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Remote longitudinal studies are on the rise and promise to increase reach and reduce participation barriers in chronic disease research. However, maintaining long-term retention in these studies remains challenging. Early identification of participants with different patterns of long-term retention offers the opportunity for tailored survey adaptations. Using data from the online arm of the Swiss Multiple Sclerosis Registry (SMSR), we assessed sociodemographic, health-related, and daily-life related baseline variables against measures of long-term retention in the follow-up surveys through multivariable logistic regressions and unsupervised clustering analyses. We further explored follow-up survey completion measures against survey requirements to inform future survey designs. Our analysis included data from 1,757 participants who completed a median of 4 (IQR 2-8) follow-up surveys after baseline with a maximum of 13 possible surveys. Survey start year, age, citizenship, MS type, symptom burden and independent driving were significant predictors of long-term retention at baseline. Three clusters of participants emerged, with no differences in long-term retention outcomes revealed across the clusters. Exploratory assessments of follow-up surveys suggest possible trends in increased survey complexity with lower rates of survey completion. Our findings offer insights into characteristics associated with long-term retention in remote longitudinal studies, yet they also highlight the possible influence of various unexplored factors on retention outcomes. Future studies should incorporate additional objective measures that reflect participants' individual contexts to understand their ability to remain engaged long-term and inform survey adaptations accordingly.

Abstract Background While potential risk factors for multiple sclerosis (MS) have been extensively researched, it remains unclear how persons with MS theorize about their MS. Such theories may affect mental health and treatment adherence. Using natural language processing techniques, we investigated large-scale text data about theories that persons with MS have about the causes of their disease. We examined the topics into which their theories could be grouped and the prevalence of each theory topic. Methods A total of 486 participants of the Swiss MS Registry longitudinal citizen science project provided text data on their theories about the etiology of MS. We used the transformer-based BERTopic Python library for topic modeling to identify underlying topics. We then conducted an in-depth characterization of the topics and assessed their prevalence. Results The topic modeling analysis identifies 19 distinct topics that participants theorize as causal for their MS. The topics most frequently cited are Mental Distress (31.5%), Stress (Exhaustion, Work) (29.8%), Heredity/Familial Aggregation (27.4%), and Diet, Obesity (16.0%). The 19 theory topics can be grouped into four high-level categories: physical health (mentioned by 56.2% of all participants), mental health (mentioned by 53.7%), risk factors established in the scientific literature (genetics, Epstein-Barr virus, smoking, vitamin D deficiency/low sunlight exposure; mentioned by 47.7%), and fate/coincidence (mentioned by 3.1%). Our study highlights the importance of mental health issues for theories participants have about the causes of their MS. Conclusions Our findings emphasize the importance of communication between healthcare professionals and persons with MS about the pathogenesis of MS, the scientific evidence base and mental health.

Abstract The entanglement asymmetry is an information based observable that quantifies the degree of symmetry breaking in a region of an extended quantum system. We investigate this measure in the ground state of one dimensional critical systems described by a CFT. Employing the correspondence between global symmetries and defects, the analysis of the entanglement asymmetry can be formulated in terms of partition functions on Riemann surfaces with multiple non-topological defect lines inserted at their branch cuts. For large subsystems, these partition functions are determined by the scaling dimension of the defects. This leads to our first main observation: at criticality, the entanglement asymmetry acquires a subleading contribution scaling as log ℓ/ℓ for large subsystem length ℓ. Then, as an illustrative example, we consider the XY spin chain, which has a critical line described by the massless Majorana fermion theory and explicitly breaks the U(1) symmetry associated with rotations about the z-axis. In this situation the corresponding defect is marginal. Leveraging conformal invariance, we relate the scaling dimension of these defects to the ground state energy of the massless Majorana fermion on a circle with equally-spaced point defects. We exploit this mapping to derive our second main result: the exact expression for the scaling dimension associated with n defects of arbitrary strengths. Our result generalizes a known formula for the n = 1 case derived in several previous works. We then use this exact scaling dimension to derive our third main result: the exact prefactor of the log ℓ/ℓ term in the asymmetry of the critical XY chain.

