Long-range fibre damage in small vessel brain disease affects aphasia severity

Janina Wilmskoetter, Barbara Marebwa, Alexandra Basilakos, Julius Fridriksson, Chris Rorden, Brielle C. Stark, Lisa Johnson, Gregory Hickok, Argye E. Hillis, Leonardo Bonilha

Research output: Contribution to journalArticlepeer-review

Abstract

We sought to determine the underlying pathophysiology relating white matter hyperintensities to chronic aphasia severity. We hypothesized that: (i) white matter hyperintensities are associated with damage to fibres of any length, but to a higher percentage of long-range compared to mid- and short-range intracerebral white matter fibres; and (ii) the number of long-range fibres mediates the relationship between white matter hyperintensities and chronic post-stroke aphasia severity. We measured the severity of periventricular and deep white matter hyperintensities and calculated the number and percentages of short-, mid- and long-range white matter fibres in 48 individuals with chronic post-stroke aphasia. Correlation and mediation analyses were performed to assess the relationship between white matter hyperintensities, connectome fibre-length measures and aphasia severity as measured with the aphasia quotient of the Western Aphasia Battery-Revised (WAB-AQ). We found that more severe periventricular and deep white matter hyperintensities correlated with a lower proportion of long-range fibres (r = 0.423, P = 0.003 and r = 0.315, P = 0.029, respectively), counterbalanced by a higher proportion of short-range fibres (r = 0.427, P = 0.002 and r = 0.285, P = 0.050, respectively). More severe periventricular white matter hyperintensities also correlated with a lower proportion of mid-range fibres (r = 0.334, P = 0.020), while deep white matter hyperintensities did not correlate with mid-range fibres (r = 0.169, P = 0.250). Mediation analyses revealed: (i) a significant total effect of periventricular white matter hyperintensities on WAB-AQ (standardized beta = 0.348, P = 0.008); (ii) a non-significant direct effect of periventricular white matter hyperintensities on WAB-AQ (P > 0.05); (iii) significant indirect effects of more severe periventricular white matter hyperintensities on worse aphasia severity mediated in parallel by fewer long-range fibres (effect = 6.23, bootstrapping: standard error = 2.64, 95%CI: 11.82 to 1.56) and more short-range fibres (effect = 4.50, bootstrapping: standard error = 2.59, 95%CI: 0.16 to 10.29). We conclude that small vessel brain disease seems to affect chronic aphasia severity through a change of the proportions of long- and short-range fibres. This observation provides insight into the pathophysiology of small vessel brain disease, and its relationship with brain health and chronic aphasia severity.

Original languageEnglish (US)
Pages (from-to)3190-3201
Number of pages12
JournalBrain
Volume142
Issue number10
DOIs
StatePublished - Oct 1 2019

Keywords

  • Aphasia
  • Brain connectomics
  • Magnetic resonance imaging
  • Stroke
  • White matter

ASJC Scopus subject areas

  • Clinical Neurology

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