Axonal fiber terminations concentrate on gyri

Abstract

Convoluted cortical folding and neuronal wiring are 2 prominent attributes of the mammalian brain. However, the macroscale intrinsic relationship between these 2 general cross-species attributes, as well as the underlying principles that sculpt the architecture of the cerebral cortex, remains unclear. Here, we show that the axonal fibers connected to gyri are significantly denser than those connected to sulci. In human, chimpanzee, and macaque brains, a dominant fraction of axonal fibers were found to be connected to the gyri. This finding has been replicated in a range of mammalian brains via diffusion tensor imaging and high-angular resolution diffusion imaging. These results may have shed some lights on fundamental mechanisms for development and organization of the cerebral cortex, suggesting that axonal pushing is a mechanism of cortical folding.

Figure 1.

Axonal fiber ends closely follow cortical gyral folding patterns, and gyral regions have significantly higher fiber density in human brains. (a) Segmentation of cortical surface into gyri (red) and sulci (blue). (b) Joint visualization of axonal fibers and cortical surface in the same DTI image space. Directions of axonal fibers are color coded by the bar on the top left. (c) Fiber density mapped on the cortical surface. Red and blue mean high and low fiber density, respectively. The color bar is on the right. (d) Differences of fiber density in gyral and sulcal regions in the first data set of 9 subjects. The horizontal axis is the index of subjects, and vertical axis represents normalized fiber density. (e) Differences of fiber density on gyral and sulcal regions in the second data set of 15 subjects. Annotations are the same as (d). (f) Histograms of fiber connection patterns for 9 cases in the first data set. Five types are shown here: gyri–gyri, sulci–sulci, gyri–sulci, gyri–subcortical, and sulci–subcortical. Fibers that are not in these 5 types, for example, subcortical–subcortical, are labeled as others. (g) Histograms of fiber connection patterns for 15 cases in the second data set.

Figure 2.

Axonal fiber ends closely follow cortical gyral folding patterns, and gyral regions have significantly higher fiber density in chimpanzee and macaque brains. (a–c) chimpanzee brain; (d–f) macaque monkey brain. (a) Joint visualization of axonal fibers and cortical surface of chimpanzee brain in the same DTI image space. Colored dots are the intersection points between axonal fibers and cortical surface mesh. Color bar is the same as the one in Figure 1b. (b) Parcellation of cortical surface into gyri (red) and sulci (blue). (c) Histograms of fiber connection patterns in 10 chimpanzee brains. Four patterns are considered here. (d) Joint visualization of axonal fibers and cortical surface of monkey brain in the same DTI image space. It is evident that there are significantly less fibers in monkey brain in comparison with human and chimpanzee brains. (e) Parcellation of cortical surface into gyri (red) and sulci (blue). (f) Histograms of fiber connection patterns in 10 macaque monkey brains.

Figure 3.

Axonal fiber ends closely follow cortical gyral folding patterns, and gyral regions have significantly higher fiber density in HARDI data set. (a) Fibers derived from HARDI tractography. The MEDINRIA was used for HARDI tractography. The colors of fibers encode their directions. (b) The fiber density is mapped on the cortical surface. The color bar of fiber density is at the bottom. Red and blue stand for high and low fiber density, respectively. (c) Differences of fiber density in gyral and sulcal regions in the HARDI data set of 5 subjects. The horizontal axis is the index of subjects, and vertical axis represents normalized fiber density. (d) Histograms of fiber connection patterns in 5 human brain HARDI data sets.

Figure 4.

Comparison of 3 tractography approaches. The fiber density is mapped onto the cortical surface. Red and blue represent high and low fiber density, respectively. (a) Streamline tractography result by the DTIStudio. (b) Streamline tractography result by the MEDINRIA. It is the same subject as in (a). (c) Stochastic tractography results by the FMRIB Software Library. The fiber connection strength is mapped onto the cortical surface. It is the same subject as in (a). (d) Color bars. The left and right ones are for (a–b) and (c), respectively.

Figure 5.

Comparison of cortical surface reconstruction approaches. (a) A cortical surface reconstructed from a human DTI image; (b) a cortical surface reconstructed from a structural T1 MRI image of the same subject. (c) Visualization of cortical surfaces reconstructed from T1 MRI image and DTI image, respectively; (d) visualization of overlaying 2 cortical surfaces together. It is evident that the 2 cortical surfaces are very close. (e) Visualization of surface distances from DTI surface to T1 surface. The average distance over all surface vertices is 1.26 mm; (f) visualization of surface distances from T1 surface to DTI surface. The average distance over all surface vertices is 1.22 mm. The color bar is on the right. (g) Fiber density mapped to the cortical surface from MRI image; (h) fiber density mapped to the cortical surface from DTI image of the same subject.

Figure 6.

Positive correlation between axon accumulation and convex thoracic ganglia growth in Drosophila. (a–f) Drosophila CNS at various developmental stages. Actin filaments were stained by rhodamine-conjugated phalloidin in red. (a) 72 h AED; (b) 84 h AED; (c) 96 h AED; (d) 108 h AED; (e) 120 h AED; (f) 1 h AEM. White arrows point to the actin dynamics in the thoracic morphogenesis. T1: thoracic ganglia 1; T2: thoracic ganglia 2; T3: thoracic ganglia 3. Scale bar: 100 um. (g) The topographical image of thoracic ganglia tissue that shows concave and convex regions labeled as B region and C region, respectively. (h) Force curves measured in different thoracic ganglia regions. The solid gray line (A) with Young’s modulus of around 10 000 kPa was taken on rigid mica surface, which was used as a reference to calculate the indentation. The 3 blue lines with Young’s modulus of approximately 51 kPa were collected in the B region. The 3 blue curves were overlapped with each other due to their closeness. The 3 red lines with Young’s modulus of approximately 500 kPa were acquired in the C region. (i) Time-lapse AFM measurement of Young’s modulus on convex thoracic ganglia surface. The location of AFM probe on the thoracic ganglia tissue is illustrated by the orange arrow in (c). Black dots in (i) represent the average Young’s modulus in different time points. The time window is 210 min. It clearly shows the rapid increase of Young’s modulus during live Drosophila development.