The interplay between symmetries and entanglement in out-of-equilibrium quantum systems is currently at the center of an intense multidisciplinary research effort. Here we introduce a setting where these questions can be characterized exactly by considering dual-unitary circuits with an arbitrary number of U(1) charges. After providing a complete characterization of these systems we show that one can introduce a class of solvable states, which extends that of generic dual-unitary circuits, for which the nonequilibrium dynamics can be solved exactly. In contrast to the known class of solvable states, which relax to the infinite-temperature state, these states relax to a family of nontrivial generalized Gibbs ensembles. The relaxation process of these states can be simply described by a linear growth of the entanglement entropy followed by saturation to a nonmaximal value but with maximal entanglement velocity. We then move on to consider the dynamics from nonsolvable states, combining the exact results with the entanglement membrane picture we argue that the entanglement dynamics from these states is qualitatively different from that of the solvable ones. It shows two different growth regimes characterized by two distinct slopes, both corresponding to submaximal entanglement velocities. Moreover, we show that nonsolvable initial states can give rise to the quantum Mpemba effect, where less symmetric initial states restore the symmetry faster than more symmetric ones.

Abstract We investigate how entanglement in the mixed state of a quantum field theory can be described using the cross-computable norm or realignment (CCNR) criterion, employing a recently introduced negativity. We study its symmetry resolution for two disjoint intervals in the ground state of the massless Dirac fermion field theory, extending previous results for the case of adjacent intervals. By applying the replica trick, this problem boils down to computing the charged moments of the realignment matrix. We show that, for two disjoint intervals, they correspond to the partition function of the theory on a torus with a non-contractible charged loop. This confers a great advantage compared to the negativity based on the partial transposition, for which the Riemann surfaces generated by the replica trick have higher genus. This result empowers us to carry out the replica limit, yielding analytic expressions for the symmetry-resolved CCNR negativity. Furthermore, these expressions provide also the symmetry decomposition of other related quantities such as the operator entanglement of the reduced density matrix or the reflected entropy.

Abstract We study the Rényi entanglement entropies along the massless renormalisation group flow that connects the tricritical and critical Ising field theories. Similarly to the massive integrable field theories, we derive a set of bootstrap equations, from which we can analytically calculate the twist field form factors in a recursive way. Additionally, we also obtain them as a non-trivial ‘roaming limit’ of the sinh-Gordon theory. Then the Rényi entanglement entropies are obtained as expansions in terms of the form factors of these branch point twist fields. We find that the form factor expansion of the entanglement entropy along the flow organises in two different kind of terms. Those that couple particles with the same chirality, and reproduce the entropy of the infrared Ising theory, and those that couple particles with different chirality, which provide the ultraviolet contributions. The massless flow under study possesses a global ℤ2 spin-flip symmetry. We further consider the composite twist fields associated to this group, which enter in the study of the symmetry resolution of the entanglement. We derive analytical expressions for their form factors both from the bootstrap equations and from the roaming limit of the sinh-Gordon theory.

BackgroundImproving health-related quality of life (HRQoL) is an important disease management goal in persons with Multiple Sclerosis (PwMS). HRQoL decreases with increasing age and prolonged disease duration; other factors remain less understood.ObjectiveTo identify associations of multiple sclerosis (MS) disease characteristics and symptom burden with low HRQoL.MethodsUsing the Swiss MS Registry, we applied quantile regression adjusted for age and MS disease duration to determine 25th (low HRQoL) and 75th (high HRQoL) percentiles of the EuroQol-5-Dimension (EQ-5D) distribution for PwMS. We compared PwMS across HRQoL groups by analyzing differences in sociodemographics, symptom burden, MS risk factors, gait impairment, and the MS Severity Score (MSSS), all measured at the same time as HRQoL. The analyses included descriptive methods, multivariable multinomial regression, and simultaneous quantile regression as a sensitivity analysis.ResultsWe included 1697 PwMS with median age and time-to-diagnosis of 49 and 9 years. Multivariable regression revealed low HRQoL to be associated with receiving invalidity insurance benefits, reporting depression, muscle weakness, memory problems, pain, and severe gait impairment. The analysis for individuals with available MSSS (n = 937) showed an increasing probability of low HRQoL with higher MSSS.ConclusionOur segmentation method identified symptom burden and MS severity as factors associated with low HRQoL. Pharmacological and non-pharmacological MS symptom management, especially for depression, fatigue, pain, and muscle weakness, may warrant increased attention to preserve or improve HRQoL.

