Functional Imaging of Neurocognition

Mark D'Esposito, M.D., Helen Wills Neuroscience Institute and Department of Psychology, University of California, Berkeley, California.

Semin Neurol. 2000;20(4) 

In This Article

Integration of Methods

Ultimately, the most powerful approach to under-standing brain behavior relationships will come from obtaining converging data from multiple methods. The following is an example of such an approach. The notion that the temporal lobes subserve the retrieval of semantic knowledge arose from studies of patients with focal lesions.[71] These traditional beliefs have been called into question by a number of functional neuroimaging studies that have consistently found activation of the left inferior frontal gyrus (IFG) during the retrieval of semantic knowledge. For example, one of the original cognitive activation studies using PET observed activation in this region during a verb generation task when compared with a task that required simply repeating words. In an fMRI study by Thompson-Schill et al,[72] a fundamentally different interpretation has been provided that it is not retrieval of semantic knowledge per se that is associated with left IFG activity but rather the need to select some relevant feature of semantic knowledge from a set of competing alternatives. This interpretation was supported by data during an fMRI experiment in which selection but not retrieval demands were varied across three semantic tasks in a single group of subjects. For example, in a verb generation task, in a high-selection condition, subjects were required to generate verbs to nouns with many appropriate associated responses without any clearly dominant response (e.g., "wheel"), whereas in the low-selection condition nouns with few associated responses or with a clear dominant response (e.g., "scissor) were used. In this way, all tasks required semantic retrieval but they differed on the amount of selection that was required. It was found that there was increasing fMRI signal within left IFG with increasing selection demands (Fig. 6). When the degree of semantic processing was varied independently of selection demands, no difference in left IFG activity was observed, suggesting that it is selection, not retrieval, of semantic knowledge that drives activity in the left IFG.

Regions of overlap of fMRI activity during the performance of three semantic memory tasks in normal human subjects (top) with the convergence of activity found within the left IFG (black region). Regions of overlap in lesion location for patients who had selection-related deficits on the verb generation task with maximal overlap within left inferior frontal gyrus (bottom).

In order to determine whether left IFG activity was correlated with but not causally related to the process of selecting information from semantic memory, Thompson-Schill and colleagues also examined the ability of patients with focal frontal lesions to perform the verb generation task used in their fMRI study.[73] Supporting their claim regarding the function of the left IFG, it was found that the overlap of the lesions of these patients with deficits on this task corresponded to the site of maximum fMRI activation during performance of the verb generation task (Fig. 6). In this example, the approach of using converging evidence of lesion and fMRI studies differs in a subtle but important way from the example previously described regarding the isolation of a face processing module. Patients with left IFG lesions do not present with an identifiable neurobehavioral syndrome that reflects the nature of the processing of this region. However, guided by imaging results, patients with left IFG lesions were sought to confirm a hypothesis regarding the necessity of this region in a specific cognitive process. Moreover, coupled with the well-established finding that left temporal lesions can cause a loss of semantic knowledge, these studies further our understanding of the network of brain regions that subserve semantic memory.