Schematic of neurobiological hierarchies and modularity in spinal cord, and topographic organization and ISMS. (A)
The current understanding of the spinal motor hierarchy in modular terms. On the left are the neurobiological component labels. A rhythm generator and pattern shaper layer form the CPG. In, or just below the pattern shaping layer are the modular motor primitives which recruit specific motor pools in specific balances (e.g., heavy black lines). On the right are levels of ISMS stimulation targeting into this hierarchy: S1 stimulation of afferent or descending controls into the hierarchy (e.g., reticulospinal drive, or afferent feedback to synergists); S2 stimulation of rhythm generation; S3 stimulation of motor primitives; S4 stimulation of motor pools. (B,C)
Schematic topography of circuitry and best targets of ISMS in spinal cord (These need not be identical). (B) Lateral or sagittal view of cord gray matter (cell bodies and dendrites). (C) Cross section of cord gray. CPG rhythm centers (yellow), synergies/primitives (blue) and motor pools (red) are organized both along the cord and at different depths and mediolateral locations. (D) Gray matter and targets in white matter in a more realistic cross section. (E)
Top view of a frog cord with different targets and the relations of importance for ISMS interactions. S2,R1: stimulation of CPG rhythm generation R1 in gray matter. S3,P1 and S3, P2: stimulation of primitives in gray matter on same side of cord (expected vector superposition). We do not know if S3,P1 and S3,P2 stimulation operate similarly when S2, R1 is activated in parallel. S3,P3: stimulation of a contralateral primitive in spinal cord. This might alter superposition of S3,P1 and S3,P2 and may not show vector superposition with S3,P1 alone. S1,R2 stimulation of afferent driving a CPG rhythm generator R2. We do not know if ISMS (e.g., S2,R1) or afferents (S1,R2) take precedence, or how S1,R2 affects the other stimulation responses (e.g., S3,P1). Minimally, we need an understanding of these interactions and topographic effects to drive an isolated spinal cord effectively with ISMS. Each may also have autonomic sequelae.