Hemodynamic and electrophysiological responses of the human amygdala during face imitation-a study using functional MRI and intracranial EEG.

The involvement of the human amygdala in facial mimicry remains a matter of debate. We investigated neural activity in the human amygdala during a task in which an imitation task was separated in time from an observation task involving facial expressions. Neural activity in the amygdala was measured using functional magnetic resonance imaging in 18 healthy individuals and using intracranial electroencephalogram in six medically refractory patients with epilepsy. The results of functional magnetic resonance imaging experiment showed that mimicry of negative and positive expressions activated the amygdala more than mimicry of non-emotional facial movements. In intracranial electroencephalogram experiment and time-frequency analysis, emotion-related activity of the amygdala during mimicry was observed as a significant neural oscillation in the high gamma band range. Furthermore, spectral event analysis of individual trial intracranial electroencephalogram data revealed that sustained oscillation of gamma band activity originated from an increased number and longer duration of neural events in the amygdala. Based on these findings, we conclude that during facial mimicry, visual information of expressions and feedback from facial movements are combined in the amygdalar nuclei. Considering the time difference of information approaching the amygdala, responses to facial movements are likely to modulate rather than initiate affective processing in human participants.

Humor Appreciation Involves Parametric and Synchronized Activity in the Medial Prefrontal Cortex and Hippocampus.

Humor perception is a ubiquitous phenomenon in human societies. In theories of humor perception, three factors, non-seriousness, social context, and incongruity, have been implicated in humor. In another theory, however, elaboration and reinterpretation of contexts are considered to play a role in eliciting humor. Although the neural correlates of humor appreciation have been investigated using neuroimaging methods, only a few studies have conducted such experiments under natural conditions. In the present study, two functional magnetic resonance imaging experiments, using a comedy movie as a stimulus, were conducted to investigate the neural correlates of humor under natural conditions. The subjects' brain activity was measured while watching and enjoying a movie. In experiment 1, a parametric analysis showed that the medial prefrontal cortex (MPFC) and hippocampus/amygdala had a positive relationship with the subjective rating of funniness. In experiment 2, intersubject correlation was analyzed to investigate synchronized activity across all participants. Signal synchronization that paralleled increased funniness ratings was observed in the MPFC and hippocampus. Thus, it appears that both parametric and synchronized activity in the MPFC and hippocampus are important during humor appreciation. The present study has revealed the brain regions that are predominantly involved in humor sensation under natural condition.

Cultural influences on neural basis of inhibitory control.

Research on neural basis of inhibitory control has been extensively conducted in various parts of the world. It is often implicitly assumed that neural basis of inhibitory control is universally similar across cultures. Here, we investigated the extent to which culture modulated inhibitory-control brain activity at both cultural-group and cultural-value levels of analysis. During fMRI scanning, participants from different cultural groups (including Caucasian-Americans and Japanese-Americans living in the United States and native Japanese living in Japan) performed a Go/No-Go task. They also completed behavioral surveys assessing cultural values of behavioral consistency, or the extent to which one's behaviors in daily life are consistent across situations. Across participants, the Go/No-Go task elicited stronger neural activity in several inhibitory-control areas, such as the inferior frontal gyrus (IFG) and anterior cingulate cortex (ACC). Importantly, at the cultural-group level, we found variation in left IFG (L-IFG) activity that was explained by a cultural region where participants lived in (as opposed to race). Specifically, L-IFG activity was stronger for native Japanese compared to Caucasian- and Japanese-Americans, while there was no systematic difference in L-IFG activity between Japanese- and Caucasian-Americans. At the cultural-value level, we found that participants who valued being "themselves" across situations (i.e., having high endorsement of behavioral consistency) elicited stronger rostral ACC activity during the Go/No-Go task. Altogether, our findings provide novel insight into how culture modulates the neural basis of inhibitory control.

Social insecurity in relation to orbitofrontal activity in patients with eating disorders: a near-infrared spectroscopy study.

