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Following the published behavioral and cognitive results of this single-blind parallel sham-controlled randomized clinical trial, the current study aimed to explore the impact of intermittent theta burst stimulation (iTBS), a variant of excitatory transcranial magnetic stimulation, over the bilateral posterior superior temporal sulci (pSTS) on white matter macro/microstructure in intellectually able children and adolescents with autism. Participants were randomized and blindly received active or sham iTBS for 4 weeks (the single-blind sham-controlled phase). Then, all participants continued to receive active iTBS for another 4 weeks (the open-label phase). The clinical results were published elsewhere. Here, we present diffusion magnetic resonance imaging data on potential changes in white matter measures after iTBS. Twenty-two participants in Active-Active group and 27 participants in Sham-Active group underwent multi-shell high angular resolution diffusion imaging (64-direction for b = 2000 & 1000 s/mm2, respectively) at baseline, week 4, and week 8. With longitudinal fixel-based analysis, we found no white matter changes following iTBS from baseline to week 4 (a null treatment by time interaction and a null within-group paired comparison in the Active-Active group), nor from baseline to week 8 (null within-group paired comparisons in both Active-Active and Sham-Active groups). As for the brain-symptoms relationship, we did not find baseline white matter metrics associated with symptom changes at week 4 in either group. Our results raise the question of what the minimal cumulative stimulation dose required to induce the white matter plasticity is.

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Scanning young children while they watch short, engaging, commercially-produced movies has emerged as a promising approach for increasing data retention and quality. Movie stimuli also evoke a richer variety of cognitive processes than traditional experiments, allowing the study of multiple aspects of brain development simultaneously. However, because these stimuli are uncontrolled, it is unclear how effectively distinct profiles of brain activity can be distinguished from the resulting data. Here we develop an approach for identifying multiple distinct subject-specific Regions of Interest (ssROIs) using fMRI data collected during movie-viewing. We focused on the test case of higher-level visual regions selective for faces, scenes, and objects. Adults (N = 13) were scanned while viewing a 5.6-min child-friendly movie, as well as a traditional localizer experiment with blocks of faces, scenes, and objects. We found that just 2.7 min of movie data could identify subject-specific face, scene, and object regions. While successful, movie-defined ssROIS still showed weaker domain selectivity than traditional ssROIs. Having validated our approach in adults, we then used the same methods on movie data collected from 3 to 12-year-old children (N = 122). Movie response timecourses in 3-year-old children's face, scene, and object regions were already significantly and specifically predicted by timecourses from the corresponding regions in adults. We also found evidence of continued developmental change, particularly in the face-selective posterior superior temporal sulcus. Taken together, our results reveal both early maturity and functional change in face, scene, and object regions, and more broadly highlight the promise of short, child-friendly movies for developmental cognitive neuroscience.

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The Self-Attention Network (SAN) has been proposed to describe the underlying neural mechanism of the self-prioritization effect, yet the roles of the key nodes in the SAN-the left posterior superior temporal sulcus (LpSTS) and the dorsolateral prefrontal cortex (DLPFC)-still need to be clarified. One hundred and nine participants were randomly assigned into the LpSTS group, the DLPFC group, or the sham group. We used the transcranial magnetic stimulation (TMS) technique to selectively disrupt the functions of the corresponding targeted region, and observed its impacts on self-prioritization effect based on the difference between the performance of the self-matching task before and after the targeted stimulation. We analyzed both model-free performance measures and HDDM-based performance measures for the self-matching task. The results showed that the inhibition of LpSTS could lead to reduced performance in processing self-related stimuli, which establishes a causal role for the LpSTS in self-related processing and provide direct evidence to support the SAN framework. However, the results of the DLPFC group from HDDM analysis were distinct from the results based on response efficiency. Our investigation further the understanding of the differentiated roles of key nodes in the SAN in supporting the self-salience in information processing.

