Noninvasive brain stimulation in autism: review and outlook for personalized interventions in adult patients.

Noninvasive brain stimulation (NIBS) has been increasingly investigated during the last decade as a treatment option for persons with autism spectrum disorder (ASD). Yet, previous studies did not reach a consensus on a superior treatment protocol or stimulation target. Persons with ASD often suffer from social isolation and high rates of unemployment, arising from difficulties in social interaction. ASD involves multiple neural systems involved in perception, language, and cognition, and the underlying brain networks of these functional domains have been well documented. Aiming to provide an overview of NIBS effects when targeting these neural systems in late adolescent and adult ASD, we conducted a systematic search of the literature starting at 631 non-duplicate publications, leading to six studies corresponding with inclusion and exclusion criteria. We discuss these studies regarding their treatment rationale and the accordingly chosen methodological setup. The results of these studies vary, while methodological advances may allow to explain some of the variability. Based on these insights, we discuss strategies for future clinical trials to personalize the selection of brain stimulation targets taking into account intersubject variability of brain anatomy as well as function.

A machine-learning approach for differentiating borderline personality disorder from community participants with brain-wide functional connectivity.

BACKGROUND: Functional connectivity has garnered interest as a potential biomarker of psychiatric disorders including borderline personality disorder (BPD). However, small sample sizes and lack of within-study replications have led to divergent findings with no clear spatial foci. AIMS: Evaluate discriminative performance and generalizability of functional connectivity markers for BPD. METHOD: Whole-brain fMRI resting state functional connectivity in matched subsamples of 116 BPD and 72 control individuals defined by three grouping strategies. We predicted BPD status using classifiers with repeated cross-validation based on multiscale functional connectivity within and between regions of interest (ROIs) covering the whole brain-global ROI-based network, seed-based ROI-connectivity, functional consistency, and voxel-to-voxel connectivity-and evaluated the generalizability of the classification in the left-out portion of non-matched data. RESULTS: Full-brain connectivity allowed classification (∼70 %) of BPD patients vs. controls in matched inner cross-validation. The classification remained significant when applied to unmatched out-of-sample data (∼61-70 %). Highest seed-based accuracies were in a similar range to global accuracies (∼70-75 %), but spatially more specific. The most discriminative seed regions included midline, temporal and somatomotor regions. Univariate connectivity values were not predictive of BPD after multiple comparison corrections, but weak local effects coincided with the most discriminative seed-ROIs. Highest accuracies were achieved with a full clinical interview while self-report results remained at chance level. LIMITATIONS: The accuracies vary considerably between random sub-samples of the population, global signal and covariates limiting the practical applicability. CONCLUSIONS: Spatially distributed functional connectivity patterns are moderately predictive of BPD despite heterogeneity of the patient population.

Case report-Depression with psychotic features as an atypical presentation of neurosyphilis.

Recurrent depression with psychotic features is an atypical presentation of neurosyphilis. This case emphasizes the polymorphic clinical presentation of neurosyphilis and how it mimics affective disorders with psychotic symptoms.

Resting-state alterations in behavioral variant frontotemporal dementia are related to the distribution of monoamine and GABA neurotransmitter systems.

