Effective modulation from the ventral medial to the dorsal medial portion of the prefrontal cortex in memory confidence-based behavioral control.

Metacognition includes the ability to refer to one's own cognitive states, such as confidence, and adaptively control behavior based on this information. This ability is thought to allow us to predictably control our behavior without external feedback, for example, even before we take action. Many studies have suggested that metacognition requires a brain-wide network of multiple brain regions. However, the modulation of effective connectivity within this network during metacognitive tasks remains unclear. This study focused on medial prefrontal regions, which have recently been suggested to be particularly involved in metacognition. We examined whether modulation of effective connectivity specific to metacognitive behavioral control is observed using model-based network analysis and dynamic causal modeling (DCM). The results showed that negative modulation from the ventral medial prefrontal cortex to the dorsal medial prefrontal cortex was observed in situations that required metacognitive behavioral control but not in situations that did not require such metacognitive control. Furthermore, this modulation was particularly pronounced in the group of participants who could better use metacognition for behavioral control. These results imply hierarchical properties of metacognition-related brain networks.

Depressive states in healthy subjects lead to biased processing in frontal-parietal ERPs during emotional stimuli.

Subthreshold depressive (sD) states and major depression are considered to occur on a continuum, and there are only quantitative and not qualitative differences between depressive states in healthy individuals and patients with depression. sD is showing a progressively increasing prevalence and has a lifelong impact, and the social and clinical impacts of sD are no less than those of major depressive disorder (MDD). Because depression leads to biased cognition, patients with depression and healthy individuals show different visual processing properties. However, it remains unclear whether there are significant differences in visual information recognition among healthy individuals with various depressive states. In this study, we investigated the event-related potentials (ERPs) and event-related spectrum perturbation (ERSP) of healthy individuals with various depressive states during the perception of emotional visual stimulation. We show that different neural activities can be detected even among healthy individuals. We divided healthy participants into high, middle, and low depressive state groups and found that participants in a high depressive state had a lower P300 amplitude and significant differences in fast and slow neural responses in the frontal and parietal lobes. We anticipate our study to provide useful parameters for assessing the evaluation of depressive states in healthy individuals.

Neural Basis of Social Influence of Observing Other's Perception in Dot-Number Estimation.

Our perceptions and decisions are often implicitly influenced by observing another's actions. However, it is unclear how observing other people's perceptual decisions without interacting with them can engage the processing of self-other discrepancies and change the observer's decisions. In this study, we employed functional magnetic resonance imaging and a computational model to investigate the neural basis of how unilaterally observing the other's perceptual decisions modulated one's own decisions. The experimental task was to discriminate whether the number of presented dots was higher or lower than a reference number. The participants performed the task solely while unilaterally observing the performance of another "participant," who produced overestimations and underestimations in the same task in separate sessions. Results of the behavioral analysis showed that the participants' decisions were modulated to resemble those of the other. Image analysis based on computational model revealed that the activation in the medial prefrontal cortex was associated with the discrepancy between the inferred participant's and the presented other's decisions. In addition, the number-sensitive region in the superior parietal region showed altered activation patterns after observing the other's overestimations and underestimations. The activity of the superior parietal region was not involved in assessing the observation of other's perceptual decisions, but it was engaged in plain numerosity perception. These results suggest that computational modeling can capture the neuro-behavioral processing of self-other discrepancies in perception followed by the activity modulation in the number-sensitive region in the task of dot-number estimation.

Respective Involvement of the Right Cerebellar Crus I and II in Syntactic and Semantic Processing for Comprehension of Language.

The right posterolateral portions of the cerebellum (crus-I/II) are involved in language processing. However, their functional role in language remains unknown. The cerebellum is hypothesized to acquire an internal model that is a functional copy of mental representations in the cerebrum and to contribute to cognitive function. In this research, based on the cerebellar internal model hypothesis, we conducted task-based and resting-state functional magnetic resonance imaging (fMRI) experiments to investigate the role of the cerebellum in the syntactic and semantic aspects of comprehension of sentences. In a syntactic task, participants read sentences with center-embedded hierarchical structures. The hierarchical level-dependent activity was found in the right crus-I as well as Broca's area (p < 0.05, voxel-based small volume correction (SVC)). In a semantic task, the participants read three types of sentences for investigation of sentence-level, phrase-level, and word-level semantic processing. The semantic level-dependent activity was found in the right crus-II as well as in the left anterior temporal lobe and the left angular gyrus (p < 0.05, voxel-based SVC). Moreover, the right crus-I/II showed significant activity when the cognitive load was high. Resting-state fMRI demonstrated intrinsic functional connectivity between the right crus-I/II and language-related regions in the left cerebrum (p < 0.05, voxel-based SVC). These findings suggest that the right crus-I and crus-II are involved, respectively, in the syntactic and semantic aspects of sentence processing. The cerebellum assists processing of language in the cerebrum when the cognitive load is high.

