Junichi Chikazoe

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.

Population coding of affect across stimuli, modalities and individuals

It remains unclear how the brain represents external objective sensory events alongside our internal subjective impressions of them—affect. Representational mapping of population activity evoked by complex scenes and basic tastes in humans revealed a neural code supporting a continuous axis of pleasant-to-unpleasant valence. This valence code was distinct from low-level physical and high-level object properties. Although ventral temporal and anterior insular cortices supported valence codes specific to vision and taste, both the medial and lateral orbitofrontal cortices (OFC) maintained a valence code independent of sensory origin. Furthermore, only the OFC code could classify experienced affect across participants. The entire valence spectrum was represented as a collective pattern in regional neural activity as sensory-specific and abstract codes, whereby the subjective quality of affect can be objectively quantified across stimuli, modalities and people.

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.

Sub-centimeter scale functional organization in human inferior frontal gyrus.

Functional areas in sensory/motor cortices are usually organized, on a finer scale, in a seamless manner along related functional units that represent, for example, certain visual fields to analyze and certain body parts to control. However, fine-scale functional organization in the prefrontal cortex has rarely been reported. In the present functional magnetic resonance imaging study, we show an example of sub-centimeter scale functional organization in the posterior part of the inferior frontal gyrus (IFG) in the right hemisphere. The spatial relationship was examined in the same subjects with regard to the activations associated with response inhibition and negative feedback processing, which are known to activate similar right IFG regions. We found that these activations were segregated, the activation during response inhibition being more caudal than that during feedback processing, and that the distance between the two activations was only 8.7 mm. Examination of the two-dimensional surface mapping of individual subjects confirmed that the two activations were located in adjacent but different regions. These results provide a specific example of a pair of functionally characterized regions that are located in the close vicinity within the right IFG.

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.

Formation of Long-Term Memory Representation in Human Temporal Cortex Related to Pictorial Paired Associates

It is widely held that long-term memory gradually develops in the temporal neocortex after initial memory encoding into the hippocampus. However, little is known as to whether and where long-term memory can be newly created in the human temporal neocortex. In this functional magnetic resonance imaging study, we detected brain activity in the temporal neocortex that was developed ∼8 weeks after study of unfamiliar pictorial paired associates. Two sets of paired Fourier figures were studied, one ∼8 weeks before test and the other immediately before test, keeping the correct performance during the tests balanced across the two sets of stimuli. Significant signal increase was observed in the right hippocampus during retrieval of newly studied pairs relative to initially studied pairs. In contrast, significant signal increase was observed in the anterior temporal cortex during retrieval of initially studied pairs relative to newly studied pairs. The greater activity during retrieval of older memory developed in the temporal neocortex provides direct evidence of formation of temporal neocortical representation for stable long-term memory.

Prediction of subsequent recognition performance using brain activity in the medial temporal lobe.

Application of multivoxel pattern analysis (MVPA) to functional magnetic resonance imaging (fMRI) data enables reconstruction and classification of cognitive status from brain activity. However, previous studies using MVPA have extracted information about cognitive status that is experienced simultaneously with fMRI scanning, but not one that will be observed after the scanning. In this study, by focusing on activity in the medial temporal lobe (MTL), we demonstrate that MVPA on fMRI data is capable of predicting subsequent recognition performance. In this experiment, six runs of fMRI signals were acquired during encoding of phonogram stimuli. In the analysis, using data acquired in runs 1-3, we first conducted MVPA-based voxel-wise search for the clusters in the MTL whose signals contained the most information about subsequent recognition performance. Next, using the fMRI signals acquired in runs 1-3 from the selected clusters, we trained a classifier function in MVPA. Finally, the trained classifier function was applied to fMRI signals acquired in runs 4-6. Consequently, we succeeded in predicting the subsequent recognition performance for stimuli studied in runs 4-6 with significant accuracy. This accurate prediction suggests that MVPA can extract information that is associated not only with concurrent cognitive status, but also with behavior in the near future.

Differential temporo-parietal cortical networks that support relational and item-based recency judgments

There is a growing interest in the parietal cortical role for episodic memory retrieval. Previous functional magnetic resonance imaging (fMRI) studies of recency judgments, judgments of the relative temporal order of two studied items, have highlighted the involvement of the lateral prefrontal and medial temporal regions. However, the parietal cortical contribution to recency judgments has rarely been highlighted. To examine the parietal involvement, in this study, we conducted a re-analysis to increase the statistical power using three data sets (N=73) from our previous fMRI studies of recency judgments. Recency judgments can be achieved by at least two mechanisms, relational and item-based ones. It has been revealed that the left hippocampus/parahippocampal region is related to relational recency judgments, and that the right anterior temporal region is related to item-based recency judgments. We examined whether the parietal cortex is involved in these two types of recency judgments. Significant brain activity related to relational recency judgments was observed in the left ventral parietal region and, as reported previously, the left parahippocampal region. On the other hand, significant brain activity related to item-based recency judgments was observed in the left dorsal parietal region and, as reported previously, the right anterior temporal region. Furthermore, correlation analyses of resting-state BOLD signals detected significant correlations between the ventral parietal region and the parahippocampal region, as well as between the dorsal parietal region and anterior temporal region. These results suggest that the two temporo-parietal networks differentially contribute to relational and item-based recency judgments.