Background: Aside to clinical changes, behavioral variant frontotemporal dementia (bvFTD) is characterized by progressive structural and functional alterations in frontal and temporal regions. We examined if there is a selective vulnerability of specific neurotransmitter systems in bvFTD by evaluating the link between disease-related functional alterations and the spatial distribution of specific neurotransmitter systems and their underlying gene expression levels. Methods: Maps of fractional amplitude of low-frequency fluctuations (fALFF) were derived as a measure of local activity from resting-state functional magnetic resonance imaging for 52 bvFTD patients (mean age = 61.5 ± 10.0 years; 14 females) and 22 healthy controls (HC) (mean age = 63.6 ± 11.9 years; 13 females). We tested if alterations of fALFF in patients co-localize with the non-pathological distribution of specific neurotransmitter systems and their coding mRNA gene expression. Furthermore, we evaluated if the strength of co-localization is associated with the observed clinical symptoms. Results: Patients displayed significantly reduced fALFF in frontotemporal and frontoparietal regions. These alterations co-localized with the distribution of serotonin (5-HT1b and 5-HT2a) and γ-aminobutyric acid type A (GABAa) receptors, the norepinephrine transporter (NET), and their encoding mRNA gene expression. The strength of co-localization with NET was associated with cognitive symptoms and disease severity of bvFTD. Conclusions: Local brain functional activity reductions in bvFTD followed the distribution of specific neurotransmitter systems indicating a selective vulnerability. These findings provide novel insight into the disease mechanisms underlying functional alterations. Our data-driven method opens the road to generate new hypotheses for pharmacological interventions in neurodegenerative diseases even beyond bvFTD. Funding: This study has been supported by the German Consortium for Frontotemporal Lobar Degeneration, funded by the German Federal Ministry of Education and Research (BMBF; grant no. FKZ01GI1007A).

Peripheral oxytocin levels are linked to hypothalamic gray matter volume in autistic adults: a cross-sectional secondary data analysis.

Oxytocin (OXT) is known to modulate social behavior and cognition and has been discussed as pathophysiological and therapeutic factor for autism spectrum disorder (ASD). An accumulating body of evidence indicates the hypothalamus to be of particular importance with regard to the underlying neurobiology. Here we used a region of interest voxel-based morphometry (VBM) approach to investigate hypothalamic gray matter volume (GMV) in autistic (n = 29, age 36.03 ± 11.0) and non-autistic adults (n = 27, age 30.96 ± 11.2). Peripheral plasma OXT levels and the autism spectrum quotient (AQ) were used for correlation analyses. Results showed no differences in hypothalamic GMV in autistic compared to non-autistic adults but suggested a differential association between hypothalamic GMV and OXT levels, such that a positive association was found for the ASD group. In addition, hypothalamic GMV showed a positive association with autistic traits in the ASD group. Bearing in mind the limitations such as a relatively small sample size, a wide age range and a high rate of psychopharmacological treatment in the ASD sample, these results provide new preliminary evidence for a potentially important role of the HTH in ASD and its relationship to the OXT system, but also point towards the importance of interindividual differences.

Autistic adults show enhanced generosity to socially distant others.

LAY ABSTRACT: Autistic people show differences in their social behaviour. But how autism affects decisions to share resources, an important part of cooperation, was previously unclear. In our study, participants made decisions about how to share money with different people, including people they felt close to, such as a friend, and people they felt less close to, such as a stranger. We found that compared to a group of non-autistic participants, autistic adults shared more money overall and this was driven by greater generosity to strangers. The results suggest that autistic adults were more generous because they made fair decisions (an equal split of the money) more consistently regardless of how close they felt to the person they were sharing with. By showing that autistic adults display greater generosity, our results could help to change public perceptions of autism and potentially improve opportunities for autistic people.

An Active-Inference Approach to Second-Person Neuroscience.

Social neuroscience has often been criticized for approaching the investigation of the neural processes that enable social interaction and cognition from a passive, detached, third-person perspective, without involving any real-time social interaction. With the emergence of second-person neuroscience, investigators have uncovered the unique complexity of neural-activation patterns in actual, real-time interaction. Social cognition that occurs during social interaction is fundamentally different from that unfolding during social observation. However, it remains unclear how the neural correlates of social interaction are to be interpreted. Here, we leverage the active-inference framework to shed light on the mechanisms at play during social interaction in second-person neuroscience studies. Specifically, we show how counterfactually rich mutual predictions, real-time bodily adaptation, and policy selection explain activation in components of the default mode, salience, and frontoparietal networks of the brain, as well as in the basal ganglia. We further argue that these processes constitute the crucial neural processes that underwrite bona fide social interaction. By placing the experimental approach of second-person neuroscience on the theoretical foundation of the active-inference framework, we inform the field of social neuroscience about the mechanisms of real-life interactions. We thereby contribute to the theoretical foundations of empirical second-person neuroscience.

