PhD Project 25

Language function in stroke and small vessel disease




PIs: VitorĂ­a Piai (Tenure Track), Roy Kessels (WP6), and Frank-Erik de Leeuw (RUMC)
PhD-candidate: Ileana Camerino
Start date: March 01, 2017

(last update 2019-07-01)

Research Content

This project will investigate the impact of stroke and small vessel disease on language function. It will help clarify how damage to certain brain structures affect patients’ ability to recover language function.

Highlight

White-matter bottleneck in small vessel disease: A lesion-symptom mapping study of executive-language functions.
Team members: Camerino, Sierpowska, Kessels, De Leeuw (RUMC), and Piai

Cerebral small vessel disease (CSVD), characterized by the presence of white matter lesions (WML), is among the main causes of vascular cognitive impairment. A voxel-based lesion symptom mapping (VLSM) approach was used to investigate whether WML location is associated with poorer performance in executive-language tasks.

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.  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.

The statistical significant cluster of voxels associated with worse performance in each of the cognitive measures are shown. The maps show colorized depictions of t-test results evaluating performance of the patients on a voxel-by-voxel basis. High t-scores (red) indicate that lesions to these voxels have a stronger relationship with behavior. Dark purple voxels indicate regions where the presence of a lesion has a weaker relationship with the behavioral measure. Only voxels that were significant at P = 0.05 (controlling for the expected proportion of false positives) are shown. All results are corrected for age, sex, education and lesion volume.

This project is highly interdisciplinary since it combines imaging technique, a neurological population and neuropsychological testing. The project is also innovative as language functioning in this population have remained understudied. All together, the findings of this study contribute to the quest of LiI investigating language functioning and its neurobiological substrate.
This project enormously benefitted from the scientific discussion with members of BQ1. The interdisciplinary composition of the team substantially contributed to the interpretation of the findings.

Progress 2018

A relationship was found between white-matter lesions in a core fronto-striatal network and language-executive functioning in small vessel disease independent of lesion size. This circuitry, formed by the caudate nuclei, forceps minor and thalamic radiations, seems to underlie language-executive functioning beyond the role of processing speed. Finally, the contribution of this circuitry seems stronger for tasks requiring language functioning. This manuscript is undergoing the final round of feedback for submission to a peer-reviewed journal.

For the next study, two groups of patients were selected with small vessel disease, from the same cohort of the previous study, based on their change in performance in verbal fluency over the course of 10 years. One group of patients had declined performance and the other had stable performance. The integrity of the thalamic radiation between these two groups will be compared. The expectation is that the patients who had declined performance in verbal fluency will have lower integrity of the anterior thalamic radiation in comparison with the group that did not have declined performance.

Groundbreaking characteristics

This project has an added value in several aspects. It is the first to examine the contribution of functional connectivity and integrity of brain structures among and within the two hemispheres to word production in neurologic population. Secondly, this project will illuminate about the intersection between language production and executive function, which has not been investigated before.