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Autism is a neurodevelopmental condition associated with altered resting-state brain function. An increased excitation-inhibition ratio is discussed as a pathomechanism but in-vivo evidence of disturbed neurotransmission underlying functional alterations remains scarce. We compare local resting-state brain activity and neurotransmitter co-localizations between autism (N = 405, N = 395) and neurotypical controls (N = 473, N = 474) in two independent cohorts and correlate them with excitation-inhibition changes induced by glutamatergic (ketamine) and GABAergic (midazolam) medication. Autistic individuals exhibit consistent reductions in local activity, particularly in default mode network regions. The whole-brain differences spatially overlap with glutamatergic and GABAergic, as well as dopaminergic and cholinergic neurotransmission. Functional changes induced by NMDA-antagonist ketamine resemble the spatial pattern observed in autism. Our findings suggest that consistent local activity alterations in autism reflect widespread disruptions in neurotransmission and may be resembled by pharmacological modulation of the excitation-inhibition balance. These findings advance understanding of the neurophysiological basis of autism. Trial registration number: ACTRN12616000281493 Consistent local activity reductions in autism co-localize with glutamatergic and GABAergic neurotransmission. These patterns resemble brain changes induced by ketamine, highlighting altered excitation-inhibition balance underlying autism’s neurophysiology.

Cognitive dysfunction and brain structural connectivity alterations have been observed in major depressive disorder (MDD). However, little is known about their interrelation. The present study follows a network approach to evaluate alterations in cognition-related brain structural networks. Cognitive performance of = 805 healthy and = 679 acutely depressed or remitted individuals was assessed using 14 cognitive tests aggregated into cognitive factors. The structural connectome was reconstructed from structural and diffusion-weighted magnetic resonance imaging. Associations between global connectivity strength and cognitive factors were established using linear regressions. Network-based statistics were applied to identify subnetworks of connections underlying these global-level associations. In exploratory analyses, effects of depression were assessed by evaluating remission status-related group differences in subnetwork-specific connectivity. Partial correlations were employed to directly test the complete triad of cognitive factors, depressive symptom severity, and subnetwork-specific connectivity strength. All cognitive factors were associated with global connectivity strength. For each cognitive factor, network-based statistics identified a subnetwork of connections, revealing, for example, a subnetwork positively associated with processing speed. Within that subnetwork, acutely depressed patients showed significantly reduced connectivity strength compared to healthy controls. Moreover, connectivity strength in that subnetwork was associated to current depressive symptom severity independent of the previous disease course. Our study is the first to identify cognition-related structural brain networks in MDD patients, thereby revealing associations between cognitive deficits, depressive symptoms, and reduced structural connectivity. This supports the hypothesis that structural connectome alterations may mediate the association of cognitive deficits and depression severity.

Abstract Electroconvulsive Therapy (ECT) is arguably the most effective intervention for treatment-resistant depression. While large interindividual variability exists, a theory capable of explaining individual response to ECT remains elusive. To address this, we posit a quantitative, mechanistic framework of ECT response based on Network Control Theory (NCT). Then, we empirically test our approach and employ it to predict ECT treatment response. To this end, we derive a formal association between Postictal Suppression Index (PSI)—an ECT seizure quality index—and whole-brain modal and average controllability, NCT metrics based on white-matter brain network architecture, respectively. Exploiting the known association of ECT response and PSI, we then hypothesized an association between our controllability metrics and ECT response mediated by PSI. We formally tested this conjecture in N = 50 depressive patients undergoing ECT. We show that whole-brain controllability metrics based on pre-ECT structural connectome data predict ECT response in accordance with our hypotheses. In addition, we show the expected mediation effects via PSI. Importantly, our theoretically motivated metrics are at least on par with extensive machine learning models based on pre-ECT connectome data. In summary, we derived and tested a control-theoretic framework capable of predicting ECT response based on individual brain network architecture. It makes testable, quantitative predictions regarding individual therapeutic response, which are corroborated by strong empirical evidence. Our work might constitute a starting point for a comprehensive, quantitative theory of personalized ECT interventions rooted in control theory.

Electroconvulsive Therapy (ECT) is arguably the most effective intervention for treatment-resistant depression. While large interindividual variability exists, a theory capable of predicting individual response to ECT remains elusive. To address this, we posit a quantitative, mechanistic framework of ECT response based on Network Control Theory (NCT). Then, we empirically test our approach and employ it to predict ECT treatment response. To this end, we derive a formal association between Postictal Suppression Index (PSI) - an ECT seizure quality index - and whole-brain modal and average controllability, NCT metrics based on white matter brain network architecture, respectively. Exploiting the known association of ECT response and PSI, we then hypothesized an association between our controllability metrics and ECT response mediated by PSI. We formally tested this conjecture in N=50 depressive patients undergoing ECT. We show that whole-brain controllability metrics based on pre-ECT structural connectome data predict ECT response in accordance with our hypotheses. In addition, we show the expected mediation effects via PSI. Importantly, our theoretically motivated metrics are at least on par with extensive machine learning models based on pre-ECT connectome data. In summary, we derived and tested a control-theoretic framework capable of predicting ECT response based on individual brain network architecture. It makes testable, quantitative predictions regarding individual therapeutic response, which are corroborated by strong empirical evidence. Our work might constitute a starting point for a comprehensive, quantitative theory of personalized ECT interventions rooted in control theory.