BACKGROUND: Functional neuroimaging techniques are widely used to elucidate changes in brain activity, and various questionnaires are used to investigate psychopathological features in patients with eating disorders (ED). It is well known that social skills and interpersonal difficulties are strongly associated with the psychopathology of patients with ED. However, few studies have examined the association between brain activity and social relationships in patients with ED, particularly in patients with extremely low body weight. METHODS: In this study, 22-channel near-infrared spectroscopy was used to quantify regional hemodynamic changes during a letter fluency task (LFT) in 20 female patients with ED with a mean body mass index of 14.0 kg/m(2) and 31 female controls (CTLs). Symptoms were assessed using the Eating Disorder Inventory-2 and Beck Depression Inventory. We hypothesized that frontal activity in patients with ED would be lower than in CTLs and would show different correlations with psychopathological features compared with CTLs. RESULTS: The LFT performance and score on the social insecurity subscale of the Eating Disorder Inventory-2 were significantly higher in the ED group than in the CTL group. The mean change in oxygenated hemoglobin (oxy-Hb) in bilateral frontal regions during the LFT was significantly smaller in the ED group than in the CTL group. Social insecurity score was positively correlated with the concentration of oxy-Hb in the bilateral orbitofrontal cortex in the ED group but not in the CTL group. CONCLUSIONS: These results suggest that activity of the orbitofrontal cortex is associated with social insecurity and disturbed in patients with ED. Therefore, disturbed orbitofrontal cortex activity may underlie the lack of insight and social isolation that is characteristic of patients with ED.

The effects of acute treatment with paroxetine, amitriptyline, and placebo on the equilibrium function in healthy subjects: a double-blind crossover trial.

OBJECTIVE: Depression is common in old age, and is treatable with antidepressants. However, antidepressants use can increase the risk of falls. Thus, we assessed the effects of antidepressants on equilibrium function using posturography. METHODS: This study recruited 10 healthy male volunteers (35.3 ± 3.7 years). In this double-blinded, three-way crossover trial, they received acute doses of 10 mg paroxetine, 25 mg amitriptyline, and placebo. They were administered posturography at baseline and 4-h postdosing. RESULTS: At 4-h postdosing, amitriptyline significantly decreased the locus length per unit area (L/A) and increased the envelope area compared with those at baseline. Meanwhile, the total length and the locus length per time (L/T) at 4-h postdosing of amitriptyline did not show significant differences from those at baseline. After paroxetine treatment, there were no significant differences in total length, L/T, L/A, and the envelope area between baseline and 4-h postdosing. CONCLUSION: An acute dose of amitriptyline significantly decreased L/A and increased the envelope area as markers of body sway. Evaluation of equilibrium function is important for preventing the potential risk of falls and body sway after taking antidepressants.

Neuroanatomical substrates involved in true and false memories for face.

We often mistake an unknown person for a familiar person because of the similarities in facial features. This phenomenon, known as false memory, has been investigated mainly using words, pictures, and shapes. Previous neuroimaging studies on false memory have shown that both true and false memories trigger a similar activation in the medial temporal lobe, suggesting that it plays a common role in both. However, no study to date has investigated neural substrates of false memories for faces. In the present fMRI study, we applied a modified version of the standard false memory paradigm, using morphed pictures of faces, to induce false memory in an MRI environment. We found that activity in the amygdala and orbital cortices was associated with the degree of familiarity of items. In particular, false responses to "lure" items evoked a level of activity in the amygdala between that evoked for correct or incorrect responses to "true" items. This indicates a possible role of the amygdala in false memory. A specific region in the anterior cingulate cortex was involved in false recognition; the activity being correlated to reaction times for the response types. These results suggest that the amygdala is involved in determining the relevance of items; therefore, ambiguousness of lure items in terms of familiarity and novelty may be related to decreased activity in the amygdala. The anterior cingulate activity in false memory may be caused not only by increased effort and motor demand but also by higher mnemonic processing of lure items.

Slower adaptation to driving simulator and simulator sickness in older adults.

