We report our findings as pathways for conceptual purposes only, with the understanding that “pathways” represent coherent tissue structure. We use the term “radial coherence” or “radial structure” as pathways running across the cerebral mantle or a part of cerebral mantle perpendicular to the brain surface. Radial coherent structure could arise from radial glial fibers and streams of migrating neurons, as well as from efferent and afferent axons (Takahashi et al. 2011
). We present the evolution of fiber pathways as main results and the relationships between fibers and gyral structures as preliminary findings to be fully studied with histologic correlations in the future.
Tractography at W17—Dominant Radial Pathways with Immature Forms of Projection, Limbic and Few Emergent Association Pathways
Predominant coherent radial pathways from the ventricular margin to the brain surface were found in most brain areas (), coursing throughout the cortical pate (CP), subplate (SP), intermediate zone (IZ), and ventricular zone (VZ) ( coronal images). These radial structures tended to be longer in dorsal frontal and parietal areas (e.g., areas labeled (a) in ) than in ventral frontal, temporal, and occipital areas (e.g., areas labeled (b) in ). This reflected differences in the thickness of the cerebral mantle in these locations. Radial pathways in the dorsal frontal areas running in the mediolateral horizontal direction (labeled red (c) in ) were abundant at this stage.
Figure 2. Tractography pathways at W17 (A), W20 (B), W24 (C), W31 (D), and W40 (E). (A) Tractography at W17—dominant radial pathways with immature forms of projection, limbic, and few emergent association pathways. a: radial pathways (in dorsal areas), (more ...)
Figure 3. Coronal, sagittal, and oblique images of mean diffusion images and superimposed tractography pathways at (A) W17, (B) W20, (C) W24, (D) W31, and (E) W40. CP: cortical plate, SP: subplate, IZ: intermediate zone, VZ: ventricular zone. g: ganglionic eminence, (more ...)
Projection pathways such as the corticospinal tracts (marked (d) in ; in blue) and corticothalamic/thalamocortical fibers (marked (e) in ; in green) were clearly delineated. Some limbic structures, for instance, the fornix (marked (f) in ; in purple and green), were clearly observed at this stage, whereas the cingulum bundle was small and not completely resolved (marked (h) in ; in blue). We also noted another pathway, separate from the fornix, running along the ventricular margin (marked (g) in ; in blue) that corresponded to the lateral ganglionic eminence. Thus, the ganglionic eminence showed a strongly tangential organization (). Pathways branching from the ganglionic eminence were running throughout CP, SP, IZ, and VZ ( sagittal images).
Figure 4. (A) Sagittal, (B) axial, and (C) coronal views of tangential pathways associated with the ganglionic eminence at W17 (a). (b) Pathways continuous from the tangential pathways to the cerebral mantle and (c) thalamocortical and corticospinal tracts. These (more ...)
Callosal pathways (marked (i) in ; in green) appeared to terminate prior to reaching the midline, but this finding reflected the artifactual division of the corpus callosum during brain removal. Similarly, the anterior commissure was artifactually divided in the midline.
Interestingly, within-lobes, short-range corticocortical pathways were found only in specific areas of the parietal and occipital lobes ( (l)) and not in the temporal and frontal lobes. These pathways were oriented in the dorsal–ventral direction on coronal slices. The emerging short-range corticocortical pathways were observed through the subplate and intermediate zone ( coronal images).
We observed a frontotemporal pathway running between the inferior frontal lobe and the anterior temporal pole (probably the uncinate fasciculus, marked (j) in , in purple) as well as a cluster of fronto-occipital pathways projecting from the inferior frontal lobe to the posterior areas in the brain (probably the inferior fronto-occipital fasciculus, marked (k) in ; in grayish blue). The other corticocortical pathways were found only in a restricted dorsal brain area (marked (l) in , in green). These between-lobe pathways were oriented in the anterior–posterior direction on sagittal slices.
Overall, brain structure at this stage can be characterized by a strong radial coherence with minimal regional variation. Only a few long-range association pathways were visible. The minimal regional variation resulted from the coherent structures that had the expected shape and location of the limbic and emergent corticocortical association pathways connecting specific brain areas: between dorsal and ventral parietal areas, between dorsal and ventral occipital areas, and between ventral frontal and anterior temporal areas.
