Published papers

Autonomic nervous system (ANS) is a mechanism that regulates our internal environment. In recent years, the interest in how tactile stimuli presented directly to the body affect ANS function and cortical processing in humans has been renewed. However, it is not yet clear how subtle tactile stimuli below the level of consciousness affect human heart rate and cortical processing. To examine this, subthreshold electrical stimuli were presented to the left forearm of 43 participants during an image-viewing task, and electrocardiogram (ECG) and electroencephalogram (EEG) data were collected. The changes in the R-wave interval of the ECG immediately after the subthreshold electrical presentation and heartbeat-evoked potential (HEP), the afferent signal processing of cardiac activity, were measured. The results showed that heart rate decelerated immediately after the presentation of subthreshold electrical stimuli. The HEP during stimulus presentation was amplified for participants with greater heart rate acceleration immediately after this deceleration. The magnitude of these effects depended on the type of the subthreshold tactile stimuli. The results suggest that even with subthreshold stimulation, the changes in autonomic activity associated with orienting response and related afferent signal processing differ depending on the clarity of the tactile stimuli.

Mild cognitive impairment (MCI), representing the 'transitional zone' between normal cognition and dementia, has become a novel topic in clinical research. Although early detection is crucial, it remains logistically challenging at the same time. While traditional pen-and-paper tests require in-depth training to ensure standardized administration and accurate interpretation of findings, significant technological advancements are leading to the development of procedures for the early detection of Alzheimer's disease (AD) and facilitating the diagnostic process. Some of the diagnostic protocols, however, show significant limitations that hamper their widespread adoption. Concerns about the social and economic implications of the increasing incidence of AD underline the need for reliable, non-invasive, cost-effective, and timely cognitive scoring methodologies. For instance, modern clinical studies report significant oculomotor impairments among patients with MCI, who perform poorly in visual paired-comparison tasks by ascribing less attentional resources to novel stimuli. To accelerate the Global Action Plan on the Public Health Response to Dementia 2017-2025, this work provides an overview of research on saccadic and exploratory eye-movement deficits among older adults with MCI. The review protocol was drafted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic databases were systematically searched to identify peer-reviewed articles published between 2017 and 2022 that examined visual processing in older adults with MCI and reported gaze parameters as potential biomarkers. Moreover, following the contemporary trend for remote healthcare technologies, we reviewed studies that implemented non-commercial eye-tracking instrumentation in order to detect information processing impairments among the MCI population. Based on the gathered literature, eye-tracking-based paradigms may ameliorate the screening limitations of traditional cognitive assessments and contribute to early AD detection. However, in order to translate the findings pertaining to abnormal gaze behavior into clinical applications, it is imperative to conduct longitudinal investigations in both laboratory-based and ecologically valid settings.

Cognitive behavioral therapy (CBT) is a psychotherapy that challenges distorted cognitions; however, the neural mechanisms that underpin CBT remain unclear. Hence, we aimed to assess the treatment-related resting-state functional connectivity (rsFC) changes in the brain regions associated with future thinking and the associations between rsFC changes and clinical improvements. Thirty-eight adult patients with MDD were randomly assigned with equal likelihood to receive 16-week individual CBT or talking control with a 12-month follow-up period. We evaluated the rsFC changes in the frontal regions, nucleus accumbens, amygdala, and limbic structures key to the depression pathophysiology and future thinking with 2 × 2 mixed ANOVA interaction analysis. Pearson's correlation analysis with Bonferroni's correction was also performed to examine the associations with clinical symptoms, such as depression severity and automatic thoughts in follow-up evaluations. Treatment-specific changes include enhancement in frontopolar connectivity with the nucleus accumbens. An increased rsFC was associated with lower negative automatic thoughts postoperatively, together with lower depressive symptoms and higher positive automatic thoughts at follow-up. Conclusively, rsFC changes in the fronto-limbic neural control circuit after CBT, particularly between the frontal pole and nucleus accumbens, may be clinically meaningful functional changes related to the depression recovery process.

Interoception, the ability to perceive internal bodily signals, involves various mental processes. This study investigated moments when individuals experienced a change in their interoceptive state. Interoception affects the subjective feelings of emotions. However, whether changes in interoceptive processing occur when visceral changes are perceived as interoceptive sensations remains unclear. This study examined the psychophysiological markers of perceptual changes in the interoceptive state using heartbeat evoked potentials (HEP). Emotional photos were viewed by participants who were asked whether they experienced changes in their interoceptive state. The results showed that the HEP amplitude increased when participants had subjective awareness of changes in their interoceptive state. Notably, the HEP amplitude did not correlate with individual differences in interoceptive accuracy measured by the heartbeat counting task. When individuals perceive changes in their interoceptive state, this perception is reflected in the HEP amplitude. Multiple aspects of interoception are related to the emotional recognition and conscious attention to changing bodily states.

