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Sonia Leslie Elaine Brownsett Using fMRI and Behavioural Measures to Investigate Rehabilitation in Post-Stroke Aphasic Deficits Sonia Leslie Elaine Brownsett 2013 Imperial College London, Department of Medicine This thesis is submitted for the degree of Doctor of Philosophy 1 Acknowledgments Firstly, I would like to thank all the volunteers that participated in my studies, especially the patients. Thanks also to the C3NL lab (past and present) for their support, especially those that appreciated the trials and tribulations of stroke studies. I would also like to thank David Howard, for his support, sensible perspective and for pointing me in the direction of this PhD. The largest dose of gratitude must go to Professor Wise (honFRCSLT) for his unique supervisory style, which has supported and encouraged throughout many a difficult result. I’m sure the sense of futility was mutual but he did a remarkable job of being optimistic and was, indeed, proved right in the end. I must also thank my family for their obvious contribution, but most importantly Tony and Thomas for their continued unconditional support and patience at many a missed bedtime. To Hannah, Noah, Joshua, Erin, Niall, Isla, Sophie and Thomas. 2 Statement of Publications The results from this thesis have been submitted for publication. The results presented in Chapter Three have been submitted to Brain and Language and are currently under review. The results from Chapters Four and Five have been provisionally accepted for publication in Brain. Brownsett, S; Wise R; Warren, J, Geranmayeh, F; Parry, A; Howard, D. Self- administered aphasia therapy- is lesion localisation important? Under Review. Brownsett, S; Warren, J; Geranmayeh, F; Woodhead, Z; Leech, R; Wise, R. Cognitive control and its impact on recovery from aphasic stroke. Brain. 2013. doi:10.1093/brain/awt289. 3 Declaration of Originality Metal Beetle Ltd, who were financially reimbursed for their services, programmed the software described in Chapter Three. Dr. Jane Warren contributed to the design of the experiments in Chapters 4 and 5. I declare that the rest of the work presented in this thesis is my own and conforms to the rules and guidelines set out for PhD theses by Imperial College London and all else is appropriately referenced. 4 Copyright Declaration The copyright of this thesis rests with the author and is made available under a Creative Commons Attribution Non-Commercial No Derivatives licence. Researchers are free to copy, distribute or transmit the thesis on the condition that they attribute it, that they do not use it for commercial purposes and that they do not alter, transform or build upon it. For any reuse or redistribution, researchers must make clear to others the licence terms of this work. 5 Abbreviations A1 Primary auditory cortex ACC Anterior cingulate cortex AG Angular gyrus aI Anterior Insula ANOVA Analysis of variances ATL Anterior temporal lobe B0 External magnetic field BET Brain extraction tool BKB Bamford-Kowal-Bench sentences BOLD Blood oxygenated haemodynamic response CEN Central executive network CI Confidence intervals DAP Dorsal auditory pathway DLPFC Dorsolateral prefrontal cortex DMN Default mode network dof Degrees of freedom EPI Echo-planar imaging EV Experimental variable FEAT FMRI Expert Analysis Tool FLAME FMRIB's Local Analysis of Mixed Effects FLIRT FMRIB's Linear Image Registration Tool fMRI Functional magnetic resonance imaging FSL FMRIB's Software Library G Read gradient GLM General linear model Gx Frequency encoding gradient Gy Phase-encoding gradient Gz Slice gradient HRF Haemodynamic response function IFG Inferior frontal gyrus ListNorm Listening to normal speech trials 6 ListVoc Listening to vocoded speech trials ListWhite Listening to white noise M0 Net magnetisation MNI Montreal Neurological Institute MTG Middle temporal gyrus PACE Promoting Communication Effectiveness in Aphasia PC Dorsal inferior parietal cortex and adjacent lateral intraparietal sulcus pCC Posterior cingulate cortex PE Parameter estimate PET Positron emitting tomography pSTS Posterior superior temporal gyrus PT Planum temporale QALY Quality-adjusted life year rCBF Regional cerebral blood flow RCT Randomised controlled trial RepNorm Repeating the ListNorm trials RepVoc Repeating the vocoded speech trials RF Radiofrequency ROIs Regions-of-interest rTMS Repetitive transcranial magnetic stimulation SALT Speech and Language Therapy SD Standard deviation SFG Superior frontal gyrus (SFG) SMA Supplementary motor area SN Saliency network STC Superior temporal cortex STG Superior temporal gyrus STP Superior temporal plane STS Superior temporal sulcus TE Echo time TR Repetition time TROG Test of reception of grammar vACC Ventral anterior cingulate cortex 7 Table of Contents List of Figures List of Tables Abstract 1. Introduction ............................................................................................................................... 