Autobiographical memory following weight gain in adult patients with Anorexia Nervosa: A longitudinal study.

BACKGROUND: Patients with anorexia nervosa (AN) show overgeneralization of memory (OGM) when generating autobiographical episodes related to food and body shape. These memories are central for the construction of a coherent self-concept, interpersonal relationships, and problem-solving abilities. The current study aims to investigate changes in autobiographical memory following weight gain. METHODS: OGM was assessed with an adapted version of the Autobiographical Memory Test including food-, body-, depression-related, and neutral cues. N = 41 female patients with AN (28 restricting-, 13 binge-eating/purging-subtype; mean disease duration: 4.5 years; mean BMI: 14.5 kg/m2) and N = 27 healthy controls (HC) were included at baseline. After inpatient treatment (mean duration: 11 weeks), 24 patients with AN and 24 age-matched HC were reassessed. Group differences were assessed using independent samples t-tests for cross-sectional comparisons and repeated measures ANOVAs for longitudinal data. RESULTS: At baseline, patients with AN generated significantly fewer specific memories than HC, independent of word category (F(1.66) = 27.167, p < 0.001). During inpatient stay, the average weight gain of patients with AN was 3.1 body mass index points. At follow-up, patients with AN showed a significant improvement in the number of specific memories for both depression-related and neutral cues, but not for food- and body-related cues. CONCLUSIONS: Generalised OGM (i.e., independent of word category) in patients with AN before weight restoration may be a general incapacity to recall autobiographical memory. After weight gain, the previously well-studied pattern of eating disorder-related OGM emerges. The clinical relevance of the continuing disorder-related OGM in patients with AN after weight gain is discussed.

CTPS1 is a novel therapeutic target in multiple myeloma which synergizes with inhibition of CHEK1, ATR or WEE1.

Targeting nucleotide biosynthesis is a proven strategy for the treatment of cancer but is limited by toxicity, reflecting the fundamental nucleotide requirement of dividing cells. The rate limiting step in de novo pyrimidine synthesis is of interest, being catalyzed by two homologous enzymes, CTP synthase 1 (CTPS1) and CTPS2, that could be differentially targeted. Herein, analyses of publicly available datasets identified an essential role for CTPS1 in multiple myeloma (MM), linking high expression of CTPS1 (but not CTPS2) with advanced disease and poor outcomes. In cellular experiments, CTPS1 knockout induced apoptosis of MM cell lines. Exposure of MM cells to STP-B, a novel and highly selective pharmacological inhibitor of CTPS1, inhibited proliferation, induced S phase arrest and led to cell death by apoptosis. Mechanistically, CTPS1 inhibition by STP-B activated DNA damage response (DDR) pathways and induced double-strand DNA breaks which accumulated in early S phase. Combination of STP-B with pharmacological inhibitors of key components of the DDR pathway (ATR, CHEK1 or WEE1) resulted in synergistic growth inhibition and early apoptosis. Taken together, these findings identify CTPS1 as a promising new target in MM, either alone or in combination with DDR pathway inhibition.

Mast cell deficiency prevents BCR::ABL1 induced splenomegaly and cytokine elevation in a CML mouse model.

The persistence of leukemic stem cells (LSCs) represents a problem in the therapy of chronic myeloid leukemia (CML). Hence, it is of utmost importance to explore the underlying mechanisms to develop new therapeutic approaches to cure CML. Using the genetically engineered ScltTA/TRE-BCR::ABL1 mouse model for chronic phase CML, we previously demonstrated that the loss of the docking protein GAB2 counteracts the infiltration of mast cells (MCs) in the bone marrow (BM) of BCR::ABL1 positive mice. Here, we show for the first time that BCR::ABL1 drives the cytokine independent expansion of BM derived MCs and sensitizes them for FcεRI triggered degranulation. Importantly, we demonstrate that genetic mast cell deficiency conferred by the Cpa3Cre allele prevents BCR::ABL1 induced splenomegaly and impairs the production of pro-inflammatory cytokines. Furthermore, we show in CML patients that splenomegaly is associated with high BM MC counts and that upregulation of pro-inflammatory cytokines in patient serum samples correlates with tryptase levels. Finally, MC-associated transcripts were elevated in human CML BM samples. Thus, our study identifies MCs as essential contributors to disease progression and suggests considering them as an additional target in CML therapy. Mast cells play a key role in the pro-inflammatory tumor microenvironment of the bone marrow. Shown is a cartoon summarizing our results from the mouse model. BCR::ABL1 transformed MCs, as part of the malignant clone, are essential for the elevation of pro-inflammatory cytokines, known to be important in disease initiation and progression.

