The sensitivity and criterion of sense of agency.

The sense of agency, which refers to the subjective feeling of control, is an essential aspect of self-consciousness. We argue that distinguishing between the sensitivity and criterion of this feeling is important for discussing individual differences in the sense of agency and its connections with other cognitive functions.

Fear in action: Fear conditioning and alleviation through body movements.

Fear memories enhance survival especially when the memories guide defensive movements to minimize harm. Accordingly, fear memories and body movements have tight relationships in animals: Fear memory acquisition results in adapting reactive defense movements, while training active defense movements reduces fear memory. However, evidence in humans is scarce because their movements are typically suppressed in experiments. Here, we tracked adult participants' body motions while they underwent ecologically valid fear conditioning in a 3D virtual space. First, with body motion tracking, we revealed that distinct spatiotemporal body movement patterns emerge through fear conditioning. Second, subsequent training to actively avoid threats with naturalistic defensive actions led to a long-term (24 h) reduction of physiological and embodied conditioned responses, while extinction or vicarious training only transiently reduced the responses. Together, our results highlight the role of body movements in human fear memory and its intervention.

Proprioceptive short-term memory in passive motor learning.

A physical trainer often physically guides a learner's limbs to teach an ideal movement, giving the learner proprioceptive information about the movement to be reproduced later. This instruction requires the learner to perceive kinesthetic information and store the instructed information temporarily. Therefore, (1) proprioceptive acuity to accurately perceive the taught kinesthetics and (2) short-term memory to store the perceived information are two critical functions for reproducing the taught movement. While the importance of proprioceptive acuity and short-term memory has been suggested for active motor learning, little is known about passive motor learning. Twenty-one healthy adults (mean age 25.6 years, range 19-38 years) participated in this study to investigate whether individual learning efficiency in passively guided learning is related to these two functions. Consequently, learning efficiency was significantly associated with short-term memory capacity. In particular, individuals who could recall older sensory stimuli showed better learning efficiency. However, no significant relationship was observed between learning efficiency and proprioceptive acuity. A causal graph model found a direct influence of memory on learning and an indirect effect of proprioceptive acuity on learning via memory. Our findings suggest the importance of a learner's short-term memory for effective passive motor learning.

Generalizable neuromarker for autism spectrum disorder across imaging sites and developmental stages: A multi-site study.

Autism spectrum disorder (ASD) is a lifelong condition, and its underlying biological mechanisms remain elusive. The complexity of various factors, including inter-site and development-related differences, makes it challenging to develop generalizable neuroimaging-based biomarkers for ASD. This study used a large-scale, multi-site dataset of 730 Japanese adults to develop a generalizable neuromarker for ASD across independent sites and different developmental stages. Our adult ASD neuromarker achieved successful generalization for the US and Belgium adults and Japanese adults. The neuromarker demonstrated significant generalization for children and adolescents. We identified 141 functional connections (FCs) important for discriminating individuals with ASD from TDCs. Finally, we mapped schizophrenia (SCZ) and major depressive disorder (MDD) onto the biological axis defined by the neuromarker and explored the biological continuity of ASD with SCZ and MDD. We observed that SCZ, but not MDD, was located proximate to ASD on the biological dimension defined by the ASD neuromarker. The successful generalization in multifarious datasets and the observed relations of ASD with SCZ on the biological dimensions provide new insights for a deeper understanding of ASD.

Generalizable neuromarker for autism spectrum disorder across imaging sites and developmental stages: A multi-site study.