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BACKGROUND: Theta burst stimulation (TBS), a patterned repetitive transcranial magnetic stimulation (rTMS) protocol with shorter simulation duration and lower stimulus intensity, could be a better protocol for individuals with autism spectrum disorder (ASD). Our study aimed to explore the impacts of intermittent TBS (iTBS) over the bilateral posterior superior temporal sulcus (pSTS) on intellectually able adults with ASD. METHODS: In this randomized, single-blinded, sham-controlled crossover trial, 13 adults with ASD completed iTBS for 5 consecutive days over the bilateral pSTS and inion (as a sham control) in a 16-weeks interval and in a randomly assigned order. The neuropsychological function was measured with the Wisconsin Card Sorting Test (WCST) for cognitive flexibility while the clinical outcomes were measured with both self-rate and parents-rate Autism Spectrum Quotient (AQ) before and after 5-day iTBS interventions. RESULTS: The results revealed significantly immediate effects of multi-session iTBS over the bilateral pSTS on parent-rate autistic symptoms in adults with ASD. The post-hoc analysis revealed the impacts of multi-session iTBS on cognitive flexibility were affected by baseline social-communicative impairment and baseline cognitive performance. Besides, the impacts of multi-session iTBS on clinical symptoms was affected by the concurrent psychotropic medication use and baseline autistic symptoms. CONCLUSIONS: Given the caveat of the small sample size and discrepancy of multiple informants, this pilot study suggests the therapeutic potential of 5-day multi-session iTBS over the pSTS in adults with ASD. Individual factors modulating the response to rTMS should be explicitly considered in the future trial.

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Doll play provides opportunities for children to practice social skills by creating imaginary worlds, taking others' perspectives, and talking about others' internal states. Previous research using functional near-infrared spectroscopy (fNIRS) found a region over the posterior superior temporal sulcus (pSTS) was more active during solo doll play than solo tablet play, implying that doll play might present opportunities for rehearsing theory of mind and empathy skills, even when playing alone. In this research, we addressed this more directly by investigating 4-8-year-old children's (N = 33) use of internal state language (ISL; i.e., references to emotions, desires, and cognitions) when playing with dolls and on tablets, both by themselves and with a social partner, and their associated brain activity in the pSTS using fNIRS. We found that children used more ISL about others when playing with dolls than when playing on tablets, particularly when they were playing alone. This mirrored the patterns seen in pSTS activity in previous research. When individual variability in ISL about others was considered, more ISL about others was linked to stronger pSTS activation. Thus, variability in pSTS activity during play is not about the perceptual or physical differences between toys (e.g., dolls are more human-like) but about what children think about when they engage in different kinds of play. This is the first research to investigate brain activity during spontaneously occurring ISL and indicates that children have a tendency to take and discuss others' perspectives during doll play, with implications for social processing in the brain. A video abstract of this article can be viewed at https://youtu.be/58HgxbuhBzU.

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Prior studies have shown that the left posterior superior temporal sulcus (pSTS) and left temporo-parietal junction (TPJ) both contribute to phonological short-term memory, speech perception and speech production. Here, by conducting a within-subjects multi-factorial fMRI study, we dissociate the response profiles of these regions and a third region - the anterior ascending terminal branch of the left superior temporal sulcus (atSTS), which lies dorsal to pSTS and ventral to TPJ. First, we show that each region was more activated by (i) 1-back matching on visually presented verbal stimuli (words or pseudowords) compared to 1-back matching on visually presented non-verbal stimuli (pictures of objects or non-objects), and (ii) overt speech production than 1-back matching, across 8 types of stimuli (visually presented words, pseudowords, objects and non-objects and aurally presented words, pseudowords, object sounds and meaningless hums). The response properties of the three regions dissociated within the auditory modality. In left TPJ, activation was higher for auditory stimuli that were non-verbal (sounds of objects or meaningless hums) compared to verbal (words and pseudowords), irrespective of task (speech production or 1-back matching). In left pSTS, activation was higher for non-semantic stimuli (pseudowords and hums) than semantic stimuli (words and object sounds) on the dorsal pSTS surface (dpSTS), irrespective of task. In left atSTS, activation was not sensitive to either semantic or verbal content. The contrasting response properties of left TPJ, dpSTS and atSTS was cross-validated in an independent sample of 59 participants, using region-by-condition interactions. We also show that each region participates in non-overlapping networks of frontal, parietal and cerebellar regions. Our results challenge previous claims about functional specialisation in the left posterior superior temporal lobe and motivate future studies to determine the timing and directionality of information flow in the brain networks involved in speech perception and production.