BACKGROUND: Rumination prolongs depressive mood and impairs executive functioning including working memory and attentional control, even in healthy individuals. Distraction can potentially counteract these effects; however, many experimental paradigms have relied on neutral, self-unrelated content and have failed to reflect the self-focused nature of everyday rumination or the possible benefits of emotionally meaningful distractions. This study investigated the effects of rumination and positive and neutral distractions based on personally relevant content on working memory performance in healthy undergraduate students with varying levels of depressive and anxiety tendencies. METHODS: Participants completed an operation-span task at three time points: baseline, immediately after rumination induction, and immediately after distraction induction. The induction phases involved participants reflecting on self-relevant negative events (rumination) or self-relevant positive/neutral events (distractions). RESULTS: Working memory performance significantly improved only among participants with higher depressive tendencies and trait anxiety after engaging in brief, self-relevant positive thinking, compared with performance after rumination induction. This suggests that emotionally meaningful distraction temporarily facilitates recovery of executive functioning by releasing cognitive resources previously consumed by ruminative processing. LIMITATIONS: This study included healthy undergraduate students. Further research should determine whether similar effects are observed in populations with clinical depression. CONCLUSIONS: Self-relevant positive distractions may enhance executive functioning, particularly in individuals vulnerable to rumination such as those with depressive tendencies or trait anxiety. These results provide insight into low-intensity content-based strategies for cognitive recovery after negative thought engagement and have potential applications in preventive interventions for subclinical emotional dysregulation.

In this study, we report the development of a virtual reality (VR) system that evaluates executive function based on cleaning behaviors in real-time. It is known that patients with acquired brain injuries present adverse symptoms such as attention, memory, and functional disorders, as well as aphasia. Current methods to evaluate acquired brain injuries include tests such as the behavioral assessment of the dysexecutive syndrome (BADS) and digital clinical assessment for attention (D-CAT) tests; however, these tests require special/specific toolkits, and the methods are rigorous when applied for real-time dynamic evaluation. Moreover, patients are often burdened by the need to undergo paper tests as required by the evaluation methods. In this context, we propose and verify the efficacy of a method that offers real-time dynamic evaluation of acquired brain injury based on daily-living activities such as cooking, cleaning, and shopping. In this study, we focus on executive function relating to acquired brain injury, and we propose a real-time dynamic evaluation method for executive functioning using VR, which enables the automatic evaluation of subjects’ table-cleaning behavior. Our results indicate that our system can automatically assess subjects’ table cleaning behavior based on BADS test, while affording a cleaning behavior maximum average accuracy of 75.5%.

Our thoughts often drift away from the tasks at hand. Various factors influence this phenomenon, including changes in the external environment, individual cognitive characteristics, and fluctuations in bodily reactions. This study investigated the relationship between fluctuations in cardiac activity and thought state transitions, focusing on individual differences such as cardiac interoception. First, the heartbeat counting task was conducted as an index of interoceptive accuracy. Participants then completed an auditory attention task with simultaneous electrocardiogram monitoring, during which they periodically reported on their thoughts. We estimated trial-by-trial thought states in a data-driven manner and examined the interplay among the current thought state, cardiac activity, and individual cardiac interoceptive accuracy. The results revealed that for individuals with high cardiac interoceptive accuracy, the persistence of self-related thought states was associated with concurrent heart rate acceleration. Furthermore, participants with higher depressive tendencies and interoceptive accuracy exhibited an increased likelihood of transitioning to self-related states when experiencing decreased heart rate during task-focused states. These findings suggest that interoception plays a dynamic role in shaping consciousness; the accurate detection of physiological arousal co-occurring with a specific thought might amplify that thought's salience, thereby influencing its persistence. This study provides new insights into the cognitive and physiological mechanisms underlying the dynamics of spontaneous thought.

Prospective memory is memory of future intentions or plans in everyday life. Although some previous neuropsychological studies have stated that the prefrontal cortex and the medial temporal lobe are essential for successful prospective remembering, how the two regions contribute to prospective remembering remains unclear. We therefore used prospective memory training in the present study to investigate the neural mechanism of two components of prospective remembering: remembering to remember and remembering content. Two brain-damaged patients participated in this study: patient Y.O., who had lesions in the medial temporal lobe bilaterally, and patient T.K., who had a lesion in the basal forebrain and right medial frontal lobe. Both participants exhibited a severe antero-grade amnesic syndrome and had normal IQ scores. Before the prospective memory training the participants underwent several index memory tests to examine their general memory and prospective memory performance. The training consisted of requesting the participants to perform an original mini-day task, in which they were first asked to memorize five simple daily actions with their times for execution, and then to recall the content of the actions when shown a drawing of a clock showing the proper time for execution. A training session was carried out once a week for 3 months. After completing training, the participants were again requested to take the same index memory tests. The results of the training task showed that Y.O.'s memory performance had gradually improved across all sessions of training, but T.K.'s improvement was not as marked. A more detailed analysis revealed that Y.O.'s memory performance was better for recalling time than for recalling content, whereas T.K.'s memory performance was better for recalling content than for recalling time. Furthermore, the results of the final index memory tests showed that the only improvement in Y.O.'s prospective memory was in remembering to remember, and that the only improvement in T.K.'s prospective memory was in remembering content. These results provide strong evidence that these two remembering components of prospective memory have independent neural bases, with the basal forebrain and right medial frontal lobe being required for remembering to remember, and the medial temporal lobe being required for remembering content. The results also suggest that memory training is an effective, means of improving everyday memory. © Freund & Pettman.