Verbal memory following weight gain in adult patients with anorexia nervosa: A longitudinal study.

BACKGROUND: Patients with Anorexia Nervosa (AN) show a moderate deficit in overall neuropsychological functioning. Since previous studies on memory performance mainly employed cross-sectional designs, the present study aims to investigate changes in verbal memory following weight-gain. METHODS: Verbal memory was assessed with the Wechsler Memory Scale-Revised (WMS-R; 'logical memory'-story-recall-subtest) and the California Verbal Learning Test-II (CVLT-II; 'verbal learning'). Included were 31 female patients with AN (18 restricting-, 13 purging-subtype; average disease duration: 5.1 years; average baseline BMI: 14.4 kg/m2 ) and 24 medication-free normal-weight healthy women adjusted for age at baseline (T0). In a post-treatment assessment of approx. 6 weeks with weight increase (T1), 18 patients with AN and 20 healthy women were assessed again. Group differences in verbal memory (i.e., WMS-R, CVLT-II) were assessed for the baseline comparisons with a multivariate ANOVA and longitudinal data were analysed with repeated measures (RM) ANOVAs. RESULTS: At baseline, patients with AN as compared to healthy women displayed deficits in logical memory. In the follow-up assessment, patients with AN improved their logical memory significantly compared to healthy controls (p < 0.006). Furthermore, groups did not differ in verbal learning neither before nor after inpatient treatment. CONCLUSIONS: Enhanced logical memory in patients with AN following weight-gain is probably due to the impaired memory as compared to healthy controls at T0. A survivorship bias could explain the improved memory performance in longitudinal data in contrast to cross-sectional studies. Patients with AN with poorer memory performance before inpatient treatment are at higher risk to drop out and need support.

Neurophysiological correlates of disorder-related autobiographical memory in anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is characterized by an overgeneralization of food/body-related autobiographical memories (AM). This is regarded as an emotion regulation strategy with adverse long-term effects implicated in disorder maintenance and treatment resistance. Therefore, we aimed to examine neural correlates of food/body-related AM-recall in AN. METHODS: Twenty-nine female patients with AN and 30 medication-free age-sex-matched normal-weight healthy controls (HC) underwent functional magnetic resonance imaging while recalling AMs in response to food/body-related and neutral cue words. To control for general knowledge retrieval, participants engaged in a semantic generation and riser detection task. RESULTS: In comparison to HC, patients with AN generated fewer and less specific AMs in response to food/body-related words, but not for neutral cue words. Group comparisons revealed reduced activation in regions associated with self-referential processing and memory retrieval (precuneus and angular gyrus) during the retrieval of specific food/body-related AM in patients with AN. Brain connectivity in regions associated with memory functioning and executive control was reduced in patients with AN during the retrieval of specific food/body-related AM. Finally, resting-state functional connectivity analysis revealed no differences between groups, arguing against a general underlying disconnection of brain networks implicated in memory and emotional processing in AN. CONCLUSIONS: These results indicate impaired neural processing of food/body-related AM in AN, with a reduced involvement of regions involved in self-referential processing. Our findings are discussed as possible neuronal correlates of emotional avoidance in AN and provide new insights of AN-pathophysiology underscoring the importance of targeting dysfunctional emotion regulation strategies during treatment.