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Recent studies have shown that neural activity in a well-defined patch in the posterior superior temporal sulcus (the "gaze-following patch," GFP) of the primate brain is strongly modulated when the other's gaze attracts the observer's attention to locations/objects, the other is looking at. Changes of the mean discharge rate of neurons in the monkey GFP indicate that they are involved in two distinct computations: the allocation of spatial attention guided by the other's gaze vector and the suppression of gaze following if inappropriate in a given situation. Here, we asked if and how the discharge variability of neurons in the GFP is related to the task and if it carries information on behavioral performance. To this end, we calculated the Fano factor as a measure of across-trial discharge variability as a function of time. Our results show that all neurons exhibiting a task-related discharge-rate modulation also exhibit a stimulus onset-dependent drop in the Fano factor. Furthermore, the amplitude of the Fano factor reduction is modulated by task condition and the neuron's selectivity in this regard. We found that these effects are directly related to the monkeys' behavioral performance in that the Fano factor is predictive about upcoming correct or wrong decisions. Our results indicate that neuronal discharge variability as gauged by the Fano factor, hitherto primarily studied in the context of visual perception or motor control, is an informative measure also in studies of the neural underpinnings of complex social behavior.NEW & NOTEWORTHY Quenching of neural variability following stimulus onset is a widely accepted phenomenon. However, the relevance of quenching for the shaping of complex social behaviors remains to be explored. Here, we show that task selective neurons in the GFP exhibit a higher degree of variability quenching than their neighboring unselective neurons. Furthermore, we demonstrate that behavioral errors are not only associated with lower firing rates but also less variability quenching, suggesting that both facilitate optimal performance.

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Attention is the dynamic process of allocating limited resources to the information that is most relevant to our goals. Accumulating studies have demonstrated the crucial role of frontal and parietal areas in attention. However, the effect of posterior superior temporal sulcus (pSTS) in attention is still unclear. To address this question, in this study, we measured transcranial magnetic stimulation (TMS)-induced event-related potentials (ERPs) to determine the extent of involvement of the right pSTS in attentional processing. We hypothesized that TMS would enhance the activation of the right pSTS during feature discrimination processing. We recruited 21 healthy subjects who performed the dual-feature delayed matching task while undergoing single-pulse sham or real TMS to the right pSTS 300 ms before the second stimulus onset. The results showed that the response time was reduced by real TMS of the pSTS as compared to sham stimulation. N270 amplitude was reduced during conflict processing, and the time-varying network analysis revealed increased connectivity between the frontal lobe and temporo-parietal and occipital regions. Thus, single-pulse TMS of the right pSTS enhances feature discrimination processing and task performance by reducing N270 amplitude and increasing connections between the frontal pole and temporo-parietal and occipital regions. These findings provide evidence that the right pSTS facilitates feature discrimination by accelerating the formation of a dynamic network.

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LAY ABSTRACT: Neurofeedback is an emerging therapeutic approach in neuropsychiatric disorders. Its potential application in autism spectrum disorder remains to be tested. Here, we demonstrate the feasibility of real-time functional magnetic resonance imaging volitional neurofeedback in targeting social brain regions in autism spectrum disorder. In this clinical trial, autism spectrum disorder patients were enrolled in a program with five training sessions of neurofeedback. Participants were able to control their own brain activity in this social brain region, with positive clinical and neural effects. Larger, controlled, and blinded clinical studies will be required to confirm the benefits.

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LAY ABSTRACT: Intermittent theta burst stimulation is a varied form of repetitive transcranial magnetic non-invasive brain stimulation technique used to treat several neurological and psychiatric disorders. Its feasibility and therapeutic effects on the bilateral posterior superior temporal sulcus in children with autism are unknown. We conducted a single-blind, sham-controlled parallel randomized clinical trial in a hitherto largest sample of intellectually able children with autism (N = 78). Participants randomized to the active group received two-session/week intermittent theta burst stimulation for continuous 8 weeks. Those in the sham group received two-session/week sham stimulations in the first 4 weeks and then active intervention for the following 4 weeks after unblinding. First, we found that continuous 8-week intermittent theta burst stimulation on the bilateral posterior superior temporal sulcus in children with autism is safe and tolerable. Second, we found that 8-week intermittent theta burst stimulation produced greater therapeutic efficacy, although we did not find any significant effects of 4-week intermittent theta burst stimulation on core symptoms and social cognitive performances in autism. Further analysis revealed that participants with higher intelligence and better social cognitive performance, alongside less attention-deficit hyperactivity disorder severity at baseline, were more likely to be responders. This study identified that the factors contribute to responders and the results suggest that longer courses of non-invasive brain stimulation may be needed to produce therapeutic benefits in autism, with consideration of heterogeneous responses.

