Diurnal Variation of Brain Activity in the Human Suprachiasmatic Nucleus.

The suprachiasmatic nucleus (SCN) is the central clock for circadian rhythms. Animal studies have revealed daily rhythms in the neuronal activity in the SCN. However, the circadian activity of the human SCN has remained elusive. In this study, to reveal the diurnal variation of the SCN activity in humans, we localized the SCN by employing an areal boundary mapping technique to resting-state functional images and investigated the SCN activity using perfusion imaging. In the first experiment (n = 27, including both sexes), we scanned each participant four times a day, every 6 h. Higher activity was observed at noon, while lower activity was recorded in the early morning. In the second experiment (n = 20, including both sexes), the SCN activity was measured every 30 min for 6 h from midnight to dawn. The results showed that the SCN activity gradually decreased and was not associated with the electroencephalography. Furthermore, the SCN activity was compatible with the rodent SCN activity after switching off the lights. These results suggest that the diurnal variation of the human SCN follows the zeitgeber cycles of nocturnal and diurnal mammals and is modulated by physical lights rather than the local time.

More widespread functionality of posterior language area in patients with brain tumors.

Damage to the posterior language area (PLA), or Wernicke's area causes cortical reorganization in the corresponding regions of the contralateral hemisphere. However, the details of reorganization within the ipsilateral hemisphere are not fully understood. In this context, direct electrical stimulation during awake surgery can provide valuable opportunities to investigate neuromodulation of the human brain in vivo, which is difficult through the non-invasive approaches. Thus, in this study, we aimed to investigate the characteristics of the cortical reorganization of the PLA within the ipsilateral hemisphere. Sixty-two patients with left hemispheric gliomas were divided into groups depending on whether the lesion extended to the PLA. All patients underwent direct cortical stimulation with a picture-naming task. We further performed functional connectivity analyses using resting-state functional magnetic resonance imaging (MRI) in a subset of patients and calculated betweenness centrality, an index of the network importance of brain areas. During direct cortical stimulation, the regions showing positive (impaired) responses in the non-PLA group were localized mainly in the posterior superior temporal gyrus (pSTG), whereas those in the PLA group were widely distributed from the pSTG to the posterior supramarginal gyrus (pSMG). Notably, the percentage of positive responses in the pSMG was significantly higher in the PLA group (47%) than in the non-PLA group (8%). In network analyses of functional connectivity, the pSMG was identified as a hub region with high betweenness centrality in both the groups. These findings suggest that the language area can spread beyond the PLA to the pSMG, a hub region, in patients with lesion progression to the pSTG. The change in the pattern of the language area may be a compensatory mechanism to maintain efficient brain networks.

Role of right temporoparietal junction for counterfactual evaluation of partner's decision in ultimatum game.

Humans assess the distributions of resources based on their aversion to unfairness. If a partner distributes in an unfair manner even though the partner had a less unfair distribution option, a recipient will believe that the partner should have chosen the counterfactual option. In this study, we investigated the neural basis for fairness evaluation of actual and counterfactual options in the ultimatum game. In this task, a partner chose one distribution option out of two options, and a participant accepted or rejected the option. The behavioral results showed that the acceptance rate was influenced by counterfactual evaluation (CE), among others, as defined by the difference of monetary amount between the actual and counterfactual options. The functional magnetic resonance imaging results showed that CE was associated with the right ventral angular gyrus (vAG) that provided one of convergent inputs to the supramarginal gyrus related to decision utility, which reflects gross preferences for the distribution options. Furthermore, inhibitory repetitive transcranial magnetic stimulation administered to the right vAG reduced the behavioral component associated with CE. These results suggest that our acceptance/rejection of distribution options relies on multiple processes (monetary amount, disadvantageous inequity, and CE) and that the right vAG causally contributes to CE.

Reduced gray matter volume in the default-mode network associated with insulin resistance.

