Amygdalar modulation of frontotemporal connectivity during the inkblot test.

Unique and unusual responses to inkblot stimuli evoked by emotionally vulnerable psychiatric patients have been considered as examples of interference of emotion with perceptual processes. However, few studies have investigated the interaction between emotion-related and perception-related neural circuits during performance of the inkblot test. In our recent studies using the inkblot stimuli, enlargement of the amygdala was revealed in association with frequent production of unique responses to the inkblot stimuli. Additionally, our studies demonstrated right temporopolar activation associated with the production of unique responses, as well as left anterior prefrontal and bilateral occipitotemporal activation associated with the production of typical responses. On the basis of these results, we hypothesized that the amygdala is involved in modulation of the connectivity among the frontotemporal regions identified in the activation analysis. To address this issue, we performed a functional connectivity analysis of functional magnetic resonance imaging data, using physiophysiological interaction implemented in Statistical Parametric Mapping 2 (SPM2). This analysis revealed that the amygdala imposed a positive modulation on the connection from the anterior prefrontal region to the temporopolar region, and a negative modulation on the connection from the temporopolar region to the occipitotemporal regions. These results suggest that interference of emotion affects perception during the inkblot test.

Functional dissociation in right inferior frontal cortex during performance of go/no-go task.

The contribution of the right inferior frontal cortex to response inhibition has been demonstrated by previous studies of neuropsychology, electrophysiology, and neuroimaging. The inferior frontal cortex is also known to be activated during processing of infrequent stimuli such as stimulus-driven attention. Response inhibition has most often been investigated using the go/no-go task, and the no-go trials are usually given infrequently to enhance prepotent response tendency. Thus, it has not been clarified whether the inferior frontal activation during the go/no-go task is associated with response inhibition or processing of infrequent stimuli. In the present functional magnetic resonance imaging study, we employed not only frequent-go trials but also infrequent-go trials that were presented as infrequently as the no-go trials. The imaging results demonstrated that the posterior inferior frontal gyrus (pIFG) was activated during response inhibition as revealed by the no-go vs. infrequent-go trials, whereas the inferior frontal junction (IFJ) region was activated primarily during processing of infrequent stimuli as revealed by the infrequent-go versus frequent-go trials. These results indicate that the pIFG and IFJ within the inferior frontal cortex are spatially close but are associated with different cognitive control processes in the go/no-go paradigm.

Transient activation of superior prefrontal cortex during inhibition of cognitive set.

The prefrontal cortex implements a set-shifting function that includes inhibition of a previously acquired cognitive set. The impairment of the inhibitory function results in perseverative behavior that forms one characteristic feature of frontal lobe dysfunction. Previous neuroimaging studies have revealed inhibitory mechanisms in the inferior prefrontal cortex. The present functional magnetic resonance imaging study devised "dual-match" stimuli in a set-shifting paradigm that allowed us to temporally isolate the inhibitory processes recruited during exposure to a previously acquired set. Transient activation time-locked to the isolated inhibition was revealed in the left middle frontal gyrus near the superior frontal sulcus. In a control experiment conducted after subjects had been informed and made aware of the exposure, however, the superior prefrontal activation disappeared, and prominent activation was revealed in a set of brain regions that included the left posterior inferior frontal sulcus. These double dissociation results indicate inhibitory mechanisms in the superior prefrontal cortex, alternative to the inferior prefrontal ones, that are activated depending on the subjects' strategy for inhibition of cognitive set.

Temporal pole activity during understanding other persons' mental states correlates with neuroticism trait.

Comprehension of other persons' mental states is one of the representative cognitive functions involved in social situations. It has been suggested that this function sometimes recruits emotional processes. The present fMRI study examined the neural mechanisms associated with understanding others' mental states, and the conditions that determine the recruitment of the emotional processes. The false belief paradigm, a traditional behavioral paradigm to investigate comprehension of others, was applied to an event-related fMRI analysis, allowing for the extraction of brain activity time-locked to successful understanding of others' mental states. Prominent brain activity was observed in multiple cortical regions including the medial prefrontal cortex, temporo-parietal junction, precuneus, and temporal pole. Then, correlational analyses were performed between the activations and individuals' scores of neuroticism, a personality trait that reflects emotional instability in daily life. It was revealed that the neuroticism scores were positively correlated with the activity in the temporal pole region, but not in the other regions. These results suggest that the emotional processes implemented in the temporal pole are recruited during successful understanding of other persons' mental states, and that the recruitment may be modulated by an emotional personality trait of individual subjects.