The interplay between agency and therapeutic bond in predicting symptom severity in long-term psychotherapy.

This study investigated the interplay between agency and therapeutic bond in predicting patient symptoms in outpatient psychotherapy. A total of N = 731 patients provided measurements of agency (Therapeutic Agency Inventory; TAI), therapeutic bond (bond subscale of Working Alliance Inventory-Short Form Revised [WAI-SR]), and symptoms (Symptom Checklist Short Form [SCL-K11]) every fifth session of long-term treatment for up to 60 sessions. When investigated in separate models, both more agency and a stronger therapeutic bond predicted symptom improvement. However, within-person changes and between-person differences in agency predicted symptom improvement over and above the effects of therapeutic bond. Multilevel response surface analysis was used to further investigate the interplay between agency and therapeutic bond. When both agency and therapeutic bond levels were high, symptoms improved the most. When agency and therapeutic bond ratings differed, symptom ratings were significantly lower when agency exceeded therapeutic bond levels than when therapeutic bond ratings exceeded agency. Findings suggest that both agency and therapeutic bond are important treatment factors, but outcome could be improved when a strong therapeutic bond is combined with an equally strong sense of agency that empowers patients to pursue changes in their lives. When a strong therapeutic bond is present, but the patient feels less agentic, therapists may want to foster agency to improve outcomes. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Heterogeneous modulation of Bcl-2 family members and drug efflux mediate MCL-1 inhibitor resistance in multiple myeloma.

Antiapoptotic Bcl-2 family members have recently (re)emerged as key drug targets in cancer, with a tissue- and tumor-specific activity profile of available BH3 mimetics. In multiple myeloma, MCL-1 has been described as a major gatekeeper of apoptosis. This discovery has led to the rapid establishment of clinical trials evaluating the impact of various MCL-1 inhibitors. However, our understanding about the clinical impact and optimal use of MCL-1 inhibitors is still limited. We therefore explored mechanisms of acquired MCL-1 inhibitor resistance and optimization strategies in myeloma. Our findings indicated heterogeneous paths to resistance involving baseline Bcl-2 family alterations of proapoptotic (BAK, BAX, and BIM) and antiapoptotic (Bcl-2 and MCL-1) proteins. These manifestations depend on the BH3 profile of parental cells that guide the enhanced formation of Bcl-2:BIM and/or the dynamic (ie, treatment-induced) formation of Bcl-xL:BIM and Bcl-xL:BAK complexes. Accordingly, an unbiased high-throughput drug-screening approach (n = 528) indicated alternative BH3 mimetics as top combination partners for MCL-1 inhibitors in sensitive and resistant cells (Bcl-xL>Bcl-2 inhibition), whereas established drug classes were mainly antagonistic (eg, antimitotic agents). We also revealed reduced activity of MCL-1 inhibitors in the presence of stromal support as a drug-class effect that was overcome by concurrent Bcl-xL or Bcl-2 inhibition. Finally, we demonstrated heterogeneous Bcl-2 family deregulation and MCL-1 inhibitor cross-resistance in carfilzomib-resistant cells, a phenomenon linked to the MDR1-driven drug efflux of MCL-1 inhibitors. The implications of our findings for clinical practice emphasize the need for patient-adapted treatment protocols, with the tracking of tumor- and/or clone-specific adaptations in response to MCL-1 inhibition.

Treatment with HIV-Protease Inhibitor Nelfinavir Identifies Membrane Lipid Composition and Fluidity as a Therapeutic Target in Advanced Multiple Myeloma.