Insulin resistance may lead to structural and functional abnormalities of the human brain. However, the mechanism by which insulin resistance impairs the brain remains elusive. In this study, we used two large neuroimaging databases to investigate the brain regions where insulin resistance was associated with the gray matter volume and to examine the resting-state functional connectivity between these brain regions and each hypothalamic nucleus. Insulin resistance was associated with reduced gray matter volume in the regions of the default-mode and limbic networks in the cerebral cortex in older adults. Resting-state functional connectivity was prominent between these networks and the paraventricular nucleus of the hypothalamus, a hypothalamic interface connecting functionally with the cerebral cortex. Furthermore, we found a significant correlation in these networks between insulin resistance-related gray matter volume reduction and network paraventricular nucleus of the hypothalamus resting-state functional connectivity. These results suggest that insulin resistance-related gray matter volume reduction in the default-mode and limbic networks emerged through metabolic homeostasis mechanisms in the hypothalamus.

Hypothalamic interaction with reward-related regions during subjective evaluation of foods.

The reward system implemented in the midbrain, ventral striatum, orbitofrontal cortex, and ventromedial prefrontal cortex evaluates and compares various types of rewards given to the organisms. It has been suggested that autonomic factors influence reward-related processing via the hypothalamus, but how the hypothalamus modulates the reward system remains elusive. In this functional magnetic resonance imaging study, the hypothalamus was parcellated into individual hypothalamic nuclei performing different autonomic functions using boundary mapping parcellation analyses. The effective interaction during subjective evaluation of foods in a reward task was then investigated between the human hypothalamic nuclei and the reward-related regions. We found significant brain activity decrease in the paraventricular nucleus (PVH) and lateral nucleus in the hypothalamus in food evaluation compared with monetary evaluation. A psychophysiological interaction analysis revealed dual interactions between the PVH and (1) midbrain region and (2) ventromedial prefrontal cortex, with the former correlated with the stronger tendency of participants toward food-seeking. A dynamic causal modeling analysis further revealed unidirectional interactions from the PVH to the midbrain and ventromedial prefrontal cortex. These results suggest that the PVH in the human hypothalamus interacts with the reward-related regions in the cerebral cortex via multiple pathways (i.e., the midbrain pathway and ventromedial prefrontal pathway) to evaluate rewards for subsequent decision-making.

Functional Organization for Response Inhibition in the Right Inferior Frontal Cortex of Individual Human Brains.

The right inferior frontal cortex (IFC) is critical to response inhibition. The right IFC referred in the human studies of response inhibition is located in the posterior part of the inferior frontal gyrus and the surrounding regions and consists of multiple areas that implement distinct functions. Recent studies using resting-state functional connectivity have parcellated the cerebral cortex and revealed across-subject variability of parcel-based cerebrocortical networks. However, how the right IFC of individual brains is functionally organized and what functional properties the IFC parcels possess regarding response inhibition remain elusive. In the present functional magnetic resonance imaging study, precision functional mapping of individual human brains was adopted to the parcels in the right IFC to evaluate their functional properties related to response inhibition. The right IFC consisted of six modules or subsets of subregions, and the spatial organization of the modules varied considerably across subjects. Each module revealed unique characteristics of brain activity and its correlation to behavior related to response inhibition. These results provide updated functional features of the IFC and demonstrate the importance of individual-focused approaches in studying response inhibition in the right IFC.

An Essential Role of the Intraparietal Sulcus in Response Inhibition Predicted by Parcellation-Based Network.