Synergistic effects of disgust and anger on amygdala activation while recalling memories of interpersonal stress: An fMRI study.

Occurrence of an unpleasant interpersonal event in daily life may cause an individual to experience unpleasant emotions and recall memories regarding it. These emotions, manifesting in daily social interactions, are often complex and mixed. In the laboratory, autobiographical recall is frequently used to induce emotions; however, it often involves recalling memories associated with a specific discrete emotion (e.g., sadness). To examine the neural activity of emotions similar to real-life experiences, we examined neural activity while recalling memories of stressful interpersonal events in daily life, without specifying a discrete emotion. Of the 23 university students recruited, 21 were analyzed and asked to freely recall memories and answer a series of questions on a monitor concerning their recalled memories while their neural activity was measured with functional magnetic resonance imaging. Amygdala activity increased while receiving the instructions, followed by a decrease in activity. This indicates that the participants' arousal and vigilance initially increased in response to a novel stimulus, and then decreased by habituation. Disgust and anger, which frequently occur as negative interpersonal feelings, were most prominently produced with strong associations with each other. More importantly, activation of the right amygdala while responding to questions regarding the recalled memories was positively correlated with disgust or anger only when not controlling for anger or disgust, respectively. These results indicate that responding to questions facilitated the generation of a mixed emotional response compared to during free recall alone. Furthermore, disgust and anger as a mixed emotion can synergistically activate amygdala.

Application of a Machine Learning Algorithm for Structural Brain Images in Chronic Schizophrenia to Earlier Clinical Stages of Psychosis and Autism Spectrum Disorder: A Multiprotocol Imaging Dataset Study.

BACKGROUND AND HYPOTHESIS: Machine learning approaches using structural magnetic resonance imaging (MRI) can be informative for disease classification; however, their applicability to earlier clinical stages of psychosis and other disease spectra is unknown. We evaluated whether a model differentiating patients with chronic schizophrenia (ChSZ) from healthy controls (HCs) could be applied to earlier clinical stages such as first-episode psychosis (FEP), ultra-high risk for psychosis (UHR), and autism spectrum disorders (ASDs). STUDY DESIGN: Total 359 T1-weighted MRI scans, including 154 individuals with schizophrenia spectrum (UHR, n = 37; FEP, n = 24; and ChSZ, n = 93), 64 with ASD, and 141 HCs, were obtained using three acquisition protocols. Of these, data regarding ChSZ (n = 75) and HC (n = 101) from two protocols were used to build a classifier (training dataset). The remainder was used to evaluate the classifier (test, independent confirmatory, and independent group datasets). Scanner and protocol effects were diminished using ComBat. STUDY RESULTS: The accuracy of the classifier for the test and independent confirmatory datasets were 75% and 76%, respectively. The bilateral pallidum and inferior frontal gyrus pars triangularis strongly contributed to classifying ChSZ. Schizophrenia spectrum individuals were more likely to be classified as ChSZ compared to ASD (classification rate to ChSZ: UHR, 41%; FEP, 54%; ChSZ, 70%; ASD, 19%; HC, 21%). CONCLUSION: We built a classifier from multiple protocol structural brain images applicable to independent samples from different clinical stages and spectra. The predictive information of the classifier could be useful for applying neuroimaging techniques to clinical differential diagnosis and predicting disease onset earlier.

Volumetric differences in gray and white matter of cerebellar Crus I/II across the different clinical stages of schizophrenia.

