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Background: Lesion studies in human and non-human primates have linked several different regions of prefrontal cortex (PFC) with the ability to inhibit inappropriate motor responses. However, recent functional neuroimaging studies have specifically implicated right inferior PFC in response inhibition. Right frontal dominance for inhibitory motor control has become a commonly accepted view, although support for this position has not been consistent. Particularly conspicuous is the lack of data on the importance of the homologous region in the left hemisphere. To investigate whether the left inferior frontal gyrus (IFG) is critical for response inhibition, we used neuropsychological methodology with carefully characterized brain lesions in neurological patients.

What are the neural bases of semantic memory? Traditional beliefs that the temporal lobes subserve the retrieval of semantic knowledge, arising from lesion studies, have been recently called into question by functional neuroimaging studies finding correlations between semantic retrieval and activity in left prefrontal cortex. Has neuroimaging taught us something new about the neural bases of cognition that older methods could not reveal or has it merely identified brain activity that is correlated with but not causally related to the process of semantic retrieval? We examined the ability of patients with focal frontal lesions to perform a task commonly used in neuroimaging experiments, the generation of semantically appropriate action words for concrete nouns, and found evidence of the necessity of the left inferior frontal gyrus for certain components of the verb generation task. Notably, these components did not include semantic retrieval per se.One of the earliest findings in cognitive neuroimaging was that the left inferior frontal gyrus (IFG) is activated when subjects are shown a concrete noun and must generate a semantically appropriate verb (1-5). This finding, which now has been replicated many times, has been interpreted as evidence that the left IFG plays a role in the retrieval of semantic knowledge. This interpretation is supported by other neuroimaging studies finding left IFG activation during different tasks requiring semantic retrieval, such as living͞nonliving classification (6-8). In contrast, the literature on cognitive impairments after focal brain lesions reveals no particular association between semantic retrieval and left prefrontal cortex (9). Patients with prefrontal lesions have normal language comprehension; although lesions to either left or right prefrontal cortex do impair the ability to generate semantically related words on a category fluency task, they also impair performance in nonsemantic fluency tasks (10), consistent with an underlying impairment that is not semantic per se (11). Impairments of semantic knowledge are most associated with temporal lobe, not frontal lobe, pathology (12)(13)(14).In this paper, we consider two possible explanations for the discrepancy between the findings from neuroimaging and neuropsychological studies of the role of prefrontal cortex in semantic retrieval. First, differences in the outcomes from these two types of studies may reflect simply the different types of inferences to which neuroimaging studies and lesion studies lend themselves. Neuroimaging studies are limited to inferences about brain regions that are engaged by a cognitive process as revealed by correlated changes in activity related to processing demands. In contrast, a neuropsychological approach allows one to make inferences about brain regions that are necessary for a cognitive process, when that process can be shown to depend on the integrity of a given brain region (15). Thus, one interpretation of the neuroimaging findings that can be tested in patients with frontal...