Impairment of unconscious emotional processing after unilateral medial temporal structure resection.

The role of the amygdala in unconscious emotional processing remains a topic of debate. Past lesion studies have indicated that amygdala damage leads to impaired electrodermal activity in response to subliminally presented emotional stimuli. However, electrodermal activity can reflect both emotional and nonemotional processes. To provide behavioral evidence highlighting the critical role of the amygdala in unconscious emotional processing, we examined patients (n = 16) who had undergone unilateral resection of medial temporal lobe structures, including the amygdala. We utilized the subliminal affective priming paradigm in conjunction with unilateral visual presentation. Fearful or happy dynamic facial expressions were presented in unilateral visual fields for 30 ms, serving as negative or positive primes. Subsequently, neutral target faces were displayed, and participants were tasked with rating the valence of these targets. Positive primes, compared to negative ones, enhanced valence ratings of the target to a greater extent when they stimulated the intact hemisphere (i.e., were presented in the contralateral visual field of the intact hemisphere) than when they stimulated the resected hemisphere (i.e., were presented in the contralateral visual field of the resected hemisphere). These results suggest that the amygdala is causally involved in unconscious emotional processing.

Spindle cell lipoma of the floor of mouth.

The patient was a man in his 60s with the gradually increasing mass in his mouth. A well-defined, elastic soft mass with a major diameter of 60 mm was found on the right floor of mouth. The magnetic resonance imaging findings showed a well-defined mass with high signal on both T1 and T2-weighted image in the right sublingual space. The mass was slightly heterogeneous inside and had a septum-like appearance. The tumor was resected with care not to damage the capsule. Histopathological findings showed mature adipocytes, spindle-shaped cells, and collagenous components. Spindle cells were CD34-positive. The tumor was diagnosed as spindle cell lipoma. The patient was followed up for 6 months with no recurrence. Spindle cell lipoma is a rare entity and this is the largest case in the oral cavity. Because there are wide variety of adipocytic tumors, the careful examination of their imaging and histopathological findings is essential.

The structural neural correlates of atypical facial expression recognition in autism spectrum disorder.

Previous studies have demonstrated that individuals with autism spectrum disorder (ASD) are worse at recognizing facial expressions than are typically developing (TD) individuals. The present study investigated the differences in structural neural correlates of emotion recognition between individuals with and without ASD using voxel-based morphometry (VBM). We acquired structural MRI data from 27 high-functioning adults with ASD and 27 age- and sex-matched TD individuals. The ability to recognize facial expressions was measured using a label-matching paradigm featuring six basic emotions (anger, disgust, fear, happiness, sadness, and surprise). The behavioural task did not find deficits of emotion recognition in ASD after controlling for intellectual ability. However, the VBM analysis for the region of interest showed a positive correlation between the averaged percent accuracy across six basic emotions and the grey matter volume of the right inferior frontal gyrus in TD individuals, but not in individuals with ASD. The VBM for the whole brain region under each emotion condition revealed a positive correlation between the percent accuracy for disgusted faces and the grey matter volume of the left dorsomedial prefrontal cortex in individuals with ASD, but not in TD individuals. The different pattern of correlations suggests that individuals with and without ASD use different processing mechanisms for recognizing others' facial expressions.

Inter-Brain Synchronization During Sandplay Therapy: Individual Analyses.