AIM: Schizophrenia is considered to be a disorder of progressive structural brain abnormalities. Previous studies have indicated that the cerebellar Crus I/II plays a critical role in schizophrenia. We aimed to investigate how specific morphological features in the Crus I/II at different critical stages of the schizophrenia spectrum contribute to the disease. METHODS: The study involved 73 participants on the schizophrenia spectrum (28 with ultra-high risk for psychosis [UHR], 17 with first-episode schizophrenia [FES], and 28 with chronic schizophrenia) and 79 healthy controls. We undertook a detailed investigation into differences in Crus I/II volume using a semiautomated segmentation method optimized for the cerebellum. We analyzed the effects of group and sex, as well as their interaction, on Crus I/II volume in gray matter (GM) and white matter (WM). RESULTS: Significant group × sex interactions were found in WM volumes of the bilateral Crus I/II; the males with UHR demonstrated significantly larger WM volumes compared with the other male groups, whereas no significant group differences were found in the female groups. Additionally, WM and GM volumes of the Crus I/II had positive associations with symptom severity in the UHR group, whereas, in contrast, GM volumes in the FES group were negatively associated with symptom severity. CONCLUSIONS: The present findings provide evidence that the morphology of Crus I/II is involved in schizophrenia in a sex- and disease stage-dependent manner. Additionally, alterations of WM volumes of Crus I/II may have potential as a biological marker of early detection and treatment for individuals with UHR.

Frequency-dependent effects of EEG phase resetting on reaction time.

There is trial-to-trial variability in the reaction time to stimulus presentation. Since this variability exists even in an identical stimulus condition, it reflects the internal neural dynamics of the brain. To understand the neural dynamics that influence the reaction time, we conducted an electroencephalogram (EEG) experiment in which participants were asked to press a response button as quickly as possible when a stimulus was visually presented. Phase-locking factor analysis revealed that phase resetting in two frequency bands, which appeared 0.2 s after the stimulus presentation, characterized the reaction time. The combination of the theta band phase resetting in the left parietal region and the delta band phase resetting mainly in the posterior region was associated with the fastest reaction time, whereas delta band phase resetting without theta band phase resetting was associated with the faster reaction time. The results indicated that there were frequency-dependent effects in the relationships between the EEG phase resetting and reaction time.

Dietary Restraint Related to Body Weight Maintenance and Neural Processing in Value-Coding Areas in Adolescents.

BACKGROUND: There is an alarming increase in the obesity prevalence among children in an environment of increasing availability of preprocessed high-calorie foods. However, some people maintain a healthy weight even in such obesogenic environments. This difference in body weight management could be attributed to individual differences in dietary restraint; however, its underlying neurocognitive mechanisms in adolescents remain unclear. OBJECTIVES: This study aimed to elucidate these neurocognitive mechanisms in adolescents by examining the relationships between dietary restraint and the food-related value-coding region located in the ventromedial prefrontal cortex (vmPFC). METHODS: The association between dietary restraint and BMI was tested using a multilinear regression analysis in a large early adolescent cohort (n = 2554; age, 12.2 ± 0.3 years; BMI, 17.9 ± 2.5 kg/m2; 1354 boys). Further, an fMRI experiment was designed to assess the association between the vmPFC response to food images and dietary restraint in 30 adolescents (age, 17.6 ± 1.9 years; BMI, 20.7 ± 2.2 kg/m2; 13 boys). Additionally, using 54 individuals from the cohort (age, 14.5 ± 0.6 years; BMI, 18.8 ± 2.6 kg/m2; 31 boys), we assessed the association between dietary restraint and intrinsic vmPFC-related functional connectivity. RESULTS: In the cohort, adolescents with increased dietary restraint showed a lower BMI (ß = -0.38; P < 0.001; B = -0.06; SE = 0.003). The fMRI results showed a decreased vmPFC response to high-calorie food were correlated with greater dietary restraint. Moreover, there was an association of attenuated intrinsic vmPFC-related functional connectivity in the superior and middle frontal gyrus and the middle temporal gyrus with greater dietary restraint. CONCLUSIONS: Our findings suggest that dietary restraint in adolescents could be a preventive factor for weight gain; its effect involves modulating the vmPFC, which is associated with food value coding.

Trait Respect Is Linked to Reduced Gray Matter Volume in the Anterior Temporal Lobe.