Amygdalar enlargement associated with unique perception.

Interference by amygdalar activity in perceptual processes has been reported in many previous studies. Consistent with these reports, previous clinical studies have shown amygdalar volume change in multiple types of psychotic disease presenting with unusual perception. However, the relationship between variation in amygdalar volume in the normal population and the tendency toward unusual or unique perception has never been investigated. To address this issue, we defined an index to represent the tendency toward unique perception using ambiguous stimuli: subjects were instructed to state what the figures looked like to them, and "unique responses" were defined depending on the appearance frequency of the same responses in an age- and gender-matched control group. The index was defined as the ratio of unique responses to total responses per subject. We obtained structural brain images and values of the index from sixty-eight normal subjects. Voxel-based morphometry analyses revealed a positive correlation between amygdalar volume and the index. Since previous reports have indicated that unique responses were observed at higher frequency in the artistic population than in the nonartistic normal population, this positive correlation suggests that amygdalar enlargement in the normal population might be related to creative mental activity.

Involvement of medial prefrontal cortex in emotion during feedback presentation.

It has been suggested that the posterior medial prefrontal cortex (pMPFC) implements cognitive functions involved during negative feedback processing. It has also been suggested that the presentation of the feedback elicits emotional processes. This functional MRI study examined whether pMPFC was associated with the emotional component in feedback processing. Participants were exposed to feedback while performing a version of a motion prediction task. The pMPFC was activated during negative feedback presentation and emotion-related activity was extracted from the pMPFC activation through parametric imaging analysis. It was found that the emotional pMPFC activity was greater in participants who scored higher on depressive mood scales. The results suggest that pMPFC also implements feedback-related emotional functions, which individually vary depending on depressive moods.

Right temporopolar activation associated with unique perception.

Unique mode of perception, or the ability to see things differently from others, is one of the psychological resources required for creative mental activities. Behavioral studies using ambiguous visual stimuli have successfully induced diverse responses from subjects, and the unique responses defined in this paradigm were observed in higher frequency in the artistic population as compared to the nonartistic population. However, the neural substrates that underlie such unique perception have yet to be investigated. In the present study, ten ambiguous figures were used as stimuli. The subjects were instructed to say what the figures looked like during functional MRI scanning. The responses were classified as "frequent", "infrequent" or "unique" responses based on the appearance frequency of the same response in an independent age- and gender-matched control group. An event-related analysis contrasting unique vs. frequent responses revealed the greatest activation in the right temporal pole, which survived a whole brain multiple comparison. An alternative parametric modulation analysis was also performed to show that potentially confounding perceptual effects deriving from differences in visual stimuli make no significant contribution to this temporopolar activation. Previous neuroimaging and neuropsychological studies have shown the involvement of the temporal pole in perception-emotion linkage. Thus, our results suggest that unique perception is produced by the integration of perceptual and emotional processes, and this integration might underlie essential parts of creative mental activities.

Differential superior prefrontal activity on initial versus subsequent shifts in naive subjects.

Flexible adaptation to changing environments requires shifting of a cognitive set, one basic function of the prefrontal cortex. Set shifting, as instantiated in the Wisconsin Card Sorting Task (WCST) administered in a neuropsychological testing room, is typically achieved when subjects have no prior experiences of updating one WCST behavior to another. By contrast, earlier neuroimaging studies typically involved examination of repeated transitions between particular behaviors, to which situation subjects are far from naive. Naive subjects with no prior knowledge of the WCST were recruited in the present functional magnetic resonance imaging study to test set shifting under unknown situations that they experienced for the first time. Prominent activation was revealed in the left superior prefrontal cortex selectively on the initial shifts. On the other hand, the inferior prefrontal cortex was significantly activated on both the initial and subsequent shifts. The superior prefrontal activation distinguishable from the conventional inferior prefrontal activation suggests a selective role of this region in performance of the WCST in naive subjects.

