The frontal lobes have long been implicated in inhibitory control, but a full understanding of the underlying mechanisms remains elusive. The stop-signal task has been widely used to probe instructed response inhibition in cognitive neuroscience. The processes involved have been modeled and related to putative brain substrates. However, there has been surprisingly little human lesion research using this task, with the few existing studies implicating different prefrontal regions. Here, we tested the effects of focal prefrontal damage on stop-signal task performance in a large sample of people with chronic focal damage affecting the frontal lobes ( n = 42) and demographically matched healthy individuals ( n = 60). Patients with damage to the left lateral, right lateral, dorsomedial, or ventromedial frontal lobe had slower stop-signal RT compared to healthy controls. There were systematic differences in the patterns of impairment across frontal subgroups: Those with damage to the left or right lateral and dorsomedial frontal lobes, but not those with ventromedial frontal damage, were slower than controls to “go” as well as to stop. These findings suggest that multiple prefrontal regions make necessary but distinct contributions to stop-signal task performance. As a consequence, stop-signal RT slowing is not strongly localizing within the frontal lobes.

Although the ventromedial frontal lobe (VMF) has been implicated in several complex cognitive tasks such as decision-making and problem solving, the processes for which this region is critical remain unclear. Laboratory studies have largely focused on how the VMF contributes to decision-making when outcomes or options are provided, but in the real world generating appropriate options is likely a crucial and rate-limiting initial step. Here, we determined how VMF damage affected the option generation phase of naturalistic problem solving. A group of patients with VMF damage and two controls groups—age-matched healthy participants and patients with frontal damage sparing VMF—were asked to generate as many options as possible to five scenarios depicting open-ended, real-world problems (e.g., having lunch at a restaurant and forgetting your wallet at home). Both the number of options and the effectiveness of each option generated were examined. Damage to VMF led to a significant reduction in both the number of options produced across all problem-solving scenarios and the ability to generate effective options, most notably for scenarios that were social in nature. We discuss these findings in terms of the mechanisms by which the VMF may contribute to option generation, focusing on proposals suggesting this region is important for integrating subjective value and retrieving schematic representations.

Although prefrontal cortex is clearly important in executive function, the specific processes carried out by particular regions within human prefrontal cortex remain a matter of debate. A rapidly growing corpus of functional imaging work now implicates various areas within prefrontal cortex in a wide range of “executive” tasks. Loss-of-function studies can help constrain the interpretation of such evidence by testing to what extent particular brain areas are necessary for a given cognitive process. Here we apply a component process analysis to understand prefrontal contributions to the n -back task, a widely used test of working memory, in a cohort of patients with focal prefrontal damage. We investigated letter 2-back task performance in 27 patients with focal damage to various regions within prefrontal cortex, compared to 29 demographically matched control subjects. Both “behavior-defined” approaches, using qualitative lesion analyses and voxel-based lesion–symptom mapping methods, and more conventional “lesion-defined” groupwise comparisons were undertaken to determine the relationships between specific sites of damage within prefrontal cortex and particular aspects of n -back task performance. We confirmed a critical role for left lateral prefrontal cortex in letter 2-back performance. We also identified a critical role for medial prefrontal cortex in this task: Damage to dorsal anterior cingulate cortex and adjacent dorsal fronto-medial cortex led to a pattern of impairment marked by high false alarm rates, distinct from the impairment associated with lateral prefrontal damage. These findings provide converging support for regionally specific models of human prefrontal function.

Neuropsychological work is the historical foundation of cognitive neuroscience and continues to be an important method in the study of the neural basis of human behavior, complementing newer techniques for investigating brain structure-function relationships in human subjects. Recent advances in neuroimaging, statistics and information management provide powerful tools to support neuropsychological research. At the same time, changing ethical requirements and privacy concerns impose increasingly high standards on the procedures used to recruit research participants, and on subsequent data management. Shared, centrally managed research registries provide a framework for facilitating access to this method for nonclinicians, addressing ethical concerns, streamlining recruitment and screening procedures, and coordinating subsequent research contacts and data storage. We report the experience of two such registries: the patient database of the Center for Cognitive Neuroscience at the University of Pennsylvania, and the Cognitive Neuroscience Research Registry at McGill University.

The ventromedial prefrontal cortex has been implicated in a variety of emotion processes. However, findings regarding the role of this region specifically in emotion recognition have been mixed. We used a sensitive facial emotion recognition task to compare the emotion recognition performance of 7 subjects with lesions confined to ventromedial prefrontal regions, 8 subjects with lesions elsewhere in prefrontal cortex, and 16 healthy control subjects. We found that emotion recognition was impaired following ventromedial, but not dorsal or lateral, prefrontal damage. This impairment appeared to be quite general, with lower overall ratings or more confusion between all six emotions examined. We also explored the relationship between emotion recognition performance and the ability of the same patients to experience transient happiness and sadness during a laboratory mood induction. We found some support for a relationship between sadness recognition and experience. Taken together, our results indicate that the ventromedial frontal lobe plays a crucial role in facial emotion recognition, and suggest that this deficit may be related to the subjective experience of emotion.

A major thrust of cognitive neuroscience is the elucidation of structure-function relationships in the human brain. Over the last several years, functional neuroimaging has risen in prominence relative to the lesion studies that formed the historical core of work in this field. These two methods have different strengths and weaknesses. Among these is a crucial difference in the nature of evidence each can provide. Lesion studies can provide evidence for necessity claims, whereas functional neuroimaging studies do not. We hypothesized that lesion studies will continue to have greater scientific impact even as the relative proportion of such studies in the cognitive neuroscience literature declines. Using methods drawn from systematic literature review, we identified a set of original cognitive neuroscience articles that employed either functional imaging or lesion techniques, published at one of two time points in the 1990s, and assessed the effect of the method used on each article's impact across the decade. Functional neuro-imaging studies were cited three times more often than lesion studies throughout the time span we examined. This effect was in large part due to differences in the influence of the journals publishing the two methods; functional neuroimaging studies appeared disproportionately more often in higher impact journals. There were also differences in the degree to which articles using one method cited articles using the other method. Functional neuroimaging articles were less likely to include such cross-method citations.