Autism spectrum disorder (ASD) is a lifelong condition, and its underlying biological mechanisms remain elusive. The complexity of various factors, including inter-site and development-related differences, makes it challenging to develop generalizable neuroimaging-based biomarkers for ASD. This study used a large-scale, multi-site dataset of 730 Japanese adults to develop a generalizable neuromarker for ASD across independent sites (U.S., Belgium, and Japan) and different developmental stages (children and adolescents). Our adult ASD neuromarker achieved successful generalization for the US and Belgium adults (area under the curve [AUC] = 0.70) and Japanese adults (AUC = 0.81). The neuromarker demonstrated significant generalization for children (AUC = 0.66) and adolescents (AUC = 0.71; all P<0.05, family-wise-error corrected). We identified 141 functional connections (FCs) important for discriminating individuals with ASD from TDCs. These FCs largely centered on social brain regions such as the amygdala, hippocampus, dorsomedial and ventromedial prefrontal cortices, and temporal cortices. Finally, we mapped schizophrenia (SCZ) and major depressive disorder (MDD) onto the biological axis defined by the neuromarker and explored the biological continuity of ASD with SCZ and MDD. We observed that SCZ, but not MDD, was located proximate to ASD on the biological dimension defined by the ASD neuromarker. The successful generalization in multifarious datasets and the observed relations of ASD with SCZ on the biological dimensions provide new insights for a deeper understanding of ASD.

Distinctive alterations in the mesocorticolimbic circuits in various psychiatric disorders.

AIM: Increasing evidence suggests that psychiatric disorders are linked to alterations in the mesocorticolimbic dopamine-related circuits. However, the common and disease-specific alterations remain to be examined in schizophrenia (SCZ), major depressive disorder (MDD), and autism spectrum disorder (ASD). Thus, this study aimed to examine common and disease-specific features related to mesocorticolimbic circuits. METHODS: This study included 555 participants from four institutes with five scanners: 140 individuals with SCZ (45.0% female), 127 individuals with MDD (44.9%), 119 individuals with ASD (15.1%), and 169 healthy controls (HC) (34.9%). All participants underwent resting-state functional magnetic resonance imaging. A parametric empirical Bayes approach was adopted to compare estimated effective connectivity among groups. Intrinsic effective connectivity focusing on the mesocorticolimbic dopamine-related circuits including the ventral tegmental area (VTA), shell and core parts of the nucleus accumbens (NAc), and medial prefrontal cortex (mPFC) were examined using a dynamic causal modeling analysis across these psychiatric disorders. RESULTS: The excitatory shell-to-core connectivity was greater in all patients than in the HC group. The inhibitory shell-to-VTA and shell-to-mPFC connectivities were greater in the ASD group than in the HC, MDD, and SCZ groups. Furthermore, the VTA-to-core and VTA-to-shell connectivities were excitatory in the ASD group, while those connections were inhibitory in the HC, MDD, and SCZ groups. CONCLUSION: Impaired signaling in the mesocorticolimbic dopamine-related circuits could be an underlying neuropathogenesis of various psychiatric disorders. These findings will improve the understanding of unique neural alternations of each disorder and will facilitate identification of effective therapeutic targets.

Aberrant Large-Scale Network Interactions Across Psychiatric Disorders Revealed by Large-Sample Multi-Site Resting-State Functional Magnetic Resonance Imaging Datasets.

BACKGROUND AND HYPOTHESIS: Dynamics of the distributed sets of functionally synchronized brain regions, known as large-scale networks, are essential for the emotional state and cognitive processes. However, few studies were performed to elucidate the aberrant dynamics across the large-scale networks across multiple psychiatric disorders. In this paper, we aimed to investigate dynamic aspects of the aberrancy of the causal connections among the large-scale networks of the multiple psychiatric disorders. STUDY DESIGN: We applied dynamic causal modeling (DCM) to the large-sample multi-site dataset with 739 participants from 4 imaging sites including 4 different groups, healthy controls, schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD), to compare the causal relationships among the large-scale networks, including visual network, somatomotor network (SMN), dorsal attention network (DAN), salience network (SAN), limbic network (LIN), frontoparietal network, and default mode network. STUDY RESULTS: DCM showed that the decreased self-inhibitory connection of LIN was the common aberrant connection pattern across psychiatry disorders. Furthermore, increased causal connections from LIN to multiple networks, aberrant self-inhibitory connections of DAN and SMN, and increased self-inhibitory connection of SAN were disorder-specific patterns for SCZ, MDD, and BD, respectively. CONCLUSIONS: DCM revealed that LIN was the core abnormal network common to psychiatric disorders. Furthermore, DCM showed disorder-specific abnormal patterns of causal connections across the 7 networks. Our findings suggested that aberrant dynamics among the large-scale networks could be a key biomarker for these transdiagnostic psychiatric disorders.