Role of left superior temporal gyrus during name recall process: an event-related fMRI study.

When we cannot recall the name of a well-known person despite preserved access to his/her semantic knowledge, a phonological hint such as his/her initials sometimes helps us to recall the name. This type of recall failure appeared to occur by the transmission deficit from the lexical-semantic stage to the lexical-phonological stage in name recall processes, and the phonological cue appeared to activate this transmission, which leads to successful recall. We hypothesized that the brain regions responsible for the transmission would respond to the phonological cue that facilitates name recall, and would also respond to successful recall. A famous face image was presented with a phonological cue, and the subjects were required to recall and overtly pronounce the name during fMRI scanning. The behavioral results showed that the first syllable cue induced greater number of successful recall trials than both the non-verbal sound of the chime and the non-first syllable cue, suggesting that the first syllable facilitated name recall. The fMRI results demonstrated that two regions in the left superior temporal gyrus responded more strongly to the first syllable than both to the non-verbal sound of the chime and to the non-first syllable. In addition, these two regions were activated when the name recall was successful. These results suggest that two regions in the left superior temporal gyrus may play a crucial role in the transmission from the lexical-semantic to the lexical-phonological stage in the name recall processes.

On verbal/nonverbal modality dependence of left and right inferior prefrontal activation during performance of flanker interference task.

One of the most prevailing views on the functional localization of human cognition is the hemispheric specialization, wherein the left and right hemispheres are implicated primarily in verbal and nonverbal functions, respectively. Cognitive control is known to involve the lateral prefrontal cortex. However, it remains unclear whether the hemispheric specialization in the lateral prefrontal cortex can be observed in cognitive control per se, independent of sensory aspects of stimulus materials. In this functional magnetic resonance imaging study, we tested whether the verbal/nonverbal hemispheric specialization applies to the lateral prefrontal activation by investigating interference suppression, the ability to filter out irrelevant information in the environment. The flanker task was employed using a compound stimulus that contained a target and a flanker. The flanked stimulus was either a color word flanked by a colored patch or a colored patch flanked by a color word, which allowed us to manipulate the modality of the presented flanker stimulus from which interference originates, keeping the total stimulus modality balanced. The inferior frontal gyrus (IFG) showed prominent Modality-by-Hemisphere interaction in interference suppression, the left IFG being activated when a word flanker (plus a patch target) was presented and the right IFG being activated when a patch flanker (plus a word target) was presented. These results suggest that the verbal/nonverbal hemispheric specialization in the IFG can be explained by cognitive control processes per se, independent of sensory aspects of presented materials.

Activation of right inferior frontal gyrus during response inhibition across response modalities.

The go/no-go task, which effectively taps the ability to inhibit prepotent response tendency, has consistently activated the lateral prefrontal cortex, particularly the right inferior frontal gyrus (rIFG). On the other hand, rIFG activation has rarely been reported in the antisaccade task, seemingly an oculomotor version of the manual go/no-go task. One possible explanation for the variable IFG activation is the modality difference of the two tasks: The go/no-go task is performed manually, whereas the antisaccade task is performed in the oculomotor modality. Another explanation is that these two tasks have different task structures that require different cognitive processes: The traditional antisaccade task requires (i) configuration of a preparatory set prior to antisaccade execution and (ii) response inhibition at the time of antisaccade execution, whereas the go/no-go task requires heightened response inhibition under a minimal preparatory set. To test these possibilities, the traditional antisaccade task was modified in the present functional magnetic resonance imaging study such that it required heightened response inhibition at the time of antisaccade execution under a minimal preparatory set. Prominent activation related to response inhibition was observed in multiple frontoparietal regions, including the rIFG. Moreover, meta-analyses revealed that the rIFG activation in the present study was observed in the go/no-go tasks but not in the traditional antisaccade task, indicating that the rIFG activation was sensitive to the task structure difference, but not to the response modality difference. These results suggest that the rIFG is part of a network active during response inhibition across different response modalities.