BACKGROUND AND AIMS: Methods of assessing driving abilities in the elderly are urgently needed. Although the driving simulator (DS) appears to be a safe and cost-effective method of objectively evaluating driving performance, it may pose adaptation problems for elderly adults. In this study, we examined age-related adaptation deficits on the DS. METHODS: Healthy young adults (n=15) and healthy elderly persons (n=17) completed some neuropsychological tests, and then performed a road-tracking task with the DS, which was repeated four times (Trials 1-4). RESULTS: After simulated driving in DS, simulator sickness (SS) was observed in 18.8% of participants. The frequency of SS was 29.4% in elderly adults and 6.7% in young adults, and 17.6% of the elderly participants dropped out of the experiment. Performance on the Necker cube copying task was significantly correlated with the onset of SS. Driving performance also showed a significant interaction between group and trial, for both driving accuracy and vehicle speed. In addition, the performance of elderly adults significantly improved between trials 1 and 4, reaching a plateau in trial 4, whereas that of young adults did not change across trials. CONCLUSION: This study provides preliminary evidence of slower adaptation to a DS-based driving task by older adults, which was associated with cognitive aging. Age affected driving accuracy and velocity when a road-tracking task was simply repeated. It is concluded that the capacity of elderly people to adapt to DS environments should be taken into consideration when evaluating their performance on DS tasks.

Involvement of cerebellar and subcortical connector hubs in schizophrenia.

BACKGROUND: Schizophrenia is considered a brain connectivity disorder in which functional integration within the brain fails. Central to the brain's integrative function are connector hubs, brain regions characterized by strong connections with multiple networks. Given their critical role in functional integration, we hypothesized that connector hubs, including those located in the cerebellum and subcortical regions, are severely impaired in patients with schizophrenia. METHODS: We identified brain voxels with significant connectivity alterations in patients with schizophrenia (n = 76; men = 43) compared to healthy controls (n = 80; men = 43) across multiple large-scale resting state networks (RSNs) using a network metric called functional connectivity overlap ratio (FCOR). From these voxels, candidate connector hubs were identified and verified using seed-based connectivity analysis. RESULTS: We found that most networks exhibited connectivity alterations in the patient group. Specifically, connectivity with the basal ganglia and high visual networks was severely affected over widespread brain areas in patients, affecting subcortical and cerebellar regions and the regions involved in visual and sensorimotor processing. Furthermore, we identified critical connector hubs in the cerebellum, midbrain, thalamus, insula, and calcarine with connectivity to multiple RSNs affected in the patients. FCOR values of these regions were also associated with clinical data and could classify patient and control groups with > 80 % accuracy. CONCLUSIONS: These findings highlight the critical role of connector hubs, particularly those in the cerebellum and subcortical regions, in the pathophysiology of schizophrenia and the potential role of FCOR as a clinical biomarker for the disorder.

Fluctuations in Arousal Correlate with Neural Activity in the Human Thalamus.

The neural basis of consciousness has been explored in humans and animals; however, the exact nature of consciousness remains elusive. In this study, we aimed to elucidate which brain regions are relevant to arousal in humans. Simultaneous recordings of brain activity and eye-tracking were conducted in 20 healthy human participants. Brain activity was measured by resting-state functional magnetic resonance imaging with a multiband acquisition protocol. The subjective levels of arousal were investigated based on the degree of eyelid closure that was recorded using a near-infrared eye camera within the scanner. The results showed that the participants were in an aroused state for 79% of the scan time, and the bilateral thalami were significantly associated with the arousal condition. Among the major thalamic subnuclei, the mediodorsal nucleus (MD) showed greater involvement in arousal when compared with other subnuclei. A receiver operating characteristic analysis with leave-one-out crossvalidation conducted using template-based brain activity and arousal-level data from eye-tracking showed that, in most participants, thalamic activity significantly predicted the subjective levels of arousal. These results indicate a significant role of the thalamus, and in particular, the MD, which has rich connectivity with the prefrontal cortices and the limbic system in human consciousness.

Lateralization of Color Discrimination Performance and Lexical Effects in Patients With Chronic Schizophrenia.

Introduction: Patients with schizophrenia experience various visual disturbances. However, information regarding color perception in these patients is rare. In this study, we used a lateralized color search task to investigate whether difference in color name affects color recognition in patients with schizophrenia. Methods: In a color search task, we controlled the position of the target that emerged from the left visual field (LVF) or right visual field (RVF) as well as the color category. In this task, both the target and the distractors had the same or different color name (e.g., blue or green). Results: Patients with schizophrenia showed faster performance in the color search task with different color names for target-distractors when the target emerged from the LVF than when it emerged from the RVF. However, the same laterality was not observed in healthy controls. This finding indicates that semantic processing for color name differences influenced visual discrimination performance in patients with schizophrenia more profoundly in the LVF than in the RVF. Conclusion: This lateralized performance could imply the failure of the left hemisphere language processing dominance in schizophrenia. A search paradigm combining target position and category may indicate that automatic language processing depends on imbalanced hemispheric function in schizophrenia.

