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The Modulation of Visuospatial Awareness in the Human Brain Using Transcranial Magnetic Stimulation

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The Modulation of Visuospatial Awareness in the Human Brain Using Transcranial Magnetic Stimulation To Catherine 1 The Modulation of Visuospatial Awareness in the Human Brain using Transcranial Magnetic Stimulation Rupert Max Oliver UCL Thesis submitted for the degree of PhD November 2010 2 'I, Rupert Max Oliver, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis.' Signature: Rupert Oliver 3 Abstract This thesis describes a series of studies, involving healthy subjects and a carefully selected stroke patient, in which the techniques of Transcranial Magnetic Stimulation (TMS) and Signal Detection Theory (SDT) were combined to explore processing in the posterior parietal cortex (PPC) and the phenomenon of unilateral spatial neglect: 1) A new SDT-based TMS ‗hunting‘ technique was developed and then employed successfully over the right PPC. This revealed a cortical node which could be modulated with ‗online‘ 10Hz-TMS to exert control over subjects‘ visuospatial perception. 2) By targeting this ‗hotspot‘ and an equivalent area in the left PPC with disruptive ‗cTBS‘ (continuous ‗Theta Burst‘ simulation), neglect-like effects in the healthy brain could be induced and alleviated. These effects were quantified using a newly developed, fully balanced, bihemifield detection paradigm 3) By using TMS to map visuospatial function over healthy right PPC, the ‗hotspot‘ could be enlarged after exposure to excitatory, intermittent TBS (iTBS). 4) cTBS was applied to the left PPC of a patient with a right sided stroke and visuospatial neglect. In doing this, neglect and its alleviation were described for the first time in fully balanced SDT terms. 5) The cerebellum was targeted in healthy subjects with 1Hz inhibitory TMS which induced a shift in their subjective midline for ‗imaginary‘ but not ‗real‘ space, as measured with number or physical line bisection respectively. These TBS studies lend support to Kinsbourne‘s hemispheric rivalry hypothesis and suggest that the extent of ‗spatially eloquent‘ cortex in the right PPC can be increased. Both strategies could be useful in larger therapeutic studies of patients suffering from USN after right sided brain injury. The final study opens up an additional therapeutic target for patients with imaginal neglect and, for the first time, implicates the cerebellum in number line bisection. 4 Contents Abstract .............................................................................................................................................4 Abbreviations .................................................................................................................................. 10 Units................................................................................................................................................ 12 Acknowledgements.......................................................................................................................... 13 Overall Summary ............................................................................................................................. 14 Introduction .................................................................................................................................... 16 i) Visual Processing and Attention in the Normal Brain ...................................................................... 17 i.1 Anatomical and Functional Pathways ................................................................................................ 17 i.1.1 Early Visual Areas ....................................................................................................................... 17 i.1.2 Higher Level Visual Processing: the ‘What’ and ‘Where’ Pathways ........................................... 19 i.2 Selective Attention ............................................................................................................................. 21 i.2.1 Attention as a Filter ..................................................................................................................... 21 i.2.2 Feature Integration and Visual Search ........................................................................................ 24 i.2.3 Attention as a ‘Spotlight’............................................................................................................. 26 i.2.4 ‘Covert’ and ‘Overt’ Attention. ................................................................................................... 27 i.2.5 Spaced-based and Object based Selection. ................................................................................ 28 i.2.6 Spatial and Temporal Competition for Selection ........................................................................ 29 i.2.7 ‘Bottom-up’ Versus ‘Top-down’ Influences on Attention .......................................................... 30 i.2.8 Attention as a Gradient ............................................................................................................... 32 ii) Disordered Attention: Unilateral Spatial Neglect ........................................................................... 34 ii.1 Definitions ........................................................................................................................................ 34 ii.2 Historical Context .............................................................................................................................. 34 ii.3 Clinical aspects of Spatial Neglect ..................................................................................................... 36 ii.3.1 Epidemiology, Natural History ................................................................................................... 36 ii.3.2 Clinical Features - Outline .......................................................................................................... 37 ii.3.3 Neglect as distinguished from hemianopia ................................................................................ 38 ii.3.4 Clinical Features – Classification ................................................................................................ 40 ii.3.5 The Anatomical Lesions Associated with Spatial Neglect .......................................................... 42 ii.4 Clinical Tests Used to Measure Spatial Neglect ................................................................................ 44 5 ii.5 Treatment of Spatial Neglect ............................................................................................................ 47 ii.5.1 Behavioural Approaches ............................................................................................................ 47 ii.5.2 Eye Patching and Hemifield Occlusion ....................................................................................... 48 ii.5.3 Prism Adaptation ........................................................................................................................ 48 ii.5.4 Neck Muscle Vibration ............................................................................................................... 50 ii.5.5 Pharmacological intervention .................................................................................................... 50 ii.5.6 Transcranial Magnetic Stimulation (TMS) .................................................................................. 51 iii) Transcranial Magnetic Stimulation ............................................................................................... 52 iii.1 Historical Context ............................................................................................................................. 52 iii.2 Magnetic Induction as a Means of Stimulating the Brain ................................................................ 53 iii.3 TMS as a Probe of Motor Cortical Excitability .................................................................................. 55 iii.4 Frequency-dependent Excitatory and Inhibitory Effects of TMS .................................................... 56 iii.5 Neuroplasticity and TMS .................................................................................................................. 58 iii.5.1 Cortical Maps............................................................................................................................. 58 iii.5.2 Synaptogenesis .......................................................................................................................... 59 iii.5.3 Long-term Potentiation and ‘Theta Burst’ Stimulation ............................................................. 60 iii.6 ‘Theta Burst’ Stimulation and Spatial Neglect- A New Therapy? ..................................................... 61 Chapter One: General Methods ....................................................................................................... 63 1.1 Participants ....................................................................................................................................... 63 1.2 Materials ........................................................................................................................................... 64 1.2.1 Visual Stimuli .............................................................................................................................. 65 1.2.2 Transcranial Magnetic Stimulation ............................................................................................ 67 1.2.3 Eyetracking ................................................................................................................................
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