Interactions between the client (Cl) and therapist (Th) evolve therapeutic relationships in psychotherapy. An interpersonal link or therapeutic space is implicitly developed, wherein certain important elements are expressed and shared. However, neural basis of psychotherapy, especially of non-verbal modalities, have scarcely been explored. Therefore, we examined the neural backgrounds of such therapeutic alliances during sandplay, a powerful art/play therapy technique. Real-time and simultaneous measurement of hemodynamics was conducted in the prefrontal cortex (PFC) of Cl-Th pairs participating in sandplay and subsequent interview sessions through multichannel near-infrared spectroscopy. As sandplay is highly individualized, and no two sessions and products (sandtrays) are the same, we expected variation in interactive patterns in the Cl-Th pairs. Nevertheless, we observed a statistically significant correlation between the spatio-temporal patterns in signals produced by the homologous regions of the brains. During the sandplay condition, significant correlations were obtained in the lateral PFC and frontopolar (FP) regions in the real Cl-Th pairs. Furthermore, a significant correlation was observed in the FP region for the interview condition. The correlations found in our study were explained as a "remote" synchronization (i.e., unconnected peripheral oscillators synchronizing through a hub maintaining free desynchronized dynamics) between two subjects in a pair, possibly representing the neural foundation of empathy, which arises commonly in sandplay therapy (ST).

Atypical Amygdala-Neocortex Interaction During Dynamic Facial Expression Processing in Autism Spectrum Disorder.

Atypical reciprocal social interactions involving emotional facial expressions are a core clinical feature of autism spectrum disorder (ASD). Previous functional magnetic resonance imaging (fMRI) studies have demonstrated that some social brain regions, including subcortical (e.g., amygdala) and neocortical regions (e.g., fusiform gyrus, FG) are less activated during the processing of facial expression stimuli in individuals with ASD. However, the functional networking patterns between the subcortical and cortical regions in processing emotional facial expressions remain unclear. We investigated this issue in ASD (n = 31) and typically developing (TD; n = 31) individuals using fMRI. Participants viewed dynamic facial expressions of anger and happiness and their corresponding mosaic images. Regional brain activity analysis revealed reduced activation of several social brain regions, including the amygdala, in the ASD group compared with the TD group in response to dynamic facial expressions vs. dynamic mosaics (p < 0.05, η p 2 = 0.19). Dynamic causal modeling (DCM) analyses were then used to compare models with forward, backward, and bi-directional effective connectivity between the amygdala and neocortical networks. The results revealed that: (1) the model with effective connectivity from the amygdala to the neocortex best fit the data of both groups; and (2) the same model best accounted for group differences. Coupling parameter (i.e., effective connectivity) analyses showed that the modulatory effects of dynamic facial processing were substantially weaker in the ASD group than in the TD group. These findings suggest that atypical modulation from the amygdala to the neocortex underlies impairment in social interaction involving dynamic facial expressions in individuals with ASD.

Resting-state neural activity and connectivity associated with subjective happiness.

The majority of people throughout the world rate subjective happiness as the top of the important thing in life. A recent structural neuroimaging study exploring neurocognitive mechanisms underlying subjective happiness has suggested that the gray matter volume of the right precuneus is associated with Subjective Happiness Scale (SHS) scores. However, how the neural activity in this region, as well as the neural functional coupling between this and other regions, could be related to SHS scores remains unclear. To investigate these issues, we performed resting-state functional magnetic resonance imaging and analyzed the fractional amplitude of low-frequency fluctuation (fALFF) in participants, whose subjective happiness was evaluated using the SHS. Lower fALFF values in the right precuneus were associated with higher SHS scores. Furthermore, functional connectivity and spectral dynamic causal modeling analyses showed that both functional and effective connectivity of the right precuneus with the right amygdala were positively associated with SHS scores. These findings, together with other evidence on the information-processing functions of these brain regions, suggest the possibility that subjective happiness is associated with a reduction in self-referential mental processes, which are well integrated with emotional processing.

Extracellular calcium stimulates osteogenic differentiation of human adipose-derived stem cells by enhancing bone morphogenetic protein-2 expression.