15 1.1 Speech Comprehension ............................................................................................... 15 1.1.1 The Auditory Pathway ......................................................................................................... 15 1.1.2 Primary Auditory Cortex .................................................................................................... 17 1.1.3 Dual Stream Processing ...................................................................................................... 19 1.1.4 Neurological basis of Speech Production .................................................................... 21 1.1.5 Compensatory Mechanisms in Healthy Volunteers ................................................ 22 1.2 Speech Comprehension Deficits in Aphasia ......................................................... 25 1.2.1 The Neurological Basis of Comprehension Deficits in Post-Stroke Aphasia 25 1.2.2 Linguistic Basis of Speech Comprehension Deficits ............................................... 31 1.2.3 Auditory Discrimination Deficits and Comprehension ......................................... 34 1.2.4 Summary of Speech Perception in Aphasia ................................................................ 38 1.3 Domain General Networks in Language ................................................................ 39 1.3.1 Domain General Deficits in Aphasia .............................................................................. 42 1.4 Mechanisms of Recovery in Aphasia ....................................................................... 44 1.4.1 Neural Mechanisms of Spontaneous Improvement in Humans ........................ 44 1.4.2 Mechanisms of Recovery in Aphasia Using Functional Imaging ....................... 47 1.4.3 Behavioural Approaches to Recovery in Aphasia .................................................... 51 1.4.4 The Evidence Base for Aphasia Therapy ..................................................................... 54 1.5 Therapy for Speech Comprehension Deficits in Aphasia ................................. 57 1.5.1 Therapy for phonological discrimination deficits ................................................... 60 1.5.2 Dosage in Aphasia Therapy ............................................................................................... 64 1.5.3 Computer-Based Rehabilitation in Aphasia ............................................................... 64 1.6 Main Aims and Hypothesis of the Thesis ............................................................... 67 1.7 Outline of the Thesis .................................................................................................... 69 2 Methods .................................................................................................................................... 73 2.1 Introduction to Nuclear Magnetic Resonance ..................................................... 73 2.1.1 Principles of MRI .................................................................................................................... 73 2.1.2 T1 Relaxation ........................................................................................................................... 74 2.1.3 T2 and T2* Relaxation ......................................................................................................... 75 8 2.1.4 Signal Localisation ................................................................................................................. 75 2.1.5 Echo-planar Imaging ............................................................................................................ 77 2.2 Introduction to Functional Magnetic Resonance Imaging .............................. 77 2.2.1 Neurovascular Coupling ..................................................................................................... 77 2.2.2 Blood-oxygen Level Dependent (BOLD) fMRI ........................................................... 77 2.2.3 The Haemodynamic Response Function ..................................................................... 78 2.3 Acquisition Parameters .............................................................................................. 79 2.3.1 ‘Sparse’ Scanning ................................................................................................................... 79 2.4 Analysis of Functional Magnetic Resonance Imaging Data ............................. 80 2.4.1 Pre-processing of Functional Magnetic Resonance Imaging Data .................... 80 2.4.2 Statistical Analysis of Functional Magnetic Resonance Imaging ......................
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