Second-person neuroscience holds social cognition as embodied meaning co-regulation through reciprocal interaction, modeled here as coupled active inference with affect emerging as inference over identity-relevant surprise. Each agent maintains a self-model that tracks violations in its predictive coherence while recursively modeling the other. Valence is computed from self-model prediction error, weighted by self-relevance, and modulated by prior affective states and by what we term temporal aiming, which captures affective appraisal over time. This accommodates shifts in the self-other boundary, allowing affect to emerge at individual and dyadic levels. We propose a novel method termed geometric hyperscanning, based on the Forman-Ricci curvature, to operationalize these processes empirically: it tracks topological reconfigurations in inter-brain networks, with its entropy serving as a proxy for affective phase transitions such as rupture, co-regulation, and re-attunement.

Auditory verbal hallucinations (AVH) are a core symptom of schizophrenia and contribute substantially to patient suffering and disability. They are among the most persistent symptoms and do not respond to medication in a substantial portion of patients. Here, we report the application of task-based functional magnetic resonance imaging (fMRI)-guided repetitive transcranial magnetic stimulation (rTMS) in a patient with treatment-resistant AVH. An individualized stimulation target was identified in the left temporal cortex near Heschl’s gyrus using a validated fMRI task. Over a period of 18 months, the patient underwent three cycles of inhibitory 1 Hz rTMS of this target. As a result, AVH severity decreased by 33% and the global symptom score improved by 40%. Functional connectivity analyses revealed an increase in coupling between the temporal target seed and a fronto-cingulate-insular network that has been implicated in reality and performance monitoring. This case highlights the potential of fMRI-guided rTMS as a personalized neuromodulatory therapy for refractory AVH in schizophrenia, warranting further systematic investigation.

While modern diagnostic classification systems aim to nosologically structure psychiatric disorders, they poorly align with the genetic, neurobiological, and environmental heterogeneity observed in these disorders. This limitation has complicated the search for clinically useful biomarkers for diagnosis and treatment. Recent work on genetic and environmental contributions to mental health indicates that this heterogeneity stems from differential involvement of diverse biological pathways within and across diagnostic clusters. This complex interplay presents a many-to-many mapping problem in psychiatry, where distinct pathophysiological processes can lead to similar clinical symptoms. Here, we argue that disentangling these biological mechanisms requires development of process-specific biomarkers that could replace non-specific neuroimaging markers widely used in neuropsychiatric research. We further propose a framework for biomarker research that adopts a biologically informed perspective integrating the interactions between genes and the environment to address this problem. Such a multidimensional framework holds promise for developing biology-driven models of psychiatric disorders, enabling treatment strategies tailored to individual pathophysiology.

Atypical social functioning is a core feature of autism, yet findings remain fragmented across components and development. We aimed to systematically integrate this literature and characterize the organization, development and moderators of social functioning in autism. We conducted a systematic review and meta-analysis of behavioural studies published between January 1990 and August 2025, identified through PubMed, Web of Science and prior reviews, including studies with clinically diagnosed autistic individuals and neurotypical controls. A qualitative synthesis and two complementary quantitative meta-analyses were performed, with risk of bias evaluated through study-level characteristics. A total of 2,622 studies (94,114 autistic and 172,847 neurotypical individuals across 32 countries) were included, covering 22 social components that clustered into five domains. Overall group differences were substantial (Hedges' g = -0.744; 95% confidence interval, (-0.797, -0.690)). Differences emerged the earliest in motivation-based processes (around six months), followed by motor, emotion and inference domains, and showed age-related divergence alongside improvement in some skills. Cross-domain analyses revealed stronger interdependencies in autism and an organizational pattern most consistent with serial relationships among domains. These findings should be interpreted in the light of methodological heterogeneity, underpowered samples and uneven cultural representation. Together, the results provide an integrative framework for understanding the organization and development of social functioning in autism, with implications for precision subtyping, developmentally timed interventions and neurodiversity-informed research and policy.