Abstract The negativity Hamiltonian, defined as the logarithm of a partially transposed density matrix, provides an operatorial characterisation of mixed-state entanglement. However, so far, it has only been studied for the mixed-state density matrices corresponding to subsystems of globally pure states. Here, we consider as a genuine example of a mixed state the one-dimensional massless Dirac fermions in a system at finite temperature and size. As subsystems, we consider an arbitrary set of disjoint intervals. The structure of the corresponding negativity Hamiltonian resembles the one for the entanglement Hamiltonian in the same geometry: in addition to a local term proportional to the stress-energy tensor, each point is non-locally coupled to an infinite but discrete set of other points. However, when the lengths of the transposed and non-transposed intervals coincide, the structure remarkably simplifies and we retrieve the mild non-locality of the ground state negativity Hamiltonian. We also conjecture an exact expression for the negativity Hamiltonian associated to the twisted partial transpose, which is a Hermitian fermionic matrix. We finally obtain the continuum limit of both the local and bi-local operators from exact numerical computations in free-fermionic chains.

Abstract Symmetry and symmetry breaking are two pillars of modern quantum physics. Still, quantifying how much a symmetry is broken is an issue that has received little attention. In extended quantum systems, this problem is intrinsically bound to the subsystem of interest. Hence, in this work, we borrow methods from the theory of entanglement in many-body quantum systems to introduce a subsystem measure of symmetry breaking that we dub entanglement asymmetry. As a prototypical illustration, we study the entanglement asymmetry in a quantum quench of a spin chain in which an initially broken global U(1) symmetry is restored dynamically. We adapt the quasiparticle picture for entanglement evolution to the analytic determination of the entanglement asymmetry. We find, expectedly, that larger is the subsystem, slower is the restoration, but also the counterintuitive result that more the symmetry is initially broken, faster it is restored, a sort of quantum Mpemba effect, a phenomenon that we show to occur in a large variety of systems.

Abstract The effect of unstable quasiparticles in the out-of-equilibrium dynamics of certain integrable systems has been the subject of several recent studies. In this paper we focus on the stationary value of the entanglement entropy density, its growth rate, and related functions, after a quantum quench. We consider several quenches, each of which is characterised by a corresponding squeezed coherent state. In the quench action approach, the coherent state amplitudes K(θ) become input data that fully characterise the large-time stationary state, thus also the corresponding Yang-Yang entropy. We find that, as function of the mass of the unstable particle, the entropy growth rate has a global minimum signalling the depletion of entropy that accompanies a slowdown of stable quasiparticles at the threshold for the formation of an unstable excitation. We also observe a separation of scales governed by the interplay between the mass of the unstable particle and the quench parameter, separating a non-interacting regime described by free fermions from an interacting regime where the unstable particle is present. This separation of scales leads to a double-plateau structure of many functions, where the relative height of the plateaux is related to the ratio of central charges of the UV fixed points associated with the two regimes, in full agreement with conformal field theory predictions. The properties of several other functions of the entropy and its growth rate are also studied in detail, both for fixed quench parameter and varying unstable particle mass and viceversa.

Abstract Whenever a system possesses a conserved charge, the density matrix splits into eigenspaces associated to the each symmetry sector and we can access the entanglement entropy in a given subspace, known as symmetry resolved entanglement (SRE). Here, we first evaluate the SRE for massless Dirac fermions in a system at finite temperature and size, i.e. on a torus. Then we add a massive term to the Dirac action and we treat it as a perturbation of the massless theory. The charge-dependent entropies turn out to be equally distributed among all the symmetry sectors at leading order. However, we find subleading corrections which depend both on the mass and on the boundary conditions along the torus. We also study the resolution of the fermionic negativity in terms of the charge imbalance between two subsystems. We show that also for this quantity, the presence of the mass alters the equipartition among the different imbalance sectors at subleading order.

Abstract We consider the ground state of a theory composed by M species of massless complex bosons in one dimension coupled together via a conformal interface. We compute both the Rényi entropy and the negativity of a generic partition of wires, generalizing the approach developed in a recent work for free fermions. These entanglement measures show a logarithmic growth with the system size, and the universal prefactor depends both on the details of the interface and the bipartition. We test our analytical predictions against exact numerical results for the harmonic chain.

Abstract The aim of our study was to investigate whether self-reported feeling of loneliness (FoL) and COVID-19-specific health anxiety were associated with the presence of depressive symptoms during the first coronavirus disease 2019 (COVID-19) wave. Questionnaires of 603 persons of the Swiss Multiple Sclerosis Registry (SMSR) were cross-sectionally analyzed using descriptive and multivariable regression methods. The survey response rate was 63.9%. Depressive symptoms were assessed by the Beck Depression Inventory-Fast Screen (BDI-FS). COVID-19-specific health anxiety and FoL were measured using two 5-item Likert scaled pertinent questions. High scoring FoL (2.52, 95% confidence interval (CI) (2.06—2.98)) and/or COVID-19 specific health anxiety (1.36, 95% CI (0.87–1.85)) were significantly associated with depressive symptoms. Further stratification analysis showed that the impact of FoL on depressive symptoms affected all age groups. However, it was more pronounced in younger PwMS, whereas an impact of COVID-19 specific health anxiety on depressive symptoms was particularly observed in middle-aged PwMS. FoL and COVID-19-specific health anxiety were age-dependently associated with depressive symptoms during the first COVID-19 wave in Switzerland. Our findings could guide physicians, health authorities, and self-help groups to better accompany PwMS in times of public health crises.

