Parietal cortical structure and function in attentional disorders

When people suffer from stroke, which happens to about 150000 people each year in the UK, they often are left with a very specific type of impairment. They can see and move normally, but they act as if they ignore parts of their surroundings. Usually, following a stroke on the right side of the brain these patients ignore the left part of their surroundings. Researchers have traditionally focused on trying to determine the function of the damaged brain area in the hope of finding clues to restoring normal functioning in these patients. However, it is increasingly clear that it is important to understand the brain and disorders of brain function in terms of the interactions of networks of brain areas rather than simply focusing on a single brain area. Thus, the problems experienced by patients who have suffered a stroke might not be explained purely by the damage to a single brain region, but by the effects that damage to one area has on activity elsewhere in the brain. If this is true, to develop a treatment one should not just focus on the damaged area, but on the consequences of the damage to other brain regions. In this project, we try to investigate this possibility. In healthy volunteers, we will map the brain structures that are often damaged in stroke and investigate their contribution to the problems stroke patients experience. This will be done using a combination of neuroscientific research techniques that allow us to probe the living brain non-invasively. Also, we will investigate the possibility of alleviating the problems experienced by stroke patients by treating changes in distributed patterns of brain activity.

Damage to the parietal cortex, for example after stroke, results in severe disorders of attention. Although these patients? visual and motor capabilities seem unimpaired, they fail to react normally to their environment. The severity of such impairments is a strong negative predictor of successful recovery. Traditionally, research has focused on the specific location of the brain lesion and treatment has focused on regaining the function of the damaged area. Recent advances in the understanding of neural processes underlying attention, however, suggest such disorders are better understood in terms of the distributed function of a network of regions. According to this ?network view?, the impairments following a parietal lesion are not simply due parietal damage, but to resulting changes in neural activity throughout the cortical network. The goal of the current project is to evaluate this claim. The results will be applicable to basic research on the nature of attention, clinical understanding of the basis of attentional disorders following stroke, and treatment development. Experiment 1 will use diffusion-weighted imaging to establish the core component regions of parietal cortex on the basis of anatomical connectivity in both human and non-human primates. Experiments 2-4 will investigate the functional interactions of parietal cortex pertinent to the understanding of neglect. Although there has been interest in the possibility that parietal cortex modulates activity in early visual areas we will also investigate parietal involvement in memory updating and response selection mechanisms. We will capitalize on, first, our laboratory?s development of methods for combined transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) and event-related potential (ERP) recording during cognitive tasks. This makes it possible to manipulate or disrupt parietal activity and measure the impact on other brain regions. Second, we will exploit computational and probabilistic approaches to understanding of behaviour that we have used in other research and here adapt to the case of visuospatial function. Experiment 5 exploits our recently developed methods for combining TMS with DWI to directly relate physiological indices of functional interaction with structural indices of anatomical connectivity. Finally, we will exploit the results of the previous experiments to investigate changes in parietal network function in neglect patients. The proposed research will provide an important step in our understanding of the neural control of attention, the causes of attentional disorders, and avenues for their possible treatment.