Temporal characterization of memory retrieval processes: an fMRI study of the "tip of the tongue" phenomenon.

"Tip of the tongue" (TOT) is a natural phenomenon in which people cannot retrieve a target word immediately, even though they feel confident that they know the target. This provides us an opportunity to understand the human memory system, because cognitive components of memory retrieval such as retrieval effort and successful retrieval are temporally dissociated from each other during the TOT states. The purpose of the present study was to reveal the neural correlates of the cognitive components of the retrieval process by separating cognitive phases of the TOT phenomenon using event-related functional magnetic resonance imaging with multiple regression analysis. We demonstrated that the left dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex were activated at the time of successful retrieval, and the left DLPFC also showed activation when the subjects successfully retrieved the target names as compared to when they gave up. This result suggests that the left DLPFC is specific to the successful retrieval process. During the TOT state, a number of regions were activated, and this suggests that widely distributed brain regions are engaged when people make a hard effort to retrieve a proper name in the TOT state. Our new approach employing temporal resolution of the TOT phenomenon may contribute to the understanding of the mechanisms of the human memory system.

Contribution of working memory to transient activation in human inferior prefrontal cortex during performance of the Wisconsin Card Sorting Test.

The Wisconsin Card Sorting Test (WCST) is the standard task paradigm to detect human frontal lobe dysfunction. In this test, subjects sort card stimuli with respect to one of three possible dimensions (color, form and number). These dimensions are changed intermittently, whereupon subjects are required to identify by trial and error a new correct dimension and flexibly shift cognitive set. We decomposed the cognitive requirements at the time of the dimensional changes of the WCST, using functional magnetic resonance imaging (fMRI). By explicitly informing subjects of a new correct dimension, the working memory load for the trial-and-error identification of the new dimension was removed. Event-related fMRI still revealed transient activation time-locked to the dimensional changes in areas in the posterior part of the inferior frontal sulci. However, the activation was significantly smaller than in the original WCST in which subjects had to use working memory to identify the new dimension by trial and error. Furthermore, these areas were found to spatially overlap the areas activated by a working memory task. These results suggest that working memory and set-shifting act cooperatively in the same areas of prefrontal cortex to adapt us to changing environments.

Common inhibitory mechanism in human inferior prefrontal cortex revealed by event-related functional MRI.

Inhibition of an ongoing reaction tendency for adaptation to changing environments is a major function of the human prefrontal cortex. This function has been investigated frequently using the go/no-go task and set-shifting tasks such as the Wisconsin Card Sorting Test (WCST). Studies in humans and monkeys suggest the involvement of the dorsolateral prefrontal cortex in the two task paradigms. However, it remains unknown where in the dorsolateral prefrontal cortex this function is localized, whether a common inhibitory mechanism is used in these task paradigms and how this inhibitory function acts on two different targets, i.e. the go response in the go/no-go task and the cognitive set in the WCST. In the go/no-go task of this study, subjects were instructed to either respond (go trial) or not respond (no-go trial), depending on the cue stimulus presented. The signals of functional MRI (fMRI) related to the inhibitory function should be transient by nature. Thus, we used the temporal resolution of fMRI (event-related fMRI) by which transient signals in go and no-go trials can be analysed separately and compared with each other. We found a focus that showed transient no-go dominant activity in the posterior part of the inferior frontal sulcus in the right hemisphere. This was true irrespective of whether the subjects used their right or left hands. These results suggest that the transient activation in the right inferior prefrontal area is related to the neural mechanism underlying the response inhibition function. Furthermore, this area was found to be overlapped spatially with the area that was activated transiently during cognitive set shifting in the WCST. The transient signals in the go/no-go task peaked 5 s after the transient expression of the inhibitory function, and the transient signals in the WCST peaked 7s after the transient expression, reflecting different durations of neuronal activity in the two inhibitory task paradigms. These results imply that the right inferior prefrontal area is commonly involved in the inhibition of different targets, i.e. the go response during performance of the go/no-go task and the cognitive set during performance of the WCST.

Activation of lateral extrastriate areas during orthographic processing of Japanese characters studied with fMRI.

We investigated the early orthographic processing in the occipital cortex using Japanese morphogram by functional magnetic resonance imaging. Kanji (Japanese morphogram) is one system of character used in the Japanese language, each character of which has a specific meaning and pronunciations. To ensure that the effects of the general visual properties of Kanji were excluded from Kanji-related activation, we created strict control stimuli, the "scrambled Kanji" that had the same luminance, contrast, and retinotopical size as those of the original Kanji. In the Kanji vs scrambled Kanji task, we found significant activation in the left inferior occipital gyrus. However, we found no activation in earlier visual cortices, including the primary visual cortex, indicating that the scrambled Kanji served as an effective control stimulus for this task. In the Kanji vs blank screen task, much more areas, including earlier visual cortices, were activated. The activation that we found in the Kanji vs scrambled Kanji task was compatible with the results of previous studies of English letter strings by other groups, suggesting that the left inferior occipital gyrus plays an essential role in orthographic processing common to these two different writing systems.