Abstract We study the multi-charged moments for two disjoint intervals in the ground state of two 1 + 1 dimensional CFTs with central charge c = 1 and global U(1) symmetry: the massless Dirac field theory and the compact boson (Luttinger liquid). For this purpose, we compute the partition function on the higher genus Riemann surface arising from the replica method in the presence of background magnetic fluxes between the sheets of the surface. We consider the general situation in which the fluxes generate different twisted boundary conditions at each branch point. The obtained multi-charged moments allow us to derive the symmetry resolution of the Rényi entanglement entropies and the mutual information for non complementary bipartitions. We check our findings against exact numerical results for the tight-binding model, which is a lattice realisation of the massless Dirac theory.

Abstract We investigate the ground state of a (1+1)-dimensional conformal field theory (CFT) built with M species of massless free Dirac fermions coupled at one boundary point via a conformal junction/interface. Each CFT represents a wire of finite length L. We develop a systematic strategy to compute the Rényi entropies for a generic bipartition between the wires and the entanglement negativity between two non-complementary sets of wires. Both these entanglement measures turn out to grow logarithmically with L with an exactly calculated universal prefactor depending on the details of the junction and of the bipartition. These analytic predictions are tested numerically for junctions of free Fermi gases, finding perfect agreement.

Abstract In this paper, we apply the form factor bootstrap approach to branch point twist fields in the q-state Potts model for q ≤ 3. For q = 3 this is an integrable interacting quantum field theory with an internal discrete ℤ3 symmetry and therefore provides an ideal starting point for the investigation of the symmetry resolved entanglement entropies. However, more generally, for q ≤ 3 the standard Rényi and entanglement entropies are also accessible through the bootstrap programme. In our work we present form factor solutions both for the standard branch point twist field with q ≤ 3 and for the composite (or symmetry resolved) branch point twist field with q = 3. In both cases, the form factor equations are solved for two particles and the solutions are carefully checked via the ∆-sum rule. Using our analytic predictions, we compute the leading finite-size corrections to the entanglement entropy and entanglement equipartition for a single interval in the ground state.

Abstract We introduce and study generalized Rényi entropies defined through the traces of products of Tr B (| Ψ i ⟩⟨Ψ j | ) where ∣Ψ i ⟩ are eigenstates of a two-dimensional conformal field theory (CFT). When ∣Ψ i ⟩ = ∣Ψ j ⟩ these objects reduce to the standard Rényi entropies of the eigenstates of the CFT. Exploiting the path integral formalism, we show that the second generalized Rényi entropies are equivalent to four point correlators. We then focus on a free bosonic theory for which the mode expansion of the fields allows us to develop an efficient strategy to compute the second generalized Rényi entropy for all eigenstates. As a byproduct, our approach also leads to new results for the standard Rényi and relative entropies involving arbitrary descendent states of the bosonic CFT.

IntroductionThe presence of focal cortical and white matter damage in patients with multiple sclerosis (pwMS) might lead to specific alterations in brain networks that are associated with cognitive impairment. We applied microstructure-weighted connectomes to investigate (i) the relationship between global network metrics and information processing speed in pwMS, and (ii) whether the disruption provoked by focal lesions on global network metrics is associated to patients’ information processing speed.Materials and methodsSixty-eight pwMS and 92 healthy controls (HC) underwent neuropsychological examination and 3T brain MRI including multishell diffusion (dMRI), 3D FLAIR, and MP2RAGE. Whole-brain deterministic tractography and connectometry were performed on dMRI. Connectomes were obtained using the Spherical Mean Technique and were weighted for the intracellular fraction. We identified white matter lesions and cortical lesions on 3D FLAIR and MP2RAGE images, respectively. PwMS were subdivided into cognitively preserved (CPMS) and cognitively impaired (CIMS) using the Symbol Digit Modalities Test (SDMT) z-score at cut-off value of −1.5 standard deviations. Statistical analyses were performed using robust linear models with age, gender, and years of education as covariates, followed by correction for multiple testing.ResultsOut of 68 pwMS, 18 were CIMS and 50 were CPMS. We found significant changes in all global network metrics in pwMS vs HC (p < 0.05), except for modularity. All global network metrics were positively correlated with SDMT, except for modularity which showed an inverse correlation. Cortical, leukocortical, and periventricular lesion volumes significantly influenced the relationship between (i) network density and information processing speed and (ii) modularity and information processing speed in pwMS. Interestingly, this was not the case, when an exploratory analysis was performed in the subgroup of CIMS patients.DiscussionOur study showed that cortical (especially leukocortical) and periventricular lesions affect the relationship between global network metrics and information processing speed in pwMS. Our data also suggest that in CIMS patients increased focal cortical and periventricular damage does not linearly affect the relationship between network properties and SDMT, suggesting that other mechanisms (e.g. disruption of local networks, loss of compensatory processes) might be responsible for the development of processing speed deficits.