I Hear My Voice; Therefore I Spoke: The Sense of Agency Over Speech Is Enhanced by Hearing One's Own Voice.

The subjective experience of causing an action is known as the sense of agency. Dysfunctional sense of agency over speech has been suggested as a cause of auditory hallucinations. However, agency over speech has not been extensively characterized in previous empirical studies. Here, we manipulated self-voice identity, an indicator of self, embedded in the acoustic quality of voice and examined implicit and explicit measures of the sense of agency. Experiment 1 (N = 29 adults) demonstrated more compression of a perceived interval between action and outcome when participants heard their undistorted voices than their pitch-distorted voices. Experiment 2 (N = 28 adults) revealed a strong top-down effect of self-voice identity: Specifically, the judgment of agency over speech was more resistant than the judgment of agency over hand/limb movement to low-level sensorimotor inconsistency. Our findings provide new insight into the sense of agency over speech and an informative perspective for understanding aberrant experience in auditory hallucinations.

Neuroimaging Examination of Driving Mode Switching Corresponding to Changes in the Driving Environment.

Car driving is supported by perceptual, cognitive, and motor skills trained through continuous daily practice. One of the skills that characterize experienced drivers is to detect changes in the driving environment and then flexibly switch their driving modes in response to the changes. Previous functional neuroimaging studies on motor control investigated the mechanisms underlying behaviors adaptive to changes in control properties or parameters of experimental devices such as a computer mouse or a joystick. The switching of multiple internal models mainly engages adaptive behaviors and underlies the interplay between the cerebellum and frontoparietal network (FPN) regions as the neural process. However, it remains unclear whether the neural mechanisms identified in previous motor control studies also underlie practical driving behaviors. In the current study, we measure functional magnetic resonance imaging (fMRI) activities while participants control a realistic driving simulator inside the MRI scanner. Here, the accelerator sensitivity of a virtual car is abruptly changed, requiring participants to respond to this change flexibly to maintain stable driving. We first compare brain activities before and after the sensitivity change. As a result, sensorimotor areas, including the left cerebellum, increase their activities after the sensitivity change. Moreover, after the change, activity significantly increases in the inferior parietal lobe (IPL) and dorsolateral prefrontal cortex (DLPFC), parts of the FPN regions. By contrast, the posterior cingulate cortex, a part of the default mode network, deactivates after the sensitivity change. Our results suggest that the neural bases found in previous experimental studies can serve as the foundation of adaptive driving behaviors. At the same time, this study also highlights the unique contribution of non-motor regions to addressing the high cognitive demands of driving.

Real-Time Detection and Feedback of Canonical Electroencephalogram Microstates: Validating a Neurofeedback System as a Function of Delay.

Recent neurotechnology has developed various methods for neurofeedback (NF), in which participants observe their own neural activity to be regulated in an ideal direction. EEG-microstates (EEGms) are spatially featured states that can be regulated through NF training, given that they have recently been indicated as biomarkers for some disorders. The current study was conducted to develop an EEG-NF system for detecting "canonical 4 EEGms" in real time. There are four representative EEG states, regardless of the number of channels, preprocessing procedures, or participants. Accordingly, our 10 Hz NF system was implemented to detect them (msA, B, C, and D) and audio-visually inform participants of its detection. To validate the real-time effect of this system on participants' performance, the NF was intentionally delayed for participants to prevent their cognitive control in learning. Our results suggest that the feedback effect was observed only under the no-delay condition. The number of Hits increased significantly from the baseline period and increased from the 1- or 20-s delay conditions. In addition, when the Hits were compared among the msABCD, each cognitive or perceptual function could be characterized, though the correspondence between each microstate and psychological ability might not be that simple. For example, msD should be generally task-positive and less affected by the inserted delay, whereas msC is more delay-sensitive. In this study, we developed and validated a new EEGms-NF system as a function of delay. Although the participants were naive to the inserted delay, the real-time NF successfully increased their Hit performance, even within a single-day experiment, although target specificity remains unclear. Future research should examine long-term training effects using this NF system.

