Disconnection after traumatic brain injury: impairments of cognitive control and their impact on learning.

Head injuries often lead to profound disability. Although patients may recover physically, many find it difficult to return to work or continue their social life. The reasons for this are often difficult to determine using conventional tests. A common and disabling problem is that patients have reduced awareness of their own physical and mental limitations. This lack of self-awareness makes attempts at rehabilitation difficult. How head injuries cause this problem is unknown. Awareness is thought to depend on long distance communication between distinct brain regions. This occurs through connections deep within the brain that are organized into bundles or ‘tracts‘, rather like electrical cabling in a switchboard. These connections are vulnerable in head injury, and new advances in brain imaging have provided tools to study damage in detail. I will investigate whether damage to the connections between brain regions involved in controlling actions produce impairments of self-awareness. As reduced self-awareness leads to difficulty in learning, I predict damage to this control network will be a critical factor in determining patient recovery. This work is important as it will identify a target within the brain for the development of new treatment strategies, which will form the next stage of my research.

The World Health Organisation has identified traumatic brain injury (TBI) as a major public health problem with a huge unmet need for effective long-term treatment. Despite this, there have been few attempts to use emerging insights from cognitive neuroscience to guide new approaches to effective rehabilitation. Frontal lobe and executive function are particularly vulnerable to the effects of head injury, and as a result patients often develop a lack of self-awareness, which limits attempts at rehabilitation and leads to more severe functional disability. Such impairment is likely to involve dysfunction in brain regions - including thalamic and frontal areas - critical for cognitive control, a network which I have studied previously. My hypothesis is that critical executive impairments after TBI result from reduced connectivity between relatively intact brain regions involved in cognitive control. I will use behavioural methods and multimodal imaging techniques to provide structural, functional, and resting state measures of connectivity. 50 TBI patients with frontal impairments and 25 normal control subjects will be recruited. Patients will be divided into those with high and low self-awareness. I propose an initial cross-sectional study with longitudinal follow up at one year. I will use diffusion tensor imaging (DTI) to investigate structural connectivity. Functional MRI (fMRI) and magnetoencephalography (MEG) will provide complementary functional measures of brain activity at different spatiotemporal scales. I will test whether integrity within specific white matter tracts connecting critical nodes in the cognitive control network correlate with cognitive impairment. A spatial variant of the Stroop task - the Simon task - will be used to probe cognitive control. I will study a subcomponent of self-awareness - the ability of patients to monitor and react to their own errors. I predict that low levels of self-awareness will result from reduced functional connectivity in the cognitive control network, secondary to diffuse axonal injury. I will also investigate whether an ‘executive‘ network identified in resting state data could be used to quantify network function after TBI, as this would have great potential as a clinical tool. Cognitive control is critical for learning and I will test whether changes in brain connectivity after TBI predict the ability of patients to learn and whether this in turn predicts functional outcome. This work will demonstrate why cognitive control breaks down after TBI and will define a target for future therapeutic interventions.