Seiki Konishi

Transient activation of inferior prefrontal cortex during cognitive set shifting

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.

No-go dominant brain activity in human inferior prefrontal cortex revealed by functional magnetic resonance imaging

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.

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.

Preparation to Inhibit a Response Complements Response Inhibition during Performance of a Stop-Signal Task

Inhibition of inappropriate responses is an essential executive function needed for adaptation to changing environments. In stop-signal tasks, which are often used to investigate response inhibition, subjects make “go” responses while they prepare to stop at a suddenly given “stop” signal. However, the preparatory processes ongoing before response inhibition have rarely been investigated, and it remains unclear how the preparation contributes to response inhibition. In the present study, a stop-signal task was designed so that the extent of the preparation could be estimated using behavioral and neuroimaging measures. Specifically, in addition to the conventional go trials where preparation to stop was required (“uncertain-go” trials), another type of go trial was introduced where a stop-signal was never given and such preparation was unnecessary (“certain-go” trials). An index reflecting the “preparation cost” was then calculated by subtracting the reaction times in the certain-go trials from those in the uncertain-go trials. It was revealed that the stop signal reaction time, a common index used to evaluate the efficiency of response inhibition, decreased as the preparation cost increased, indicating greater preparation supports more efficient inhibition. In addition, imaging data showed that response inhibition recruited frontoparietal regions (the contrast “stop vs uncertain-go”) and that preparation recruited most of the inhibition-related frontoparietal regions (the contrast “uncertain-go vs certain-go”). It was also revealed that the inhibition-related activity declined as the preparation cost increased. These behavioral and imaging results suggest preparation makes a complementary contribution to response inhibition during performance of a stop-signal task.

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.

Hemispheric asymmetry in human lateral prefrontal cortex during cognitive set shifting

Functional organization of human cerebral hemispheres is asymmetrically specialized, most typically along a verbal/nonverbal 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.

A pairwise maximum entropy model accurately describes resting-state human brain networks

The resting-state human brain networks underlie fundamental cognitive functions and consist of complex interactions among brain regions. However, the level of complexity of the resting-state networks has not been quantified, which has prevented comprehensive descriptions of the brain activity as an integrative system. Here, we address this issue by demonstrating that a pairwise maximum entropy model, which takes into account region-specific activity rates and pairwise interactions, can be robustly and accurately fitted to resting-state human brain activities obtained by functional magnetic resonance imaging. Furthermore, to validate the approximation of the resting-state networks by the pairwise maximum entropy model, we show that the functional interactions estimated by the pairwise maximum entropy model reflect anatomical connexions more accurately than the conventional functional connectivity method. These findings indicate that a relatively simple statistical model not only captures the structure of the resting-state networks but also provides a possible method to derive physiological information about various large-scale brain networks.

Efficiency of Go/No-Go Task Performance Implemented in the Left Hemisphere

It is well known that the efficiency of response inhibition differs from person to person, but the neural mechanism that implements the efficiency is less understood. In the present fMRI study, we devised an index to evaluate the efficiency of response inhibition in the go/no-go task, and investigated the neural correlates of the efficiency of response inhibition. The human subjects who perform the go/no-go task with a shorter reaction time in go trials (Go-RT) and with a higher percentage of correct no-go trials (Nogo-PC) are thought to have the ability to conduct response inhibition more efficiently. To quantify the efficiency, we defined an efficiency index as the difference in the Nogo-PC between each subject and an ordinarily efficient subject, under the same Go-RT. An across-subject correlation analysis revealed that the brain activity in multiple regions in the left frontal and parietal cortex positively correlated with the efficiency index. Moreover, a test of hemispheric asymmetry with regard to the across-subject correlation revealed left-hemispheric dominance. The significant correlation in the left frontal and parietal regions complements the results of previous studies that used the stop-signal reaction time (SSRT), a well known index to evaluate the efficiency of response inhibition used in the stop-signal task. Our results also indicate that, although it is well known that the neural substrates for response inhibition common in a subject group exist dominantly in the right hemisphere, the neural substrates for efficiency exist dominantly in the left hemisphere.

Transient brain activity used in magnetic resonance imaging to detect functional areas.

FUNCTIONAL areas were detected with short stimuli eliciting transient brain activity using the method of ‘transient’ regions of interest (ROIs) and functional magnetic resonance imaging (fMRI). This method was validated by comparing the results with sustainedly activated areas identified conventionally. Eighty-eight and 89% of the total areas of transient ROIs derived from 0.2 and 2 s stimulation, respectively, were identified at 5–7 s and 5–9 s, respectively, after stimulus onset. Eighty-eight and 76%, respectively, of these areas overlapped ‘conventional’ ROIs derived from 20 s stimulation. These results suggest that the delineation of transient ROIs, by targeting a period ∼7 s after transient neural activity, can be useful for fMRI studies of cognitive functions.

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.