Tracelet Hopf Algebras and Decomposition Spaces (Extended Abstract)

Tracelets are the intrinsic carriers of causal information in categorical rewriting systems. In this work, we assemble tracelets into a symmetric monoidal decomposition space, inducing a cocommutative Hopf algebra of tracelets. This Hopf algebra captures important combinatorial and algebraic aspects of rewriting theory, and is motivated by applications of its representation theory to stochastic rewriting systems such as chemical reaction networks.Comment: In Proceedings ACT 2021, arXiv:2211.0110

Noncanonical, Dopamine-Dependent Long-Term Potentiation at Hippocampal Output Synapses in a Rodent Model of First-Episode Psychosis

Cognitive deficits and positive symptoms in schizophrenia have both been linked to hippocampal dysfunction. Recently, subregion-specific aberrant and maladaptive hippocampal synaptic plasticity has been suggested as one of the mechanistic underpinnings. The subiculum is the final output hub of the hippocampus and orchestrates hippocampal information transfer to other brain regions. While most CA1 pyramidal neurons show regular-spiking behavior, subicular output neurons comprise bursting and regular-firing pyramidal cells. These two cell types target different brain regions and express unique forms of synaptic plasticity. Here, we used a single systemic application of the noncompetitive glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonist MK-801 to model first-episode psychosis in rats and studied long-term potentiation (LTP) in subicular regular-firing cells in acute hippocampal slices. Previously, we have reported a facilitation of a presynaptic, late-onset LTP in subicular bursting pyramidal cells after systemic NMDAR antagonism. Here, we show that single systemic NMDAR antagonist application also facilitates the induction of a noncanonical, but postsynaptic NMDAR-independent LTP in ventral subicular but not in CA1 regular-firing pyramidal cells. This form of LTP was dependent on D1/D5 dopamine receptor activation. Activation of D1/D5 dopamine receptors by a specific agonist mimicked and occluded LTP induced by electrical high-frequency stimulation (HFS). Furthermore, our results indicate that this form of LTP relies on postsynaptic Ca2+ signaling and requires the activation of protein kinase A. Considering the pivotal role of the subiculum as information gatekeeper between the hippocampus and other brain regions, this aberrant LTP in ventral subicular regular-firing neurons is expected to interfere with physiological hippocampal output processing and might thereby contribute to hippocampal dysfunction in psychotic events

Changes in Electric Brain Response to Affective Stimuli in the First Week of Antidepressant Treatment: An Exploratory Study

Introduction: Asymmetrical alpha and frontal theta activity have been discussed as neurobiological markers for antidepressant treatment response. While most studies focus on resting-state EEG, there is evidence that task-related activity assessed at multiple time points might be superior in detecting subtle early differences. Methods: This was a naturalistic study design assessing participants in a psychiatric in- and outpatient hospital setting. We investigated stimulus-related EEG asymmetry (frontal and occipital alpha-1 and alpha-2) and power (frontal midline theta) assessed at baseline and 1 week after initiation of pharmacological depression treatment while presenting affective stimuli. We then compared week 4 responders and nonresponders to antidepressant treatment. Results: Follow-up analyses of a significant group x emotion x time interaction (p < 0.04) for alpha-1 asymmetry showed that responders differed significantly at baseline in their asymmetry scores in response to sad compared to happy faces with a change in this pattern 1 week later. Nonresponders did not show this pattern. No significant results were found for alpha-2, occipital alpha-1, and occipital alpha-2 asymmetry or frontal midline theta power. Discussion: Our study addresses the gap in comparisons of task-related EEG activity changes measured at two time points and supports the potential value of this approach in detecting early differences in responders versus nonresponders to pharmacological treatment. Important limitations include the small sample size and the noncontrolled study design

disrupted relationship with memory performance and potential implications for delusions

Recent concepts have highlighted the role of the hippocampus and adjacent medial temporal lobe (MTL) in positive symptoms like delusions in schizophrenia. In healthy individuals, the MTL is critically involved in the detection and encoding of novel information. Here, we aimed to investigate whether dysfunctional novelty processing by the MTL might constitute a potential neural mechanism contributing to the pathophysiology of delusions, using functional magnetic resonance imaging (fMRI) in 16 unmedicated patients with paranoid schizophrenia and 20 age-matched healthy controls. All patients experienced positive symptoms at time of participation. Participants performed a visual target detection task with complex scene stimuli in which novel and familiar rare stimuli were presented randomly intermixed with a standard and a target picture. Presentation of novel relative to familiar images was associated with hippocampal activation in both patients and healthy controls, but only healthy controls showed a positive relationship between novelty- related hippocampal activation and recognition memory performance after 24 h. Patients, but not controls, showed a robust neural response in the orbitofrontal cortex (OFC) during presentation of novel stimuli. Functional connectivity analysis in the patients further revealed a novelty-related increase of functional connectivity of both the hippocampus and the OFC with the rostral anterior cingulate cortex (rACC) and the ventral striatum (VS). Notably, delusions correlated positively with the difference of the functional connectivity of the hippocampus vs. the OFC with the rACC. Taken together, our results suggest that alterations of fronto-limbic novelty processing may contribute to the pathophysiology of delusions in patients with acute psychosis

Reference values of impulse oscillometric lung function indices in adults of advanced age.

