Language asymmetry in the human brain: How plastic is it, and what is the best way to test for and measure it in neurotypicals and patients with epilepsy surgery?

Abstract

Hemispheric asymmetry for language has been known about for over 150 years. Recent advancements in neuroimaging and cognitive neuropsychology have greatly complicated our understanding of the biological basis of language, moving away from the earlier clinic-anatomical models of aphasia. Surprisingly, the functional implications of left hemisphere dominance, as well as the nature of its asymmetry and the factors influencing it during development and in disease (e.g. in epilepsy), remain not yet fully understood.
This thesis introduction reviews the history of language asymmetry, covering early work on aphasia, Wada testing, the relationship between language and handedness, and recent neuroimaging efforts to quantify brain asymmetry in language function and explore hypothesised language models. The first and second empirical chapters present a study that used functional MRI (fMRI) to investigate functional language reorganisation in people with temporal lobe epilepsy from 12 months to approximately 9 years after anterior temporal lobe resection (ATLR) surgery. Cognitive profiles were assessed at multiple time points and correlated with fMRI activations to evaluate the 'efficiency' of reorganised networks. In brief, the findings indicate that language network plasticity continues in the long-term following both left and right ATLR, with cognitive stability observed in both groups despite overall lower neuropsychological scores compared to controls. In left TLE, initial post-ATLR compensation by the non-lesioned hemisphere supports long-term language performance, though reorganisation effects are seen shifting the activity back to the left-dominant network. In the second part of the thesis, functional transcranial Doppler ultrasonography (fTCD) and fMRI methods were employed to test various hypotheses regarding language functional dominance across six tasks in a healthy population. Novel methods for quantifying a lateralisation index (LI) in fTCD (the GAM approach) and fMRI (the 'mirror method') were evaluated. The results highlighted the significance of methodological approaches; while there are similarities, notable differences exist in fTCD- and fMRI-derived estimates of brain lateralisation during expressive and receptive tasks. There were differences in activation and deactivation patterns between participants with typical and atypical dominance. Individual task-related deactivation may be important for calculating the lateralisation index. Moreover, different LI calculation methods in fMRI can yield varying results, affecting language dominance categorisation.
While testable hypotheses about language lateralisation have emerged, evaluating them requires robust recruitment of participants with atypical dominance patterns, which poses challenges. Unresolved questions persist regarding weak laterality and definition of bilateral language, deactivation patterns aiding language function, and differences that may exist in healthy right- dominant people, including structural, functional, or potential genetic markers.

Date of Award	2 May 2025
Original language	English
Awarding Institution	Bangor University
Supervisor	David Carey (Supervisor)