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Poster B6, Tuesday, August 20, 2019, 3:15 – 5:00 pm, Restaurant Hall

White-matter bottleneck in small vessel disease: A lesion- symptom mapping study of executive-language functions.

Ileana Camerino1, Joanna Sierpowska1, Nathalie H. Meyer1, Anil Tuladhar2, Roy P.C. Kessels1,3, Frank-Erik de Leeuw2, Vitória Piai1,3;1Radboud University, Donders Institute for Brain, Cognition, and Behaviour, Donders Centre for Cognition, 2Radboud University, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Department of Neurology, 3Radboud University Medical Center, Department of Medical Psychology

Cerebral small vessel disease (CSVD), characterized by the presence of white matter lesions (WML), is among the main causes of vascular cognitive impairment. The best-studied cognitive domains in CSVD are executive functioning and processing speed, which are correlated with total WML volume (Prins et al., 2005; Wardlaw et al., 2013). By contrast, the domain of language has received much less attention (Herbert et al., 2014; Welker et al., 2012). Recent studies indicate that WML location might be more informative than total WML volume in explaining the cognitive profile of CSVD (Biesbroek et al., 2017). However, these studies only investigated tasks of executive function and processing speed, whereas other brain functions that might be more dependent on WML location, such as language, have remained understudied (Biesbroek et al., 2016; Duering et al., 2013; Smith et al., 2011). In addition, these studies used global compound scores of executive function and processing speed with and without language involvement, precluding inferences regarding whether there is a core network underlying executive and language tasks. The present study investigates whether WML location is associated with poorer performance in executive- language tasks, as analyzed at a single task level. This study included a cohort of 445 CSVD patients without dementia, with varying burden of WML. The Stroop (word reading, color naming, and color-word naming) and the verbal fluency tests were used as measures of language production with varying degrees of executive demands. The digit symbol modality (DSMT) was used as a control task as it does not require verbal abilities. A voxel-based lesion symptom mapping (VLSM) approach (Bates et al., 2003) was used. Analyses were limited to those voxels where at least 4% (N= 18) of the individuals had a lesion with the goal of minimizing biased parameter estimates. To correct for multiple comparison, permutation testing was used. The cut-off for a significant cluster size was determined based on 6000 iterations, with a voxel-wise threshold set at an alpha level of 0.05 (Kimberg et al., 2007). All VLSM analyses were corrected for age, gender, education, and lesion size. Additionally, to control for the processing speed component in language-related tasks, all VLSM analyses were corrected by a “processing speed” score. The VLSM analyses revealed statistically significant clusters for verbal fluency, and Stroop word reading, color naming and color-word naming, but not for DSMT. Worse scores in all tests were associated with WML in the forceps minor, bilateral thalamic radiations and the caudate nuclei. This set of brain areas was similar across all tests. The lesion-symptom associations remained the same once the scores of the verbal fluency and Stroop color-word naming tests were corrected for processing speed. In conclusion, a relationship was found between WML in a core fronto-striatal network and executive-language functioning in CSVD independent of lesion size. This circuitry, formed by the caudate nuclei, forceps minor and thalamic radiations, seems to underlie executive-language functioning beyond the role of general processing speed. Finally, the contribution of this circuitry seems to be stronger for tasks requiring language functioning.

Themes: Disorders: Acquired, Language Production
Method: Other

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