Bone morphogenetic protein-2 (BMP-2) promotes the differentiation of non-osteogenic mesenchymal cells to osteogenic cells. In this study, we isolated human adipose-derived stem cells (hASCs) and investigated the effects of recombinant human BMP-2 (rhBMP-2) and extracellular Ca2+ concentration ([Ca2+]out) on the osteogenic differentiation of hASCs. rhBMP-2 promoted calcium deposition in hASCs and stimulated the mRNA expressions of six proteins known to be involved in the osteogenic differentiation of hASCs: Runx2, osterix, alkaline phosphatase, osteonectin, bone sialoprotein and osteocalcin. Elevation of [Ca2+]out enhanced the level of alkaline phosphatase enzyme, increased the mRNA expressions of Runx2 and osteocalcin and induced the expressions of BMP-2 mRNA and protein in hASCs. Elevation of [Ca2+]out transiently increased the intracellular Ca2+ concentration ([Ca2+]in) due to activation of the calcium-sensing receptor (CaSR). The Ca2+-induced expressions of BMP-2 mRNA and protein were inhibited by the calmodulin antagonist, W-7. Furthermore, elevation of [Ca2+]out decreased the cytoplasmic level of phosphorylated nuclear factor of activated T-cell-2 (NFAT-2) and increased the nuclear level of dephosphorylated NFAT2. Taken together, these results suggest that rhBMP-2 promotes the osteogenic differentiation of hASCs. Furthermore, an increase in [Ca2+]out enhances the expression of BMP-2 via activation of the CaSR, elevation of [Ca2+]in and stimulation of Ca2+/calmodulin-dependent NFAT-signaling pathways.

Widespread and lateralized social brain activity for processing dynamic facial expressions.

Dynamic facial expressions of emotions constitute natural and powerful means of social communication in daily life. A number of previous neuroimaging studies have explored the neural mechanisms underlying the processing of dynamic facial expressions, and indicated the activation of certain social brain regions (e.g., the amygdala) during such tasks. However, the activated brain regions were inconsistent across studies, and their laterality was rarely evaluated. To investigate these issues, we measured brain activity using functional magnetic resonance imaging in a relatively large sample (n = 51) during the observation of dynamic facial expressions of anger and happiness and their corresponding dynamic mosaic images. The observation of dynamic facial expressions, compared with dynamic mosaics, elicited stronger activity in the bilateral posterior cortices, including the inferior occipital gyri, fusiform gyri, and superior temporal sulci. The dynamic facial expressions also activated bilateral limbic regions, including the amygdalae and ventromedial prefrontal cortices, more strongly versus mosaics. In the same manner, activation was found in the right inferior frontal gyrus (IFG) and left cerebellum. Laterality analyses comparing original and flipped images revealed right hemispheric dominance in the superior temporal sulcus and IFG and left hemispheric dominance in the cerebellum. These results indicated that the neural mechanisms underlying processing of dynamic facial expressions include widespread social brain regions associated with perceptual, emotional, and motor functions, and include a clearly lateralized (right cortical and left cerebellar) network like that involved in language processing.

Corticostriatal-limbic correlates of sub-clinical obsessive-compulsive traits.

Obsessive-compulsive (OC) traits such as intrusive worrisome ideas or excessive concerns for threats are frequent in general population (5%-13%). However, the structural neural correlates of the sub-clinical OC traits remain largely unknown. Based on the data of obsessive-compulsive disorder (OCD), we hypothesized that the subcortical and cortical structures, constituting the cortico-striatal-thalamo-cortical circuit (CSTC) and the limbic system, could be associated with OC traits. Here we conducted voxel-based morphometry (VBM) in order to investigate fine grained volume changes of these structures in 49 non-clinical subjects. Analysis of structural covariances of these structures was also conducted. We identified volume changes associated with OC traits in the left putamen and the left amygdala. The results of structural covariance analysis revealed increased covariances in relation to the heightened OC traits between the left putamen to bilateral medial prefrontal cortex and to the left cerebellum, and between the left globus pallidus to the bilateral anterior cingulate cortices. The present finding of volume changes of the corticostriatal-limbic structures may reflect neuroplasticity associated with OC traits. Since the abnormality of these structures were also observed in the clinical OCD, the subclinical subjects with OC traits shared "neuronal obsessive traits" that might precondition OCD at the network level.

