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 brains 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.\n\nSignificance StatementThe mammalian brain exhibits strongly synchronized hemodynamic activity (i.e., functional connectivity) between symmetric, contralateral (i.e., homotopic) brain regions. This pattern is thought to be largely mediated by the corpus callosum (CC), a large white matter tract unique to mammals, which balances interhemispheric coordination and lateralization. Many complex brain functions, including human language, are thought to critically rely upon this balance. Despite lacking the CC, the zebra finch exhibits a song learning process with striking parallels to human speech acquisition, including lateralization and interhemispheric coordination. Using resting-state fMRI, we show that the zebra finch brain exhibits widespread homotopic functional connectivity within a network critical for learned song, suggesting that this symmetrical activity pattern may phylogenetically precede the evolution of the CC.