Individual Differences in the Change of Attentional Functions With Brief One-Time Focused Attention and Open Monitoring Meditations.

Mindfulness meditation is increasingly used for clinical treatment and to improve well-being. One of the most fundamental benefits of mindfulness meditation is now considered as enhanced attentional control. Mindfulness meditation is a complex technique but most of its variants consist of a combination of two types of basic meditation practice: focused attention meditation (FAM) and open monitoring meditation (OMM). Although many studies have examined the effect of relatively long-term meditation on attention, some recent studies have focused on the effect of a brief one-time meditation on cognitive processing, including attentional functions. Furthermore, it is necessary to discuss the relationship between the effect of mindfulness meditation on attentional functions and personality traits (especially traits related to mindfulness). This study investigated whether attentional control is improved by a single 30-min FAM or OMM and whether the degree of improvement in attentional functions - alerting, orienting, and conflict monitoring - induced by the meditation varies according to the participant's trait scores related to mindfulness measured by the Five Facets Mindfulness Questionnaire. Participants were randomly assigned to one of three groups, i.e., FAM, OMM, and no-meditation (noM) groups, and given an Attentional Network Test before and after each 30-min meditation session. Compared with the noM group, there was no overall improvement in attentional functions with either type of meditation. However, there were associations between the change of the alerting function's score and the personality traits: in the FAM group, alerting scores were negatively associated with the nonreactivity facet of the FFMQ, and in the OMM group, alerting scores were positively associated with describing facet scores of the FFMQ. The results indicate that the effects of meditation methods on attentional functions could depend on the individual's traits related to mindfulness and that mindfulness meditation could sometimes appear to have no impact on attentional functions.

Bayesian Estimation of Potential Performance Improvement Elicited by Robot-Guided Training.

Improving human motor performance via physical guidance by an assist robot device is a major field of interest of the society in many different contexts, such as rehabilitation and sports training. In this study, we propose a Bayesian estimation method to predict whether motor performance of a user can be improved or not by the robot guidance from the user's initial skill level. We designed a robot-guided motor training procedure in which subjects were asked to generate a desired circular hand movement. We then evaluated the tracking error between the desired and actual subject's hand movement. Results showed that we were able to predict whether a novel user can reduce the tracking error after the robot-guided training from the user's initial movement performance by checking whether the initial error was larger than a certain threshold, where the threshold was derived by using the proposed Bayesian estimation method. Our proposed approach can potentially help users to decide if they should try a robot-guided training or not without conducting the time-consuming robot-guided movement training.

Perception and control: individual difference in the sense of agency is associated with learnability in sensorimotor adaptation.