The HIV-protease inhibitor nelfinavir has shown broad anticancer activity in various preclinical and clinical contexts. In patients with advanced, proteasome inhibitor (PI)-refractory multiple myeloma, nelfinavir-based therapy resulted in 65% partial response or better, suggesting that this may be a highly active chemotherapeutic option in this setting. The broad anticancer mechanism of action of nelfinavir implies that it interferes with fundamental aspects of cancer cell biology. We combined proteome-wide affinity-purification of nelfinavir-interacting proteins with genome-wide CRISPR/Cas9-based screening to identify protein partners that interact with nelfinavir in an activity-dependent manner alongside candidate genetic contributors affecting nelfinavir cytotoxicity. Nelfinavir had multiple activity-specific binding partners embedded in lipid bilayers of mitochondria and the endoplasmic reticulum. Nelfinavir affected the fluidity and composition of lipid-rich membranes, disrupted mitochondrial respiration, blocked vesicular transport, and affected the function of membrane-embedded drug efflux transporter ABCB1, triggering the integrated stress response. Sensitivity to nelfinavir was dependent on ADIPOR2, which maintains membrane fluidity by promoting fatty acid desaturation and incorporation into phospholipids. Supplementation with fatty acids prevented the nelfinavir-induced effect on mitochondrial metabolism, drug-efflux transporters, and stress-response activation. Conversely, depletion of fatty acids/cholesterol pools by the FDA-approved drug ezetimibe showed a synergistic anticancer activity with nelfinavir in vitro. These results identify the modification of lipid-rich membranes by nelfinavir as a novel mechanism of action to achieve broad anticancer activity, which may be suitable for the treatment of PI-refractory multiple myeloma. SIGNIFICANCE: Nelfinavir induces lipid bilayer stress in cellular organelles that disrupts mitochondrial respiration and transmembrane protein transport, resulting in broad anticancer activity via metabolic rewiring and activation of the unfolded protein response.

Alteration of Tissue Marking Dyes Depends on Used Chromogen during Immunohistochemistry.

Pathological biopsy protocols require tissue marking dye (TMD) for orientation. In some cases (e.g., close margin), additional immunohistochemical analyses can be necessary. Therefore, the correlation between the applied TMD during macroscopy and the examined TMD during microscopy is crucial for the correct orientation, the residual tumour status and the subsequent therapeutic regime. In this context, our group observed colour changes during routine immunohistochemistry. Tissue specimens were marked with various TMD and processed by two different methods. TMD (blue, red, black, yellow and green) obtained from three different providers (A, B and C, and Whiteout/Tipp-Ex®) were used. Immunohistochemistry was performed manually via stepwise omission of reagents to identify the colour changing mechanism. Blue colour from provider A changed during immunohistochemistry into black, when 3,3'-Diaminobenzidine-tetrahydrochloride-dihydrate (DAB) and H2O2 was applied as an immunoperoxidase-based terminal colour signal. No other applied reagents, nor tissue texture or processing showed any influence on the colour. The remaining colours from provider A and the other colours did not show any changes during immunohistochemistry. Our results demonstrate an interesting and important pitfall in routine immunohistochemistry-based diagnostics that pathologists should be aware of. Furthermore, the chemical rationale behind the observed misleading colour change is discussed.

Agency and alliance as change factors in psychotherapy.

OBJECTIVE: This study examined the reciprocal effects between therapeutic agency, working alliance, and symptoms during psychotherapy. We aimed to predict symptom improvement by previous changes in either agency or alliance. In addition, we examined whether alliance development was predicted by previous changes in agency. METHOD: A sample of 386 patients in psychodynamic outpatient psychotherapy answered the Therapeutic Agency Inventory (TAI), the Working Alliance Inventory-SR (WAI-SR), and the Symptom Checklist-K11 (SCL-K11) after Sessions 1, 5, 10, 15, and 20. Dynamic panel models were estimated using structural equation modeling. Associations were tested while controlling for autoregressive effects and differentiating within-person changes over time from between-person differences. RESULTS: Increases in agency predicted subsequent symptom improvement. Similarly, increases in alliance predicted subsequent symptom improvement. For agency and alliance, we found a more complex pattern with varying reciprocal effects over time. CONCLUSIONS: Findings show evidence for agency and alliance as curative change factors in psychodynamic psychotherapy. The study supports the importance of both agency and alliance and further suggests that both mechanisms may need to be balanced in successful psychotherapies. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Multiple Immunostainings with Different Epitope Retrievals-The FOLGAS Protocol.

