Investigation of the neural correlates of mentalizing through the Dynamic Inference Task, a new naturalistic task of social cognition.

Understanding others' intentions requires both the identification of social cues (e.g., emotional facial expressions, gaze direction) and the attribution of a mental state to another. The neural substrates of these processes have often been studied separately, and results are heterogeneous, in part attributable to the variety of paradigms used. The aim of the present study was to explore the neural regions underlying these sociocognitive processes, using a novel naturalistic task in which participants engage with human protagonists featured in videos. A total of 51 right-handed volunteers underwent functional magnetic resonance imaging while performing the Dynamic Inference Task (DIT), manipulating the degree of inference (high vs. low), the presence of emotion (emotional vs. nonemotional), and gaze direction (direct vs. averted). High nonemotional inference elicited neural activation in temporal regions encompassing the right posterior superior temporal sulcus. The presence (vs. absence) of emotion in the high-inference condition elicited a bilateral pattern of activation in internal temporal areas around the amygdala and orbitofrontal structures, as well as activation in the right dorsomedial part of the superior frontal gyrus and the left precuneus. On account of its dynamic, naturalistic approach, the DIT seems a suitable task for exploring social interactions and the way we interact with others, both in nonclinical and clinical populations.

Fibromyalgia patients make scarce reference to pain in self-defining memories.

OBJECTIVE: Self-defining memories (SDMs) are vivid, emotionally intense and well-rehearsed autobiographical memories that provide fundamental information about one's cognitive affective motivational representation of self. Exploring SDMs in fibromyalgia (FM) is of interest for understanding the psychopathology of this disorder and improving clinical interventions. Our aim was to compare patients and healthy controls (HC) on SDM characteristics. METHOD: We included 25 patients with FM and 24 HC matched for age, sex and education level. Each participant described five SDMs, which were coded for content, specificity, integration, tension, redemption, contamination, affective response, date, and reference to pain. We statistically controlled our results for the most plausible confounding factors related to FM that could affect SDM recall, namely depression, anxiety, cognitive inhibition, pain severity and medication. RESULTS: Compared with HC, patients retrieved less specific SDMs with a more negative emotional valence but less tension. They reported more relationship-related memories, and fewer redemptive ones, with less meaning-making. The number of memories referring to physical or psychological pain did not differ between groups. None of the confounding factors we analysed could explain (either alone or in combination) the statistical differences between groups for SDMs characteristics. CONCLUSION: We discuss functional avoidance and alexithymia as two main factors for poor reference to pain in patients' SDMs that further reveal affective dysregulation in FM. In clinical practice, remediating the way in which pain is integrated into SDMs in FM may help to mitigate its negative impact on everyday life.

Impact of hypomanic personality traits on brain functional connectivity during a dynamic theory-of-mind task.

Hypomanic personality traits are present in the general population and represent a risk factor for developing bipolar disorder. This personality style, notably its social component, is linked to difficulties in theory of mind (i.e., ability to infer mental states). Exploring the neural correlates of mental states' inference in individuals with these personality traits can provide meaningful insights into the development of bipolar disorder. The aim of the present study was therefore to investigate the potential impact of hypomanic traits on brain activation and task-based connectivity strength during a dynamic theory of mind task in a nonclinical population. A total of 52 nonclinical participants were recruited, and hypomanic traits were assessed with the Hypomanic Personality Scale. The severity of hypomanic traits was positively associated with right middle and inferior frontal gyri activations (in high vs. low inference in nonemotional condition and emotion vs. no emotion in high inference, respectively). It was also associated with stronger connectivity between the salience network (i.e., bilateral putamen and pallidum) and bilateral superior temporal gyri (high inference in nonemotional condition), and between cerebellar and temporal areas (high inference in emotional condition). These changes may either reflect adaptations or differential processing, and further studies are therefore mandatory.

Activation of the left medial temporal gyrus and adjacent brain areas during affective theory of mind processing correlates with trait schizotypy in a nonclinical population.

Schizophrenia, a severe psychiatric disorder, is associated with abnormal brain activation during theory of mind (ToM) processing. Researchers recently suggested that there is a continuum running from subclinical schizotypal personality traits to fully expressed schizophrenia symptoms. Nevertheless, it remains unclear whether schizotypal personality traits in a nonclinical population are associated with atypical brain activation during ToM tasks. Our aim was to investigate correlations between fMRI brain activation during affective ToM (ToMA) and cognitive ToM (ToMC) tasks and scores on the Schizotypal Personality Questionnaire (SPQ) and the Basic Empathy Scale in 39 healthy individuals. The total SPQ score positively correlated with brain activation during ToMA processing in clusters extending from the left medial temporal gyrus (MTG), lingual gyrus and fusiform gyrus to the parahippocampal gyrus (Brodmann area: 19). During ToMA processing, the right inferior occipital gyrus, right MTG, precuneus and posterior cingulate cortex negatively correlated with the emotional disconnection subscore and the total score of self-reported empathy. These posterior brain regions are known to be involved in memory and language, as well as in creative reasoning, in nonclinical individuals. Our findings highlight changes in brain processing associated with trait schizotypy in nonclinical individuals during ToMA but not ToMC processing.

Serotonin 3A receptor subtype as an early and protracted marker of cortical interneuron subpopulations.