Adaptive motor learning refers to the ability to adjust to novel disturbances in the environment as a way of minimizing sensorimotor errors. It is known that such processes show large individual differences and are linked to multiple perceptual and cognitive processes. On the other hand, the sense of agency refers to the subjective feeling of control during voluntary motor control. Is the sense of agency just a by-product of the control outcome, or is it actually important for motor control and learning? To answer this question, this study takes an approach based on individual differences to investigate the relationship between the sense of agency and learnability in sensorimotor adaptation. Specifically, we use an adaptive motor learning task to measure individual differences in the efficiency of motor learning. Regarding the sense of agency, we measure the perceptual sensitivity of detecting an increase or a decrease in control when the actual level of control gradually increases or decreases, respectively. The results of structure equation modelling reveal a significant influence of perceptual sensitivity to increased control on motor learning efficiency. On the other hand, the link between perceptual sensitivity to decreased control and motor learning is nonsignificant. The results show that the sense of agency in detecting increased control is associated with the actual ability of sensorimotor adaptation: people who are more sensitive in detecting their control in the environment can also more quickly adjust their behaviors to novel disturbances to acquire better control, compared to people who have a less sensitive sense of agency. Finally, the results also reveal that the processes of increasing control and decreasing control may be partially independent.

A multi-site, multi-disorder resting-state magnetic resonance image database.

Machine learning classifiers for psychiatric disorders using resting-state functional magnetic resonance imaging (rs-fMRI) have recently attracted attention as a method for directly examining relationships between neural circuits and psychiatric disorders. To develop accurate and generalizable classifiers, we compiled a large-scale, multi-site, multi-disorder neuroimaging database. The database comprises resting-state fMRI and structural images of the brain from 993 patients and 1,421 healthy individuals, as well as demographic information such as age, sex, and clinical rating scales. To harmonize the multi-site data, nine healthy participants ("traveling subjects") visited the sites from which the above datasets were obtained and underwent neuroimaging with 12 scanners. All participants consented to having their data shared and analyzed at multiple medical and research institutions participating in the project, and 706 patients and 1,122 healthy individuals consented to having their data disclosed. Finally, we have published four datasets: 1) the SRPBS Multi-disorder Connectivity Dataset 2), the SRPBS Multi-disorder MRI Dataset (restricted), 3) the SRPBS Multi-disorder MRI Dataset (unrestricted), and 4) the SRPBS Traveling Subject MRI Dataset.

Common Brain Networks Between Major Depressive-Disorder Diagnosis and Symptoms of Depression That Are Validated for Independent Cohorts.

Large-scale neuroimaging data acquired and shared by multiple institutions are essential to advance neuroscientific understanding of pathophysiological mechanisms in psychiatric disorders, such as major depressive disorder (MDD). About 75% of studies that have applied machine learning technique to neuroimaging have been based on diagnoses by clinicians. However, an increasing number of studies have highlighted the difficulty in finding a clear association between existing clinical diagnostic categories and neurobiological abnormalities. Here, using resting-state functional magnetic resonance imaging, we determined and validated resting-state functional connectivity related to depression symptoms that were thought to be directly related to neurobiological abnormalities. We then compared the resting-state functional connectivity related to depression symptoms with that related to depression diagnosis that we recently identified. In particular, for the discovery dataset with 477 participants from 4 imaging sites, we removed site differences using our recently developed harmonization method and developed a brain network prediction model of depression symptoms (Beck Depression Inventory-II [BDI] score). The prediction model significantly predicted BDI score for an independent validation dataset with 439 participants from 4 different imaging sites. Finally, we found 3 common functional connections between those related to depression symptoms and those related to MDD diagnosis. These findings contribute to a deeper understanding of the neural circuitry of depressive symptoms in MDD, a hetero-symptomatic population, revealing the neural basis of MDD.

Generalizable brain network markers of major depressive disorder across multiple imaging sites.

Many studies have highlighted the difficulty inherent to the clinical application of fundamental neuroscience knowledge based on machine learning techniques. It is difficult to generalize machine learning brain markers to the data acquired from independent imaging sites, mainly due to large site differences in functional magnetic resonance imaging. We address the difficulty of finding a generalizable marker of major depressive disorder (MDD) that would distinguish patients from healthy controls based on resting-state functional connectivity patterns. For the discovery dataset with 713 participants from 4 imaging sites, we removed site differences using our recently developed harmonization method and developed a machine learning MDD classifier. The classifier achieved an approximately 70% generalization accuracy for an independent validation dataset with 521 participants from 5 different imaging sites. The successful generalization to a perfectly independent dataset acquired from multiple imaging sites is novel and ensures scientific reproducibility and clinical applicability.