Homeostatic modulation on unconscious hedonic responses to food.

OBJECTIVE: Hedonic/affective responses to food play a critical role in eating behavior. Previous behavioral studies have shown that hedonic responses to food are elicited consciously and unconsciously. Although the studies also showed that hunger and satiation have a modulatory effect on conscious hedonic responses to food, the effect of these homeostatic states on unconscious hedonic responses to food remains unknown. RESULTS: We investigated unconscious hedonic responses to food in hungry and satiated participants using the subliminal affective priming paradigm. Food images or corresponding mosaic images were presented in the left or right peripheral visual field during 33 ms. Then photographs of target faces with emotionally neutral expressions were presented, and the participants evaluated their preference for the faces. Additionally, daily eating behaviors were assessed using questionnaires. Preference for the target faces was increased by food images relative to the mosaics in the hungry, but not the satiated, state. The difference in preference ratings between the food and mosaic conditions was positively correlated with the tendency for external eating in the hungry, but not the satiated, group. Our findings suggest that homeostatic states modulate unconscious hedonic responses to food and that this phenomenon is related to daily eating behaviors.

Impaired detection of happy facial expressions in autism.

The detection of emotional facial expressions plays an indispensable role in social interaction. Psychological studies have shown that typically developing (TD) individuals more rapidly detect emotional expressions than neutral expressions. However, it remains unclear whether individuals with autistic phenotypes, such as autism spectrum disorder (ASD) and high levels of autistic traits (ATs), are impaired in this ability. We examined this by comparing TD and ASD individuals in Experiment 1 and individuals with low and high ATs in Experiment 2 using the visual search paradigm. Participants detected normal facial expressions of anger and happiness and their anti-expressions within crowds of neutral expressions. In Experiment 1, reaction times were shorter for normal angry expressions than for anti-expressions in both TD and ASD groups. This was also the case for normal happy expressions vs. anti-expressions in the TD group but not in the ASD group. Similarly, in Experiment 2, the detection of normal vs. anti-expressions was faster for angry expressions in both groups and for happy expressions in the low, but not high, ATs group. These results suggest that the detection of happy facial expressions is impaired in individuals with ASD and high ATs, which may contribute to their difficulty in creating and maintaining affiliative social relationships.

Gray matter volumes of early sensory regions are associated with individual differences in sensory processing.

Sensory processing (i.e., the manner in which the nervous system receives, modulates, integrates, and organizes sensory stimuli) is critical when humans are deciding how to react to environmental demands. Although behavioral studies have shown that there are stable individual differences in sensory processing, the neural substrates that implement such differences remain unknown. To investigate this issue, structural magnetic resonance imaging scans were acquired from 51 healthy adults and individual differences in sensory processing were assessed using the Sensory Profile questionnaire (Brown et al.: Am J Occup Ther 55 (2001) 75-82). There were positive relationships between the Sensory Profile modality-specific subscales and gray matter volumes in the primary or secondary sensory areas for the visual, auditory, touch, and taste/smell modalities. Thus, the present results suggest that individual differences in sensory processing are implemented by the early sensory regions. Hum Brain Mapp 38:6206-6217, 2017. © 2017 Wiley Periodicals, Inc.