We describe a sequential multistaining protocol for immunohistochemistry, immunofluorescence and CyTOF imaging for formalin-fixed, paraffin-embedded specimens (FFPE) in the formalin gas-phase (FOLGAS), enabling sequential multistaining, independent from the primary and secondary antibodies and retrieval. Histomorphologic details are preserved, and crossreactivity and loss of signal intensity are not detectable. Combined with a DAB-based hydrophobic masking of metal-labeled primary antibodies, FOLGAS allows the extended use of CyTOF imaging in FFPE sections.

[Level of personality functioning and attachment style as predictors of the successful referral to outpatient psychotherapy]. / Persönlichkeitsstruktur und Bindungsstil als Prädiktoren für die erfolgreiche Aufnahme einer ambulanten psychotherapeutischen Behandlung.

Level of personality functioning and attachment style as predictors of the successful referral to outpatient psychotherapy Objectives: Outpatient psychotherapy is a key element in the effective treatment of mental health problems. First results suggest that interpersonal problems lead to difficulties in receiving outpatient psychotherapeutic treatment. The relationship between these difficulties, attachment style, and the level of personality functioning is still unclear. Methods: We invited 1011 patients of a psychosomatic-psychotherapeutic university outpatient clinic to participate in the study. The clinical diagnoses according to ICD-10, as well as symptoms of depression (PHQ-D), and quality of life (SF-36) were recorded. Hypothesized predictors for the successful referral to outpatient therapy were patient age, availability of local outpatient treatment, number of ICD-10 diagnoses, the motivation for psychotherapy (FPTM), fear of stigmatization (Stig-9), level of personality functioning (OPD-SQ), and attachment style (ECR-RD). Results: We were able to catamnestically reassess n = 300 patients (67.3 % of patients initially referred to outpatient therapy). A smaller number of clinical diagnoses, greater availability of psychotherapeutic care and higher therapy motivation, as well as a lower level of personality functioning predicted the successful referral to outpatient psychotherapy, while the combination of impaired personality functioning and avoidant attachment style was a negative predictor. Conclusions: Contrary to expectations, patients with a lower level of personality functioning are more successful in receiving outpatient psychotherapy. However, patients with a combination of impaired personality functioning and a high degree of attachment avoidance run the risk of not asserting their need for treatment.

Insight into conflictual relationship patterns: Development and validation of an observer rating scale.

Objective: This study aimed to develop an observer-rated measure of Insight into Conflictual Relationship Patterns (ICR) applicable to audio- or videotapes of psychotherapy sessions and conduct a first psychometric evaluation. Method: We investigated the item properties, principal components, reliability, and validity of the ICR in a naturalistic sample of N = 125 outpatients in psychodynamic psychotherapy. Results: The ICR consists of 12 items that showed adequate item discrimination and item difficulty indices. All items represent one principal component. Using item response theory, discrimination parameters and item characteristic curves revealed that the ability of all items to differentiate patients was adequate to very good. The scale demonstrated good interrater reliability (ICC(3,1) = .76-.93), adequate internal consistency (Cronbach's α = .84), and high retest reliability (r = .91). Regarding validity, the ICR was significantly associated with insight according to the Achievement of Therapeutic Objectives Scale and patient-perceived session depth. Insight at session five predicted a symptomatic increase from session five to session ten. Conclusion: The ICR is an observer-rated measure to assess insight from psychotherapy session recordings that has demonstrated several aspects of reliability and validity. Future studies are needed to clarify the impact of ICR-assessed insight for symptomatic outcome.

Repaglinide Silences the FOXO3/Lumican Axis and Represses the Associated Metastatic Potential of Neuronal Cancer Cells.

