Interpersonal neural synchrony and mental disorders: unlocking potential pathways for clinical interventions.

Introduction: Interpersonal synchronization involves the alignment of behavioral, affective, physiological, and brain states during social interactions. It facilitates empathy, emotion regulation, and prosocial commitment. Mental disorders characterized by social interaction dysfunction, such as Autism Spectrum Disorder (ASD), Reactive Attachment Disorder (RAD), and Social Anxiety Disorder (SAD), often exhibit atypical synchronization with others across multiple levels. With the introduction of the "second-person" neuroscience perspective, our understanding of interpersonal neural synchronization (INS) has improved, however, so far, it has hardly impacted the development of novel therapeutic interventions. Methods: To evaluate the potential of INS-based treatments for mental disorders, we performed two systematic literature searches identifying studies that directly target INS through neurofeedback (12 publications; 9 independent studies) or brain stimulation techniques (7 studies), following PRISMA guidelines. In addition, we narratively review indirect INS manipulations through behavioral, biofeedback, or hormonal interventions. We discuss the potential of such treatments for ASD, RAD, and SAD and using a systematic database search assess the acceptability of neurofeedback (4 studies) and neurostimulation (4 studies) in patients with social dysfunction. Results: Although behavioral approaches, such as engaging in eye contact or cooperative actions, have been shown to be associated with increased INS, little is known about potential long-term consequences of such interventions. Few proof-of-concept studies have utilized brain stimulation techniques, like transcranial direct current stimulation or INS-based neurofeedback, showing feasibility and preliminary evidence that such interventions can boost behavioral synchrony and social connectedness. Yet, optimal brain stimulation protocols and neurofeedback parameters are still undefined. For ASD, RAD, or SAD, so far no randomized controlled trial has proven the efficacy of direct INS-based intervention techniques, although in general brain stimulation and neurofeedback methods seem to be well accepted in these patient groups. Discussion: Significant work remains to translate INS-based manipulations into effective treatments for social interaction disorders. Future research should focus on mechanistic insights into INS, technological advancements, and rigorous design standards. Furthermore, it will be key to compare interventions directly targeting INS to those targeting other modalities of synchrony as well as to define optimal target dyads and target synchrony states in clinical interventions.

Context effects, skin conductance responses and personality traits - Influencing variables on risk-taking within a modified version of the balloon analog risk task.

When individuals take risks, they must weigh potential costs and benefits associated with a decision. Differences in risk-taking appear to be influenced by contextual, and inter-individual factors. However, it is still ambiguous to what extent these characteristics jointly influence risk-taking. We investigated how risk-taking varies as function of context effects, incentives, skin conductance responses (SCR), and personality traits such as impulsivity and sensitivity to reward and punishment. Sixty-eight healthy participants conducted a modified version of the Balloon Analogue Risk Task (BART) composed of a gain-framed (G-BART) and loss-framed (L-BART) context with each a low and a high outcome magnitude condition. While the goal in G-BART was to maximize gains, the goal in L-BART was to minimize losses. In both versions, participants can potentially accumulate the same amounts. We conducted trial-by-trial mixed model analyses to account for within- and between-participant effects. Participants showed greater risk-taking when playing L-BART than G-BART; more risk-taking was observed in the high compared to the low outcome magnitude condition. Furthermore, higher SCR were associated with less risk-taking. Lower impulsivity was related to a greater difference in risk-taking in both contexts, with greater risk-taking in L-BART. Likewise, sensitivity to reward was associated with a greater difference in risk-taking in both contexts, with greater risk-taking in G-BART. Finally, greater sensitivity to punishment was related to risk-taking among participants describing themselves as sensitive to rewards. Results support a multidimensional state-trait model of risk-taking suggesting that risk-taking is favored by loss-aversion along with incentives, psychophysiological arousal, and personality traits.

Structural imaging studies of patients with chronic pain: an anatomical likelihood estimate meta-analysis.

ABSTRACT: Neuroimaging is a powerful tool to investigate potential associations between chronic pain and brain structure. However, the proliferation of studies across diverse chronic pain syndromes and heterogeneous results challenges data integration and interpretation. We conducted a preregistered anatomical likelihood estimate meta-analysis on structural magnetic imaging studies comparing patients with chronic pain and healthy controls. Specifically, we investigated a broad range of measures of brain structure as well as specific alterations in gray matter and cortical thickness. A total of 7849 abstracts of experiments published between January 1, 1990, and April 26, 2021, were identified from 8 databases and evaluated by 2 independent reviewers. Overall, 103 experiments with a total of 5075 participants met the preregistered inclusion criteria. After correction for multiple comparisons using the gold-standard family-wise error correction ( P < 0.05), no significant differences associated with chronic pain were found. However, exploratory analyses using threshold-free cluster enhancement revealed several spatially distributed clusters showing structural alterations in chronic pain. Most of the clusters coincided with regions implicated in nociceptive processing including the amygdala, thalamus, hippocampus, insula, anterior cingulate cortex, and inferior frontal gyrus. Taken together, these results suggest that chronic pain is associated with subtle, spatially distributed alterations of brain structure.