Statistical Learning Model of the Sense of Agency.

A sense of agency (SoA) is the experience of subjective awareness regarding the control of one's actions. Humans have a natural tendency to generate prediction models of the environment and adapt their models according to changes in the environment. The SoA is associated with the degree of the adaptation of the prediction models, e.g., insufficient adaptation causes low predictability and lowers the SoA over the environment. Thus, identifying the mechanisms behind the adaptation process of a prediction model related to the SoA is essential for understanding the generative process of the SoA. In the first half of the current study, we constructed a mathematical model in which the SoA represents a likelihood value for a given observation (sensory feedback) in a prediction model of the environment and in which the prediction model is updated according to the likelihood value. From our mathematical model, we theoretically derived a testable hypothesis that the prediction model is updated according to a Bayesian rule or a stochastic gradient. In the second half of our study, we focused on the experimental examination of this hypothesis. In our experiment, human subjects were repeatedly asked to observe a moving square on a computer screen and press a button after a beep sound. The button press resulted in an abrupt jump of the moving square on the screen. Experiencing the various stochastic time intervals between the action execution (button-press) and the consequent event (square jumping) caused gradual changes in the subjects' degree of their SoA. By comparing the above theoretical hypothesis with the experimental results, we concluded that the update (adaptation) rule of the prediction model based on the SoA is better described by a Bayesian update than by a stochastic gradient descent.

Categorical Perception of Control.

The self is a distinct entity from the rest of the world, and actions and sensory feedback are our channels of interaction with the external world. This study examined how the sense of control influences people's perception of sensorimotor input under the framework of categorical perception. Twenty human participants (18 males, two females) took part in both experiments. Experiment 1 showed that the sensitivity (d') of detecting a 20% change in control from no change was higher when the changes occurred at the control-category boundary than within each category. Experiment 2 showed that the control categories greatly affected early attention allocation, even when the judgment of control was unnecessary to the task. Taken together, these results showed that our perceptual and cognitive systems are highly sensitive to small changes in control that build up to a determinant change in the control category within a relatively narrow boundary zone between categories, compared with a continuous, gradual physical change in control.

Passive training with upper extremity exoskeleton robot affects proprioceptive acuity and performance of motor learning.

Sports trainers often grasp and move trainees' limbs to give instructions on desired movements, and a merit of this passive training is the transferring of instructions via proprioceptive information. However, it remains unclear how passive training affects the proprioceptive system and improves learning. This study examined changes in proprioceptive acuity due to passive training to understand the underlying mechanisms of upper extremity training. Participants passively learned a trajectory of elbow-joint movement as per the instructions of a single-arm upper extremity exoskeleton robot, and the performance of the target movement and proprioceptive acuity were assessed before and after the training. We found that passive training improved both the reproduction performance and proprioceptive acuity. We did not identify a significant transfer of the training effect across arms, suggesting that the learning effect is specific to the joint space. Furthermore, we found a significant improvement in learning performance in another type of movement involving the trained elbow joint. These results suggest that participants form a representation of the target movement in the joint space during the passive training, and intensive use of proprioception improves proprioceptive acuity.

The Active Sensing of Control Difference.

In everyday life, people control objects in the world around them to varying degrees. The processes people actively use to establish their control, while interacting with an environment containing large ambiguity, remain unknown. This study examines how people explore their control over the environment and how they detect small differences in control among objects. In the experimental task, participants moved three dots on a screen and identified one dot over which the level of control is different from that of the other two. The results support a two-step behavior mechanism underlying the sensing of control difference: People first explore their overall control in the environment, and then the results of the initial exploration are used to selectively tune the direction (i.e., either more or less) of the detected control difference, ensuring efficient and rapid detection of the type of control difference that is potentially important for further action selections.