Dynamic functional connectivity in the right temporoparietal junction captures variations in male autistic trait expression.

Autistic individuals can experience difficulties with attention reorienting and Theory of Mind (ToM), which are closely associated with anterior and posterior subdivisions of the right temporoparietal junction. While the link between these processes remains unclear, it is likely subserved by a dynamic crosstalk between these two subdivisions. We, therefore, examined the dynamic functional connectivity (dFC) between the anterior and posterior temporoparietal junction, as a biological marker of attention and ToM, to test its contribution to the manifestation of autistic trait expression in Autism Spectrum Condition (ASC). Two studies were conducted, exploratory (14 ASC, 15 TD) and replication (29 ASC, 29 TD), using resting-state fMRI data and the Social Responsiveness Scale (SRS) from the Autism Brain Imaging Data Exchange repository. Dynamic Independent Component Analysis was performed in both datasets using the CONN toolbox. An additional sliding-window analysis was performed in the replication study to explore different connectivity states (from highly negatively to highly positively correlated). Dynamic FC was reduced in ASC compared to TD adults in both the exploratory and replication datasets and was associated with increased SRS scores (especially in ASC). Regression analyses revealed that decreased SRS autistic expression was predicted by engagement of highly negatively correlated states, while engagement of highly positively correlated states predicted increased expression. These findings provided consistent evidence that the difficulties observed in ASC are associated with altered patterns of dFC between brain regions subserving attention reorienting and ToM processes and may serve as a biomarker of autistic trait expression.

The Reflection of Self-Esteem on the Brain Structure: A Voxel Based Morphometry Study in Healthy Young Adults.

Introduction: Low self-esteem is a known risk factor for mental illnesses. Neuroimaging studies have identified evidence for a functional association between default mode network (DMN) and self-esteem levels. However, it is not clear whether there is a similar association between trait self-esteem and the structures composing DMN. This study aimed to investigate the relationship between the DMN associated brain structures and trait self-esteem. Methods: We obtained 3T structural magnetic resonance imaging (MRI) data of 75 healthy subjects and detected anatomical regions correlated with their Rosenberg Self-Esteem scores via voxel-based morphometry (VBM). Results: We found positive associations between self-esteem and regional grey matter volumes in the right temporoparietal junction/inferior parietal lobule (BA 39), cortical midline regions at precuneus/dorsal cingulate cortex (BA 31), rostral and dorsal anterior cingulate cortices (BA 32). Conclusion: The results of the current study support the fMRI studies suggesting self-esteem levels associated with DMN. Further neuroimaging studies should consider the functional and structural coupling of the default mode network during the execution of the functions related to self-esteem.

The Interaction Between Caudate Nucleus and Regions Within the Theory of Mind Network as a Neural Basis for Social Intelligence.

The organization of socio-cognitive processes is a multifaceted problem for which many sophisticated concepts have been proposed. One of these concepts is social intelligence (SI), i.e., the set of abilities that allow successful interaction with other people. The theory of mind (ToM) human brain network is a good candidate for the neural substrate underlying SI since it is involved in inferring the mental states of others and ourselves and predicting or explaining others' actions. However, the relationship of ToM to SI remains poorly explored. Our recent research revealed an association between the gray matter volume of the caudate nucleus and the degree of SI as measured by the Guilford-Sullivan test. It led us to question whether this structural peculiarity is reflected in changes to the integration of the caudate with other areas of the brain associated with socio-cognitive processes, including the ToM system. We conducted seed-based functional connectivity (FC) analysis of resting-state fMRI data for 42 subjects with the caudate as a region of interest. We found that the scores of the Guilford-Sullivan test were positively correlated with the FC between seeds in the right caudate head and two clusters located within the right superior temporal gyrus and bilateral precuneus. Both regions are known to be nodes of the ToM network. Thus, the current study demonstrates that the SI level is associated with the degree of functional integration between the ToM network and the caudate nuclei.

The emergent relationship between temporoparietal junction and anosognosia in Alzheimer's disease.

Anosognosia and impairment of insight are characteristic features of Alzheimer's disease (AD), which can lead to delays in appropriate medical care and significant family discord. The default mode network (DMN), a distributed but highly connected network of brain regions more active during rest than during task, is integrally involved in awareness. DMN dysfunction is common in AD, and disrupted communication between memory-related and self-related DMN networks is associated with anosognosia in AD patients. In addition, the temporoparietal junction (TPJ) is a key region of the "social brain" and also contributes to representations of the self. The exact classification of the TPJ within the DMN is unclear, though connections between the TPJ and DMN have been highlighted in multiple avenues of research. Here we discuss the relationship between the TPJ, DMN, and AD, as well as the potential involvement of the TPJ in anosognosia in AD. We review past and present findings to raise attention to the TPJ, with a specific emphasis on neuroimaging technologies which suggest a pivotal role of the TPJ within large-scale brain networks linked to anosognosia in AD.

Early interpersonal trauma reduces temporoparietal junction activity during spontaneous mentalising.

Experience of interpersonal trauma and violence alters self-other distinction and mentalising abilities (also known as theory of mind, or ToM), yet little is known about their neural correlates. This fMRI study assessed temporoparietal junction (TPJ) activation, an area strongly implicated in interpersonal processing, during spontaneous mentalising in 35 adult women with histories of childhood physical, sexual, and/or emotional abuse (childhood abuse; CA) and 31 women without such experiences (unaffected comparisons; UC). Participants watched movies during which an agent formed true or false beliefs about the location of a ball, while participants always knew the true location of the ball. As hypothesised, right TPJ activation was greater for UCs compared to CAs for false vs true belief conditions. In addition, CAs showed increased functional connectivity relative to UCs between the rTPJ and dorsomedial prefrontal cortex. Finally, the agent's belief about the presence of the ball influenced participants' responses (ToM index), but without group differences. These findings highlight that experiencing early interpersonal trauma can alter brain areas involved in the neural processing of ToM and perspective-taking during adulthood.