Reduced Gray Matter Volume in the Social Brain Network in Adults with Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by behavioral impairment in social interactions. Although theoretical and empirical evidence suggests that impairment in the social brain network could be the neural underpinnings of ASD, previous structural magnetic resonance imaging (MRI) studies in adults with ASD have not provided clear support for this, possibly due to confounding factors, such as language impairments. To further explore this issue, we acquired structural MRI data and analyzed gray matter volume in adults with ASD (n = 36) who had no language impairments (diagnosed with Asperger's disorder or pervasive developmental disorder not otherwise specified, with symptoms milder than those of Asperger's disorder), had no comorbidity, and were not taking medications, and in age- and sex-matched typically developing (TD) controls (n = 36). Univariate voxel-based morphometry analyses revealed that regional gray matter volume was lower in the ASD than in the control group in several brain regions, including the right inferior occipital gyrus, left fusiform gyrus, right middle temporal gyrus, bilateral amygdala, right inferior frontal gyrus, right orbitofrontal cortex, and left dorsomedial prefrontal cortex. A multivariate approach using a partial least squares (PLS) method showed that these regions constituted a network that could be used to discriminate between the ASD and TD groups. A PLS discriminant analysis using information from these regions showed high accuracy, sensitivity, specificity, and precision (>80%) in discriminating between the groups. These results suggest that reduced gray matter volume in the social brain network represents the neural underpinnings of behavioral social malfunctioning in adults with ASD.

Structural Correlates of Reading the Mind in the Eyes in Autism Spectrum Disorder.

Behavioral studies have shown that individuals with autism spectrum disorder (ASD) have impaired ability to read the mind in the eyes. Although this impairment is central to their social malfunctioning, its structural neural correlates remain unclear. To investigate this issue, we assessed Reading the Mind in the Eyes Test, revised version (Eyes Test) and acquired structural magnetic resonance images in adults with high-functioning ASD (n = 19) and age-, sex- and intelligence quotient-matched typically developing (TD) controls (n = 19). On the behavioral level, the Eyes Test scores were lower in the ASD group than in the control group. On the neural level, an interaction between group and Eyes Test score was found in the left temporoparietal junction (TPJ). A positive association between the Eyes Test score and gray matter volume of this region was evident in the control group, but not in the ASD group. This finding suggests that the failure to develop appropriate structural neural representations in the TPJ may underlie the impaired ability of individuals with ASD to read the mind in the eyes. These behavioral and neural findings provide support for the theories that impairments in processing eyes and the ability to infer others' mental states are the core symptoms of ASD, and that atypical features in the social brain network underlie such impairments.

Putamen Volume is Negatively Correlated with the Ability to Recognize Fearful Facial Expressions.

Findings of previous functional magnetic resonance imaging (MRI) and neuropsychological studies have suggested that specific aspects of the basal ganglia, particularly the putamen, are involved in the recognition of emotional facial expressions. However, it remains unknown whether variations in putamen structure reflect individual differences in the ability to recognize facial expressions. Thus, the present study assessed the putamen volumes and shapes of 50 healthy Japanese adults using structural MRI scans and evaluated the ability of participants to recognize facial expressions associated with six basic emotions: anger, disgust, fear, happiness, sadness, and surprise. The volume of the bilateral putamen was negatively associated with the recognition of fearful faces, and the local shapes of both the anterior and posterior subregions of the bilateral putamen, which are thought to support cognitive/affective and motor processing, respectively, exhibited similar negative relationships with the recognition of fearful expressions. These results suggest that individual differences in putamen structure can predict the ability to recognize fearful facial expressions in others. Additionally, these findings indicate that cognitive/affective and motor processing underlie this process.

Atypical Gaze Cueing Pattern in a Complex Environment in Individuals with ASD.

Clinically, social interaction, including gaze-triggered attention, has been reported to be impaired in autism spectrum disorder (ASD), but psychological studies have generally shown intact gaze-triggered attention in ASD. These studies typically examined gaze-triggered attention under simple environmental conditions. In real life, however, the environment is complex. Previous studies have shown that an enhanced cueing effect was found when using eye gaze compared with arrow cues in unpredictably complex conditions in typically developing (TD) individuals. However, in the current study, compared with TD individuals, the cueing effect failed to enhance when using eye gaze compared with arrow cues under complex conditions in individuals with ASD. This may reflect the atypical style of gaze-triggered attention when individuals with ASD adapt to environmental complexity.

Neural substrates of the ability to recognize facial expressions: a voxel-based morphometry study.