This proof-of-concept study provides a novel method for robust-stable scheduling in dynamic flow shops based on deep reinforcement learning (DRL) implemented with OpenAI frameworks. In realistic manufacturing environments, dynamic events endanger baseline schedules, which can require a cost intensive re-scheduling. Extensive research has been done on methods for generating proactive baseline schedules to absorb uncertainties in advance and in balancing the competing metrics of robustness and stability. Recent studies presented exact methods and heuristics based on Monte Carlo experiments (MCE), both of which are very computationally intensive. Furthermore, approaches based on surrogate measures were proposed, which do not explicitly consider uncertainties and robustness metrics. Surprisingly, DRL has not yet been scientifically investigated for generating robust-stable schedules in the proactive stage of production planning. The contribution of this article is a proposal on how DRL can be applied to manipulate operation slack times by stretching or compressing plan durations. The method is demonstrated using different flow shop instances with uncertain processing times, stochastic machine failures and uncertain repair times. Through a computational study, we found that DRL agents achieve about 98% result quality but only take about 2% of the time compared to traditional metaheuristics. This is a promising advantage for the use in real-time environments and supports the idea of improving proactive scheduling methods with machine learning based techniques.

This feasibility study utilized regression models to predict makespan robustness in dynamic production processes with uncertain processing times. Previous methods for robustness determination were computationally intensive (Monte Carlo experiments) or inaccurate (surrogate measures). However, calculating robustness efficiently is crucial for field-synchronous scheduling techniques. Regression models with multiple input features considering uncertain processing times on the critical path outperform traditional surrogate measures. Well-trained regression models internalize the behavior of a dynamic simulation and can quickly predict accurate robustness (correlation: r>0.98). The proposed method was successfully applied to a permutation flow shop scheduling problem, balancing makespan and robustness. Integrating regression models into a metaheuristic model, schedules could be generated that have a similar quality to using Monte Carlo experiments. These results suggest that employing machine learning techniques for robustness prediction could be a promising and efficient alternative to traditional approaches. This work is an addition to our previous extensive study about creating robust stable schedules based on deep reinforcement learning and is part of the applied research project, Predictive Scheduling.

Recognizing that traditional forecasting models often rely solely on historical demand, this work investigates the potential of data-driven techniques to automatically select and integrate market indicators for improving customer demand predictions. By adopting an exploratory methodology, we integrate macroeconomic time series, such as national GDP growth, from the \\textit{Eurostat} database into \\textit{Neural Prophet} and \\textit{SARIMAX} forecasting models. Suitable time series are automatically identified through different state-of-the-art feature selection methods and applied to sales data from our industrial partner. It could be shown that forecasts can be significantly enhanced by incorporating external information. Notably, the potential of feature selection methods stands out, especially due to their capability for automation without expert knowledge and manual selection effort. In particular, the Forward Feature Selection technique consistently yielded superior forecasting accuracy for both SARIMAX and Neural Prophet across different company sales datasets. In the comparative analysis of the errors of the selected forecasting models, namely Neural Prophet and SARIMAX, it is observed that neither model demonstrates a significant superiority over the other.

The following interdisciplinary article presents a memetic algorithm with applying deep reinforcement learning (DRL) for solving practically oriented dual resource constrained flexible job shop scheduling problems (DRC-FJSSP). From research projects in industry, we recognize the need to consider flexible machines, flexible human workers, worker capabilities, setup and processing operations, material arrival times, complex job paths with parallel tasks for bill of material (BOM) manufacturing, sequence-dependent setup times and (partially) automated tasks in human-machine-collaboration. In recent years, there has been extensive research on metaheuristics and DRL techniques but focused on simple scheduling environments. However, there are few approaches combining metaheuristics and DRL to generate schedules more reliably and efficiently. In this paper, we first formulate a DRC-FJSSP to map complex industry requirements beyond traditional job shop models. Then we propose a scheduling framework integrating a discrete event simulation (DES) for schedule evaluation, considering parallel computing and multicriteria optimization. Here, a memetic algorithm is enriched with DRL to improve sequencing and assignment decisions. Through numerical experiments with real-world production data, we confirm that the framework generates feasible schedules efficiently and reliably for a balanced optimization of makespan (MS) and total tardiness (TT). Utilizing DRL instead of random metaheuristic operations leads to better results in fewer algorithm iterations and outperforms traditional approaches in such complex environments.

Deep Reinforcement Learning (DRL) is a frequently employed technique to solve scheduling problems. Although DRL agents ace at delivering viable results in short computing times, their reasoning remains opaque. We conduct a case study where we systematically apply two explainable AI (xAI) frameworks, namely SHAP (DeepSHAP) and Captum (Input x Gradient), to describe the reasoning behind scheduling decisions of a specialized DRL agent in a flow production. We find that methods in the xAI literature lack falsifiability and consistent terminology, do not adequately consider domain-knowledge, the target audience or real-world scenarios, and typically provide simple input-output explanations rather than causal interpretations. To resolve this issue, we introduce a hypotheses-based workflow. This approach enables us to inspect whether explanations align with domain knowledge and match the reward hypotheses of the agent. We furthermore tackle the challenge of communicating these insights to third parties by tailoring hypotheses to the target audience, which can serve as interpretations of the agent's behavior after verification. Our proposed workflow emphasizes the repeated verification of explanations and may be applicable to various DRL-based scheduling use cases.

Transnational flows of goods, capital, and labor are accurately monitored, and are included by governmental agencies in their economic metrics as critical information used by policy makers. Although transnational flows of data can be intuitively identified as equally important, they have been so far largely ignored by economists and are poorly monitored by public authorities. In this paper, we study the extent to which local and foreign intermediation platforms in Asia have developed their activities in Asia, and their contribution to cross-border data exchanges. We rely on preliminary measure of transnational as well as global data exchanges in Asia. We identify various patterns; China is mostly relying on national platforms, while Japan is highly dependent from platforms based in the United States, Korea and Taiwan are experiencing some sort of balance between national and foreign platforms.