The posterior parietal cortex (PPC) features close anatomical and functional relationships with the prefrontal cortex. However, the necessity of the PPC in executive functions has been questioned. The present study used the stop-signal task to examine response inhibition, an executive function that inhibits prepotent response tendency. The brain activity and resting-state functional connectivity were measured to analyze a parcellation-based network that was aimed at identifying a candidate PPC region essential for response inhibition in humans. The intraparietal sulcus (IPS) was activated during response inhibition and connected with the inferior frontal cortex and the presupplementary motor area, the two frontal regions known to be necessary for response inhibition. Next, transcranial magnetic stimulation (TMS) was used to test the essential role of the IPS region for response inhibition. TMS over the IPS region prolonged the stop-signal reaction time (SSRT), the standard behavioral index used to evaluate stopping performance, when stimulation was applied 30-0 ms before stopping. On the contrary, stimulation over the temporoparietal junction region, an area activated during response inhibition but lacking connectivity with the two frontal regions, did not show changes in SSRT. These results indicate that the IPS identified using the parcellation-based network plays an essential role in executive functions.SIGNIFICANCE STATEMENT Based on the previous neuropsychological studies reporting no impairment in executive functions after lesions in the posterior parietal cortex (PPC), the necessity of PPC in executive functions has been questioned. Here, contrary to the long-lasting view, by using recently developed analysis in functional MRI ("parcellation-based network analysis"), we identified the intraparietal sulcus (IPS) region in the PPC as essential for response inhibition: one executive function to stop actions that are inaccurate in a given context. The necessity of IPS for response inhibition was further tested by an interventional technique of transcranial magnetic stimulation. Stimulation to the IPS disrupted the performance of stopping. Our findings suggest that the IPS plays essential roles in executive functions.

Connectivity-based localization of human hypothalamic nuclei in functional images of standard voxel size.

Despite their critical roles in autonomic functions, individual hypothalamic nuclei have not been extensively investigated in humans using functional magnetic resonance imaging, partly due to the difficulty in resolving individual nuclei contained in the small structure of the hypothalamus. Areal parcellation analyses enable discrimination of individual hypothalamic nuclei but require a higher spatial resolution, which necessitates long scanning time or large amounts of data to compensate for the low signal-to-noise ratio in 3T or 1.5T scanners. In this study, we present analytic procedures to estimate likely locations of individual nuclei in the standard 2-mm resolution based on our higher resolution dataset. The spatial profiles of functional connectivity with the cerebral cortex for each nucleus in the medial hypothalamus were calculated using our higher resolution dataset. Voxels in the hypothalamus in standard resolution images from the Human Connectome Project (HCP) database that predominantly shared connectivity profiles with the same nucleus were subsequently identified. Voxels representing individual nuclei, as identified with the analytic procedures, were reproducible across 20 HCP datasets of 20 subjects each. Furthermore, the identified voxels were spatially separate. These results suggest that these analytic procedures are capable of refining voxels that represent individual hypothalamic nuclei in standard resolution. Our results highlight the potential utility of these procedures in various settings such as patient studies, where lengthy scans are infeasible.

Rawlsian maximin rule operates as a common cognitive anchor in distributive justice and risky decisions.

Distributive justice concerns the moral principles by which we seek to allocate resources fairly among diverse members of a society. Although the concept of fair allocation is one of the fundamental building blocks for societies, there is no clear consensus on how to achieve "socially just" allocations. Here, we examine neurocognitive commonalities of distributive judgments and risky decisions. We explore the hypothesis that people's allocation decisions for others are closely related to economic decisions for oneself at behavioral, cognitive, and neural levels, via a concern about the minimum, worst-off position. In a series of experiments using attention-monitoring and brain-imaging techniques, we investigated this "maximin" concern (maximizing the minimum possible payoff) via responses in two seemingly disparate tasks: third-party distribution of rewards for others, and choosing gambles for self. The experiments revealed three robust results: (i) participants' distributive choices closely matched their risk preferences-"Rawlsians," who maximized the worst-off position in distributions for others, avoided riskier gambles for themselves, whereas "utilitarians," who favored the largest-total distributions, preferred riskier but more profitable gambles; (ii) across such individual choice preferences, however, participants generally showed the greatest spontaneous attention to information about the worst possible outcomes in both tasks; and (iii) this robust concern about the minimum outcomes was correlated with activation of the right temporoparietal junction (RTPJ), the region associated with perspective taking. The results provide convergent evidence that social distribution for others is psychologically linked to risky decision making for self, drawing on common cognitive-neural processes with spontaneous perspective taking of the worst-off position.