Activation shift from medial to lateral temporal cortex associated with recency judgements following impoverished encoding.

Recency judgements can be performed on the basis of across-event relational information that directly provides temporal order among past events. Non-relational item-based information internal to individual past events, such as information retrieved through familiarity, may also contribute to recency judgements. The present functional magnetic resonance imaging study examined neural substrates for item-based processing during recency judgements as an alternative to relational recency judgements. One half of word stimuli were encoded relationally prior to recency judgements, and the relational encoding of the other half was hampered such that the words were processed relatively in an item-based manner. Brain activity in the medial temporal lobe was observed during recency judgements for words studied with relational memory processing, whereas brain activity in the lateral temporal cortex was observed during recency judgements for words studied relatively in an item-based manner. It was revealed further that recognition of individual words per se, which can also be regarded as familiarity/recency judgements but is non-relational in nature, also activated the lateral temporal region. These results indicate multiple routes for recency judgements within the temporal lobe that are recruited depending on how past episodes are represented and retrieved for judgements of their temporal order.

Multiple components of lateral posterior parietal activation associated with cognitive set shifting.

Posterior parietal activation has commonly been observed in previous neuroimaging studies in association with flexible shifting of cognitive set. However, it is not clear whether the parietal activation reflects cognitive processes intrinsic to the shifting itself or other confounding factors such as spatial attention. To address this issue, the Wisconsin Card Sorting Task (WCST) was modified such that spatial components were eliminated from the sensory and motor aspects of the task. Moreover, a visual instruction of a next dimension was introduced to eliminate cognitive processes related to trial and error identification of a next rule, and a control null-instruction was also introduced to eliminate perceptual/oddball effects of the instruction cue. Localizer scans using a visually guided saccade task were also conducted to identify eye movement/spatial attention-related areas. Activity related to set shifting with trial and error was revealed in the lateral parts of the intraparietal regions, while activity related to eye movements/spatial attention was revealed in the medial parts of the intraparietal regions, confirming little spatial contribution to the modified WCST as indexed by the double dissociation. The lateral intraparietal activity was bilateral, but when the instructed shifting was contrasted with the null-instructed shifting to purify the shift-related activity further, the left intraparietal activation was significantly greater than that in the right hemisphere. These results reveal the left hemisphere dominance of purified shifting-related activity in the lateral posterior parietal cortex that may cooperate with the lateral prefrontal cortex whose left hemisphere dominance has already been reported.

Neural mechanism in anterior prefrontal cortex for inhibition of prolonged set interference.

Once one cognitive set dominates our behavior, it continues to influence subsequent behavior for a while even after a task to be performed is changed to another. Despite abundant knowledge of the inhibitory mechanisms that are recruited at the first trial after the change (the first inhibition trial), little is known about the inhibition of prolonged proactive interference from a previous set that lingers for several trials after the first inhibition trial. The present functional MRI study explored the neural mechanisms for inhibition of a previous set that were recruited after the first inhibition trial. A modified Wisconsin Card Sorting Test was used where "dual-match stimuli" were intermittently presented and allowed subjects to perform correctly based on previously appropriate, now inappropriate, responses. In response to the dual-match stimulus at "release" trials presented after the first inhibition trials, the subjects were transiently exempted from inhibiting the prolonged previous set. As expected from the exempted inhibitory demands, significant reaction time decrease was revealed in the release trials. Consistent with the behavioral results, transient signal decrease time-locked to the release trials was revealed in the left anterior part of the superior frontal sulcus. Moreover, the anterior prefrontal region was not sensitive to the task change, which exhibited a marked contrast to the left posterior inferior prefrontal region that showed significant signal changes in both events. These results revealed multiple inhibitory mechanisms in the lateral prefrontal cortex that are recruited in different temporal contexts of the interference from a previous cognitive set.