Functional Trade-Offs in White Matter Axonal Scaling

Abstract

The brains of large mammals have lower rates of metabolism than those of small mammals, but the functional consequences of this scaling are not well understood. An attractive target for analysis is axons, whose size, speed and energy consumption are straightforwardly related. Here we show that from shrews to whales, the composition of white matter shifts from compact, slow-conducting, and energetically expensive unmyelinated axons to large, fast-conducting, and energetically inexpensive myelinated axons. The fastest axons have conduction times of 1-5 ms across the neocortex and Ͻ1 ms from the eye to the brain, suggesting that in select sets of communicating fibers, large brains reduce transmission delays and metabolic firing costs at the expense of increased volume. Delays and potential imprecision in cross-brain conduction times are especially great in unmyelinated axons, which may transmit information via firing rate rather than precise spike timing. In neocortex, axon size distributions can account for the scaling of per-volume metabolic rate and suggest a maximum supportable firing rate, averaged across all axons, of 7 Ϯ 2 Hz. Axon size distributions also account for the scaling of white matter volume with respect to brain size. The heterogeneous white matter composition found in large brains thus reflects a metabolically constrained trade-off that reduces both volume and conduction time.

Human frontal lobes are not relatively large

“…However, these data are consistent with known allometric effects. Cortical neuron density correlates negatively with brain size across mammals (16,18,32), and reflecting this general relationship gray matter density is lower and minicolumn spacing greater in human compared to nonhuman primary somatosensory and primary visual cortices, as well as in BA10 (31). Although the differences are most marked for BA10 (31), the explanation is still likely to be allometric scaling, because frontal regions expand faster with brain size than do nonfrontal regions (Table S1) (9,11,19).…”

“…The ballooning of cortical volume as brain size increases seems to be due largely to allometric constraints on connectivity, because cortical white matter volume increases substantially faster than gray matter volume (12,15,17,18), and explains the positive allometry of neocortex size (15). This allometry is especially marked for frontal regions (8,9,11,19).…”

“…This allometry is especially marked for frontal regions (8,9,11,19). Although allometric scaling among brain structures is an interesting issue in its own right and probably reflects the way that functional properties such as connectivity and neural processing speed are conserved across body and brain sizes (17,18), it would be illogical to conclude from the observation that human values are closely predicted from a general scaling relationship for other species that humans are specialized for frontal lobe functions in particular (as opposed to functions mediated by more distributed networks connecting different brain regions).…”

Mice selectively bred for high voluntary wheel running have larger midbrains: support for the mosaic model of brain evolution

“…Cellular changes have also been observed with increased brain size. As brain volume increases, axon diameters and the fraction of myelinated axons increase, thereby reducing the delay in neural signaling between more distant regions (Wang et al, 2008). Moreover, different cellular scaling rules apply across different mammalian orders (Herculano-Houzel, 2010).…”

The remarkable, yet not extraordinary, human brain as a scaled-up primate brain and its associated cost

“…A number of models of cortical expansion in evolution assume such a uniform distribution of neurons across species, based on the initial findings of Rockel et al (39) of a constant number of ∼147,000 neurons beneath 1 mm 2 of cortical surface of various mammalian species. A second common assumption in evolutionary models of cortical expansion is that a constant fraction of cortical neurons sends axons into the white matter, that is, cortical connectivity does not scale with brain size (37,40,41), although some models predict a decrease in cortical connectivity through the white matter in larger cortices (42)(43)(44)(45).…”