Visualizing Emotional Arousal within the Context of Body Size Evaluation: A Pilot Study of Steady-State Visual Evoked Potentials in Women with Anorexia Nervosa and Healthy Controls.

Maladaptive body size evaluation processes and body dissatisfaction are known as central risk factors for the development and maintenance of anorexia nervosa (AN). This study aimed to experimentally test potential key facets, such as (psycho)physiological, cognitive-verbal and behavioral mechanisms, within the context of these evaluation processes. Twenty-two females with AN (AN-G) and 22 healthy controls (HC-G) looked at pictures of their body gradually increasing in weight using a morphing technique. Implicit emotional arousal was assessed using steady-state visual evoked potentials (SSVEP) in electroencephalography. Additionally, in a forced-choice body size evaluation task, participants were asked to classify pictures of their own body as not big or big while reaction times were captured. A significantly earlier increase in SSVEPs emerged in AN-G compared to HC-G (p <.05), with AN-G evaluating their bodies in the morphing process as big at a significantly thinner body size (p <.05). The AN-G showed faster reaction times in the categorical evaluation of body stimuli (p <.05). Findings from this multimodal paradigm underline the importance of body size evaluation mechanisms and underlying emotional arousal for AN. A differentiated understanding of these processes is essential, since the effectiveness of therapeutic interventions for AN is limited and relapses are frequent.

Adaptation and validation of a German version of the Dickman impulsivity inventory for the assessment of functional and dysfunctional impulsivity.

Impulsive behavior tends to have a negative connotation in the sense that it is usually associated with detrimental or dysfunctional outcomes. However, under certain circumstances, impulsive behaviors may also have beneficial or functional outcomes. Dickman's Impulsivity Inventory (DII) measures these two distinct aspects of impulsivity, namely, dysfunctional impulsivity (the tendency to act with less forethought than do most people which leads to difficulties) and functional impulsivity (the tendency to act with little forethought when the situation is optimal). In the present study, we translated the DII into German and validated the German version in a sample of 543 adults. The original 23-item model was considered unsuitable for the German version as suggested by fit indices of a confirmatory factor analysis. Exploratory factor analyses rather supported a 16-item version. Further psychometric analyses and inferential statistical analyses on the final German DII indicated its appropriateness for use in German-speaking populations and support a two-factor solution of the DII. Finally, exploratory analyses on the German DII suggest differential relationships between dysfunctional and functional impulsivity and self-reported lifestyle-related variables (smoking, alcohol usage, and sports behavior).

Proactive vs. Reactive Aggression Within Two Modified Versions of the Taylor Aggression Paradigm.

The Taylor Aggression Paradigm (TAP) has been widely used to measure reactive aggression following provocation during competitive interactions. Besides being reactive, aggression can be goal-directed (proactive aggression). Our study presents a novel paradigm to investigate proactive aggression during competitive interactions. Sixty-seven healthy participants competed in two modified versions of the TAP against an ostensible opponent while skin conductance responses (SCRs) were recorded. During the proactive TAP (pTAP), only the participant could interfere with the ostensible opponent's performance by blurring the screen. In the reactive TAP (rTAP), the opponent repeatedly provoked the participant by blurring the screen of the participant, impeding their chance to win. In both versions, the blurriness levels chosen by the participant served as a measure of aggression (unprovoked in the pTAP and provoked in the rTAP). In the pTAP, trial-by-trial mixed model analyses revealed higher aggression with higher self-reported selfishness. SCRs decreased with increasing proactive aggression. An interaction effect between gender and proactive aggression for the SCRs revealed increased SCRs at higher aggression levels in females, but lower SCRs at higher aggression levels in males. In the rTAP, SCRs were not associated with reactive aggression but aggression increased with increasing provocation and especially after losing against the opponent when provoked. While males showed higher aggression levels than females when unprovoked, reactive aggression increased more strongly in females with higher provocation. Mean levels of aggression in both tasks showed a high positive correlation. Our results highlight that, despite being intercorrelated and both motivated by selfishness, proactive and reactive aggression are differentially influenced by gender and physiological arousal. Proactive aggression is related to lower physiological arousal, especially in males, with females showing the opposite association. Reactive aggressive behavior is a result of individual responses to provocation, to which females seem to be more sensitive.

Brain Responses to Noxious Stimuli in Patients With Chronic Pain: A Systematic Review and Meta-analysis.