Striatal subdivisions that coherently interact with multiple cerebrocortical networks.

The striatum constitutes the cortical-basal ganglia loop and receives input from the cerebral cortex. Previous MRI studies have parcellated the human striatum using clustering analyses of structural/functional connectivity with the cerebral cortex. However, it is currently unclear how the striatal regions functionally interact with the cerebral cortex to organize cortical functions in the temporal domain. In the present human functional MRI study, the striatum was parcellated using boundary mapping analyses to reveal the fine architecture of the striatum by focusing on local gradient of functional connectivity. Boundary mapping analyses revealed approximately 100 subdivisions of the striatum. Many of the striatal subdivisions were functionally connected with specific combinations of cerebrocortical functional networks, such as somato-motor (SM) and ventral attention (VA) networks. Time-resolved functional connectivity analyses further revealed coherent interactions of multiple connectivities between each striatal subdivision and the cerebrocortical networks (i.e., a striatal subdivision-SM connectivity and the same striatal subdivision-VA connectivity). These results suggest that the striatum contains a large number of subdivisions that mediate functional coupling between specific combinations of cerebrocortical networks.

Functional subdivisions of the hypothalamus using areal parcellation and their signal changes related to glucose metabolism.

The hypothalamus consists of numerous nuclei, and is regarded as the highest center for various autonomic functions. Although each hypothalamic nucleus implements a distinct function, it remains difficult to investigate the human hypothalamus at the nucleus level. In the present high-resolution functional MRI study, we utilized areal parcellation to discriminate individual nuclei in the human hypothalamus based on areal profiles of resting-state functional connectivity. The areal parcellation detected ten foci that were expected to represent hypothalamic nuclei, and the locations of the foci were consistent with those of the hypothalamic nuclei identified in previous histological studies. Regions of interest (ROI) analyses revealed contrasting brain activity changes following glucose ingestion: decrease in the ventromedial hypothalamic nucleus and increase in the lateral hypothalamic area in parallel with blood glucose increase. Moreover, decreased brain activity in the arcuate nucleus predicted future elevation of blood insulin during the first 10 min after glucose ingestion. These results suggest that the hypothalamic nuclei can putatively be determined using areal parcellation, and that the ROI analysis of the human hypothalamic nuclei is useful for future scientific and clinical investigations into the autonomic functions.

Orienting of visuo-spatial attention in complex 3D space: Search and detection.

The ability to detect changes in the environment is necessary for appropriate interactions with the external world. Changes in the background go more unnoticed than foreground changes, possibly because attention prioritizes processing of foreground/near stimuli. Here, we investigated the detectability of foreground and background changes within natural scenes and the influence of stereoscopic depth cues on this. Using a flicker paradigm, we alternated a pair of images that were exactly same or differed for one single element (i.e., a color change of one object in the scene). The participants were asked to find the change that occurred either in a foreground or background object, while viewing the stimuli either with binocular and monocular cues (bmC) or monocular cues only (mC). The behavioral results showed faster and more accurate detections for foreground changes and overall better performance in bmC than mC conditions. The imaging results highlighted the involvement of fronto-parietal attention controlling networks during active search and target detection. These attention networks did not show any differential effect as function of the presence/absence of the binocular cues, or the detection of foreground/background changes. By contrast, the lateral occipital cortex showed greater activation for detections in foreground compared to background, while area V3A showed a main effect of bmC vs. mC, specifically during search. These findings indicate that visual search with binocular cues does not impose any specific requirement on attention-controlling fronto-parietal networks, while the enhanced detection of front/near objects in the bmC condition reflects bottom-up sensory processes in visual cortex.

Audio-visual interactions for motion perception in depth modulate activity in visual area V3A.

