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The anatomy and functional role of the inferior fronto-occipital fascicle (IFOF) remain poorly known. We accurately analyze its course and the anatomical distribution of its frontal terminations. We propose a classification of the IFOF in different subcomponents. Ten hemispheres (5 left, 5 right) were dissected with Klingler's technique. In addition to the IFOF dissection, we performed a 4-T diffusion tensor imaging study on a single healthy subject. We identified two layers of IFOF. The first one is superficial and antero-superiorly directed, terminating in the inferior frontal gyrus. The second is deeper and consists of three portions: posterior, middle and anterior. The posterior component terminates in the middle frontal gyrus (MFG) and dorso-lateral prefrontal cortex. The middle component terminates in the MFG and lateral orbito-frontal cortex. The anterior one is directed to the orbito-frontal cortex and frontal pole. In vivo tractography study confirmed these anatomical findings. We suggest that the distribution of IFOF fibers within the frontal lobe corresponds to a fine functional segmentation. IFOF can be considered as a "multi-function" bundle, with each anatomical subcomponent subserving different brain processing. The superficial layer and the posterior component of the deep layer, which connects the occipital extrastriate, temporo-basal and inferior frontal cortices, might subserve semantic processing. The middle component of the deep layer could play a role in a multimodal sensory-motor integration. Finally, the anterior component of the deep layer might be involved in emotional and behavioral aspects.

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