Background:Social impairments and low-grade inflammation (LGI) are associated with psychotic disorders (e.g. schizophrenia spectrum disorders). Social impairments are important symptoms of the disease nonetheless a disturbed social interaction and inflammatory processes are further discussed as being part of the underlying pathophysiology, which is also characterized by blood-cerebrospinal fluid barrier (BCSFB) dysfunction. The relationship between social impairments, peripheral LGI (pLGI) and BCSFB permeability in psychotic disorders, however, is poorly understood. Therefore, we hypothesized that social impairment might be linked to pLGI, which, in turn, might affect BCSFB function in schizophrenia. Method:We conducted a retrospective chart review of all psychiatric inpatients who underwent lumbar puncture as part of their diagnostic work-up between January 1, 2021, and June 30, 2023 (n = 53). Thirty-one patients diagnosed with SSD (n = 27) or affective psychosis (n = 4) with a C-reactive protein (CRP) serum level <10 mg/L upon admission, indicating the absence of acute inflammation, were included in the analysis. Results:The cerebrospinal fluid (CSF)/serum albumin ratio - as a measure of BCSFB permeability - was shown to be positively correlated with our measure of pLGI (r = 0.418, p = 0.019) using the pLGI score (previously also named "INFLA-score", "LGI score"), as well as with age (r = 0.415, p = 0.020) . Additionally, a trend toward a negative correlation with global functioning (GAF) was observed (r = -0.349, p = 0.054).A multiple linear regression including pLGI, age, and sex yielded the best-fitting model (p = 0.003, corrected R2 = 0.337), with all predictors showing independent significant effects.Interestingly, regarding single parameters of the pLGI score a significant correlation between platelets and the CSF/serum albumin ratio (r = 0.490, p = 0.005) was found. Positive and Negative Syndrome Scale (PANSS6) and social isolation score did not correlate with the model. Conclusion:These data demonstrate - for the first time - a link between an established peripheral marker of LGI and BCSFB permeability in schizophrenia. Platelets were found to be the main driver of the pLGI score regarding BCSFB permeability. Future research will need to replicate these findings and could explore whether measures of peripheral inflammation could be useful in the diagnostic work-up of patients with psychotic disorders.

Background Autism is a neurodevelopmental disorder characterized by repetitive behaviors and difficulties in social communication and interaction. Previous research has shown that these symptoms are linked to idiosyncratic behavioral and brain activity patterns while viewing natural social events in movies. This study aimed to investigate the replicability of brain activity idiosyncrasy in adult autistic individuals by comparing their inter-subject functional connectivity (ISFC) with that of neurotypical individuals. Methods We tested for ISFC differences between adult autistic and neurotypical groups using functional magnetic resonance imaging (fMRI) data from two independent datasets from Germany (N-neurotypical = 25, 7 Males, 18 Females; N-autism = 22, 12 Males, 10 Females) and Finland (N-neurotypical = 19, N-autism = 18; All males). Participants watched short movie stimuli, and pairwise ISFCs were computed across 273 brain regions. Group differences were evaluated using subject-wise permutation tests for each dataset. Results In both datasets, the autistic group showed lower ISFCs compared to the neurotypical group, specifically between visual regions (e.g., occipital gyrus, cuneus) and parietal regions (e.g., superior and inferior parietal lobules), as well as between visual regions and frontal regions (e.g., inferior frontal gyrus, precentral gyrus). ISFC was higher in the Finnish autistic group in temporal regions associated with sound and speech processing. Limitations Larger multi-site datasets using diverse analysis pipelines are needed to evaluate the robustness and replicability of current findings. They are also essential for evaluating the reliability of the subject-wise permutation method without explicit correction for multiple comparisons. Conclusions The study confirmed the replicability of reduced ISFCs in adult autistic individuals during naturalistic movie-watching, especially between visual and parietal/frontal brain regions. These findings reinforce the utility of ISFC and naturalistic movie-watching paradigm in studying neural connectivity alterations in autism.

Conversational AI is increasingly optimized for fluent engagement through high-fidelity mirroring, simulating interpersonal attunement, an interactional style we term hyperalignment. While experienced as empathic, hyperalignment skews reciprocal adaptation and attenuates cues that make mismatch salient and recruit repair, short-circuiting reflective judgment. Drawing on second-person and dialectical accounts, we distinguish three recurrent interactional modes: constructive misattunement (salient mismatch elicits correction), divergent misattunement (misattributed mismatch escalates), and convergent misattunement (masked mismatch short-circuits correction). Hyperalignment drives convergent dynamics through synthetic consensus, metacognitive miscalibration, and preference sculpting. The resulting interactive passivity entails elevated apparent engagement alongside reduced epistemic work, increasing risk in high-stakes contexts. We advance constructive misattunement as a design and evaluation target, motivating deployment constraints, since responsiveness cannot substitute shared responsibility.

Purpose Paired Associative Stimulation (PAS) is a non-invasive neuromodulation tool for inducing changes in motor cortex excitability. However, its applicability is limited by substantial inter-individual variability and inconsistent replicability. We tested whether an individualized PAS protocol (iPAS), in which the interstimulus interval (ISI) is calibrated to each participant's peripheral-cortical conduction time, enhances the efficacy and consistency of cortical plasticity induction compared to the conventional fixed-ISI protocol (PAS25, 25 ms. Methods In a randomized, single-blind, within-subject crossover study, 99 healthy participants each completed one PAS25 and one iPAS session in counterbalanced order. Motor evoked potentials (MEP) were recorded at baseline, and at 5-, 10-, and 20-minutes post-stimulation. The primary outcome was MEP amplitude modeled across all timepoints using a linear mixed-effects model with raw MEP amplitudes as the dependent variable. Results Both protocols increased MEP amplitudes relative to baseline. The primary analysis revealed a significant Condition × Timepoint interaction at 20 min (p = 0.018). Post hoc contrasts showed that iPAS produced significantly greater MEP amplitudes than PAS25 at 5 min (ratio = 1.15, p = 0.023) and 20 min (ratio = 1.23, p < 0.001), with a trend at 10 min (ratio = 1.12, p = 0.058). Conclusions By improving both the magnitude and reliability of motor cortex plasticity induction, and being readily implementable with standard neurophysiological equipment, iPAS may serve as the preferred alternative to conventional PAS, with potential applications in neurology, rehabilitation, and precision psychiatry.