Increasing the Difference in Decision Making for Oneself and for Others by Stimulating the Right Temporoparietal Junction.

The right temporoparietal junction (rTPJ) has been thought to be associated with the difference in self-other decision making. In the present study, using noninvasive transcranial direct current stimulation (tDCS), we examined whether stimulating the rTPJ could modulate the self-other decision-making difference. We found that after receiving anodal stimulation of the rTPJ, participants were more likely to choose a high-value item for others than for themselves in the situations where the win probability of the high-value item was equal to or greater than that of a low-value item, indicating that elevating the cortical excitability of the rTPJ might increase the self-other decision-making difference in certain decision contexts. Our results suggest that decision making for others depends on neural activity in the rTPJ and regulation of the excitability of the rTPJ can influence the self-other decision-making difference.

Visual, sensorimotor and cognitive routes to understanding others' enjoyment: An individual differences rTMS approach to empathic accuracy.

Functional imaging studies suggest that accurate understanding of others' emotional feelings (i.e., empathic accuracy, EA) recruits high-order visual, sensorimotor and mentalizing brain networks. However, the behavioral relevance of these findings is unclear. To fill in this gap, we used repetitive transcranial magnetic stimulation (rTMS) to interfere with the right superior temporal sulcus (STS), inferior frontal gyrus (IFG) and temporoparietal junction (TPJ) during an EA task requiring participants to infer the enjoyment felt by a social target while smiling/laughing. Relative to a baseline condition (sham rTMS), active rTMS of STS, IFG and TPJ (but not of a control site) disrupted the efficiency of EA task performance, mainly by lowering task accuracy; rTMS of IFG and TPJ also slowed down response speeds. Importantly, the effects of rTMS on EA task efficiency were predicted by baseline EA performance, with high-performers showing a performance decrease when the TPJ was targeted, and low-performers showing a performance decrease when the STS or the IFG was targeted. The double dissociation in the effect of rTMS between low- and high-performers suggests distinct roles of STS, IFG and TPJ in efficient understanding of the enjoyment felt by others. These findings provide causal evidence of distinct visual, sensorimotor and cognitive routes to EA and suggest that individual differences in EA are underpinned by differential recruitment of these routes.

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.

Transcranial Direct Current Stimulation of the Temporoparietal Junction and Inferior Frontal Cortex Improves Imitation-Inhibition and Perspective-Taking with no Effect on the Autism-Spectrum Quotient Score.

Lesions to brain regions such as the temporoparietal junction (TPJ) and inferior frontal cortex (IFC) are thought to cause autism-spectrum disorder (ASD). Previous studies indicated that transcranial direct current stimulation (tDCS) of the right TPJ improves social cognitive functions such as imitation-inhibition and perspective-taking. Although previous work shows that tDCS of the right IFC improves imitation-inhibition, its effects on perspective-taking have yet to be determined. In addition, the role of the TPJ and IFC in determining the Autism-Spectrum Quotient (AQ), which is a measure of autism spectrum traits, is still unclear. Thus, the current study performed tDCS on the right TPJ and the right IFC of healthy adults, and examined its effects on imitation-inhibition, perspective-taking and AQ scores. Based on previous studies, we hypothesized that anodal tDCS of the right IFC and right TPJ would improve imitation-inhibition, perspective-taking and the AQ score. Anodal tDCS of the right TPJ or IFC significantly decreased the interference effect in an imitation-inhibition task and the cost of perspective-taking in a perspective-taking task, in comparison to the sham stimulation control. These findings indicated that both the TPJ and the IFC play a role in imitation-inhibition and perspective-taking, i.e., control of self and other representations. However, anodal stimulation of the right TPJ and the right IFC did not alter participants' AQ. This finding conflicts with results from previous brain imaging studies, which could be attributed to methodological differences such as variation in sex, age and ASD. Therefore, further research is necessary to determine the relationship between the TPJ and IFC, and the AQ.

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.

Children's belief- and desire-reasoning in the temporoparietal junction: evidence for specialization from functional near-infrared spectroscopy.

Behaviorally, children's explicit theory of mind (ToM) proceeds in a progression of mental-state understandings: developmentally, children demonstrate accurate explicit desire-reasoning before accurate explicit belief-reasoning. Given its robust and cross-cultural nature, we hypothesize this progression may be paced in part by maturation/specialization of the brain. Neuroimaging research demonstrates that the right temporoparietal junction (TPJ) becomes increasingly selective for ToM reasoning as children age, and as their ToM improves. But this research has narrowly focused on beliefs or on undifferentiated mental-states. A recent ERP study in children included a critical contrast to desire-reasoning, and demonstrated that right posterior potentials differentiated belief-reasoning from desire-reasoning. Taken together, the literature suggests that children's desire-belief progression may be paced by specialization of the right TPJ for belief-reasoning specifically, beyond desire-reasoning. In the present study, we tested this hypothesis directly by examining children's belief- and desire-reasoning using functional near-infrared spectroscopy in conjunction with structural magnetic resonance imaging to pinpoint brain activation in the right TPJ. Results showed greatest activation in the right TPJ for belief-reasoning, beyond desire-reasoning, and beyond non-mental reasoning (control). Findings replicate and critically extend prior ERP results, and provide clear evidence for a specific neural mechanism underlying children's progression from understanding desires to understanding beliefs.