Constrained by our connections: white matter's key role in interindividual variability in visual working memory capacity.

Visual working memory (VWM) plays an essential role in many perceptual and higher-order cognitive processes. Despite its reliance on a broad network of brain regions, VWM has a capacity limited to a few objects. This capacity varies substantially across individuals and relates closely to measures of overall cognitive function (Luck and Vogel, 2013). The mechanisms underlying these properties are not completely understood, although the amplitude of neural signal oscillations (Vogel and Machizawa, 2004) and brain activation in specific cortical regions (Todd and Marois, 2004) have been implicated. Variability in VWM performance may also reflect variability in white matter structural properties. However, data based primarily on diffusion tensor imaging approaches remain inconclusive. Here, we investigate the relationship between white matter and VWM capacity in human subjects using an advanced diffusion imaging technique, diffusion kurtosis imaging. Diffusion kurtosis imaging provides several novel quantitative white mater metrics, among them the axonal water fraction (f(axon)), an index of axonal density and caliber. Our results show that 59% of individual variability in VWM capacity may be explained by variations in f(axon) within a widely distributed network of white matter tracts. Increased f(axon) associates with increased VWM capacity. An additional 12% in VWM capacity variance may be explained by diffusion properties of the extra-axonal space. These data demonstrate, for the first time, the key role of white matter in limiting VWM capacity in the healthy adult brain and suggest that white matter may represent an important therapeutic target in disorders of impaired VWM and cognition.