Transient neural activation in human amygdala involved in aversive conditioning of face and voice.

Elucidating the neural mechanisms involved in aversive conditioning helps find effective treatments for psychiatric disorders such as anxiety disorder and phobia. Previous studies using fMRI and human subjects have reported that the amygdala plays a role in this phenomenon. However, the noxious stimuli that were used as unconditioned stimuli in previous studies (e.g., electric shock) might have been ecologically invalid because we seldom encounter such stimuli in daily life. Therefore, we investigated whether a face stimulus could be conditioned by using a voice that had negative emotional valence and was collected from a real-life environment. A skin conductance response showed that healthy subjects were conditioned by using these stimuli. In an fMRI study, there was greater amygdala activation in response to the faces that had been paired with the voice than to those that had not. The right amygdala showed transient activity in the early stage of acquisition. A psychophysiological interaction analysis indicated that the subcortical pathway from the medial geniculate body to the amygdala played a role in conditioning. Modulation of the subcortical pathway by voice stimuli preceded the transient activity in the amygdala. The finding that an ecologically valid stimulus elicited the conditioning and amygdala response suggests that our brain is automatically processing unpleasant stimuli in daily life.

Dynamic cultural influences on neural representations of the self.

People living in multicultural environments often encounter situations which require them to acquire different cultural schemas and to switch between these cultural schemas depending on their immediate sociocultural context. Prior behavioral studies show that priming cultural schemas reliably impacts mental processes and behavior underlying self-concept. However, less well understood is whether or not cultural priming affects neurobiological mechanisms underlying the self. Here we examined whether priming cultural values of individualism and collectivism in bicultural individuals affects neural activity in cortical midline structures underlying self-relevant processes using functional magnetic resonance imaging. Biculturals primed with individualistic values showed increased activation within medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC) during general relative to contextual self-judgments, whereas biculturals primed with collectivistic values showed increased response within MPFC and PCC during contextual relative to general self-judgments. Moreover, degree of cultural priming was positively correlated with degree of MPFC and PCC activity during culturally congruent self-judgments. These findings illustrate the dynamic influence of culture on neural representations underlying the self and, more broadly, suggest a neurobiological basis by which people acculturate to novel environments.

EEG evidence of face-specific visual self-representation.

Cognitive science has regarded an individual's face as a form of representative stimuli to engage self-representation. The domain-generality of self-representation has been assumed in several reports, but was recently refuted in a functional magnetic resonance imaging study (Sugiura et al., 2008). The general validity of this study's criticism should be tested by other measures to compensate for the limitation of the time resolution of the blood-oxygen-level-dependent (BOLD) signal. In this article, we report an EEG study on the domain-generality of visual self-representation. Domain-general self-representation was operationally defined as the self-relevance common to one's own Face and Cup; three levels of familiarity, Self, Familiar, and Unfamiliar, were prepared for each. There was another condition, Visual Field, that manipulated visual hemifield during stimulus presentation, but it was collapsed because it produced no interaction with stimulus familiarity. Our results confirmed comparable phase resetting in both domains in response to familiarity manipulation, which occurred within the medial frontal area during 270-390 ms poststimulus and in the theta band. However, self-specific dissociation was observed only for Face. The results here support the conclusion that visual self-representation is domain-specific and that the oscillatory responses observed suggest evidence of face-specific visual self-representation. Results also revealed an inter-trial phase coherency decrease specifically for Self-Face within the right fusiform area during 170-290 ms poststimulus and in the alpha and theta band, suggesting reduced functional demand for Self-Face represented by sharpened networks.

The effects of acute treatment with tandospirone, diazepam, and placebo on driving performance and cognitive function in healthy volunteers.

