Demystifying The Myelin <i>g</i> Ratio: Its Origin, Derivation and Interpretation

Most studies involving myelin <i>g</i> ratios over the past 120 years assume this metric enumerates differences in myelin thickness (larger <i>g</i> 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, <i>g</i> ratios can easily under- or overestimate the rate of change for this relation in excess of 10%, especially for small caliber fibers. Typical analyses of myelin internodes rely on an explicit mathematical model, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>g</mml:mi><mml:mi> </mml:mi><mml:mtext>ratio</mml:mtext><mml:mo>=</mml:mo><mml:mrow><mml:mfrac><mml:mrow><mml:mrow><mml:msub><mml:mrow><mml:mi>D</mml:mi></mml:mrow><mml:mrow><mml:mi>A</mml:mi></mml:mrow></mml:msub></mml:mrow></mml:mrow><mml:mrow><mml:mrow><mml:msub><mml:mrow><mml:mi>D</mml:mi></mml:mrow><mml:mrow><mml:mi>F</mml:mi></mml:mrow></mml:msub></mml:mrow></mml:mrow></mml:mfrac></mml:mrow><mml:mtext>,</mml:mtext></mml:math> 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, <i>g</i> ratios may not accurately describe myelin structure. Acceptance of this counterintuitive assertion is predicated on a detailed understanding of the <i>g</i> ratio - its origins, properties and the biology represented - which has been heretofore unexplored. In light of such <i>g</i> ratio limitations, and toward consistency with experimental data, two more reliable metrics are proposed, the myelin <i>g_c</i> ratio and the <i>g'</i> cline. But irrespective which of metric is preferred , the analysis herein shows that the axon-to-fiber diameter ratio under normal physiological conditions is a constant for all fiber diameters.