To identify neocortical neurons expressing the type 3 serotonergic receptor, here we used transgenic mice expressing the enhanced green fluorescent protein (GFP) under the control of the 5-HT(3A) promoter (5-HT(3A):GFP mice). By means of whole-cell patch-clamp recordings, biocytin labeling, and single-cell reversed-transcriptase polymerase chain reaction on acute brain slices of 5-HT(3A):GFP mice, we identified 2 populations of 5-HT(3A)-expressing interneurons within the somatosensory cortex. The first population was characterized by the frequent expression of the vasoactive intestinal peptide and a typical bipolar/bitufted morphology, whereas the second population expressed predominantly the neuropeptide Y and exhibited more complex dendritic arborizations. Most interneurons of this second group appeared very similar to neurogliaform cells according to their electrophysiological, molecular, and morphological properties. The combination of 5-bromo-2-deoxyuridine injections with 5-HT(3A) mRNA detection showed that cortical 5-HT(3A) interneurons are generated around embryonic day 14.5. Although at this stage the 5-HT(3A) receptor subunit is expressed in both the caudal ganglionic eminence and the entopeduncular area, homochronic in utero grafts experiments revealed that cortical 5-HT(3A) interneurons are mainly generated in the caudal ganglionic eminence. This protracted expression of the 5-HT(3A) subunit allowed us to study specific cortical interneuron populations from their birth to their final functional phenotype.

Neural Correlates of Mentalizing in Individuals With Clinical High Risk for Schizophrenia: ALE Meta-Analysis.

Psychotic disorder refers to a spectrum of disorders that have multiple etiologies, due to the complex interaction of biological and genetic vulnerability with familial and cultural factors. A clinical high risk (CHR) for schizophrenia is defined as the presence of brief, attenuated, or intermittent psychotic symptoms in non-schizophrenic individuals. The transition to schizophrenia appears significantly more frequent in this at-risk population than in the general population. Moreover, the ability to attribute mental states to others, known as mentalizing or theory of mind, and its neural correlates found in individuals with CHR are similar to those described in patients with schizophrenia. We have therefore explored neurofunctional correlates of mentalizing in individuals with CHR vs. healthy controls, in order to identify the differences in brain activation. A neural coordinate-based activation likelihood estimation meta-analysis of existing neuroimaging data revealed that three regions displayed decreased activation in individuals with CHR, compared with healthy controls: the right temporoparietal junction, the right middle temporal gyrus, and the left precuneus. These results, combined with those in the literature, further support the hypothesis that abnormal activation of posterior brain regions involved in mentalizing correlates with psychotic symptoms in help-seeking individuals.

How to project oneself without positive and integrated memories? Exploration of self-defining memories and future projections in bipolar disorder.

Bipolar disorder (BD) is a disabling disorder with functional impact on everyday life. Recent studies suggest that autobiographical memory impairment may contribute to the maintenance of psychopathology, leading to enduring altered self-construct. Moreover, past personal experiences also support the ability to project oneself into the future to pre-experience an event, this capacity can be modified by psychiatric disorders. Self-defining memories and future projections by accessing highly significant events that are vivid and focused on central goals or enduring concerns can both provide a better understanding of the impact of disorders on self-perception and on the ability to project oneself into the future. Therefore we proposed to explore self-defining memories and future projections in BD patients (n = 25) compared to control participants (n = 25). BD patients' self-defining events were associated with more tension, life-threatening events, and negative emotion. BD patients also reported less integrated past but not less integrated future self-defining events. And their future projections were more closely related to leisure, and associated with positive emotions, compared to controls. For both groups, the future projections were less specific, integrated, and tense than the memories. These results question the self-coherence of patients' identity and should be confirmed to propose appropriate interventions to project oneself adaptively into the future and contribute to a better outcome.

Neural correlates of theory of mind and empathy in schizophrenia: An activation likelihood estimation meta-analysis.

Social cognition impairment predicts social functioning in schizophrenia. Several studies have found abnormal brain activation in patients with schizophrenia during social cognition tasks. Nevertheless, no coordinate-based meta-analysis comparing the neural correlates of theory of mind and empathy had been done in this population. Our aim was to explore neural correlates related to theory of mind and empathy in patients with schizophrenia compared to healthy controls, in order to identify abnormal brain activation related to emotional content during mental state attribution in schizophrenia. We performed a neural-coordinate-based Activation Likelihood Estimation (ALE) meta-analysis of existing neuroimaging data in the literature to distinguish between abnormal brain maps associated with emotional attribution and those associated with intention/belief inference. We found that brain activation in patients group was significantly decreased in the right ventrolateral prefrontal cortex (VLPFC) during emotional attribution, while there was a significant decrease in the left posterior temporo-parietal junction (TPJ) during intention/belief attribution. Using a meta-analytic connectivity modeling approach (MACM), we demonstrated that both regions are coactivated with other brain regions known to play a role in social cognition, including the bilateral anterior insula, right TPJ, left amygdala and dorsolateral prefrontal cortex. In addition, abnormal activation in both the left TPJ and right VLPFC was previously reported in association with verbal-auditory hallucinations and a "jumping to conclusions" cognitive bias. Thus, these regions could be valuable targets for therapeutic interventions in schizophrenia.

Bipolar affective disorder and early dementia onset in a male patient with SHANK3 deletion.

The SHANK3 protein is a scaffold protein known to stabilize metabotropic glutamate receptor mGluR5 in the post-synaptic membrane of neurons. It is associated with genetic vulnerability in autism and schizophrenia. Here we report the case of an 18 year-old male patient who displayed psychiatric features of bipolar affective disorder associated with early setting of dementia. This mental status is related to sporadic occurrence of SHANK3 gene complex multiple deletions. A low beta amyloid protein rate (479 mg/L) found in cerebrospinal fluid suggests a possible link between SHANK3 deletion syndrome-associated regression and dementia of Alzheimers's type. In addition, we propose an overview of the phenotype related to SHANK3 deletion.