OBJECTIVE: To assess the effects of two anxiolytics, diazepam and tandospirone, on driving performance from methodological viewpoints taking frequent rear-end collisions into account. METHODS: In this double-blinded, three-way crossover trial, 18 healthy males received acute doses of 20 mg tandospirone (TSP), 5 mg diazepam (DZP), and placebo (PCB). The subjects were administered three driving tasks-road tracking, car following, and harsh braking-performed using a driving simulator and three cognitive tasks-Wisconsin Card Sorting Test, Continuous Performance Test, and N-back test-at baseline and at 1 and 4 h post-dosing. The Stanford Sleepiness Scale scores were also assessed. RESULTS: DZP nonsignificantly increased the percent change of brake reaction time (BRT) as compared to PCB at 4 h post-dosing. TSP nonsignificantly decreased the percent change of BRT as compared to PCB. Consequently, there was a significant difference in the percent change of BRT between DZP and TSP at 4 h post-dosing. For the remaining tasks, no statistically significant effects of treatment were observed. CONCLUSIONS: Acute doses of DZP significantly impaired the harsh-braking performance as compared to acute doses of TSP. These findings suggest that TSP may be used more safely in patients' driving activities.

Relationship of psychopathological symptoms and cognitive function to subjective quality of life in patients with chronic schizophrenia.

AIMS: The purpose of the present study was to examine the extent of the effects of psychopathological symptoms and cognitive function on quality of life (QOL) in patients with chronic schizophrenia. METHODS: Data were obtained using the Japanese Schizophrenia Quality of Life Scale (JSQLS), Positive and Negative Syndrome Scale (PANSS), Wisconsin Card-Sorting Test (WCST) Keio version, and Continuous Performance Test (CPT) for 52 schizophrenia patients. RESULTS: Stepwise regression analysis showed that PANSS depression/anxiety factors predicted JSQLS psychosocial conditions and motivation/energy, and that WCST Categories Achieved predicted JSQLS symptoms/side-effects. CONCLUSIONS: Psychopathological symptoms and cognitive function affect subjective QOL in patients with schizophrenia. If the final goal is treatment that improves QOL in a manner that patients themselves are aware of, clinicians probably need to consider a treatment strategy that improves depression/anxiety symptom.

Support vector machine-based classification of schizophrenia patients and healthy controls using structural magnetic resonance imaging from two independent sites.

Structural brain alterations have been repeatedly reported in schizophrenia; however, the pathophysiology of its alterations remains unclear. Multivariate pattern recognition analysis such as support vector machines can classify patients and healthy controls by detecting subtle and spatially distributed patterns of structural alterations. We aimed to use a support vector machine to distinguish patients with schizophrenia from control participants on the basis of structural magnetic resonance imaging data and delineate the patterns of structural alterations that significantly contributed to the classification performance. We used independent datasets from different sites with different magnetic resonance imaging scanners, protocols and clinical characteristics of the patient group to achieve a more accurate estimate of the classification performance of support vector machines. We developed a support vector machine classifier using the dataset from one site (101 participants) and evaluated the performance of the trained support vector machine using a dataset from the other site (97 participants) and vice versa. We assessed the performance of the trained support vector machines in each support vector machine classifier. Both support vector machine classifiers attained a classification accuracy of >70% with two independent datasets indicating a consistently high performance of support vector machines even when used to classify data from different sites, scanners and different acquisition protocols. The regions contributing to the classification accuracy included the bilateral medial frontal cortex, superior temporal cortex, insula, occipital cortex, cerebellum, and thalamus, which have been reported to be related to the pathogenesis of schizophrenia. These results indicated that the support vector machine could detect subtle structural brain alterations and might aid our understanding of the pathophysiology of these changes in schizophrenia, which could be one of the diagnostic findings of schizophrenia.

Cultural influences on neural systems of intergroup emotion perception: An fMRI study.

