Cortical microstructural gradients capture memory network reorganization in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE), one of the most common pharmaco-resistant epilepsies, is associated with pathology of paralimbic brain regions, particularly in the mesiotemporal lobe. Cognitive dysfunction in TLE is frequent, and particularly affects episodic memory. Crucially, these difficulties challenge the quality of life of patients, sometimes more than seizures, underscoring the need to assess neural processes of cognitive dysfunction in TLE to improve patient management. Our work harnessed a novel conceptual and analytical approach to assess spatial gradients of microstructural differentiation between cortical areas based on high-resolution MRI analysis. Gradients track region-to-region variations in intracortical lamination and myeloarchitecture, serving as a system-level measure of structural and functional reorganization. Comparing cortex-wide microstructural gradients between 21 patients and 35 healthy controls, we observed a reorganization of this gradient in TLE driven by reduced microstructural differentiation between paralimbic cortices and the remaining cortex with marked abnormalities in ipsilateral temporopolar and dorsolateral prefrontal regions. Findings were replicated in an independent cohort. Using an independent post-mortem dataset, we observed that in vivo findings reflected topographical variations in cortical cytoarchitecture. We indeed found that macroscale changes in microstructural differentiation in TLE reflected increased similarity of paralimbic and primary sensory/motor regions. Disease-related transcriptomics could furthermore show specificity of our findings to TLE over other common epilepsy syndromes. Finally, microstructural dedifferentiation was associated with cognitive network reorganization seen during an episodic memory functional MRI paradigm and correlated with interindividual differences in task accuracy. Collectively, our findings showing a pattern of reduced microarchitectural differentiation between paralimbic regions and the remaining cortex provide a structurally-grounded explanation for large-scale functional network reorganization and cognitive dysfunction characteristic of TLE.

Differential relational memory impairment in temporal lobe epilepsy.

OBJECTIVE: Temporal lobe epilepsy (TLE) is typically associated with pathology of the hippocampus, a key structure involved in relational memory, including episodic, semantic, and spatial memory processes. While it is widely accepted that TLE-associated hippocampal alterations underlie memory deficits, it remains unclear whether impairments relate to a specific cognitive domain or multiple ones. METHODS: We administered a recently validated task paradigm to evaluate episodic, semantic, and spatial memory in 24 pharmacoresistant TLE patients and 50 age- and sex-matched healthy controls. We carried out two-way analyses of variance to identify memory deficits in individuals with TLE relative to controls across different relational memory domains, and used partial least squares correlation to identify factors contributing to variations in relational memory performance across both cohorts. RESULTS: Compared to controls, TLE patients showed marked impairments in episodic and spatial memory, with mixed findings in semantic memory. Even when additionally controlling for age, sex, and overall cognitive function, between-group differences persisted along episodic and spatial domains. Moreover, age, diagnostic group, and hippocampal volume were all associated with relational memory behavioral phenotypes. SIGNIFICANCE: Our behavioral findings show graded deficits across relational memory domains in people with TLE, which provides further insights into the complex pattern of cognitive impairment in the condition.

Atypical intrinsic neural timescales in temporal lobe epilepsy.

OBJECTIVE: Temporal lobe epilepsy (TLE) is the most common pharmacoresistant epilepsy in adults. Here we profiled local neural function in TLE in vivo, building on prior evidence that has identified widespread structural alterations. Using resting-state functional magnetic resonance imaging (rs-fMRI), we mapped the whole-brain intrinsic neural timescales (INT), which reflect temporal hierarchies of neural processing. Parallel analysis of structural and diffusion MRI data examined associations with TLE-related structural compromise. Finally, we evaluated the clinical utility of INT. METHODS: We studied 46 patients with TLE and 44 healthy controls from two independent sites, and mapped INT changes in patients relative to controls across hippocampal, subcortical, and neocortical regions. We examined region-specific associations to structural alterations and explored the effects of age and epilepsy duration. Supervised machine learning assessed the utility of INT for identifying patients with TLE vs controls and left- vs right-sided seizure onset. RESULTS: Relative to controls, TLE showed marked INT reductions across multiple regions bilaterally, indexing faster changing resting activity, with strongest effects in the ipsilateral medial and lateral temporal regions, and bilateral sensorimotor cortices as well as thalamus and hippocampus. Findings were similar, albeit with reduced effect sizes, when correcting for structural alterations. INT reductions in TLE increased with advancing disease duration, yet findings differed from the aging effects seen in controls. INT-derived classifiers discriminated patients vs controls (balanced accuracy, 5-fold: 76% ± 2.65%; cross-site, 72%-83%) and lateralized the focus in TLE (balanced accuracy, 5-fold: 96% ± 2.10%; cross-site, 95%-97%), with high accuracy and cross-site generalizability. Findings were consistent across both acquisition sites and robust when controlling for motion and several methodological confounds. SIGNIFICANCE: Our findings demonstrate atypical macroscale function in TLE in a topography that extends beyond mesiotemporal epicenters. INT measurements can assist in TLE diagnosis, seizure focus lateralization, and monitoring of disease progression, which emphasizes promising clinical utility.