Respect is a positive other-oriented social emotion upon the recognition of excellence in others. We previously reported that respect-related brain activity in the left anterior temporal lobe (ATL). Since brain activity and structure are often involved in common cognitive functions, we investigated the morphological properties of the left ATL using voxel-based morphometry analysis. We found an association of trait respect with reduced gray matter volume (GMV) in part of the left ATL. Moreover, since the ATL is involved in general conceptual knowledge, we investigated the relationships between other social emotions with similar properties as respect and the GMV of the left ATL. We observed an association of reduced GMV with empathic concern, which is an other-oriented and affective aspect of trait empathy. Our findings indicated an association of the left ATL with other-oriented and affective aspect of social emotions.

Machine-learning classification using neuroimaging data in schizophrenia, autism, ultra-high risk and first-episode psychosis.

Neuropsychiatric disorders are diagnosed based on behavioral criteria, which makes the diagnosis challenging. Objective biomarkers such as neuroimaging are needed, and when coupled with machine learning, can assist the diagnostic decision and increase its reliability. Sixty-four schizophrenia, 36 autism spectrum disorder (ASD), and 106 typically developing individuals were analyzed. FreeSurfer was used to obtain the data from the participant's brain scans. Six classifiers were utilized to classify the subjects. Subsequently, 26 ultra-high risk for psychosis (UHR) and 17 first-episode psychosis (FEP) subjects were run through the trained classifiers. Lastly, the classifiers' output of the patient groups was correlated with their clinical severity. All six classifiers performed relatively well to distinguish the subject groups, especially support vector machine (SVM) and Logistic regression (LR). Cortical thickness and subcortical volume feature groups were most useful for the classification. LR and SVM were highly consistent with clinical indices of ASD. When UHR and FEP groups were run with the trained classifiers, majority of the cases were classified as schizophrenia, none as ASD. Overall, SVM and LR were the best performing classifiers. Cortical thickness and subcortical volume were most useful for the classification, compared to surface area. LR, SVM, and DT's output were clinically informative. The trained classifiers were able to help predict the diagnostic category of both UHR and FEP Individuals.

Development of Metacognition in Adolescence: The Congruency-Based Metacognition Scale.

INTRODUCTION: Previous studies on metacognitive ability were explored using self-report questionnaires that are difficult to adequately measure and evaluate when the capacity for self-reference is undeveloped. This study aimed to validate the Congruency-based Metacognition Scale (CMS) to measure metacognition and the feeling of confidence abilities and to investigate the development of metacognition during adolescence. METHODS: The CMS was administered to 633 child-parent pairs in Japan (child, mean age = 16.0 years, 46.0% female; parent, mean age = 48.3 years, 94.9% mother). The CMS metacognition score was assessed based on congruency scores between the self-report of the child from a third-person perspective (3PP) and the parent's report from the first-person perspective (1PP). The CMS self-judgment accuracy score was assessed by the congruency scores between the children's self-report from the 1PP and 3PP. For both measures, the more distant the 3PP on the self-report was from the 1PP on the parent's report and child self-report means low ability. An exploratory factor analysis (EFA) was conducted to examine construct validity and then a confirmatory factor analysis (CFA) was used. Criterion validity was examined by calculating Pearson's correlation coefficients with scores on the Beck Cognitive Insight Scale (BCIS) and Autism Quotient (AQ). We used intraclass correlation and Cronbach's alpha to examine the test-retest and internal consistency reliability. RESULTS: Based on the results of the EFA and CFA, we adopted one factor structure with five items. The CMS metacognition and CMS self-judgment accuracy showed evidence criterion validity, exhibiting significant correlations with the BCIS self-reflectiveness (r = 0.16) and self-certainty scores (r = 0.17), respectively. Regarding to the AQ, only the CMS metacognition score had significant correlations with the social skills (r = 0.22) and total scale score (r = 0.20). The test-retest reliability showed adequate (intraclass correlation coefficient 0.70-0.81 and the Cronbach's alpha coefficient 0.63-0.59). Adolescents were found to have significantly lower metacognitive ability compared to young adults. CONCLUSION: CMS could be a valid and reliable measure to examine metacognitive abilities for adolescents.

Difference in neural reactivity to taste stimuli and visual food stimuli in neural circuits of ingestive behavior.