Cultural factors, such as cultural group membership, have been shown to affect neural bases of face and emotion perception. However, little is known about how cultural factors influence neural processing of emotional faces expressed by in-group and out-group members. In this study, we examined cultural influences on neural activation during the intergroup perception of negative emotional faces. We used functional magnetic resonance imaging to compare neural activation during intergroup emotion processing across cultures in three participants groups; two monocultural groups (i.e. Caucasian-Americans and native Japanese) and a bicultural group (i.e. Japanese-Americans). During scanning, the participants completed an emotional match-to-sample task consisting of negative facial expressions of Japanese and Caucasians. Our results show cultural modulation of neural response in the bilateral amygdala as a function of in-group biases and collectivistic values. Additionally, bicultural Japanese-Americans showed enhanced neural responses in the ventral medial prefrontal and posterior cingulate cortices, which had been related to self-related processing, during the perception of negative facial expression of Japanese. Neural activation in the ventral and posterior cingulate cortices reflected individuals' collectivistic tendencies only in the Japanese-American group, possibly due to greater sensitivity to ingroup biases in bicultural individuals. Our results demonstrate the influence of culture on neural responses during the perception of intergroup emotion from faces.

Neural basis of individualistic and collectivistic views of self.

Individualism and collectivism refer to cultural values that influence how people construe themselves and their relation to the world. Individualists perceive themselves as stable entities, autonomous from other people and their environment, while collectivists view themselves as dynamic entities, continually defined by their social context and relationships. Despite rich understanding of how individualism and collectivism influence social cognition at a behavioral level, little is known about how these cultural values modulate neural representations underlying social cognition. Using cross-cultural functional magnetic resonance imaging (fMRI), we examined whether the cultural values of individualism and collectivism modulate neural activity within medial prefrontal cortex (MPFC) during processing of general and contextual self judgments. Here, we show that neural activity within the anterior rostral portion of the MPFC during processing of general and contextual self judgments positively predicts how individualistic or collectivistic a person is across cultures. These results reveal two kinds of neural representations of self (eg, a general self and a contextual self) within MPFC and demonstrate how cultural values of individualism and collectivism shape these neural representations.

Changes after behavior therapy among responsive and nonresponsive patients with obsessive-compulsive disorder.

Neuroimaging studies have suggested that behavior therapy (BT) might change abnormal activity in the frontal-subcortical circuits of the brain in patients with obsessive-compulsive disorder (OCD). However, the results of these studies have been rather inconsistent. The aim of the present study was to use statistical parametric mapping (SPM) analysis to explore the effects of successful BT on regional cerebral blood flow (rCBF) in patients with OCD. Forty-five OCD patients who were treatment-resistant to a single serotonin reuptake inhibitor (SRI) trial were examined. Single photon emission computed tomography (SPECT) using 99mTc-ECD was performed before and after the completion of 12 weeks of BT. Although no significant differences in pre-treatment rCBF were observed between responders and nonresponders to BT, the post-treatment rCBF values in the left medial prefrontal cortex (Brodmann area 10) and bilateral middle frontal gyri (Brodmann area 10) were significantly lower in the responders than in the nonresponders. Furthermore, the baseline rCBF in the bilateral orbitofrontal cortex (OFC) was significantly correlated with the change in the Y-BOCS score among the responders. Our results support the hypothesis that while the OFC may be associated with the BT response, BT may result in changes in rCBF in the medial and middle frontal cortex.

Neural correlates of memory in depression measured by brain perfusion SPECT at rest.

AIM: Brain metabolism activated studies have indicated associations between memory and the anterior cingulate cortex and hippocampus in patients with depression. The aim of the present study was therefore to investigate memory function, measured as performance on the Wechsler Memory Scale-Revised (WMS-R), and its relationship to brain perfusion using single-photon emission computed tomography (SPECT) at rest in patients with depression. METHODS: The Hamilton Rating Scale for Depression (HAMD) and WMS-R were measured for 17 patients with depression by an independent clinical evaluation team. Voxel-based correlation analyses were performed with statistical parametric mapping at an extent threshold of 200 voxels. Associations were controlled for state and trait factors. RESULTS: WMS-R measurements of verbal, visual, and general memory were inversely correlated with brain perfusion in the right anterior cingulate cortex, left premotor cortices, and both regions, respectively. The HAMD directly correlated with brain perfusion in the right anterior cingulate cortex. CONCLUSION: Brain perfusion SPECT measurements of the anterior cingulate cortex at rest were associated with the severity of depression and immediate memory scores measured with the WMS-R.