Multisensory signals can enhance the spatial perception of objects and events in the environment. Changes of visual size and auditory intensity provide us with the main cues about motion direction in depth. However, frequency changes in audition and binocular disparity in vision also contribute to the perception of motion in depth. Here, we presented subjects with several combinations of auditory and visual depth-cues to investigate multisensory interactions during processing of motion in depth. The task was to discriminate the direction of auditory motion in depth according to increasing or decreasing intensity. Rising or falling auditory frequency provided an additional within-audition cue that matched or did not match the intensity change (i.e. intensity-frequency (IF) "matched vs. unmatched" conditions). In two-thirds of the trials, a task-irrelevant visual stimulus moved either in the same or opposite direction of the auditory target, leading to audio-visual "congruent vs. incongruent" between-modalities depth-cues. Furthermore, these conditions were presented either with or without binocular disparity. Behavioral data showed that the best performance was observed in the audio-visual congruent condition with IF matched. Brain imaging results revealed maximal response in visual area V3A when all cues provided congruent and reliable depth information (i.e. audio-visual congruent, IF-matched condition including disparity cues). Analyses of effective connectivity revealed increased coupling from auditory cortex to V3A specifically in audio-visual congruent trials. We conclude that within- and between-modalities cues jointly contribute to the processing of motion direction in depth, and that they do so via dynamic changes of connectivity between visual and auditory cortices.

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.

Behavioral and neuro-cognitive bases for emergence of norms and socially shared realities via dynamic interaction.

In the digital era, new socially shared realities and norms emerge rapidly, whether they are beneficial or harmful to our societies. Although these are emerging properties from dynamic interaction, most research has centered on static situations where isolated individuals face extant norms. We investigated how perceptual norms emerge endogenously as shared realities through interaction, using behavioral and fMRI experiments coupled with computational modeling. Social interactions fostered convergence of perceptual responses among people, not only overtly but also at the covert psychophysical level that generates overt responses. Reciprocity played a critical role in increasing the stability (reliability) of the psychophysical function within each individual, modulated by neural activity in the mentalizing network during interaction. These results imply that bilateral influence promotes mutual cognitive anchoring of individual views, producing shared generative models at the collective level that enable endogenous agreement on totally new targets-one of the key functions of social norms.

A causal role of anterior prefrontal-putamen circuit for response inhibition revealed by transcranial ultrasound stimulation in humans.

Stopping an inappropriate response requires the involvement of the prefrontal-subthalamic hyperdirect pathway. However, how the prefrontal-striatal indirect pathway contributes to stopping is poorly understood. In this study, transcranial ultrasound stimulation is used to perform interventions in a task-related region in the striatum. Functional magnetic resonance imaging (MRI) reveals activation in the right anterior part of the putamen during response inhibition, and ultrasound stimulation to the anterior putamen, as well as the subthalamic nucleus, results in significant impairments in stopping performance. Diffusion imaging further reveals prominent structural connections between the anterior putamen and the right anterior part of the inferior frontal cortex (IFC), and ultrasound stimulation to the anterior IFC also shows significant impaired stopping performance. These results demonstrate that the right anterior putamen and right anterior IFC causally contribute to stopping and suggest that the anterior IFC-anterior putamen circuit in the indirect pathway serves as an essential route for stopping.

Time-varying measures of cerebral network centrality correlate with visual saliency during movie watching.

The extensive development of graph-theoretic analysis for functional connectivity has revealed the multifaceted characteristics of brain networks. Network centralities identify the principal functional regions, individual differences, and hub structure in brain networks. Neuroimaging studies using movie-watching have investigated brain function under naturalistic stimuli. Visual saliency is one of the promising measures for revealing cognition and emotions driven by naturalistic stimuli. This study investigated whether the visual saliency in movies was associated with network centrality. The study examined eigenvector centrality (EC), which is a measure of a region's influence in the brain network, and the participation coefficient (PC), which reflects the hub structure in the brain, was used for comparison. Static and time-varying EC and PC were analyzed by a parcel-based technique. While EC was correlated with brain activity in parcels in the visual and auditory areas during movie-watching, it was only correlated with parcels in the visual areas in the retinotopy task. In addition, high PC was consistently observed in parcels in the putative hub both during the tasks and the resting-state condition. Time-varying EC in the parietal parcels and time-varying PC in the primary sensory parcels significantly correlated with visual saliency in the movies. These results suggest that time-varying centralities in brain networks are distinctively associated with perceptual processing and subsequent higher processing of visual saliency.