Importance: Functional neuroimaging is a valuable tool for understanding how patients with chronic pain respond to painful stimuli. However, past studies have reported heterogenous results, highlighting opportunities for a quantitative meta-analysis to integrate existing data and delineate consistent associations across studies. Objective: To identify differential brain responses to noxious stimuli in patients with chronic pain using functional magnetic resonance imaging (fMRI) while adhering to current best practices for neuroimaging meta-analyses. Data Sources: All fMRI experiments published from January 1, 1990, to May 28, 2019, were identified in a literature search of PubMed/MEDLINE, EMBASE, Web of Science, Cochrane Library, PsycINFO, and SCOPUS. Study Selection: Experiments comparing brain responses to noxious stimuli in fMRI between patients and controls were selected if they reported whole-brain results, included at least 10 patients and 10 healthy control participants, and used adequate statistical thresholding (voxel-height P < .001 or cluster-corrected P < .05). Two independent reviewers evaluated titles and abstracts returned by the search. In total, 3682 abstracts were screened, and 1129 full-text articles were evaluated. Data Extraction and Synthesis: Thirty-seven experiments from 29 articles met inclusion criteria for meta-analysis. Coordinates reporting significant activation differences between patients with chronic pain and healthy controls were extracted. These data were meta-analyzed using activation likelihood estimation. Data were analyzed from December 2019 to February 2020. Main Outcomes and Measures: A whole-brain meta-analysis evaluated whether reported differences in brain activation in response to noxious stimuli between patients and healthy controls were spatially convergent. Follow-up analyses examined the directionality of any differences. Finally, an exploratory (nonpreregistered) region-of-interest analysis examined differences within the pain network. Results: The 37 experiments from 29 unique articles included a total of 511 patients and 433 controls (944 participants). Whole-brain meta-analyses did not reveal significant differences between patients and controls in brain responses to noxious stimuli at the preregistered statistical threshold. However, exploratory analyses restricted to the pain network revealed aberrant activity in patients. Conclusions and Relevance: In this systematic review and meta-analysis, preregistered, whole-brain analyses did not reveal aberrant fMRI activity in patients with chronic pain. Exploratory analyses suggested that subtle, spatially diffuse differences may exist within the pain network. Future work on chronic pain biomarkers may benefit from focus on this core set of pain-responsive areas.

Impact of timing of adjuvant chemotherapy following radical cystectomy for bladder cancer on patient survival.

BACKGROUND: Trials of adjuvant chemotherapy following radical cystectomy generally require chemotherapy to start within 90 days postoperatively. However, it is unclear, whether the interval between surgery and start of adjuvant therapy (S-AC-interval) impacts the oncological outcome. METHODS: Using the Retrospective International Study of Invasive/Advanced Cancer of the Urothelium (RISC) data base, we identified patients who underwent radical cystectomy for muscle invasive bladder cancer and subsequent adjuvant chemotherapy. Univariate analysis of patient characteristics, surgical factors and tumor characteristics regarding their impact on S-AC-interval was performed using Kruskal-Wallis testing and Fisher's exact test. Analysis of progression-free (PFS) and overall survival (OS) (follow-up time beginning with the start date of adjuvant chemotherapy) was analyzed in relation to S-AC-interval (continuous and dichotomous with a cut-off at 90 days) using Kaplan-Meier method and COX regression analysis. RESULTS: We identified 238 eligible patients (83.5% male, mean age: 63.4 years, 76.1% T3/T4, 66.4% pN+, 14.7% R+, 70.6% urothelial carcinoma, 71% cisplatin-based adjuvant chemotherapy). The majority of patients (n = 207, 87%) started chemotherapy within 90 days after surgery. Median S-AC-interval was 57 days (interquartile range 32.8). S-AC-interval did not have consistent association with any patient/tumor characteristics or surgery related factors (type of surgery, urinary diversion). Survival analysis using continuous S-AC-interval revealed a trend toward an impact of S-AC-interval on OS (hazard ratio 1.004, 95% confidence ratio 0.9997-1.0084, P = 0.071). With regards to PFS, that impact was shown to be statistically significant (hazard ratio 1.004, 95% confidence ratio 1.0003-1.0075, P = 0.032). In multivariate analysis, however, S-AC-interval was negated by tumor and patient related factors (pathological T-stage, N-stage, ECOG performance status). Accounting for eligibility criteria defined in some clinical trials, we extended our analysis dividing S-AC-interval in ≤90 and >90 days. Although we could confirm the trend toward better outcome in patients with a shorter S-AC interval in dichotomous analysis, neither differences in OS nor in PFS reached statistical significance (P = 0.438 and P = 0.056). CONCLUSIONS: In a large multi-institutional experience, 87% of patients who received adjuvant chemotherapy received it within the guideline recommended window of 90 days. While it was not possible to determine whether this is the optimal cut-off, early start of adjuvant chemotherapy seems to be reasonable. Regarding prognosis, tumor-related pathological factors abrogated the importance of the S-AC-interval in our analysis.

