The inferior fronto-occipital fasciculus: bridging phylogeny, ontogeny and functional anatomy

The inferior-fronto-occipital fasciculus (IFOF) is a long-range white matter tract that connects the prefrontal cortex with parietal, posterior temporal and occipital cortices. First identified in the 19th century through the pioneering studies of Mayo and Meynert using blunt dissection, its anatomy and function remain contentious topics. Structurally, its projections are well documented in human blunt dissection and tractography literature, yet its existence has been questioned by tract-tracing studies in macaques. Functionally, while traditional results from direct white matter stimulation during awake surgery suggested a contribution to language, recent evidence from stimulation and lesion data may indicate a broader role in executive control, extending to attention, motor cognition, memory, reading, emotion recognition and theory of mind. This review begins by examining anatomical evidence suggesting that the IFOF evolved in non-human primates to connect temporal and occipital cortices to prefrontal regions involved in context-dependent selection of visual features for action. We then integrate developmental, electrophysiological, functional and anatomical evidence for the human IFOF to propose it has a similar role in manipulation of visual features in our species-particularly when inhibition of overriding but task-irrelevant stimuli is required to prioritize a second, task-relevant stimulus. Next, we introduce a graded model in which dorsal (orbitofrontal, superior and middle frontal to precuneal, angular and supero-occipital projections) and ventral (inferior frontal to posterotemporal, basal temporal and infero-occipital) projections of the IFOF support perceptual or conceptual control of visual representations for action, respectively. Leveraging this model, we address controversies in the current literature regarding language, motor cognition, attention and emotion under the unifying view of cognitive control. Finally, we discuss surgical implications for this model and its impact on predicting and preventing neurological deficits in neurosurgery.