Associations of Cerebral Blood Flow Patterns With Gray and White Matter Structure in Patients With Temporal Lobe Epilepsy.

BACKGROUND AND OBJECTIVES: Neuroimaging studies in patients with temporal lobe epilepsy (TLE) show widespread brain network alterations beyond the mesiotemporal lobe. Despite the critical role of the cerebrovascular system in maintaining whole-brain structure and function, changes in cerebral blood flow (CBF) remain incompletely understood in the disease. Here, we studied whole-brain perfusion and vascular network alterations in TLE and assessed its associations with gray and white matter compromises and various clinical variables. METHODS: We included individuals with and without pharmaco-resistant TLE who underwent multimodal 3T MRI, including arterial spin labelling, structural, and diffusion-weighted imaging. Using surface-based MRI mapping, we generated individualized cortico-subcortical profiles of perfusion, morphology, and microstructure. Linear models compared regional CBF in patients with controls and related alterations to morphological and microstructural metrics. We further probed interregional vascular networks in TLE, using graph theoretical CBF covariance analysis. The effects of disease duration were explored to better understand the progressive changes in perfusion. We assessed the utility of perfusion in separating patients with TLE from controls using supervised machine learning. RESULTS: Compared with control participants (n = 38; mean ± SD age 34.8 ± 9.3 years; 20 females), patients with TLE (n = 24; mean ± SD age 35.8 ± 10.6 years; 12 females) showed widespread CBF reductions predominantly in fronto-temporal regions (Cohen d -0.69, 95% CI -1.21 to -0.16), consistent in a subgroup of patients who remained seizure-free after surgical resection of the seizure focus. Parallel structural profiling and network-based models showed that cerebral hypoperfusion may be partially constrained by gray and white matter changes (8.11% reduction in Cohen d) and topologically segregated from whole-brain perfusion networks (area under the curve -0.17, p < 0.05). Negative effects of progressive disease duration further targeted regional CBF profiles in patients (r = -0.54, 95% CI -0.77 to -0.16). Perfusion-derived classifiers discriminated patients from controls with high accuracy (71% [70%-82%]). Findings were robust when controlling for several methodological confounds. DISCUSSION: Our multimodal findings provide insights into vascular contributions to TLE pathophysiology affecting and extending beyond mesiotemporal structures and highlight their clinical potential in epilepsy diagnosis. As our work was cross-sectional and based on a single site, it motivates future longitudinal studies to confirm progressive effects, ideally in a multicentric setting.

Atypical connectome topography and signal flow in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common pharmaco-resistant epilepsy in adults. While primarily associated with mesiotemporal pathology, recent evidence suggests that brain alterations in TLE extend beyond the paralimbic epicenter and impact macroscale function and cognitive functions, particularly memory. Using connectome-wide manifold learning and generative models of effective connectivity, we examined functional topography and directional signal flow patterns between large-scale neural circuits in TLE at rest. Studying a multisite cohort of 95 patients with TLE and 95 healthy controls, we observed atypical functional topographies in the former group, characterized by reduced differentiation between sensory and transmodal association cortices, with most marked effects in bilateral temporo-limbic and ventromedial prefrontal cortices. These findings were consistent across all study sites, present in left and right lateralized patients, and validated in a subgroup of patients with histopathological validation of mesiotemporal sclerosis and post-surgical seizure freedom. Moreover, they were replicated in an independent cohort of 30 TLE patients and 40 healthy controls. Further analyses demonstrated that reduced differentiation related to decreased functional signal flow into and out of temporolimbic cortical systems and other brain networks. Parallel analyses of structural and diffusion-weighted MRI data revealed that topographic alterations were independent of TLE-related cortical thinning but partially mediated by white matter microstructural changes that radiated away from paralimbic circuits. Finally, we found a strong association between the degree of functional alterations and behavioral markers of memory dysfunction. Our work illustrates the complex landscape of macroscale functional imbalances in TLE, which can serve as intermediate markers bridging microstructural changes and cognitive impairment.

Business models for local energy market and circular economy establishment in municipalities: A case study in an Austrian municipality.

Energy communities often lack authority for establishment and operation management. Municipal authorities could take the role of such community operators. Therefore, Local Sustainable Municipalities are introduced, providing a local energy market on the municipal level with inclusion of sustainable resource utilization. The analyses include examinations of the scope of local markets in a municipality, portfolio investigations on different waste treatment plants and greywater system installation analyses. Furthermore, different adopted municipality strategies and their impact on municipal portfolio and market operation are examined. A clustering-based optimization framework for portfolio and market optimization is developed to perform these analyses. The proposed modeling approach leads to a significant model size reduction compared with hourly data optimization while providing location determination and portfolio estimation. The results indicate energy-sharing differences between municipal markets and local markets in energy communities. Decentralized energy provision is similar to centralized energy provision but on the municipal level. Furthermore, results show that waste incineration energy recovery can provide dispatchable low-emission energy with a high level of energy security and should be supported until the energy transition is more advanced. Finally, results on local strategies show that specific municipal goals always lead to increased costs for the municipality.

