White matter disruption is an important determinant of cognitive impairment after brain injury, but conventional neuroimaging underestimates its extent. In contrast, diffusion tensor imaging provides a validated and sensitive way of identifying the impact of axonal injury. The relationship between cognitive impairment after traumatic brain injury and white matter damage is likely to be complex. We applied a flexible technique—tract-based spatial statistics—to explore whether damage to specific white matter tracts is associated with particular patterns of cognitive impairment. The commonly affected domains of memory, executive function and information processing speed were investigated in 28 patients in the post-acute/chronic phase following traumatic brain injury and in 26 age-matched controls. Analysis of fractional anisotropy and diffusivity maps revealed widespread differences in white matter integrity between the groups. Patients showed large areas of reduced fractional anisotropy, as well as increased mean and axial diffusivities, compared with controls, despite the small amounts of cortical and white matter damage visible on standard imaging. A stratified analysis based on the presence or absence of microbleeds (a marker of diffuse axonal injury) revealed diffusion tensor imaging to be more sensitive than gradient-echo imaging to white matter damage. The location of white matter abnormality predicted cognitive function to some extent. The structure of the fornices was correlated with associative learning and memory across both patient and control groups, whilst the structure of frontal lobe connections showed relationships with executive function that differed in the two groups. These results highlight the complexity of the relationships between white matter structure and cognition. Although widespread and, sometimes, chronic abnormalities of white matter are identifiable following traumatic brain injury, the impact of these changes on cognitive function is likely to depend on damage to key pathways that link nodes in the distributed brain networks supporting high-level cognitive functions.

Stopping an action in response to an unexpected event requires both that the event is attended to, and that the action is inhibited. Previous neuroimaging investigations of stopping have failed to adequately separate these cognitive elements. Here we used a version of the widely used Stop Signal Task that controls for the attentional capture of stop signals. This allowed us to fractionate the contributions of frontal regions, including the right inferior frontal gyrus and medial frontal cortex, to attentional capture, response inhibition, and error processing. A ventral attentional system, including the right inferior frontal gyrus, has been shown to respond to unexpected stimuli. In line with this evidence, we reasoned that lateral frontal regions support attentional capture, whereas medial frontal regions, including the presupplementary motor area (pre-SMA), actually inhibit the ongoing action. We tested this hypothesis by contrasting the brain networks associated with the presentation of unexpected stimuli against those associated with outright stopping. Functional MRI images were obtained in 26 healthy volunteers. Successful stopping was associated with activation of the right inferior frontal gyrus, as well as the pre-SMA. However, only activation of the pre-SMA differentiated stopping from a high-level baseline that controlled for attentional capture. As expected, unsuccessful attempts at stopping activated the anterior cingulate cortex. In keeping with work in nonhuman primates these findings demonstrate that successful motor inhibition is specifically associated with pre-SMA activation.attention | functional MRI | presupplementary motor area | stop signal task | stopping T he control of voluntary action depends critically upon the ability to inhibit unwanted responses. This process has been extensively studied using the Stop Signal Task (SST) (1). Previous work with this task provides evidence that both medial frontal regions, including the presupplementary motor area (pre-SMA), and more lateral regions, including the right inferior frontal gyrus (IFG; rIFG) and insula (Ins), are involved in stopping. However, the specific contributions of these regions to motor control are unresolved (2-4). Many functional imaging studies have demonstrated activation of right inferior frontal regions during stopping (2, 5-8) and individual differences in response inhibition correlate with the magnitude of the IFG/Ins activation during the SST (5). Activation of medial prefrontal regions are also observed during stopping (2, 5). Pre-SMA activation is correlated with the efficiency of inhibitory processing (2), and work in nonhuman primates supports a role for the medial prefrontal regions in behavioral inhibition (9, 10). Neuropsychological studies provide discrepant results, with correlations between the extent of damage and impairments of inhibitory function reported for both the right lateral and medial frontal regions (3, 4).A limitation of much of the previous neuroimaging literature is that "stop trials" conflate p...