Parallel cognitive processing streams in human prefrontal cortex: Parsing areal-level brain network for response inhibition.

Multiple cognitive processes are recruited to achieve adaptive behavior. However, it is poorly understood how such cognitive processes are implemented in temporal cascades of human cerebral cortical areas as processing streams to achieve behavior. In the present study, we identify cortical processing streams for response inhibition and examine relationships among the processing streams. Functional magnetic resonance imaging (MRI) and time-resolved single-pulse transcranial magnetic stimulation (TMS) reveal three distinct critical timings of transient disruption in the functionally essential cortical areas that belong to two distinct cerebrocortical networks. Furthermore, single-pulse TMS following suppression of the ventral posterior inferior frontal cortex (vpIFC) with repetitive TMS reveals information flow from the vpIFC to the presupplementary motor area (preSMA) within the same network but not to the dorsal posterior inferior frontal cortex (dpIFC) across different networks. These causal behavioral effects suggest two parallel processing streams (vpIFC-preSMA versus dpIFC-intraparietal sulcus) that act concurrently during response inhibition.

Neural correlates of species-typical illogical cognitive bias in human inference.

The ability to think logically is a hallmark of human intelligence, yet our innate inferential abilities are marked by implicit biases that often lead to illogical inference. For example, given AB ("if A then B"), people frequently but fallaciously infer the inverse, BA. This mode of inference, called symmetry, is logically invalid because, although it may be true, it is not necessarily true. Given pairs of conditional relations, such as AB and BC, humans reflexively perform two additional modes of inference: transitivity, whereby one (validly) infers AC; and equivalence, whereby one (invalidly) infers CA. In sharp contrast, nonhuman animals can handle transitivity but can rarely be made to acquire symmetry or equivalence. In the present study, human subjects performed logical and illogical inferences about the relations between abstract, visually presented figures while their brain activation was monitored with fMRI. The prefrontal, medial frontal, and intraparietal cortices were activated during all modes of inference. Additional activation in the precuneus and posterior parietal cortex was observed during transitivity and equivalence, which may reflect the need to retrieve the intermediate stimulus (B) from memory. Surprisingly, the patterns of brain activation in illogical and logical inference were very similar. We conclude that the observed inference-related fronto-parietal network is adapted for processing categorical, but not logical, structures of association among stimuli. Humans might prefer categorization over the memorization of logical structures in order to minimize the cognitive working memory load when processing large volumes of information.

Inferential reasoning by exclusion recruits parietal and prefrontal cortices.

When one is asked to select a label for a novel object from a given group of labels that includes both novel and familiar labels, one tends to choose a novel label. In other words, people spontaneously assume that an unfamiliar label goes with an unfamiliar object, even though logically, familiar labels may also be valid choices. This may seem natural and even trivial, but the fact that nonhuman animals robustly fail to demonstrate this same tendency suggests that it is not. This tendency of choice, called "exclusion," can bias human behavior, and seems relevant to aspects of human language (e.g., word learning), although substantially more research is required to validate. In this functional magnetic resonance imaging study, we investigated the neural correlates of this bias using a matching-to-sample procedure. The subjects were first trained on two sample-to-comparison associations between abstract visual stimuli. Then, in a test of exclusion, they were shown a novel sample and were asked to choose between a trained but incorrect comparison and a novel comparison. The subjects readily chose the novel comparison and rejected the trained one, thus demonstrating exclusion. Significant activation was observed in the prefrontal cortex (PFC) and inferior parietal lobule (IPL) during exclusion. Medial frontal activation was also observed, which was related to the appearance of the novel stimuli. These results suggest that the medial frontal cortex is associated with novelty detection and that the PFC and IPL are involved in rejecting the defined comparison in favor of the novel one.