Neural compensatory mechanisms that support the retention and recovery of language function post stroke

Abstract

Aphasia is a prevalent and debilitating consequence of stroke that often persists chronically. The overarching purpose of this thesis was to better understand the neural compensatory mechanisms that take place to minimise language dysfunction, and promote language recovery, in post-stroke aphasia. This thesis proposes that existing theories of aphasia recovery can be conceptualised as specific examples of two more fundamental principles, degeneracy and variable neurodisplacement (Chapter 2). 'Degeneracy' predicts that upregulated compensatory regions should not be engaged during language in health, while 'variable neurodisplacement' predicts that such regions might be downregulated during health to save resources but upregulated when task difficulty is increased in controls. The thesis then investigates the neural regions that are functionally involved in language recovery post-stroke. Chapter 3 reports an Activation Likelihood Estimation meta-analysis of coordinate-based language functional neuroimaging studies. The language network is bilateral in aphasia and controls. Regions of the right anterior insula and inferior frontal gyrus were more likely to be activated during language in aphasia than controls, overlap with the Multiple Demand network and were more likely to be activated during higher than lower demand language tasks, consistent with enhanced utilisation of spare capacity within right hemisphere executive regions via variable neurodisplacement. Unexpectedly, Chapter 3 found that multiple undamaged midline and right hemisphere regions were less likely to be activated during language in aphasia than controls, consistent with functional diaschisis. Chapter 4 reports one of the first language multivariate pattern analysis functional imaging experiments in post-stroke aphasia and controls. Chapter 4 suggests the existence of a novel form of 'information diaschisis' in which having a stroke is associated with lower language information processing in a bilateral set of undamaged, predominantly domain-general regions which in turn is associated with, and might contribute to, language impairment post-stroke. Chapter 5 analysed longitudinal functional imaging and neuropsychological data from participants with aphasia poststroke. Language profiles were multidimensional at 2 weeks post-stroke and could be represented by three orthogonal components representing fluency, semantic/executive function and phonology. Different language components had uncorrelated recovery trajectories that were associated with changing activation in different neural regions during aphasia recovery. This provides insights into the multidimensional nature of aphasia recovery and suggests that future clinical rehabilitation trials should take a 'personalised medicine' approach that accounts for each patient's specific language profile when deciding targets for non-invasive brain stimulation.

Date of Award	1 Aug 2022
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Matthew Lambon Ralph (Supervisor)