Impulse oscillometry (IOS) is a non-demanding lung function test. Its diagnostic use may be particularly useful in patients of advanced age with physical or mental limitations unable to perform spirometry. Only few reference equations are available for Caucasians, none of them covering the old age. Here, we provide reference equations up to advanced age and compare them with currently available equations. IOS was performed in a population-based sample of 1990 subjects, aged 45-91 years, from KORA cohorts (Augsburg, Germany). From those, 397 never-smoking, lung healthy subjects with normal spirometry were identified and sex-specific quantile regression models with age, height and body weight as predictors for respiratory system impedance, resistance, reactance, and other parameters of IOS applied. Women (n = 243) showed higher resistance values than men (n = 154), while reactance at low frequencies (up to 20 Hz) was lower (p<0.05). A significant age dependency was observed for the difference between resistance values at 5 Hz and 20 Hz (R5-R20), the integrated area of low-frequency reactance (AX), and resonant frequency (Fres) in both sexes whereas reactance at 5 Hz (X5) was age dependent only in females. In the healthy subjects (n = 397), mean differences between observed values and predictions for resistance (5 Hz and 20 Hz) and reactance (5 Hz) ranged between -1% and 5% when using the present model. In contrast, differences based on the currently applied equations (Vogel & Smidt 1994) ranged between -34% and 76%. Regarding our equations the indices were beyond the limits of normal in 8.1% to 18.6% of the entire KORA cohort (n = 1990), and in 0.7% to 9.4% with the currently applied equations. Our study provides up-to-date reference equations for IOS in Caucasians aged 45 to 85 years. We suggest the use of the present equations particularly in advanced age in order to detect airway dysfunction

Depression in primary care and the role of evidence-based guidelines: cross-sectional data from primary care physicians in Germany

Background: Depression is the most common mental health burden worldwide. Primary care physicians (PCPs) play a key role in the care provision for people with depression. The first objective of the present study was to examine the health care situation of depression in primary care, focusing on the cooperation between PCPs and mental health specialists. Secondly, we aimed at examining the role of the German S3 Guideline for Unipolar Depression in the primary care provision. Methods: Data of N = 75 PCPs were analysed from a cross-sectional online survey. Analysis of descriptive information on the current status of primary health care and depression was conducted. Further, to examine factors that are related to the usage of guidelines, multiple regression was performed. Results: Only 22.1% of PCPs described the quality of cooperation with ambulatory mental health specialist as good. The most frequent problems in the cooperation were of structural nature (49.3%, long waiting list, few therapy units, as well as barriers in the communication and the information exchange). With regard to the role of the guideline, 65% of PCPs reported never or seldom using the guideline and 31.7% of PCPs perceived the guideline as not useful at all. In addition, perceived usefulness of the S3 guideline was positively associated with the usage of the guideline. Results of the logistic regression revealed a significant association between the usage of the German S3 Guideline for Unipolar Depression and rating of perceived usefulness of the guideline (OR: 4.771; 95% CI: 2.15-10.59; p < 0.001). Conclusion: This study highlights the central role of PCPs and demonstrates major barriers in the outpatient health care provision of depression. Present findings suggest a strong need for collaborative health care models to resolve obstacles resulting from fragmented mental health care systems. Finally, reported perceived barriers in the implementation of the German S3 Guideline for Unipolar Depression indicate the urge to involve PCPs in the development of evidence-based guidelines, in order to ensure a successful implementation and usage of guidelines in clinical practice

Loss of long-term potentiation at hippocampal output synapses in experimental temporal lobe epilepsy

Patients suffering from temporal lobe epilepsy (TLE) show severe problems in hippocampus dependent memory consolidation. Memory consolidation strongly depends on an intact dialog between the hippocampus and neocortical structures. Deficits in hippocampal signal transmission are known to provoke disturbances in memory formation. In the present study, we investigate changes of synaptic plasticity at hippocampal output structures in an experimental animal model of TLE. In pilocarpine-treated rats, we found suppressed long-term potentiation (LTP) in hippocampal and parahippocampal regions such as the subiculum and the entorhinal cortex (EC). Subsequently we focused on the subiculum, serving as the major relay station between the hippocampus proper and downstream structures. In control animals, subicular pyramidal cells express different forms of LTP depending on their intrinsic firing pattern. In line with our extracellular recordings, we could show that LTP could only be induced in a minority of subicular pyramidal neurons. We demonstrate that a well-characterized cAMP-dependent signaling pathway involved in presynaptic forms of LTP is perturbed in pilocarpine-treated animals. Our findings suggest that in TLE, disturbances of synaptic plasticity may influence the information flow between the hippocampus and the neocortex

Impact of Lung Function Decline on Mortality in Lung Transplant Recipients: Long-Term Results From the L-CsA-i Study for the Prevention of Bronchiolitis Obliterans Syndrome

BackgroundChronic lung allograft dysfunction (CLAD) is defined by a progressive loss of FEV1 and is associated with premature mortality. The aim of this study was to investigate the direct association between FEV1 decline and risk of mortality in patients after lung transplantation (LTx). Methods10-year follow up data from lung transplant recipients participating in randomized placebo-controlled clinical trial investigating the role of liposomal Cyclosporine A for inhalation (L-CsA-i) in the prevention of bronchiolitis obliterans syndrome (NCT01334892) was used. The association between the course of FEV1 over time and the risk of mortality was assessed using joint modeling and Cox regression analysis. ResultsA total of 130 patients were included. Predictors of FEV1 decline were a higher absolute FEV1 at baseline and male sex. The joint model analysis indicated a significant association of change of FEV1 and risk of mortality (p < 0.001), with a predicted 3.4% increase in mortality risk for each 1% decline in FEV1. Significant predictors of a progressive phenotype were single LTx and treatment with placebo (as opposed to L-CsA-i). At the end of follow-up, 82 patients (63.1%) were still alive. Cox regression analyses for mortality identified only single LTx as a predictor of higher risk. ConclusionBased on our observation of a close association between FEV1 and mortality over a period of 10 years we suggest FEV1 as a valid predictor of mortality and a suitable surrogate endpoint in the investigation of early interventions