Background: Self-disturbances in schizophrenia have recently been explained by an abnormality in the sense of agency (SoA). The cerebral structures of SoA in healthy people are considered to mainly include the insula and inferior parietal lobule. In contrast, the functional lesion of aberrant SoA in schizophrenia is not yet fully understood. Considering the recent explanation of establishing SoA from the standpoint of associative learning, the "agency network" may include not only the insula and inferior parietal lobule but also the striatum. We hypothesized that aberrant SoA in schizophrenia is based on a deficit in the "agency network." Methods: Functional magnetic resonance imaging data were acquired while patients with schizophrenia (n = 15) and matched controls (n = 15) performed our adaptation method of agency attribution task on a trial-by-trial basis to assess participants' explicit experience of the temporal causal relationship between an action and an external event with temporal biases. Analysis of functional connectivity was done using the right supramarginal gyrus and the right middle frontal gyrus as seed regions. Results: In healthy controls, analyses revealed increased activation of the right inferior parietal lobule (mainly the supramarginal gyrus), right insula, and right middle frontal gyrus as an activation of the agency condition. We defined activated Brodmann areas shown in the agency condition of healthy controls as the seed region for connectivity analysis. The connectivity analysis revealed lower connectivity between the head of the left caudate nucleus and right supramarginal gyrus in the patients compared to healthy controls. Conclusions: This dysconnectivity of the agency network in schizophrenia may lead to self-disturbance through deficits in associative learning of SoA. These findings may explain why pathological function of the striatum in schizophrenia leads to self-disturbance.

The present study aimed to investigate the effects of matured hop bitter acids (MHBAs) on human cognition, mental fatigue, and mood state. In this randomized double-blind placebo-controlled study, 60 healthy adults (age 45-64 years) with self-awareness of cognitive decline were randomly divided into 2 groups and received either orally administered MHBAs (35 mg/day) or placebo for 12 weeks. Cognitive functions and mental states were assessed using neuropsychological tests or questionnaires at baseline and weeks 6 and 12 of the intervention. The change in verbal fluency score at week 6 compared with that at baseline was significantly higher in the MHBAs-treated group compared with that in the placebo group (P = 0.034), and Stroop test score at week 12 was significantly lower in the MHBAs-treated group compared with the placebo group (P = 0.019). Furthermore, subjective fatigue and anxiety at week 12 were significantly improved in the MHBAs-treated group (P = 0.008 and 0.043, respectively) compared with the placebo group. This is the first study to evaluate the effects of bitter ingredients in beer on cognition, subjective mood, and mental fatigue in a clinical trial. Our findings suggest that hop-derived bitter acids might be beneficial for cognition and mood state.

The insular cortex is considered an important region for feeling emotions through interoception. Most studies that report the role of the insula in integrating interoception and emotion have used neuroimaging techniques such as functional magnetic resonance imaging (fMRI); however, there are limited neuropsychological studies. The effects of insular lesions on emotion and interoception have not been suitably investigated. In this study, we examined the role of the insular cortex in cardiac interoception and recognizing emotions from facial expressions by comparing them pre- and post-operatively in patients with glial tumors or brain metastases associated with the insular lobe. Although no significant difference in interoceptive accuracy was observed between the two phases, there were significant associations between the changes in interoceptive accuracy and sensitivity to expressions of anger and happiness. An increased error rate in the heartbeat counting task in the post-operation phase was associated with a decreased accuracy in recognizing anger and happiness. Since most patients had left insula lesions, generalizability of the findings to patients with right lesions is a future subject. To the best of our knowledge, this is the first study to examine the change in interoception and emotion after insular resection in humans. The study results indicate that removal of the insula affects the recognition of emotions such as anger and happiness through interoceptive processing.

To remember the prospective intention successfully, going back and forth between the background task and the intention, i.e., the dynamics of these multiple processes can be critical. An executive function like task switching has been associated with the success of prospective memory (PM) in children, but the neural mechanism of PM in children has not been investigated. The purpose of this study was to reveal the dynamic functional connectivity underlying the success of PM in children. Healthy 108 children, aged 7 to 15, were engaged in a single trial PM task, with a 30-min delay. Temporal variabilities in their resting-state functional connectivity were analyzed, using sliding windows with seed regions of interest ROIs of the PM network. About 70% of children successfully remembered the intention; they showed greater dynamics in neural connectivity between the right dorsolateral prefrontal cortex (DLPFC) and intraparietal sulcus, and between the right DLPFC and insula as compared to children with PM failure. Everyday activities and the usual attention to ongoing processes can be associated with alertness in the right frontoparietal network and internal-state monitoring in the insula network, and those dynamics might be associated with one-time event PM success in children.