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Abstract
Working memory is a complex cognitive process at the intersection of sensory processing, learning, and short-term memory and also has a general executive attention component. Impaired working memory is associated with a range of neurological and psychiatric disorders, but very little is known about how working memory relates to underlying white matter (WM) microstructure. In this study, we investigate the association between WM microstructure and performance on working memory tasks in healthy adults (right-handed, native English speakers). We combine compartment specific WM tract integrity (WMTI) metrics derived from multi-shell diffusion MRI as well as diffusion tensor/kurtosis imaging (DTI/DKI) metrics with Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) subtests tapping auditory working memory. WMTI is a novel tool that helps us describe the microstructural characteristics in both the intra- and extra-axonal environments of WM such as axonal water fraction (AWF), intra-axonal diffusivity, extra-axonal axial and radial diffusivities, allowing a more biophysical interpretation of WM changes. We demonstrate significant positive correlations between AWF and letter-number sequencing (LNS), suggesting that higher AWF with better performance on complex, more demanding auditory working memory tasks goes along with greater axonal volume and greater myelination in specific regions, causing efficient and faster information process.
Highlights
Working memory performance have been reported in right precuneal white matter (WM) in normal young adults[19]
Diffusion kurtosis imaging (DKI)[21] has been employed to characterize non-Gaussian diffusion and studies show an association between mean kurtosis (MK), a reflection of tissue microstructural complexity, and cognitive deficits in a number of pathologies including multiple sclerosis[22], mild cognitive impairment[23], Alzheimer’s23, and mild traumatic brain injury[24]
This study demonstrates statistically significant WM microstructural associations with performance on a select auditory working memory task, letter-number sequencing (LNS)
Summary
Working memory performance have been reported in right precuneal WM in normal young adults[19]. Alterations in AWF and De,⊥ appear to reflect axon density and myelination both in normal development[30] and in Alzheimer’s disease[31,32]; alterations in Daxon have been shown in conditions of axon injury including stroke[33] and mild traumatic brain injury[34]; and De, and De,⊥ demonstrate sensitivity to changes in extra-axonal diffusion (such as demyelination, gliosis and astrocytosis, extracellular inflammation) in patients with mild cognitive impairment[31]. The working memory tasks represent a progression from “simple span” tasks, focusing on short-term storage and deemphasizing the executive component of working memory, to “complex span” tasks which involve both storage and manipulation of information In this progression, DSF, requiring simple repetition of numbers in the order presented, taps the phonological loop. In order to avoid any confounding effects of language and handedness, we included only right-handed, native English speaking individuals in this study
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