Attention deficit hyperactivity disorder (ADHD) is a relatively common disorder in clinical psychiatry. Patients often suffer from symptoms long before the diagnosis due to an overlap with other psychiatric differential diagnosis. Importantly, alcohol addiction and other illicit drug dependence and withdrawal symptoms mimicking ADHD symptoms should be ruled out. Here we present a rare case of a young female patient with symptoms of ADHD and an extremely high carbohydrate-deficient transferrin (CDT) of 19,6% (< 1,3%) indicating the presence of a congenital disorder of glycosylation (CDG). A thorough diagnostic workup excluded alcohol addiction as a cause of the constantly high CDT levels. The CDT test was positive due a transferrin mutation affecting the glycosylation site. Nevertheless, psychiatric symptoms can be due to metabolic disorders which should be considered. Further, substance-use disorders (SUD) are a critical and potentially complicated differential diagnosis concerning diagnostic procedures and treatment in ADHD.

Alexithymia and autism are variably characterized by social cognitive and perceptual deficits, which can lead to profound social interaction difficulties. Such difficulties are also the hallmark of personality disorders (PDs), but the potential link between alexithymia, autism, and PDs remains unclear. Here, we investigated whether autistic and/or alexithymic traits are associated with specific PD dimensions as measured by the Assessment of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ( DSM -IV) Personality Disorders Questionnaire (ADP-IV). We included individuals with a formal autism diagnosis (AP, n = 89), individuals with a psychiatric diagnosis other than autism (NAP, n = 51), and neurotypical participants (NPs, n = 84). We applied linear regression analyses with autistic and alexithymic traits as predictors and PD dimensions as outcome variables, while controlling for age, depressive, and socially anxious symptoms. While autistic traits predicted the obsessive-compulsive PD dimension, alexithymic traits predicted the borderline PD dimension. Autistic and alexithymic traits were both significant predictors of the schizoid PD dimension. Taken together, our results point toward overlaps between autistic traits and specific PD dimensions that are well recognized as differential diagnoses of autism, while alexithymia was differentially linked to the borderline PD dimension. Lay abstract Autistic people have trouble identifying their own emotions and others’ emotions. They also struggle to describe their emotions. People with alexithymia have similar difficulties. This can make it hard for autistic and alexithymic people to react appropriately to situations. Some may avoid places, while others may start overthinking. This can lead to patterns of behavior and thinking that limit us in our daily lives. If these patterns become a part of our personality, we may develop a personality disorder (PD). In our study, we looked at whether autistic and alexithymic people have certain PD dimensions. We included autistic participants, non-autistic participants with social-interactive difficulties, and non-autistic participants without social-interactive difficulties. We found that autistic features were linked to obsessive-compulsive PD dimension. Alexithymic features were linked to borderline PD dimension. Autistic and alexithymic features were linked to schizoid PD dimension. Our results point toward overlaps between autistic traits and PD dimensions that are well recognized as differential diagnoses of autism. The exception was borderline PD dimension, which was linked to alexithymic traits.

BACKGROUND:Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments of social interaction and communication as well as repetitive, stereotyped behaviour. Previous research indicates that ASD without intellectual impairment is associated with underactivity and reduced functional connectivity of the brain's mentalizing pathway, to which the right temporo-parietal junction (rTPJ) serves as an important entry point and hub. In this study, we aim to utilize functional magnetic resonance imaging (fMRI) to localize activation maxima in the rTPJ and other regions involved in social cognition to generate individualized targets for neuro-navigated, intermittent theta burst stimulation (iTBS) in order to modulate brain activity in a region centrally engaged in social information processing. METHODS:In this single-blind, randomized, between-subject neuroimaging-guided brain stimulation study we plan to recruit 52 participants with prediagnosed ASD and 52 controls without ASD aged between 18 and 65 years. Participants will be classified into two groups and will randomly receive one session of either verum- or sham-iTBS. Effects will be assessed by using well-established experimental tasks that interrogate social behaviour, but also use computational modelling to investigate brain stimulation effects at this level. DISCUSSION:This study aims to use personalized, non-invasive brain stimulation to alter social information processing in adults with and without high-functioning ASD, which has not been studied before with a similar protocol or a sample size of this magnitude. By doing so in combination with behavioural and computational tasks, this study has the potential to provide new mechanistic insights into the workings of the social brain. TRIAL REGISTRATION:German Clinical Trial Register, DRKS-ID: DRKS00028819. Registered 14 June 2022.