Creating an indicator system for the United Nations Sustainable Development Goals in communities and municipalities: Application and analysis in an Austrian case study.

Sustainability indicators should implement the United Nations Sustainable Development Goals (UN SDGs). Indicators in literature often consider large sets of actions and are thus complex in application. Therefore, this work derives energy- and resource-related SDG indicators for communities and municipalities with low complexity. Moreover, this work analyzes three different policy paths to promote SDG contribution. The policy paths consider SDG target settings and two different incentive schemes in the form of penalties and investment subsidies. The indicators and policy actions are applied in two case studies for communities and municipalities in Austria. Therefore, an optimization model that considers the case study setups, SDG targets and policy actions is developed. The modeling approach shows applicability and positive contribution to sustainable development by indicators. Moreover, the results show the applicability of the three policy paths. Implementing the target-setting path directly leads to the desired SDG targets and provides insights into the costs for target achievement. The incentive scheme paths also lead to selected targets, but they require a cost assessment of the provided incentive schemes. A combination of both incentive schemes leads to the lowest costs. However, policymakers should implement a workflow that considers all three policy paths for policy action settings.

Atypical connectome topography and signal flow in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is one of the most common pharmaco-resistant epilepsies in adults. While hippocampal pathology is the hallmark of this condition, emerging evidence indicates that brain alterations extend beyond the mesiotemporal epicenter and affect macroscale brain function and cognition. We studied macroscale functional reorganization in TLE, explored structural substrates, and examined cognitive associations. We investigated a multisite cohort of 95 patients with pharmaco-resistant TLE and 95 healthy controls using state-of-the-art multimodal 3T magnetic resonance imaging (MRI). We quantified macroscale functional topographic organization using connectome dimensionality reduction techniques and estimated directional functional flow using generative models of effective connectivity. We observed atypical functional topographies in patients with TLE relative to controls, manifesting as reduced functional differentiation between sensory/motor networks and transmodal systems such as the default mode network, with peak alterations in bilateral temporal and ventromedial prefrontal cortices. TLE-related topographic changes were consistent in all three included sites and reflected reductions in hierarchical flow patterns between cortical systems. Integration of parallel multimodal MRI data indicated that these findings were independent of TLE-related cortical grey matter atrophy, but mediated by microstructural alterations in the superficial white matter immediately beneath the cortex. The magnitude of functional perturbations was robustly associated with behavioral markers of memory function. Overall, this work provides converging evidence for macroscale functional imbalances, contributing microstructural alterations, and their associations with cognitive dysfunction in TLE.

Dynamic participation in local energy communities with peer-to-peer trading.

Background: Energy communities and local electricity markets (e.g., as peer-to-peer trading) are on the rise due to increasingly decentralized electricity generation and favorable adjustment of the legal framework in many European countries.  Methods: This work applies a bi-level optimization model for dynamic participation in peer-to-peer electricity trading to determine the optimal parameters of new participants who want to join an energy community, based on the preferences of the members of the original community (e.g., environmental, economic, or mixed preference). The upper-level problem chooses optimal parameters by minimizing an objective function that includes the prosumers' cost-saving and emission-saving preferences, while the lower level problem maximizes community welfare by optimally allocating locally generated photovoltaic (PV) electricity between members according to their willingness-to-pay. The bi-level problem is solved by transforming the lower level problem by its corresponding Karush-Kuhn-Tucker (KKT) conditions. Results: The results demonstrate that environment-oriented prosumers opt for a new prosumer with high PV capacities installed and low electricity demand, whereas profit-oriented prosumers prefer a new member with high demand but no PV system capacity, presenting a new source of income. Sensitivity analyses indicate that new prosumers' willingness-to-pay has an important influence when the community must decide between two new members. Conclusions: The added value of this work is that the proposed method can be seen as a basis for a selection process between a large number of potential new community members. Most important future work will include optimization of energy communities over the horizon several years.

A framework to estimate the large-scale impacts of energy community roll-out.

The gradual enactment of legislation for energy communities in individual European countries has increased the public awareness of these novel concepts. While the establishment of individual, isolated energy communities is unlikely to have any far-reaching effects, it is presumed that the large-scale roll-out will indeed significantly impact different stakeholders. Since the diffusion of energy communities is expected to gain momentum within the next years, this study aims to provide a framework to assess the impact of a large-scale roll-out of solar-PV based energy communities. This nine-step framework provides guidance for determining the number of buildings per type and roof tilt, assessing the usable rooftop area for PV installation and realistically installed PV capacities, estimating the number of future residential PV systems based on renewable expansion plans, determining the shares of buildings to be equipped with PV systems, setting up model energy communities, and upscaling. The nine-step framework is not only described theoretically but also applied to Austria as a case study. Thereby, specific focus is put on Austria's rural areas and thus the single-family building stock. Results indicate the impact of a large-scale roll-out of renewable energy communities on participants' electricity bills, electricity suppliers' sales, and grid operators revenues due to reduced grid tariffs for inner-community electricity transfer. The ability to determine the future impacts of energy community roll-out supports stakeholders in their proper planning towards an energy landscape that includes energy communities.