Long-range white matter fibres and post-stroke verbal and non-verbal cognition

Abstract

Among stroke survivors, linguistic and non-linguistic impairments exhibit substantial inter-individual variability. Stroke lesion volume and location do not sufficiently explain outcomes, and the neural mechanisms underlying the severity of aphasia or non-verbal cognitive deficits remain inadequately understood. Converging evidence supports the idea that white matter is particularly susceptible to ischaemic injury, and long-range fibres are commonly associated with verbal and non-verbal function. Here, we investigated the relationship among post-stroke aphasia severity, cognition, and white matter integrity. Eighty-seven individuals in the chronic stage of stroke underwent diffusion MRI and behavioural testing, including language and cognitive measures. We used whole-brain structural connectomes from each participant to calculate the ratio of long-range fibres to short-range fibres. We found that a higher proportion of long-range fibres was associated with lower aphasia severity, more accurate picture naming, and increased performance on non-verbal semantic memory/processing and non-verbal reasoning while controlling for lesion volume, key damage areas, age, and years post stroke. Our findings corroborate the hypothesis that, after accounting for age and lesion anatomy, inter-individual differences in post-stroke aphasia severity, verbal, and non-verbal cognitive outcomes are related to the preservation of long-range white matter fibres beyond the lesion.

Keywords: aphasia; cognition; stroke; white matter.

Graphical abstract

Figure 1

Lesion overview. Lesion overlay for 87 individuals with chronic, left-hemisphere stroke, and aphasia used in this study.

Figure 2

Short-range versus long-range fibres. This figure provides a visual representation of example pathways traversed by long-range versus short-range fibres. These are tract density images in standard MNI152 space created in DSI Studio using the Human Connectome Project template from 1065 participants. The data evaluated in this study used probabilistic tractography to reconstruct whole-brain connectomes since probabilistic tractography is more accurate to resolve fibre crossings or complex anatomy. Nonetheless, probabilistic tractography does not allow for the visualization of white matter pathways in a direct manner, which can be demonstrated by deterministic examples of white matter fibre anatomy, as shown here. Thus, this figure is intended to provide a visual aid for the interpretation of the results only. The mosaic on the left demonstrates a long-range association pathway (arcuate fasciculus in the left hemisphere) including only fibres with distance travelled greater than 120 mm. Conversely, the mosaic on the right demonstrates examples of u-fibres in the right hemisphere with distance travelled lower than 20 mm. The examples used in this figure are for the visual representation of long versus short-range fibres.

Figure 3

Scatterplots of proportion of long-range fibres and behavioural measures. Note all P-values are corrected for multiple comparisons.

Figure 4

Additional variance explained in behavioural measures by the proportion of long-range fibres, specifically for language (WAB-AQ, PNT), semantic memory/processing (PPTT), and non-verbal cognitive measures (matrix reasoning). Note all P-values are corrected for multiple comparisons.