Tractography at W20 and W22—Dominant Radial Pathways and Emerging Long-Range Connectivity
Radial coherence remains dominant at W20 and W22 with regional variation in length due to differences in thickness of the cerebral mantle ( (a, b)). Radial pathways identified in the dorsal frontal areas ( (c), red pathways) were reduced compared with those at W17, suggesting a decrease in the radial coherence. In addition, the radial tractography pathways remained continuous from the ventricular margin to the brain surface, across the CP, SP, IZ (, coronal images). Pathways branching from the ganglionic eminence were less prominent at this stage (, sagittal images).
Projection pathways such as the corticospinal tracts (marked (d) in ) and corticothalamic/thalamocortical fibers (marked (e) in ) were clearly delineated. Fornix ( (f), in green) and the lateral ganglionic eminence pathways ( (g), in blue) were observed, as in W17. Intrahemispheric association pathways became more prominent at this age compared with W17. The uncinate fasciculus ( (j), in green) became thicker and increased in coherence. Superficial horizontal pathways were observed in dorsal brain areas ( (m)). In addition, the frontotemporal pathways became more prominent ( (n), in green). The inferior fronto-occipital fasciculus ( (k), in blue) also became more prominent and longer compared with that at W17.
Overall, the basic structure at W20 was comparable to that at W17, but there were newly identified corticocortical pathways as well as existing corticocortical pathways with increased coherence suggesting increasing corticocortical connectivity. In addition, the density of radial pathways was reduced compared with W17, suggesting a regression of radial coherence. Similarly, brain structure at W22 remained similar to that at W20. However, at W22, we observed parasagittal corticocortical fiber pathways running horizontally (medio-laterally) throughout the dorsal forebrain from anterior to posterior ( upper panel (A), red and orange). These pathways were found specifically at W22 and were distinct from callosal connections ( upper panel (B)). These pathways appeared to be dense intralobular frontal corticocortical association fibers. Accompanying these increases in corticocortical pathways, and perhaps because of them, radial pathways became less coherent than at earlier stages, especially in the dorsal brain regions.
Figure 5. Upper panel: Tractography pathways at W22. Colors indicate spatial relationships between fiber end points. Red: left–right, blue: anterior–posterior, and green: dorsal–ventral orientation. As we explain in greater detail in the (more ...)
Tractography at W24—Less Predominant Radial Pathways in Dorsal Frontal, Parietal and Inferior Frontal Lobes, and Emergent Short-Range Corticocortical and Long-Range Association Pathways
Long-range radial coherence in the dorsal brain regions persisted at this stage ( (a), although less prominent in several brain regions. Radial tractography pathways in dorsal brain areas became less coherent, while in ventral areas coherent radial tractography pathways were still observed ( coronal images). Interestingly, radial pathways seen running in a dorsal medio-lateral direction in earlier stages ( (c) and (c), red pathways) were not observed at W24; instead we saw emergent corticocortical pathways in an anterior–posterior direction ( (o) and (p)). Projection pathways and corticothalamic/thalamocortical fibers (marked (e) in ) were clearly delineated.
In dorsal brain areas, multiple types of emerging short corticocortical pathways were observed in IZ ( (o) and (p), in blue, and , coronal and sagittal images). Furthermore, in a small anterior region of the inferior frontal lobe, we also observed that short corticocortical pathways were beginning to emerge ( (q), in blue/green). Other areas in the frontal lobe, as well as the temporal and occipital lobes, still contain predominantly radial coherence as in earlier stages.
Gyrification has begun with formation of the parieto-occipital sulcus (, right blue arrow) and the central sulcus (, left blue arrow) above the horizontal pathways ( (c), blue pathways). However, relationships between the gyral formation and corticocortical fiber pathways are not clear at this stage. These 2 sulci in the dorsal area were close to the horizontal pathways forming the corticocortical pathways, but those pathways connected broad areas around the sulcus ( (o)) as well as areas surrounding the sulci ( (p), in blue). In the inferior frontal region, there was no gyrification superficial to the short corticocortical pathways.
