Purpose:To use MRI diffusion-tensor tracking (DTT) to test for the presence of unknown neuronal fiber pathways interconnecting the mid-fusiform cortex and anteromedial temporal lobe in humans. Such pathways are hypothesized to exist because these regions coactivate in functional MRI (fMRI) studies of emotion-valued faces and words, suggesting a functional link that could be mediated by neuronal connections. Materials and Methods:A total of 15 normal human subjects were studied using unbiased DTT approaches designed for probing unknown pathways, including wholebrain seeding and large pathway-selection volumes. Several quality-control steps verified the results.Results: Parallel amygdalo-fusiform and hippocampo-fusiform pathways were found in all subjects. The pathways begin/end at the mid-fusiform gyrus above the lateral occipitotemporal sulcus bilaterally. The superior pathway ends/ begins at the superolateral amygdala. The inferior pathway crosses medially and ends/begins at the hippocampal head. The pathways are left-lateralized, with consistently larger cross-sectional area, higher anisotropy, and lower minimum eigenvalue (D-min) on the left, where D-min assesses intrinsic cross-fiber diffusivity independent of curvature. Conclusion:A previously-undescribed pathway system interconnecting the mid-fusiform region with the amygdala/ hippocampus has been revealed. This pathway system may be important for recognition, memory consolidation, and emotional modulation of face, object, and lexical information, which may be disrupted in conditions such as Alzheimer's disease. THE HUMAN BRAIN contains specific structural regions that support functions such as language, social cognition, memory, and abstract reasoning. These structures are likely unique or greatly expanded relative to the nonhuman primate brain. The anatomical connections involved in these functions are largely unknown in humans, as such connections cannot be directly inferred from invasive tracer studies of nonhuman primates (1,2). Diffusion tensor tracking (DTT) provides a direct measurement of white matter pathway anatomy and connectivity that previously was not possible. First introduced in fixed rat brain (3) and living humans (4), DTT was subsequently applied to reconstruct several dominant macroscopic pathways in the human brain (5-9). Extension of DTT to discover previously unknown pathways requires specific techniques and unbiased approaches.Here we use DTT to test the hypothesis that a pathway system exists in humans interconnecting the midfusiform region (MFR) with the amygdala/hippocampus. The mid-fusiform region incorporates a complex high-order cortex associated with visual object recognition, including special "objects" such as faces (in both hemispheres, more so on the right), non-face objects (in both hemispheres, more so on the left), and aspects of visual-lexical function (in the left hemisphere) (10 -20). We hypothesize the existence of these pathways based on available human functional and pathological data. In several functional MRI ...
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