A team of neuroscientists in America say they have rediscovered an important neural pathway that was first described in the late nineteenth century but then mysteriously disappeared from the scientific literature until very recently.

In a study published today in Proceedings of the National Academy of Sciences, they confirm that the prominent white matter tract is present in the human brain, and argue that it plays an important and unique role in the processing of visual information.

The vertical occipital fasciculus (VOF) is a large flat bundle of nerve fibres that forms long-range connections between sub-regions of the visual system at the back of the brain. It was originally discovered by the German neurologist Carl Wernicke, who had by then published his classic studies of stroke patients with language deficits, and was studying neuroanatomy in Theodor Maynert’s laboratory at the University of Vienna. Wernicke saw the VOF in slices of monkey brain, and included it in his 1881 brain atlas, naming it the senkrechte occipitalbündel, or ‘vertical occipital bundle’.

Maynert - himself a pioneering neuroanatomist and psychiatrist, whose other students included Sigmund Freud and Sergei Korsakov - refused to accept Wernicke’s discovery, however. He had already described the brain’s white matter tracts, and had arrived at the general principle that they are oriented horizontally, running mostly from front to back within each hemisphere. But the pathway Wernicke had described ran vertically.

Another of Maynert’s students, Heinrich Obersteiner, identified the VOF in the human brain, and mentioned it in his 1888 textbook, calling it the senkrechte occipitalbündel in one illustration, and the fasciculus occipitalis perpendicularis in another. So, too, did Heinrich Sachs, a student of Wernicke’s, who labeled it the stratum profundum convexitatis in his 1892 white matter atlas.

The VOF appeared again in a number of other textbooks in the following decades, including the 1918 edition of Gray’s Anatomy, but eventually fell into obscurity. This may have been due to early confusion over the nomenclature; to Maynert, who remained influential but refused to acknowledge Wernicke’s discovery up until his death in 1892; and to changes in neuroanatomical methods, which gradually moved from brain dissections that exposed the white matter tracts in large part, to brain tissue slices, which did not.

Jason Yeatman and his colleagues at Stanford University came across the VOF by chance several years ago. They have been visualizing the brain’s long-range connections using state-of-the-art neuroimaging techniques, in order to investigate the neural mechanisms underlying language processing and reading, and in 2012, reported that the growth pattern of the white matter tracts predicts how a child’s reading skills will develop over time.

“I stumbled upon it while studying the visual word form area,” says Yeatman. “In every subject, I found this large, vertically-oriented fibre bundle terminating in that region of the brain.” He searched for it in the literature, but found no mention of it, so his then Ph.D. supervisor sent the scans to colleagues in the neurosurgery department.

Colour brain map showing the extent of the vertical occipital fasciculus (blue), averaged from scans of 37 study participants. From Yeatman, et al. (2014).

“Eventually someone remembered seeing it in an old medical textbook. With this tip, we found it in a number of atlases from the late 1800s and early 1900s, and this started the detective mission to track down how it disappeared from the modern literature.” Having identified the VOF, the researchers published another paper showing that the pathway is one of three distinct white matter tracts that either end at or pass through the visual word form area.



For this latest study, Yeatman and his colleagues performed DTI scans on 74 additional participants. Using a new open source algorithm they identified the VOF in all them, and mapped it as accurately as possible.

Wernicke had described the tract as “a massive set of association fibres, which connects the upper tip of the angular gyrus with the fusiform gyrus.” Others who recognised the pathway agreed on how far down it went, but not how far up, or forward, its fibres reached.

The new measurements delineate the full extent of the VOF, revealing it as a flat sheet of white matter tracts that extends up through the brain for a distance of 5.5cm, connecting the ‘lower’ and ‘upper’ streams of the visual pathway. These run in parallel, and are sometimes called the ‘What’ and ‘Where’ pathways, for the type of information they carry: the lower stream, connects brain regions involved in processes such as object recognition, including the fusiform gyrus, and the upper stream connects the angular gyrus to other areas involved in attention, motion detection, and visually-guided behaviour.

The front portion of the VOF links the intraparietal sulcus, which encodes information about eye movements, to the occipito-temporal sulcus, which encodes representations of word forms. The portion further back links higher order visual areas within the two streams, which encode complex maps of the visual field.

Given the functions of these brain regions, the researchers speculate that the VOF likely plays an important role in perceptual processes such as reading and recognising faces, and cite two case studies published in the 1970s which support the idea – the only academic papers, other than their own, which have referred to the pathway in the past century.

One is the case of a 50-year-old woman with a tumour that damaged the VOF, the other of a 40-year-old woman in whom the VOF was severed during surgery. Both patients developed pure alexia, or ‘word blindness’: they lost the ability to read, but could still write and understand words.

“We are now using fMRI to precisely map the function of the regions at either end of the VOF and our collaborators are using the algorithm to examine how a variety of disorders impact its structure,” says Yeatman, who is now at the University of Washington’s Institute for Learning and Brain Sciences. “I have also begun working on a study examining how learning to read impacts brain structure, and I wouldn’t be surprised if the VOF ends up playing a central role in that investigation.”

Reference: Yeatman, J. D., et al. (2014). The vertical occipital fasciculus: A century of controversy resolved by in vivo measurements. PNAS, DOI: 10.1073/pnas.1418503111.