Brain responses to sight and taste of foods have been examined to provide insights into neural substrates of ingestive behavior. Since the brain response to food images and taste stimuli are overlapped in neural circuits of eating behavior, each food cue would influence eating behavior in a partly similar manner. However, because few studies have examined the differences in brain responses to each food cue, the variation in neural sensitivity to these food cues or specific brain response to each food cue remain unclear. We thus performed a repeated measures functional magnetic resonance imaging (fMRI) study to examine brain responses to the image and taste of various foods for direct comparisons of the brain response to each food cue. Thirty-five healthy adolescents (age: 14-19 years [mean: 17 years], males = 16, females = 19) underwent two fMRI scans, a food image fMRI scan for measurement of brain response to food images, and a taste stimulus fMRI scan for measurement of brain response to taste stimuli. Food images evoked brain responses in the visual information processing regions, anterior insula, striatum, and pre-/postcentral gyrus compared to taste stimuli, whereas taste stimuli induced brain responses in the mid-insula and limbic regions compared to food images. These results imply that food images tend to evoke brain responses in regions associated with food reward anticipation and food choice, whereas taste stimuli tend to induce brain responses in regions involved in assigning existent incentive values to foods based on existent energy homeostatic status.

Regulation of action selection based on metacognition in humans via a ventral and dorsal medial prefrontal cortical network.

Metacognition is defined as cognition about one's own cognitive state; it enables us to estimate our own performance during goal-directed actions and to select a suitable strategy based on that estimation. Identifying the neural mechanisms that underlie this process will contribute to our understanding of how we realize adaptive self-control in daily life. Here, we focused on the neural substrates that allow us to voluntarily utilize prospective metacognition to carry out such action selection. Participants were asked to bet on their recall of sound stimuli presented at an earlier time in a delayed match-to-sample task of rapidly changing sound stimuli. During the task, brain activity was measured using functional magnetic resonance imaging. We found that the brain network composed of the ventral and dorsal parts of the medial prefrontal cortex and the medial precuneus regulated the strategic selection of risk/return profiles based on metacognition. In particular, increments in functional connectivity between the ventral and dorsal medial prefrontal cortices during high-risk/return bets correlated with the adaptiveness of the bet (as measured by the correspondence between choosing high risk/return bets and high accuracy of task performance). This index is considered to reflect the degree of voluntary use of metacognition to bet. These findings suggest that the strong connectivity within the network involving the ventral and dorsal medial prefrontal cortices enables us to utilize metacognition to select actions for achieving a goal efficiently.

Respect and admiration differentially activate the anterior temporal lobe.

Admiration and respect are positive social emotions often experienced when recognizing excellent behavior in another person. Although both strongly rely on appraisal of behavior, admiration focuses on the admirable behavior of a person, while respect focuses on the person as a whole. The evaluation and interpretation of the social behavior of another person are dependent on semantic memory. Social semantic knowledge is represented in the anterior temporal lobe (ATL), and ATL activity is modulated by conceptual details of semantic knowledge. As respect requires evaluation of not only excellent behavior but also of the person as a whole, we hypothesized that the ATL is differentially activated by admiration and respect. To test our hypothesis, we conducted functional magnetic resonance imaging experiments. We presented participants with vignettes describing admirable behavior of fictitious characters and asked them to imagine and report how they would normally feel when encountering the situation described in the vignettes, i.e., admiration or respect and its intensity. A part of the left ATL was more strongly modulated by the intensity of respect than of admiration. Although admiration and respect are often considered to be closely related, our results indicate that the neural substrates underlying these emotions are different.

Perceived moral traits of others differentiate the neural activation that underlies inequity-aversion.

We have a social preference to reduce inequity in the outcomes between oneself and others. Such a preference varies according to others. We performed functional magnetic resonance imaging during an economic game to investigate how the perceived moral traits of others modulate the neural activities that underlie inequity-aversion. The participants unilaterally allocated money to three partners (good, neutral, and bad). During presentation of the good and neutral partners, the anterior region of the rostral medial frontal cortex (arMFC) showed increased functional connectivity with the caudate head and the anterior insula, respectively. Following this, participants allocated more money to the good partner, and less to the bad partner, compared with the neutral partner. The caudate head and anterior insula showed greater activation during fair allocation to the good and unfair allocation to the neutral partners, respectively. However, these regions were silent during allocations to the bad partner. Therefore, the arMFC-caudate/insula circuit encompasses distinct neural processes that underlie inequity-aversion in monetary allocations that the different moral traits of others can modulate.