Social discounting describes the tendency to give fewer resources to those we feel less close to. Previous work suggests autistic individuals show a flatter decline in generosity towards socially distant others compared with non-autistic participants. We investigated whether this enhanced prosociality towards socially distant others in autism was driven by genuinely higher prosociality or instead a preference for repetitive responding. We measured prosocial preferences in 37 autistic and 38 non-autistic adults using the social value orientation questionnaire, where participants allocated money between themselves and people at six different social distances (e.g. friend vs stranger). We replicated previous findings by showing that autistic adults were more prosocial than non-autistic adults towards more socially distant others. Crucially, these effects were not driven by more repetitive responding in autism, nor by differences in attitudes to money. While autistic people often face challenges navigating their social worlds, our findings reinforce the view that autism is also associated with more prosociality. We argue that differences in fairness norms could drive more prosociality in autism, but this remains to be tested in future work.Lay abstractSharing and giving to others are important for our social relationships. Previous studies show that when given opportunities to share money, autistic and non-autistic people give the same amount of money to people they feel close to, like their friends. However, compared with non-autistic people, autistic people give more money to people they feel less close to, like strangers. In this study, we replicated this finding. Compared with non-autistic participants, autistic participants were more generous to people they did not feel close to. We also found that this increased generosity in autism was not the result of autistic participants responding more repetitively in the task. Autistic and non-autistic participants also showed similar attitudes towards money. We propose that some autistic people could be more generous because they show differences in how they think about fairness. But future studies will need to look at this more closely. We hope that our results can help to change the way people think about social behaviour in autism. While autistic people often face challenges navigating their social worlds, autism can also be associated with more generosity.

Adults with autism spectrum disorder (ASD) may compensate for their social difficulties by resorting to more sequential forms of communication. Here, we study communication preferences in individuals with ASD and neurotypical controls by monitoring smartphone-based communication for verbal, written, and mixed app categories over a period of four months. We find ASD participants to prefer written over verbal communication, underscoring the importance of considering these preferences to facilitate social integration.

Autism is a neurodevelopmental condition associated with altered resting-state brain function. An increased excitation-inhibition ratio is discussed as a pathomechanism but in-vivo evidence of disturbed neurotransmission underlying functional alterations remains scarce. We compare local resting-state brain activity and neurotransmitter co-localizations between autism (N = 405, N = 395) and neurotypical controls (N = 473, N = 474) in two independent cohorts and correlate them with excitation-inhibition changes induced by glutamatergic (ketamine) and GABAergic (midazolam) medication. Autistic individuals exhibit consistent reductions in local activity, particularly in default mode network regions. The whole-brain differences spatially overlap with glutamatergic and GABAergic, as well as dopaminergic and cholinergic neurotransmission. Functional changes induced by NMDA-antagonist ketamine resemble the spatial pattern observed in autism. Our findings suggest that consistent local activity alterations in autism reflect widespread disruptions in neurotransmission and may be resembled by pharmacological modulation of the excitation-inhibition balance. These findings advance understanding of the neurophysiological basis of autism. Trial registration number: ACTRN12616000281493

Obsessive-compulsive disorder (OCD) has been associated with altered performance monitoring, reflected in enhanced amplitudes of the error-related negativity in the event-related potential. However, this is not specific to OCD, as overactive error processing is also evident in anxiety. Although similar neural mechanisms have been proposed for error and feedback processing, it remains unclear whether the processing of errors as indexed by external feedback, reflected in the feedback-related negativity (FRN), is altered in OCD. Likewise, it is currently unknown whether performance monitoring in OCD differs between learning from self-performed and observed outcomes. The present study compared OCD patients (n = 27) with healthy controls (HCs; n = 27) and patients with social anxiety disorder (SAD; n = 29) in an active and observational variant of a probabilistic feedback learning task while EEG was recorded. Compared to HCs, OCD patients showed generally impaired task performance across both active and observational learning, as well as more indecisive choice behavior. This was accompanied by generally more positive amplitudes of the FRN, with enhanced valence coding for active compared to observational learning, driven by more positive FRN amplitudes for wins. However, no differences were found for losses. Overall, these results suggest deficient reward-rather than punishment-processing in OCD. Similar performance monitoring alterations in OCD and SAD imply reliance on shared, disorder-general mechanisms. Possible candidates for these mechanisms, such as intolerance of uncertainty, pessimism, and depressiveness are discussed.