[Gender Differences in Autism Diagnostics]. / Geschlechtsunterschiede in der Autismusdiagnostik.

Autism spectrum condition (ASC) is predominantly diagnosed in boys and men. There is evidence that this is also because girls and women with ASC don't receive a diagnosis, or, if they do, only later in life. This study investigates gender differences in diagnosis, support needs, mental health, and life satisfaction among individuals with autism spectrum condition (ASC) in Germany. Data of an online questionnaire study with 659 persons with ASC from 3-67 years of age living in Bavaria, Germany, were analyzed (215 thereof were female). It was found that women with ASC are diagnosed 7-11 years later than men and are more likely to receive at least one misdiagnosis. They are more likely than men to have unmet educational support needs and comorbid internalizing psychiatric disorders. The results of this study point towards a strong gender bias in clinical diagnosis of ASC in Germany and need for improvements in the case of women.

[Antipsychotic Treatment of Alcohol Withdrawal Syndrome with Focus on Delirium Tremens: a Systematic Review]. / Systematische Übersichtsarbeit Antipsychotische Behandlung des Alkoholentzugssyndroms: Fokus Delirium Tremens.

BACKGROUND: Delirium tremens (DT) is a common complication of alcohol withdrawal. Pharmacological treatment of hospitalized patients with DT is important in addiction medicine but also in other medical disciplines where DT can occur as a complication of hospitalization. Patients suffering from DT require treatment with benzodiazepines (short-acting benzodiazepines for elderly patients to reduce accumulation), and in cases of psychotic symptoms, treatment with antipsychotics. Benzodiazepines are a first-line treatment for DT. A specific guideline for the use of antipsychotics has yet to be developed. This review discusses the current guidelines and literature on the antipsychotic treatment options in DT. AIM: Systematic presentation of relevant antipsychotics for the treatment of DT. METHODS: A systematic literature search was conducted using Scopus and PubMed. The last search was conducted on May 22nd 2022. Original articles and reviews on antipsychotic treatment in alcohol withdrawal and DT were included in this review. Further, international guidelines were also considered. The review was registered using the PROSPERO database (https://www.crd.york.ac.uk/prospero/); CRD42021264611. RESULTS: Haloperidol is mainly recommended for use in the intensive care unit. There is little literature on the use of atypical antipsychotics to treat DT. Treatment with antipsychotics always should be combined with benzodiazepines, and physicians should watch out for complications like neuroleptic malignant syndrome, QTc interval prolongation, extrapyramidal symptoms and withdrawal seizures resulting from lowering the threshold for seizures. CONCLUSION: Antipsychotic treatment should depend on the experience of the physician. Beside haloperidol, no other clear recommendations are available.

Social belonging: brain structure and function is linked to membership in sports teams, religious groups, and social clubs.

Human behavior across the life span is driven by the psychological need to belong, right from kindergarten to bingo nights. Being part of social groups constitutes a backbone for communal life and confers many benefits for the physical and mental health. Capitalizing on the neuroimaging and behavioral data from ∼40,000 participants from the UK Biobank population cohort, we used structural and functional analyses to explore how social participation is reflected in the human brain. Across 3 different types of social groups, structural analyses point toward the variance in ventromedial prefrontal cortex, fusiform gyrus, and anterior cingulate cortex as structural substrates tightly linked to social participation. Functional connectivity analyses not only emphasized the importance of default mode and limbic network but also showed differences for sports teams and religious groups as compared to social clubs. Taken together, our findings establish the structural and functional integrity of the default mode network as a neural signature of social belonging.

Spatio-temporal dynamics of oscillatory brain activity during the observation of actions and interactions between point-light agents.