Sense of Accomplishment Is Modulated by a Proper Level of Instruction and Represented in the Brain Reward System.

Problem-solving can be facilitated with instructions or hints, which provide information about given problems. The proper amount of instruction that should be provided for learners is controversial. Research shows that tasks with intermediate difficulty induce the largest sense of accomplishment (SA), leading to an intrinsic motivation for learning. To investigate the effect of instructions, we prepared three instruction levels (No hint, Indirect hint, and Direct hint) for the same insight-problem types. We hypothesized that indirect instructions impose intermediate difficulty for each individual, thereby inducing the greatest SA per person. Based on previous neuroimaging studies that showed involvement of the bilateral caudate in learning and motivation, we expected SA to be processed in this reward system. We recruited twenty-one participants, and investigated neural activations during problem solving by functional magnetic resonance imaging (fMRI). We confirmed that the Indirect hint, which imposed intermediate difficulty, induced the largest SA among the three instruction types. Using fMRI, we showed that activations in the bilateral caudate and anterior cingulate cortex (ACC) were significantly modulated by SA. In the bilateral caudate, the indirect hint induced the largest activation, while the ACC seemed to reflect the difference between correct and incorrect trials. Importantly, such activation pattern was independent of notations (number or letter). Our results indicate that SA is represented in the reward system, and that the Indirect instruction effectively induces such sensation.

Quick concurrent responses to global and local cognitive information underlie intuitive understanding in board-game experts.

Experts have the superior cognitive capability of quickly understanding complex information in their domain; however, little is known about the neural processes underlying this ability. Here, using a board game named shogi (Japanese chess), we investigated the brain activity in expert players that was involved in their quick understanding of board-game patterns. The frontal area responded only to meaningful game positions, whereas the temporal area responded to both game and random positions with the same latency (200 ms). Subsequent to these quick responses, the temporal and parietal areas responded only to game positions, with a latency of 700 ms. During the responses, enhanced phase synchronization between these areas was observed. Thus, experts first responded to global cognitive information that was specific to game positions and to local cognitive information that was common to game and random positions concurrently. These types of information were integrated via neural synchronization at the posterior areas. As these properties were specific to experts, much of the experts' advantage in understanding game positions occurred within 1 s of perception.

Cross-frequency phase synchrony around the saccade period as a correlate of perceiver's internal state.

In active vision, eye-movements depend on perceivers' internal state. We investigated peri-fixation brain activity for internal state-specific tagging. Human participants performed a task, in which a visual object was presented for identification in lateral visual field, to which they moved their eyes as soon as possible from a central fixation point. Next, a phrase appeared in the same location; the phrase could either be an easy or hard question about the object, answered by pressing one of two alternative response buttons, or it could be an instruction to simply press one of these two buttons. Depending on whether these messages were blocked or randomly mixed, one of two different internal states was induced: either the task was known in advance or it wasn't. Eye movements and electroencephalogram (EEG) were recorded simultaneously during task performance. Using eye-event-time-locked averaging and independent component analysis, saccade- and fixation-related components were identified. Coss-frequency phase-synchrony was observed between the alpha/beta1 ranges of fixation-related and beta2/gamma1 ranges of saccade-related activity 50 ms prior to fixation onset in the mixed-phrase condition only. We interpreted this result as evidence for internal state-specific tagging.

Antecedent occipital alpha band activity predicts the impact of oculomotor events in perceptual switching.

Oculomotor events such as blinks and saccades transiently interrupt the visual input and, even though this mostly goes undetected, these brief interruptions could still influence the percept. In particular, both blinking and saccades facilitate switching in ambiguous figures such as the Necker cube. To investigate the neural state antecedent to these oculomotor events during the perception of an ambiguous figure, we measured the human scalp electroencephalogram (EEG). When blinking led to perceptual switching, antecedent occipital alpha band activity exhibited a transient increase in amplitude. When a saccade led to switching, a series of transient increases and decreases in amplitude was observed in the antecedent occipital alpha band activity. Our results suggest that the state of occipital alpha band activity predicts the impact of oculomotor events on the percept.