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.

The Wisconsin Card Sorting Test, which probes the ability to shift attention from one category of stimulus attributes to another (shifting cognitive sets), is the most common paradigm used to detect human frontal lobe pathology. However, the exact relationship of this card test to prefrontal function and the precise anatomical localization of the cognitive shifts involved are controversial. By isolating shift-related signals using the temporal resolution of functional magnetic resonance imaging, we reproducibly found transient activation of the posterior part of the bilateral inferior frontal sulci. This activation was larger as the number of dimensions (relevant stimulus attributes that had to be recognized) were increased. These results suggest that the inferior frontal areas play an essential role in the flexible shifting of cognitive sets.

We investigated the response inhibition function of the prefrontal cortex associated with the go/no-go task using functional magnetic resonance imaging in five human subjects. The go/no-go task consisted of go and no-go trials given randomly with roughly equal probability. In go trials a green square was presented and the subjects had to respond by promptly pushing a button using their right or left thumbs, but in no-go trials a red square was presented and subjects were instructed not to respond. When brain activity in no-go trials is dominant over that in go trials in areas in the prefrontal cortex, this no-go dominant brain activity would reflect the neural processes for inhibiting inherent response tendency. We used a new strategy of image data analysis by which transient brain activity in go or no-go trials can be analysed separately, and looked for the prefrontal areas in which the brain activity in no-go trials is dominant over that in go trials. We found the no-go dominant foci in the posterior part of the right inferior frontal sulcus reproducibly among the subjects. This was true whether the right or left hand was used. These results suggest that this region in the prefrontal cortex is related to the neural mechanisms underlying the response inhibition function.

Functional organization of human cerebral hemispheres is asymmetrically specialized, most typically along a verbal͞nonverbal axis. In this event-related functional MRI study, we report another example of the asymmetrical specialization. Set-shifting paradigms derived from the Wisconsin card sorting test were used, where subjects update one behavior to another on the basis of environmental feedback. The cognitive requirements constituting the paradigms were decomposed into two components according to temporal stages of task events. Double dissociation of the component brain activity was found in the three bilateral pairs of regions in the lateral frontal cortex, the right regions being activated during exposure to negative feedback and the corresponding left regions being activated during updating of behavior, to suggest that both hemispheres contribute to cognitive set shifting but in different ways. The asymmetrical hemispheric specialization within the same paradigms further implies an interhemispheric interaction of these task components that achieve a common goal.

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.

The prefrontal cortex plays a critical role in recollecting the temporal context of past events. The present study used eventrelated functional magnetic resonance imaging (fMRI) and explored the neural correlates of temporal-order retrieval during a recency judgment paradigm. In this paradigm, after study of a list of words presented sequentially, subjects were presented with two of the studied words simultaneously and were asked which of the two words was studied more recently. Two types of such retrieval trials with varied (high and low) levels of demand for temporal-order retrieval were intermixed and compared using event-related fMRI. The intraparadigm comparison of high versus low demand trials revealed brain regions with activation that was modulated on the basis of demand for temporal-order retrieval. Multiple lateral prefrontal regions including the middle and inferior lateral prefrontal cortex were prominently activated. Activation was also observed in the anterior prefrontal cortex and the medial temporal cortex, regions well documented to be related to memory retrieval in general. The modulation of brain activity in these regions suggests a detailed pathway that is engaged during recency judgment.Key words: recency; prefrontal; memory; retrieval; context; fMRIThe prefrontal cortex has been implicated in several types of mnemonic functions (Stuss and Benson, 1986;Fuster, 1997). Among them is recollection of the temporal context of past events, an ability that has most often been tested using recency judgment paradigms in which two events are to be judged as to which has occurred more recently (Yntema and Trask, 1963). Since the initial report in Milner (1971), several neuropsychological studies of humans and monkeys have provided evidence that damage to the lateral prefrontal cortex impairs temporal-order retrieval and that the effect of damage is greater in retrieving the temporal order of past events than in retrieving the past events themselves (Shimamura et al., 1990;Milner et al., 1991;Petrides, 1991;Butters et al., 1994). Previous neuroimaging studies investigating recency judgment used this temporal-order versus item retrieval contrast and revealed prefrontal activation associated with temporal-order retrieval relative to item retrieval (Eyler Zorrilla et al., 1996;Cabeza et al., 1997Cabeza et al., , 2000.The contrast of the dichotomous temporal-order versus item retrieval is useful in detecting functional characteristics that are differential among particular brain regions, as is most typically used in the demonstration of double dissociation between regions. However, this approach leaves unspecified the brain activity related to temporal-order retrieval itself at a whole-brain level because, for instance, it is possible that brain activity common to temporal-order and item retrieval is subtracted out even when the activity is related to temporal-order retrieval. An alternative approach complements the previous approach and allows us to uncover the whole neural correlates of temporal-order retr...

No abstract

Clinical studies of cerebral achromatopsia have suggested a colour centre in the human fusiform gyrus. By using functional magnetic resonance imaging, we examined whether the fusiform gyrus shows activity correlated with the perception of colour. We tested three stimulus conditions in which the subject maintained fixation: (i) a circular array of six coloured circles; (ii) the same as (i) except that each circle is equiluminant grey with its colour counterpart; and (iii) the same as (i) plus a clockwise shift of circles to neighbouring positions every 1 s. After termination of the stimulus, the subject perceived an after-image of circles with complementary colours in (i), but not in (iii). In condition (i), we found a focal signal increase in the posterior part of the fusiform gyrus. In condition (ii), the activation in the same locus during the stimulation period was weaker than that in (i). In condition (iii), the signal intensity after termination of the stimulus was weaker than that in (i). The colour effect and after-effect on activation of the fusiform gyrus observed here suggest its critical role in human colour perception.