The transcription factor FOXO3 is associated with poor outcome in high-stage neuroblastoma (NB), as it facilitates chemoprotection and tumor angiogenesis. In other tumor entities, FOXO3 stimulates metastasis formation, one of the biggest challenges in the treatment of aggressive NB. However, the impact of FOXO3 on the metastatic potential of neuronal tumor cells remains largely unknown. In the present study, we uncover the small leucine-rich proteoglycan family member lumican (LUM) as a FOXO3-regulated gene that stimulates cellular migration in NB. By a drug-library screen we identified the small molecular weight compound repaglinide (RPG) as a putative FOXO3 inhibitor. Here, we verify that RPG binds to the FOXO3-DNA-binding-domain (DBD) and thereby silences the transcriptional activity of FOXO3. Consistent with the concept that the FOXO3/LUM axis enhances the migratory capacity of aggressive NB cells, we demonstrate that stable knockdown of LUM abrogates the FOXO3-mediated increase in cellular migration. Importantly, FOXO3 inhibition by RPG represses the binding of FOXO3 to the LUM promoter, inhibits FOXO3-mediated LUM RNA and protein expression, and efficiently abrogates FOXO3-triggered cellular "wound healing" as well as spheroid-based 3D-migration. Thus, silencing the FOXO3/LUM axis by the FDA-approved compound RPG represents a promising strategy for novel therapeutic interventions in NB and other FOXO3-dependent tumors.

Therapeutic Agency Inventory: Development and psychometric validation of a patient self-report.

Objectives: Therapeutic agency is defined as a patient's intentional influence over the process of psychotherapeutic change. However, there is a lack of conceptually sound self-report measures with adequate psychometric properties. The aim of this study was to develop and psychometrically evaluate the patient-rated Therapeutic Agency Inventory (TAI).Method: Based on the literature, we developed items related to therapeutic agency and investigated their psychometric properties in a naturalistic study with a sample of 334 psychotherapy participants. We assessed changes in TAI scores in a subsample of 58 patients over the course of inpatient psychotherapy and related TAI scores to therapeutic improvement.Results: The TAI consists of 15 items. We performed exploratory factor analyses, and the following three factors were extracted: In-session activity, therapy-related processing, and therapist-oriented passivity. Internal consistency was .84 for the total score and ranged between .73 and .80 for each of the factors. The TAI was significantly associated with other psychotherapy process factors, self-efficacy expectations, control beliefs, lower overall psychological distress, and lower depression scores. Changes in agency during psychotherapy predicted therapy outcome, even after controlling for baseline distress.Conclusions: The TAI is a reliable, valid, and change-sensitive self-report instrument that can be used to assess agency in psychotherapy.

Therapeutic agency, in-session behavior, and patient-therapist interaction.

OBJECTIVE: The aim of this study was to investigate associations between patients' subjective agency, their observable in-session behavior, and the patient-therapist interaction during the early phase of psychotherapy. METHODS: The sample included 52 depressed patients in psychodynamic psychotherapy. After Session 5, the patients' agency and the quality of the therapeutic alliance were assessed. Based on session recordings, two independent observers rated the patients' involvement, their interpersonal behavior, and the therapists' directiveness. RESULTS: Higher agency was associated with stronger therapeutic alliances. Patients who indicated higher agency in their therapy participated more actively in the session and showed less hostile impact messages. Patients' agency was not related to therapists' directiveness. CONCLUSIONS: Patients' sense of agency in psychotherapy was associated with more active involvement and affiliative interaction. The findings support the idea that patients need to feel capable of acting within and having an influence on their therapy to benefit from it.

Ready to run the wards? - A descriptive follow-up study assessing future doctors' clinical skills.

