Demystifying The Myelin g ratio: Its Origin, Derivation and Interpretation

Most studies involving myelin g ratios over the past 120 years assume this metric enumerates changes in myelin thickness (larger g ratio = thinner myelin) with axon or fiber diameter. And, moreover, such changes are directly correlated with internodal function (conduction velocity). However, such assumptions are warranted only in the absence of experimental errors and artifacts (i.e. under theoretical conditions). In reality, g ratios easily under- or overestimate rates of change exceeding 10%, especially for small caliber fibers. Typical analyses of myelin internodes rely on an explicit mathematical model, , where D _A is axon diameter and D _F is fiber diameter (myelin plus axon). Shown recently and herein, this model approximates normal physiological conditions only when the axon-fiber diameter relation is directly proportional, whence it is concordant with the axomyelin unit model. However, in transient or non-steady states (development/aging, disease or myelin plasticity) with linear but not directly proportional relations, g ratios poorly describe myelin structure. Acceptance of this counterintuitive assertion is predicated on a detailed understanding of the g ratio – origins, properties and the biology represented – heretofore uncharted. In light of such g ratio limitations, more general and reliable metrics are proposed, the myelin g _c ratio and the g’ cline.