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The posterior superior temporal sulcus (pSTS) is a brain region characterized by perceptual representations of human body actions that promote the understanding of observed behavior. Increasingly, action observation is recognized as being strongly shaped by the expectations of the observer (Kilner 2011; Koster-Hale and Saxe 2013; Patel et al. 2019). Therefore, to characterize top-down influences on action observation, we evaluated the statistical structure of multivariate activation patterns from the action observation network (AON) while observers attended to the different dimensions of action vignettes (the action kinematics, goal, or identity of avatars jumping or crouching). Decoding accuracy varied as a function of attention instruction in the right pSTS and left inferior frontal cortex (IFC), with the right pSTS classifying actions most accurately when observers attended to the action kinematics and the left IFC classifying most accurately when observed attended to the actor's goal. Functional connectivity also increased between the right pSTS and right IFC when observers attended to the actions portrayed in the vignettes. Our findings are evidence that the attentive state of the viewer modulates sensory representations in the pSTS, consistent with proposals that the pSTS occupies an interstitial zone mediating top-down context and bottom-up perceptual cues during action observation.

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Face processing is mediated by a distributed neural network commonly divided into a "core system" and an "extended system." The core system consists of several, typically right-lateralized brain regions in the occipito-temporal cortex, including the occipital face area (OFA), the fusiform face area (FFA) and the posterior superior temporal sulcus (pSTS). It was recently proposed that the face processing network is initially bilateral and becomes right-specialized in the course of the development of reading abilities due to the competition between language-related regions in the left occipito-temporal cortex (e.g., the visual word form area, VWFA) and the FFA for common neural resources. In the present pilot study, we assessed the neural face processing network in 12 children (aged 7-9 years) and 10 adults with functional magnetic resonance imaging (fMRI). The hemispheric lateralization of the core face regions was compared between both groups. The study had two goals: First, we aimed to establish an fMRI paradigm suitable for assessing activation in the core system of face processing in young children at the single subject level. Second, we planned to collect data for a power analysis to calculate the necessary group size for a large-scale cross-sectional imaging study assessing the ontogenetic development of the lateralization of the face processing network, with focus on the FFA. It was possible to detect brain activity in the core system of 75% of children at the single subject level. The average scan-to-scan motion of the included children was comparable to adults, ruling out that potential activation differences between groups are caused by unequal motion artifacts. Hemispheric lateralization of the FFA was 0.07 ± 0.48 in children (indicating bilateral activation) and -0.32 ± 0.52 in adults (indicating right-hemispheric dominance). These results thus showed, as expected, a trend for increased lateralization in adults. The estimated effect size for the FFA lateralization difference was d = 0.78 (indicating medium to large effects). An adequately powered follow-up study (sensitivity 0.8) testing developmental changes of FFA lateralization would therefore require the inclusion of 18 children and 26 adults.

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BACKGROUND AND AIMS: The clinical significance of Internet gaming disorder (IGD) is spreading worldwide, but its underlying neural mechanism still remains unclear. Moreover, the prevalence of IGD seems to be the highest in adolescents whose brains are in development. This study investigated the functional connectivity between large-scale intrinsic networks including default mode network, executive control network, and salience network. We hypothesized that adolescents with IGD would demonstrate different functional connectivity patterns among large-scale intrinsic networks, implying neurodevelopmental alterations, which might be associated with executive dysfunction. METHODS: This study included 17 male adolescents with Internet gaming disorder, and 18 age-matched male adolescents as healthy controls. Functional connectivity was examined using seed-to-voxel analysis and seed-to-seed analysis, with the nodes of large-scale intrinsic networks used as region of interests. Group independent component analysis was performed to investigate spatially independent network. RESULTS: We identified aberrant functional connectivity of salience network and default mode network with the left posterior superior temporal sulcus (pSTS) in adolescents with IGD. Furthermore, functional connectivity between salience network and pSTS correlated with proneness to Internet addiction and self-reported cognitive problems. Independent component analysis revealed that pSTS was involved in social brain network. DISCUSSION AND CONCLUSIONS: The results imply that aberrant functional connectivity of social brain network with default mode network and salience network was identified in IGD that may be associated with executive dysfunction. Our results suggest that inordinate social stimuli during excessive online gaming leads to altered connections among large-scale networks during neurodevelopment of adolescents.

