Abstract

Short association fibers (U-fibers) connect proximal cortical areas and constitute the majority of white matter connections in the human brain. U-fibers play an important role in brain development, function, and pathology but are underrepresented in current descriptions of the human brain connectome, primarily due to methodological challenges in diffusion magnetic resonance imaging (dMRI) of these fibers. High spatial resolution and dedicated fiber and tractography models are required to reliably map the U-fibers. Moreover, limited quantitative knowledge of their geometry and distribution makes validation of U-fiber tractography challenging. Submillimeter resolution diffusion MRI—facilitated by a cutting-edge MRI scanner with 300 mT/m maximum gradient amplitude—was used to map U-fiber connectivity between primary and secondary visual cortical areas (V1 and V2, respectively) in vivo. V1 and V2 retinotopic maps were obtained using functional MRI at 7T. The mapped V1–V2 connectivity was retinotopically organized, demonstrating higher connectivity for retinotopically corresponding areas in V1 and V2 as expected. The results were highly reproducible, as demonstrated by repeated measurements in the same participants and by an independent replication group study. This study demonstrates a robust U-fiber connectivity mapping in vivo and is an important step toward construction of a more complete human brain connectome.

Highlights

  • Short association fibers (U-fibers) are cortico-cortical white matter fibers connecting primarily adjacent cortical areas (Meynert 1885) with estimated lengths of 3–30 mm (Schüz and Braitenberg 2002)

  • The temporal SNR (tSNR) offered by the flexible surface coil was approximately 1.7 times higher on average compared with the 32-channel coil in superficial brain areas, but less than the 32channel coil in deep brain areas

  • The tracts were delineated from the whole-brain tractogram using the retinotopically defined V1 segments and a second userdefined regions of interest (ROIs) positioned in an approximate anatomical location in the white matter corresponding to the optic radiation tract (Fig. 3a)

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Summary

Introduction

Short association fibers (U-fibers) are cortico-cortical white matter fibers connecting primarily adjacent cortical areas (Meynert 1885) with estimated lengths of 3–30 mm (Schüz and Braitenberg 2002). These fibers play an important role in brain development and aging (Phillips et al 2013; Wu et al 2014, 2016; Nazeri et al 2015), function (e.g., sensory–motor integration [Catani et al 2011, 2017] and language processing [Friederici 2011]), and pathology including Alzheimer’s disease (Fornari et al 2012; Carmeli et al 2014; Reginold et al 2016; Phillips et al 2016a), temporal lobe epilepsy (Liu et al 2016), Huntington’s disease (Phillips et al 2016b), autism spectrum disorder (Wilkinson et al 2016), and nonlesional epilepsy (O’Halloran et al 2017) Despite their significance, U-fibers are highly underrepresented in current descriptions of the human brain connectome owing to the challenges in mapping them using available postmortem and in vivo methods. U-fiber mapping in vivo has been limited by methodological challenges in diffusion-weighted imaging (DWI) of these fibers (Song et al 2014) and in their validation

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