The recognition of facial expressions of emotion is adaptive for human social interaction, but the ability to do this and the manner in which it is achieved differs among individuals. Previous functional neuroimaging studies have demonstrated that some brain regions, such as the inferior frontal gyrus (IFG), are active during the response to emotional facial expressions in healthy participants, and lesion studies have demonstrated that damage to these structures impairs the recognition of facial expressions. However, it remains to be established whether individual differences in the structure of these regions could be associated with differences in the ability to recognize facial expressions. We investigated this issue using acquired structural magnetic resonance imaging, and assessed the performance of healthy adults with respect to recognition of the facial expressions of six basic emotions. The gray matter volume of the right IFG positively correlated with the total accuracy of facial expression recognition. This suggests that individual differences in the ability to recognize facial expressions are associated with differences in the structure of the right IFG. Furthermore, the mirror neuron activity of the IFG may be important for establishing efficient facial mimicry to facilitate emotion recognition.

Time course of gamma-band oscillation associated with face processing in the inferior occipital gyrus and fusiform gyrus: A combined fMRI and MEG study.

Debate continues over whether the inferior occipital gyrus (IOG) or the fusiform gyrus (FG) represents the first stage of face processing and what role these brain regions play. We investigated this issue by combining functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in normal adults. Participants passively observed upright and inverted faces and houses. First, we identified the IOG and FG as face-specific regions using fMRI. We applied beamforming source reconstruction and time-frequency analysis to MEG source signals to reveal the time course of gamma-band activations in these regions. The results revealed that the right IOG showed higher gamma-band activation in response to upright faces than to upright houses at 100 ms from the stimulus onset. Subsequently, the right FG showed greater gamma-band response to upright faces versus upright houses at around 170 ms. The gamma-band activation in the right IOG and right FG was larger in response to inverted faces than to upright faces at the later time window. These results suggest that (1) the gamma-band activities occurs rapidly first in the IOG and next in the FG and (2) the gamma-band activity in the right IOG at later time stages is involved in configuration processing for faces. Hum Brain Mapp 38:2067-2079, 2017. © 2017 Wiley Periodicals, Inc.

Unconscious Affective Responses to Food.

Affective or hedonic responses to food are crucial for humans, both advantageously (e.g., enhancing survival) and disadvantageously (e.g., promoting overeating and lifestyle-related disease). Although previous psychological studies have reported evidence of unconscious cognitive and behavioral processing related to food, it remains unknown whether affective reactions to food can be triggered unconsciously and its relationship with daily eating behaviors. We investigated these issues by using the subliminal affective priming paradigm. Photographs of food or corresponding mosaic images were presented in the peripheral visual field for 33 ms. Target photos of faces with emotionally neutral expressions were then presented, and participants rated their preferences for the faces. Eating behaviors were also assessed using questionnaires. The food images, relative to the mosaics, increased participants' preference for subsequent target faces. Furthermore, the difference in the preference induced by food versus mosaic images was positively correlated with the tendency to engage in external eating. These results suggest that unconscious affective reactions are elicited by the sight of food and that these responses contribute to daily eating behaviors related to overeating.

Structural Neural Substrates of Reading the Mind in the Eyes.

The ability to read the minds of others in their eyes plays an important role in human adaptation to social environments. Behavioral studies have resulted in the development of a test to measure this ability (Reading the Mind in the Eyes Test, revised version; Eyes Test), and have demonstrated that this ability is consistent over time. Although functional neuroimaging studies revealed brain activation while performing the Eyes Test, the structural neural substrates supporting consistent performance on the Eyes Test remain unclear. In this study, we assessed the Eyes Test and analyzed structural magnetic resonance images using voxel-based morphometry (VBM) in healthy participants. Test performance was positively associated with the gray matter volumes of the dorsomedial prefrontal cortex, inferior parietal lobule (temporoparietal junction), and precuneus in the left hemisphere. These results suggest that the fronto-temporoparietal network structures support the consistent ability to read the mind in the eyes.