Body Image as Well as Eating Disorder and Body Dysmorphic Disorder Symptoms in Heterosexual, Homosexual, and Bisexual Women.

Body image disturbance is a core symptom of eating disorders (EDs) and body dysmorphic disorder (BDD). There is first evidence that females' body image differs depending on sexual orientation, with heterosexual women (HEW) appearing to show more body image disturbance symptoms than homosexual women (HOW). Such disparities might be moderated by everyday discrimination experiences and involvement with the lesbian community. However, to date, there has been no comprehensive assessment of a broad range of body image facets such as drive for thinness, leanness, and muscularity; body avoidance; body checking and body dissatisfaction; and ED and BDD pathology as well as moderating factors. Moreover, studies have often neglected bisexual women (BIW). A total of N = 617 women (n = 180 HOW, n = 322 HEW, n = 115 BIW) completed an online survey assessing the various facets of body image, ED and BDD pathology, discrimination experiences, and involvement with the lesbian community. Significant group differences were found regarding drive for leanness and thinness, body checking, investment behavior, and body ideal (all p<.05). BIW showed significantly more body checking than HOW. Compared to HEW, HOW reported a significantly lower drive for leanness and thinness as well as compared to HEW and BIW less investment behavior. HOW preferred a body ideal with significantly more body fat than did HEW (all p<.05). In contrast, no differences emerged in body dissatisfaction, drive for muscularity, body-related avoidance, ED and BDD pathology, and body image disturbance (all p>.05). In all groups, discrimination experiences were positively related to ED and BDD pathology and to body image disturbance (all p < .05); however, discrimination was significantly correlated with more body image facets in HEW than in HOW or BIW. Involvement with the lesbian community was positively correlated with a larger ideal body size in HOW (p < .05) and negatively correlated with drive for muscularity in BIW (p < .05). Despite the group differences in several body image facets, we found no consistent evidence of increased vulnerability to body image disturbance or associated pathology depending on sexual orientation. However, in HEW, discrimination experience might pose a risk factor for the development of body image-related pathology and single facets of body image disturbance.

Comparison of 2-Year Oncological Outcome and Early Recurrence Patterns in Patients with Urothelial Bladder Carcinoma Treated with Open or Robot-Assisted Radical Cystectomy with an Extracorporeal Urinary Diversion.

BACKGROUND: Data on oncological follow-up after robotic-assisted radical cystectomy (RARC) have been reported only scarcely and individual studies have reported an increase in early recurrences and atypical recurrences. PATIENTS AND METHODS: Clinical data of 89 patients with RARC were compared to 59 patients with open radical cystectomy (ORC) at a single institution. Two-year cancer-specific (2y-CSS) and 2-year overall survival (2y-OS) related to histopathological tumor stage of RARC patients calculated by Kaplan-Meier method were compared to ORC patients using log-rank test. Early clinical recurrence rate (eCR, progression ≤6 months post-cystectomy) and metastatic pattern of both groups were compared by chi-square test. RESULTS: Median follow-up 32 months (RARC) and 47.5 months (ORC), both groups were balanced in baseline characteristics. For RARC pts, -2y-OS and CSS-free survival rates were 80 and 90%, for ORC pts 65 and 71% (all p > 0.05). Margin status was not significantly different. eCR was observed in 10 out of 89 (11%) RARC pts and in 7 out of 59 (12%) ORC pts (p = 0.9). No difference in atypical metastases was seen between groups. CONCLUSION: Two-year oncological outcomes of RARC patients are comparable to ORC patients without differences regarding ePR or metastatic pattern.

SIX2 gene haploinsufficiency leads to a recognizable phenotype with ptosis, frontonasal dysplasia, and conductive hearing loss.

Heterozygous microdeletions of chromosome 2p21 encompassing only the SIX2 gene have been described in two families to date. The clinical phenotype comprised autosomal-dominant inherited frontonasal dysplasia with ptosis in one family. In the second family, conductive hearing loss was the major clinical feature described; however, the affected persons also had ptosis. Here, we present a large family combining all three predescribed features of SIX2 gene deletion. The phenotype in four affected family members in three generations consisted of bilateral congenital ptosis, epicanthus inversus, frontonasal dysplasia with broad nasal bridge and hypertelorism, frontal bossing and large anterior fontanel in childhood, narrow ear canals, and mild conductive hearing loss with onset in childhood. Thus, the phenotypic spectrum of SIX2 haploinsufficiency is widened. Moreover, 2p21 microdeletions with SIX2 haploinsufficiency appear to lead to a recognizable phenotype with facial features resembling blepharophimosis-ptosis-epicanthus inversus syndrome.