Pre- and post-task resting-state differs in clinical populations.

Resting-state functional connectivity has generated great hopes as a potential brain biomarker for improving prevention, diagnosis, and treatment in psychiatry. This neuroimaging protocol can routinely be performed by patients and does not depend on the specificities of a task. Thus, it seems ideal for big data approaches that require aggregating data across multiple studies and sites. However, technical variability, diverging data analysis approaches, and differences in data acquisition protocols introduce heterogeneity to the aggregated data. Besides these technical aspects, a prior task that changes the psychological state of participants might also contribute to heterogeneity. In healthy participants, studies have shown that behavioral tasks can influence resting-state measures, but such effects have not yet been reported in clinical populations. Here, we fill this knowledge gap by comparing resting-state functional connectivity before and after clinically relevant tasks in two clinical conditions, namely substance use disorders and phobias. The tasks consisted of viewing craving-inducing and spider anxiety provoking pictures that are frequently used in cue-reactivity studies and exposure therapy. We found distinct pre- vs post-task resting-state connectivity differences in each group, as well as decreased thalamo-cortical and increased intra-thalamic connectivity which might be associated with decreased vigilance in both groups. Our results confirm that resting-state measures can be strongly influenced by prior emotion-inducing tasks that need to be taken into account when pooling resting-state scans for clinical biomarker detection. This demands that resting-state datasets should include a complete description of the experimental design, especially when a task preceded data collection.

Progressive modulation of resting-state brain activity during neurofeedback of positive-social emotion regulation networks.

Neurofeedback allows for the self-regulation of brain circuits implicated in specific maladaptive behaviors, leading to persistent changes in brain activity and connectivity. Positive-social emotion regulation neurofeedback enhances emotion regulation capabilities, which is critical for reducing the severity of various psychiatric disorders. Training dorsomedial prefrontal cortex (dmPFC) to exert a top-down influence on bilateral amygdala during positive-social emotion regulation progressively (linearly) modulates connectivity within the trained network and induces positive mood. However, the processes during rest that interleave the neurofeedback training remain poorly understood. We hypothesized that short resting periods at the end of training sessions of positive-social emotion regulation neurofeedback would show alterations within emotion regulation and neurofeedback learning networks. We used complementary model-based and data-driven approaches to assess how resting-state connectivity relates to neurofeedback changes at the end of training sessions. In the experimental group, we found lower progressive dmPFC self-inhibition and an increase of connectivity in networks engaged in emotion regulation, neurofeedback learning, visuospatial processing, and memory. Our findings highlight a large-scale synergy between neurofeedback and resting-state brain activity and connectivity changes within the target network and beyond. This work contributes to our understanding of concomitant learning mechanisms post training and facilitates development of efficient neurofeedback training.

Clinical characteristics and comparison of the outcome in young versus older patients with upper gastrointestinal carcinoma.

BACKGROUND: The clinical behaviour and outcome of young patients with gastroesophageal tumours (GET) is surmised to differ from older patients, yet data on the comparison of these two patient subgroups is scarce. This study focuses on the investigation of the clinical characteristics and survival outcome of younger-age people with GET, when compared to older patients. METHODS: Patients diagnosed with GET at the Medical University of Vienna between 2004 and 2016 were included in this study. Clinical parameters and the overall survival (OS) were compared between young (≤ 45 years) and elderly (≥ 65 years) patients. RESULTS: Among 796 patients, who were eligible for this analysis, fifty-eight patients (7%) were ≤ 45 years at the initial onset of the disease. These 58 young patients were then matched to elderly patients based on the gender, tumour stage, histology and tumour location. The number of metastatic lesions was significantly higher among young patients (p < 0.05). In a non-metastatic setting younger patients showed a significant longer OS than older patients (median 1226 versus 801 days, p = 0.028). Furthermore, young patients with extensive metastatic disease (2 or more metastatic site) had a significantly poorer OS than elderly patients (median 450 versus 646 days, p = 0.033). CONCLUSION: These results indicate that young patients might be diagnosed very late, which might lead to the development of a more aggressive disease compared to older patients, but a relatively long OS when diagnosed and treated in a non-metastatic setting. Thus, screening methods for younger patients might be considerable to enhance the outcome of young patients with GET.

PD-L1 and HER2 Expression in Gastroesophageal Cancer: a Matched Case Control Study.

Immunotherapy with check-point inhibitors serves as a promising treatment strategy in patients with upper gastrointestinal (GI) tumors. Human epidermal growth factor receptor 2 (HER2) is the only identified therapeutic target in upper GI tumors, whose potential interaction with programmed death-ligand 1 (PD-L1) is unknown. The aim of this study was the investigation of PD-L1 and HER2 in upper GI tumors. We retrospectively identified patients with HER2 positive gastroesophageal cancers and matched them with a HER2 negative group. We investigated the tumor specimens for HER2 status and PD-L1 expression, with the following assessments being performed: i) staining of tumor cells in terms of tumor proportion score (TPS), ii) staining for tumor-associated immune cells (TAIs), iii) interface pattern and iv) combined positive score (CPS). Both HER2 positive and negative group consisted of 59 patients. Expression of PD-L1 in TAIs and interface pattern were associated with a favorable outcome (p = 0.02, HR = 0.8; p = 0.04, HR = 0.39; respectively) in patients with localized disease, whereas TPS was associated with an unfavorable outcome in patients with advanced tumor (p = 0.02, HR = 1.4). These effects were HER2 independent. PD-L1 expression in its different assessment is equally observed in HER2 positive and negative patients. Future studies will show whether dual inhibition of HER2 and PD-L1 improves survival of this selected patient population.