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To investigate the functional connections between the core components of the face processing network we tested Herschel, an acquired prosopagnosic patient with a right ventral occipitotemporal lesion. In Experiment 1, Herschel, and control participants, were scanned with functional magnetic resonance imaging (fMRI) while viewing videos of moving faces, or static images taken from the videos. In Experiment 2, participants viewed videos of actors making facial expressions, or static images taken from the videos. In Experiment 3, participants viewed videos of moving faces presented in the left or right visual field. Results showed the neural response in Herschel's right occipital face area (OFA) was impaired for moving and static faces (Experiment 1), moving expressions (Experiment 2) and moving faces in the left visual field (Experiment 3). The response in Herschel's right fusiform face area (FFA) to moving and static faces was impaired in Experiment 1 only, in Experiments 2 and 3 Herschel's FFA response was not significantly different from controls. By contrast, the response in Herschel's right posterior superior temporal sulcus (rpSTS) to moving and static faces and expressions (Experiments 1 and 2) and the visual field response (Experiment 3) was not significantly different from control participants. Our results demonstrate there are cortico-cortical inputs to the pSTS from early visual cortex that are independent of the OFA, a conclusion inconsistent with established models of face processing.

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Neuropsychology and neuroimaging studies provide distinct views on the key neural underpinnings of social scene understanding (SSU): the amygdala and multimodal neocortical areas such as the posterior superior temporal sulcus (pSTS), respectively. This apparent incongruity may stem from the difference in the assumed cognitive processes of the situation-response association and the integrative or creative processing of social information. To examine the neural correlates of different SSU types using functional magnetic resonance imaging (fMRI), we devised a clothing recommendation task in three types of client's standpoint. Situation-response association was induced by a situation-congruent standpoint (ecological SSU), whereas the integrative and creative processing of social information was elicited by a lack and situation incongruence of the standpoint (perceptual and elaborative SSUs, respectively). Activation characteristic of the ecological SSU was identified in the right amygdala, while that of the perceptual SSU and elaborative SSU demand was identified in the right pSTS and left middle temporal gyrus (MTG), respectively. Thus, the current results provide evidence for the conceptual and neural distinction of the three types of SSU, with basic ecological SSU being supported by a limbic structure while sophisticated integrative or creative SSUs being developed in humans by multimodal association cortices.

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BACKGROUND: Neuroimaging studies suggest that facial expression recognition is processed in the bilateral posterior superior temporal sulcus (pSTS). Our recent repetitive transcranial magnetic stimulation (rTMS) study demonstrates that the bilateral pSTS is causally involved in expression recognition, although involvement of the right pSTS is greater than involvement of the left pSTS. OBJECTIVE: /Hypothesis: In this study, we used a dual-site TMS to investigate whether the left pSTS is functionally connected to the right pSTS during expression recognition. We predicted that if this connection exists, simultaneous TMS disruption of the bilateral pSTS would impair expression recognition to a greater extent than unilateral stimulation of the right pSTS alone. METHODS: Participants attended two TMS sessions. In Session 1, participants performed an expression recognition task while rTMS was delivered to the face-sensitive right pSTS (experimental site), object-sensitive right lateral occipital complex (control site) or no rTMS was delivered (behavioural control). In Session 2, the same experimental design was used, except that continuous theta-burst stimulation (cTBS) was delivered to the left pSTS immediately before behavioural testing commenced. Session order was counter-balanced across participants. RESULTS: In Session 1, rTMS to the rpSTS impaired performance accuracy compared to the control conditions. Crucially in Session 2, the size of this impairment effect doubled after cTBS was delivered to the left pSTS. CONCLUSIONS: Our results provide evidence for a causal functional connection between the left and right pSTS during expression recognition. In addition, this study further demonstrates the utility of the dual-site TMS for investigating causal functional links between brain regions.