Predicting actions from non-verbal cues and using them to optimise one's response behaviour (i.e. interpersonal predictive coding) is essential in everyday social interactions. We aimed to investigate the neural correlates of different cognitive processes evolving over time during interpersonal predictive coding. Thirty-nine participants watched two agents depicted by moving point-light stimuli while an electroencephalogram (EEG) was recorded. One well-recognizable agent performed either a 'communicative' or an 'individual' action. The second agent either was blended into a cluster of noise dots (i.e. present) or was entirely replaced by noise dots (i.e. absent), which participants had to differentiate. EEG amplitude and coherence analyses for theta, alpha and beta frequency bands revealed a dynamic pattern unfolding over time: Watching communicative actions was associated with enhanced coupling within medial anterior regions involved in social and mentalising processes and with dorsolateral prefrontal activation indicating a higher deployment of cognitive resources. Trying to detect the agent in the cluster of noise dots without having seen communicative cues was related to enhanced coupling in posterior regions for social perception and visual processing. Observing an expected outcome was modulated by motor system activation. Finally, when the agent was detected correctly, activation in posterior areas for visual processing of socially relevant features was increased. Taken together, our results demonstrate that it is crucial to consider the temporal dynamics of social interactions and of their neural correlates to better understand interpersonal predictive coding. This could lead to optimised treatment approaches for individuals with problems in social interactions.

Interpersonal attunement in social interactions: from collective psychophysiology to inter-personalized psychiatry and beyond.

In this article, we analyse social interactions, drawing on diverse points of views, ranging from dialectics, second-person neuroscience and enactivism to dynamical systems, active inference and machine learning. To this end, we define interpersonal attunement as a set of multi-scale processes of building up and materializing social expectations-put simply, anticipating and interacting with others and ourselves. While cultivating and negotiating common ground, via communication and culture-building activities, are indispensable for the survival of the individual, the relevant multi-scale mechanisms have been largely considered in isolation. Here, collective psychophysiology, we argue, can lend itself to the fine-tuned analysis of social interactions, without neglecting the individual. On the other hand, an interpersonal mismatch of expectations can lead to a breakdown of communication and social isolation known to negatively affect mental health. In this regard, we review psychopathology in terms of interpersonal misattunement, conceptualizing psychiatric disorders as disorders of social interaction, to describe how individual mental health is inextricably linked to social interaction. By doing so, we foresee avenues for an inter-personalized psychiatry, which moves from a static spectrum of disorders to a dynamic relational space, focusing on how the multi-faceted processes of social interaction can help to promote mental health. This article is part of the theme issue 'Concepts in interaction: social engagement and inner experiences'.

Social interaction, psychotic disorders and inflammation: A triangle of interest.

Social interaction difficulties are a hallmark of psychotic disorders, which in some cases can be definitely traced back to autoimmunological causes. Interestingly, systemic and intrathecal inflammation have been shown to significantly influence social processing by increasing sensitivity to threatening social stimuli, which bears some resemblance to psychosis. In this article, we review evidence for the involvement of systemic and intrathecal inflammatory processes in psychotic disorders and how this might help to explain some of the social impairments associated with this group of disorders. Vice versa, we also discuss evidence for the immunomodulatory function of social interactions and their potential role for therapeutic interventions in psychotic disorders.

Seeing a Bayesian ghost: Sensorimotor activation leads to an illusory social perception.

Based on our prior experiences we form social expectations and anticipate another person's response. Under certain conditions, these expectations can be so strong that they lead to illusory perception of another person who is actually not there (i.e., seeing a Bayesian ghost). We used EEG to investigate the neural correlates of such illusory social perception. Our results showed that activation of the premotor cortex predicted the occurrence of the Bayesian ghost, whereas its actual appearance was later accompanied by activation in sensorimotor and adjacent parietal regions. These findings confirm that our perception of others is so strongly affected by prior expectations, in such a way they can prompt illusory social perceptions associated with activity change in brain regions relevant for action perception. They also contribute to a better understanding of social interaction in healthy individuals as well as persons with mental illnesses, which can be characterized by illusory perception and social interaction difficulties.