at the monoaminergic system can restore more normal and consistent responses.

We focus on stimulation of the dorsal surface of the spinal cord, using a subdural approach with electrodes directly resting on the cord surface. 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. This approach is becoming technically feasible, due to the development and use of surface array electrodes for control of post-SCI pain in humans [2-5].

Our experiments are carried out in the decerebrate cat preparation, in three different states: cord intact and after both acute and chronic spinal cord injury [6, 7]. 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 [8, 9]. We thus propose the following Aims:

Aim 1: Create a map of relations between DDES and motor output, with the cord intact. Rationale: The dorsal surface of the intact cord provides access to a rich array of sensory axons with strong motor effects. Hypothesis: DDES activates motor pools via sensory afferents which align with motor pool anatomy, providing a consistent motor output map that links rostral to caudal stimulus location with proximal to distal muscle outputs. Significance: Stimulation of sensory input axons may provide a substantial degree of control of spinal cord excitability as well as providing facilitation of motor output or even generation of specific movement patterns.

Aim 2: Determine whether the map loses its specificity following spinal cord injury, both acute and chronic. Rationale: Our previous studies have shown that spinal processing of sensory input becomes disorganized following acute SCI. This disorganization persists in the chronic state. Hypothesis: Acute spinal injury greatly reduces the specificity of surface stimulation of sensory axons, broadening its effects across proximal and distal muscles and inducing major inconsistencies. Significance: The loss of specificity and emergence of inconsistent muscle activations would be a serious impediment to effective stimulation therapies.

Aim 3: Determine whet
StatusActive
Effective start/end date7/31/197/30/22

Funding

  • Craig H. Neilsen Foundation (599050)

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Spinal Cord Stimulation
Spinal Cord Injuries
Electric Stimulation
Axons
Muscles
Spinal Cord
Electrodes
Norepinephrine
Spinal Injuries
Serotonin
Anatomy
Cats
Therapeutics
Anesthesia
Pharmacology
Pain
Pharmaceutical Preparations