Akkad, Haya; (2024) Optimising neuromodulation for stroke recovery: anatomy and neurophysiology of speech and motor deficits. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This thesis aims to provide a critical investigation of current non-invasive brain stimulation (NIBS) approaches for the treatment of post-stroke deficits, with a specific focus on anomia and upper limb (UL) hemiparesis. I propose that the low therapeutic efficacy of current NIBS interventions for post-stroke recovery may be driven in part by ineffective protocols and poor targeting of functional networks. To test this, I implement a general framework that integrates empirical evidence from behaviour, anatomy and physiology, with an aim to provide insight into why current NIBS targets can fail and how they may be optimised. The most common NIBS target for the treatment of anomia is Broca’s area in the left inferior frontal cortex (LIFC). Empirical findings in chapter 3 challenge the localisation of word-retrieval deficits to Broca’s area; showing that damage to Broca’s area drives a non-linguistic executive dysfunction component of anomia. This suggests that neuromodulation of Broca’s area may be suitable in a subset of patients whose anomia is driven by impaired executive processes, rather than a word retrieval deficit per se. These results lend insight into the variable efficacy of Broca’s area as a group-level neuromodulation target for the treatment of anomia. Chapter 4 investigates neurophysiological mechanisms of the word production network. This study identifies theta phase-coherence and theta-gamma phase-amplitude coupling as potential modulators of the word production network, and suggests that the posterior temporal cortex may present a more suitable NIBS target for the modulation of word-retrieval deficits in anomia. Together, findings from chapters 3 and 4 challenge the validity of a one-size-fits-all approach and motivate the exploration of mechanistically-informed stratification of NIBS targets for the treatment of anomia. In the case of UL hemiparesis, the most popular NIBS target is the hand area of the primary motor cortex (M1). Chapter 5 identifies the functional network underlying UL hemiparesis and finds that this network does not involve the M1 hand area. This sheds light on the prior failure of this neuromodulation target to improve UL function in large trials. Results further show that functional connectivity to this stimulation target influences individual response to NIBS, potentially explaining why this intervention can be effective in some patients. The study identified multiple neuromodulation targets that showed a stronger association with UL hemiparesis than the M1 hand region, and may prove more effective in future trials. Chapter 6 synthesises the empirical evidence derived from this body of work to propose revised protocols combining functional network physiology and NIBS approach in a unified mechanistic framework.

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