The arcuate fasciculus (AF) is a group of short U-shaped association fibers linking perisylvian language centers of the temporal, parietal, and frontal lobes. This collection of regions has been implicated in phonological processing, including expressive and receptive language, repetition, and short-term memory¹. The AF consists of 3 subcomponents: the direct segment (DS), the anterior indirect segment (AIS), and posterior indirect segment (PIS). These tracts connect the inferior frontal gyrus (IFG), posterior part of the superior temporal gyrus (pSTG) and inferior parietal lobule (IPL). These cortical regions are collectively known as the perisylvian language centers, however delineation of these areas has been shown to be problematic. For example, the diagonal sulcus has been traditionally used to delineate the IFG, however there is considerable inter-subject variability in the location and existence of this landmark^2,3. Therefore, the purpose of this study is to characterize the diffusion microstructural properties and functional outcomes of the cortical AF terminations in the right and left hemispheres in order to better characterize the perisylvian language centers. Diffusion MRI data was acquired through the Human Connectome Project. Diffusion-weighted scans were collected on the Siemens Skyra 3T scanner with 3 shells of b=1000, 2000, and 3000 s/mm². Each shell includes 90 diffusion-weighted directions plus 6 b0 images with 1.25 mm isotropic voxels. Fiber tracking was performed using deterministic tractography in the MRtrix package⁴. A single region of interest (ROI) was used to extract the gross AF structure (Figure 1), which was then used to extract each AF segment (Figure 2). Terminating fiber locations were used to extract the following cortical regions: DS and AIS terminations in the IFG, AIS and PIS terminations in the IPL, and DS and PIS terminations in the pSTG (Figure 3). Neurite orientation dispersion and density imaging (NODDI)⁵ and absolute tissue density from NODDI (ABTIN)⁶ parameters were calculated in each cortical region, yielding the following measures: intracellular volume fraction (FICVF), orientation dispersion index (ODI), myelin density (MylDen), and extracellular space density (CelDen) and were related to behavioral measures. Statistical tests were carried out in R and Bonferroni corrections were used (p=0.002).All three AF segments were extracted from the left hemisphere, however only the AIS and PIS were extracted from the right hemisphere (Figure 4). The DS terminates more anteriorly than the AIS in the IFG. The AIS terminates anterior and medial to the PIS in the IPL. Lastly, the DS terminates anterior and inferior to the PIS in the pSTG. Figure 5 shows the results obtained from the left hemisphere. No significant differences were seen in the right hemisphere. Significant differences were noted in the left compared with right AIS terminations in the IPL, with higher FICVF and ODI in the left hemisphere, and higher CelDen in the right hemisphere (p<.0001).These results suggest that specific cortical terminations of the AF can be spatially differentiated from one another and exhibit different microstructural features. Differences between the left and right AFs likely reflect the natural leftward asymmetry of language structures. It appears that the DS projections to the left IFG have significantly less neurite and more extracellular space than AIS projections. Increased neurite density in the cortex likely reflects elevated dendritic processes. The AIS has been implicated in higher order language skills⁷ and may require denser dendritic structures to carry out these computationally complex processes. Additionally, the location of the DS and AIS terminations reflect BA45 and BA44, respectively. Previous results have shown that BA45 has a more prominent layer IV than BA44, which may contribute to the differences in neurite density⁸. The PIS projections to the IPL have higher myelin and cell body densities than AIS projections. The AIS and PIS likely reflect the intermediate and caudal IPL, respectively. These regions exhibit different neurotransmitter receptor fingerprints⁹ and cytoarchitectonic studies also show elevated cell density and pyramidal cell size in the caudal IPL, which would yield an elevated CelDen¹⁰. The DS termination in the pSTG has higher dendritic and lower cell body densities than PIS terminations. PIS terminations correspond to area Te3 of the pSTG, while DS terminations correspond to area Te4 of the STG. Te3 is known to have increased pyramidal cell size and density, which would contribute to the elevated CelDen in PIS terminations¹¹. These results suggest that microstructural measures obtained from multi-shell dMRI models correlate with the known cytoarchitecture and functionality of these regions and may provide more specific information regarding the localization of cortical perisylvian language centers.