In summary, brain connectivity at this stage is characterized by emergent short-range corticocortical fiber pathways in dorsal brain areas and in a restricted area of the inferior frontal lobe. Radial coherence becomes less prominent in brain regions with extensive corticocortical connectivity.
Tractography at W31—Less Dominant Radial Pathways in the Temporal and Occipital Lobes, Emergent Short-Range Corticocortical and Long-Range Association Pathways Ventrally
At W31, radial pathways in the frontal and parietal lobes are further reduced in number but still are regionally present ( (a)). Radial pathways also become less predominant in the temporal and occipital lobes ( (b)), with the emergence of the short-range corticocortical pathways. Radial pathways in ventral areas were still observed ( coronal images).
In dorsal brain areas, multiple types of emerging white matter pathways were observed in IZ as at W24 (, coronal and sagittal images). The dorsal part of the cingulum bundle is also detected at this stage, but its posterior limb down to the medial temporal lobe is not yet visible ( (h), in blue). Callosal pathways are clearly imaged ( (i), in green), as they emerge from the midline and curve upward toward the cortical plate. The ganglionic eminence ( (g), blue pathways) was still observed. Projection pathways and corticothalamic/thalamocortical fibers (marked (e) in ) were clearly delineated.
Short-range U-shaped corticocortical pathways in dorsal brain regions curve along with emergent gyral structures ( (t), in blue) and are associated with increased folding the cortex between the central and parieto-occipital sulci. We also noted radial fibers running down to the ventricular margin from the crest of the gyri ( (u), in green) and corticocortical pathways without a gyrus ( (p), in blue). shows a magnified image in the same region as (t) and (u). The radial organization tended to persist longer in crests of the gyri () than at depths of the sulci (). Short-range intra-frontal pathways were first observed at 24W in a small region of the inferior frontal lobe, but by W31, they have increased in both number and length and are clearly imaged ( (q), in green). In addition to the intra-frontal pathways in the inferior frontal lobe, another group of intra-frontal pathways becomes visible in the superior frontal lobe ( (r), in green). These 2 intra-frontal pathways are located adjacent to one another, connecting the superior and middle frontal gyri and the middle and inferior frontal gyri but do not appear to be continuous with each other. The long-range inferior fronto-occipital fasciculus that was imaged at earlier stages in an immature, shorter form, is imaged clearly and in its full length at this stage ( (k), in blue). The superior fronto-occipital fasciculus, which was not detected earlier, is also clearly imaged at this stage ( (s), in blue).
In summary, connectivity at this stage is characterized by emergent short-range corticocortical fibers throughout the whole brain with clearly visible long-range association pathways and regression of radial organization with an overall dorsal ventral gradient. Developing gyri were associated with emerging subcortical U-fibers at the depth of the sulci and persistent radial pathways extending to the crest of the gyri.
Tractography at W38 and W40—No Evident Radial Pathways, Abundant Complex, Crossing Short- and Long-Range Corticocortical Association Pathways
At W38 and W40, no radial pathways were confidently identified (). Even in the right lower panel in , in which we restricted visualization of fiber pathways to those starting or ending in the sagittal slice, we did not observe a clear radial structure. Projection pathways and corticothalamic/thalamocortical fibers (marked (e) in ) were clearly delineated. The ganglionic eminence was not confidently detected at this stage. Instead, we detected many U-fibers in full length along gyral structures ( (t), in blue). ((v), in red) also shows short-range corticocortical pathways between the insula (medial) and the temporal lobe (lateral). In addition to the inferior fronto-occipital fasciculus ( (k), in blue), which was also imaged at W31, the inferior longitudinal fasciculus ( (w), in blue) was clearly detected in this stage.
In summary, connectivity at this stage is characterized by an adult-like corticocortical pattern of fiber pathways involving the whole brain and the absence of immature radial coherence and tangential organization associated with the ganglionic eminence. In other words, the initially observed highly radial coherence at W17 had regressed and given rise to multidirectional corticocortical connectivity at W40 (, lower panel).