BACKGROUND: Recent studies have shown that clinical tasks only represent a small percentage in the scope of final-year medical students' activities and often lack sufficient supervision. It appears that final-year medical students are frequently deployed to perform "routine tasks" and show deficits in the performance of more complex activities. This study aimed to evaluate final-year students' clinical performance in multiple impromptu clinical scenarios using video-based assessment. METHODS: We assessed final-year medical students' clinical performance in a prospective, descriptive, clinical follow-up study with 24 final-year medical students during their Internal Medicine rotation. Participating students were videotaped while practicing history taking, physical examination, IV cannulation, and case presentation at the beginning and end of their rotation. Clinical performance was rated by two independent, blinded video assessors using binary checklists, activity specific rating scales and a five-point global rating scale for clinical competence. RESULTS: Students' performance, assessed by the global rating scale for clinical competence, improved significantly during their rotation. However, their task performance was not rated as sufficient for independent practice in most cases. Analysis of average scores revealed that overall performance levels differed significantly, whereby average performance was better for less complex and more frequently performed activities. CONCLUSIONS: We were able to show that students' performance levels differ significantly depending on the frequency and complexity of activities. Hence, to ensure adequate job preparedness for clinical practice, students need sufficiently supervised and comprehensive on-ward medical training.

Association Between Insight and Outcome of Psychotherapy: Systematic Review and Meta-Analysis.

OBJECTIVE: An increased understanding of repetitive dysfunctional patterns and their relationship to an individual's life history is regarded as a key mechanism of change in insight-oriented therapies. At the same time, empirical research on the insight-outcome relationship is rare, and its generalizability is restricted by the use of a wide range of definitions and methods among studies. The authors conducted a meta-analysis to systematically examine the association between patient insight and psychotherapy outcome across a range of treatment modalities. METHOD: Insight was defined as patients' understanding of associations between past and present experiences, typical relationship patterns, and the relation between interpersonal challenges, emotional experience, and psychological symptoms. From 13,849 initially identified abstracts, the authors extracted 23 independent effect sizes. A random-effects meta-analysis was performed to assess the magnitude of the insight-outcome relationship. Risk of publication bias was assessed with funnel plot inspections, Egger's regression test, and Duval and Tweedie's trim-and-fill procedure as sensitivity analyses. RESULTS: A significant, moderate correlation (r=0.31) was observed between insight and treatment outcome. Sensitivity analyses demonstrated the robustness of the results. CONCLUSIONS: The findings support the importance of insight for psychotherapy outcome. Insight may be a relevant mechanism of change across different treatment modalities.

Spatial Arrangement and Set Size Influence the Coding of Non-symbolic Quantities in the Intraparietal Sulcus.

Performance in visual quantification tasks shows two characteristic patterns as a function of set size. A precise subitizing process for small sets (up to four) was contrasted with an approximate estimation process for larger sets. The spatial arrangement of elements in a set also influences visual quantification performance, with frequently perceived arrangements (e.g., dice patterns) being faster enumerated than random arrangements. Neuropsychological and imaging studies identified the intraparietal sulcus (IPS), as key brain area for quantification, both within and above the subitizing range. However, it is not yet clear if and how set size and spatial arrangement of elements in a set modulate IPS activity during quantification. In an fMRI study, participants enumerated briefly presented dot patterns with random, canonical or dice arrangement within and above the subitizing range. We evaluated how activity amplitude and pattern in the IPS were influenced by size and spatial arrangement of a set. We found a discontinuity in the amplitude of IPS response between subitizing and estimation range, with steep activity increase for sets exceeding four elements. In the estimation range, random dot arrangements elicited stronger IPS response than canonical arrangements which in turn elicited stronger response than dice arrangements. Furthermore, IPS activity patterns differed systematically between arrangements. We found a signature in the IPS response for a transition between subitizing and estimation processes during quantification. Differences in amplitude and pattern of IPS activity for different spatial arrangements indicated a more precise representation of non-symbolic numerical magnitude for dice and canonical than for random arrangements. These findings challenge the idea of an abstract coding of numerosity in the IPS even within a single notation.