Interhemispheric Integration for Complex Behaviors, Absent the Corpus Callosum in Normal Ontogeny

Abstract

Functional homotopy, or synchronous spontaneous activity between symmetric, contralateral brain regions, is a fundamental characteristic of the mammalian brain's functional architecture(1-6). In mammals, functional homotopy may be predominantly mediated by the corpus callosum (CC), a white matter structure thought to balance the interhemispheric coordination and hemispheric specialization critical for many complex brain functions, including lateralized human language abilities (7,8). The CC first emerged with the Eutherian (placental) mammals ~160 MYA and is not found in other vertebrates(9, 10). Despite this, other vertebrates also exhibit complex brain functions requiring bilateral integration and lateralization(11). For example, much as humans acquire speech, the zebra finch (Taeniopygia guttata) songbird learns to sing from tutors and must balance hemispheric specialization(12) with interhemispheric coordination to successfully learn and produce song(13). We therefore tested whether the zebra finch brain also exhibits functional homotopy despite lacking the CC. Implementing custom resting-state fMRI (rs-fMRI) functional connectivity (FC) analyses, we demonstrate widespread functional homotopy between pairs of contralateral brain regions required for learned song but which lack direct anatomical projections (i.e., structural connectivity; SC). We believe this is the first demonstration of functional homotopy in a non-Eutherian vertebrate; however, it is unlikely to be the only instance of it. The remarkable congruence between functional homotopy in the zebra finch and Eutherian brains indicates that alternative mechanisms must exist for balanced interhemispheric coordination in the absence of a CC. This insight may have broad implications for understanding complex, bilateral neural processing across phylogeny and how information is integrated between hemispheres.