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The superior temporal sulcus (STS) encompasses a complex set of regions involved in a wide range of cognitive functions. To understand its functional properties, neuromodulation approaches such brain stimulation or neurofeedback can be used. We investigated whether the posterior STS (pSTS), a core region in the face perception and imagery network, could be specifically identified based on the presence of dynamic facial expressions (and not just on simple motion or static face signals), and probed with neurofeedback. Recognition of facial expressions is critically impaired in autism spectrum disorder, making this region a relevant target for future clinical neurofeedback studies. We used a stringent localizer approach based on the contrast of dynamic facial expressions against static neutral faces plus moving dots. The target region had to be specifically responsive to dynamic facial expressions instead of mere motion and/or the presence of a static face. The localizer was successful in selecting this region across subjects. Neurofeedback was then performed, using this region as a target, with two novel feedback rules (mean or derivative-based, using visual or auditory interfaces). Our results provide evidence that a facial expression-selective cluster in pSTS can be identified and may represent a suitable target for neurofeedback approaches, aiming at social and emotional cognition. These findings highlight the presence of a highly selective region in STS encoding dynamic aspects of facial expressions. Future studies should elucidate its role as a mechanistic target for neurofeedback strategies in clinical disorders of social cognition such as autism.

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There is increasing appreciation that network-level interactions among regions produce components of face processing previously ascribed to individual regions. Our goals were to use an exhaustive data-driven approach to derive and quantify the topology of directed functional connections within a priori defined nodes of the face processing network and evaluate whether the topology is category-specific. Young adults were scanned with fMRI as they viewed movies of faces, objects, and scenes. We employed GIMME to model effective connectivity among core and extended face processing regions, which allowed us to evaluate all possible directional connections, under each viewing condition (face, object, place). During face processing, we observed directional connections from the right posterior superior temporal sulcus to both the right occipital face area and right fusiform face area (FFA), which does not reflect the topology reported in prior studies. We observed connectivity between core and extended regions during face processing, but this limited to a feed-forward connection from the FFA to the amygdala. Finally, the topology of connections was unique to face processing. These findings suggest that the pattern of directed functional connections within the face processing network, particularly in the right core regions, may not be as hierarchical and feed-forward as described previously. Our findings support the notion that topologies of network connections are specialized, emergent, and dynamically responsive to task demands.

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The posterior extent of the human superior temporal sulcus (pSTS) is an important cortical region for detecting animacy, attributing agency to others, and decoding goal-directed behavior. Theoretical accounts attribute these cognitive skills to unique neural populations that have been difficult to identify empirically (Hein and Knight, 2008). The aim of this study is to evaluate the multivariate statistical structure of pSTS activation patterns when viewing different social cues. We identified a core conjunction region on pSTS from univariate responses with preference for point-light biological motion, faces and the attribution of social concepts to simple animated shapes. In a multivariate analysis, we characterized the similarity structure of the resulting activation patterns after controlling for variance in the activation profile elicited by form and motion features. We found strong antagonistic activation profiles between the social conditions and their localizer controls, a harbinger of why these canonical localizers are so effective, even in individual subjects. We also found unique patterns of similarity between the three core social conditions. Our findings are consistent with the Shultz et al. (2015) model of pSTS function in which separate neural populations exist for animacy detection from body parts versus for extracting intentional cues from movement.

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Mentalizing is an essential component in human social interactions and the sources of individual variation in mentalizing are still very poorly understood. Utilizing the "reading the mind in the eyes" test (RMET), we examined the neuroanatomical basis of these differences with voxel-based morphometry and found that the gray matter density in the left posterior superior temporal sulcus (pSTS) could positively predict individuals' RMET scores. Furthermore, we found that the pSTS-amygdala functional connection was positively correlated to individuals' RMET scores. A test-validation procedure confirmed that the imaging results could be replicated and validated in another independent sample. Finally, mediation analysis revealed that pSTS-amygdala functional connection could account for the relationship between pSTS gray matter density and RMET scores. Present results demonstrate the contribution of brain structure of pSTS to individual variations in RMET performance and reveal an important implication of the neural circuit between core imitation and emotion regions in REMT.

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