Abstract We develop a systematic approach to compute the subsystem trace distances and relative entropies for subsystem reduced density matrices associated to excited states in different symmetry sectors of a 1+1 dimensional conformal field theory having an internal U(1) symmetry. We provide analytic expressions for the charged moments corresponding to the resolution of both relative entropies and distances for general integer n. For the relative entropies, these formulas are manageable and the analytic continuation to n = 1 can be worked out in most of the cases. Conversely, for the distances the corresponding charged moments become soon untreatable as n increases. A remarkable result is that relative entropies and distances are the same for all symmetry sectors, i.e. they satisfy entanglement equipartition, like the entropies. Moreover, we exploit the OPE expansion of composite twist fields, to provide very general results when the subsystem is a single interval much smaller than the total system. We focus on the massless compact boson and our results are tested against exact numerical calculations in the XX spin chain.

Abstract We propose an ordered set of experimentally accessible conditions for detecting entanglement in mixed states. The k-th condition involves comparing moments of the partially transposed density operator up to order k. Remarkably, the union of all moment inequalities reproduces the Peres-Horodecki criterion for detecting entanglement. Our empirical studies highlight that the first four conditions already detect mixed state entanglement reliably in a variety of quantum architectures. Exploiting symmetries can help to further improve their detection capabilities. We also show how to estimate moment inequalities based on local random measurements of single state copies (classical shadows) and derive statistically sound confidence intervals as a function of the number of performed measurements. Our analysis includes the experimentally relevant situation of drifting sources, i.e. non-identical, but independent, state copies.

Abstract We consider the problem of the decomposition of the Rényi entanglement entropies in theories with a non-abelian symmetry by doing a thorough analysis of Wess-Zumino-Witten (WZW) models. We first consider SU(2) k as a case study and then generalise to an arbitrary non-abelian Lie group. We find that at leading order in the subsystem size L the entanglement is equally distributed among the different sectors labelled by the irreducible representation of the associated algebra. We also identify the leading term that breaks this equipartition: it does not depend on L but only on the dimension of the representation. Moreover, a log log L contribution to the Rényi entropies exhibits a universal prefactor equal to half the dimension of the Lie group.

BackgroundThe increasing availability of “real-world” data in the form of written text holds promise for deepening our understanding of societal and health-related challenges. Textual data constitute a rich source of information, allowing the capture of lived experiences through a broad range of different sources of information (eg, content and emotional tone). Interviews are the “gold standard” for gaining qualitative insights into individual experiences and perspectives. However, conducting interviews on a large scale is not always feasible, and standardized quantitative assessment suitable for large-scale application may miss important information. Surveys that include open-text assessments can combine the advantages of both methods and are well suited for the application of natural language processing (NLP) methods. While innovations in NLP have made large-scale text analysis more accessible, the analysis of real-world textual data is still complex and requires several consecutive steps. ObjectiveWe developed and subsequently examined the utility and scientific value of an NLP pipeline for extracting real-world experiences from textual data to provide guidance for applied researchers. MethodsWe applied the NLP pipeline to large-scale textual data collected by the Swiss Multiple Sclerosis (MS) registry. Such textual data constitute an ideal use case for the study of real-world text data. Specifically, we examined 639 text reports on the experienced impact of the first COVID-19 lockdown from the perspectives of persons with MS. The pipeline has been implemented in Python and complemented by analyses of the “Linguistic Inquiry and Word Count” software. It consists of the following 5 interconnected analysis steps: (1) text preprocessing; (2) sentiment analysis; (3) descriptive text analysis; (4) unsupervised learning–topic modeling; and (5) results interpretation and validation. ResultsA topic modeling analysis identified the following 4 distinct groups based on the topics participants were mainly concerned with: “contacts/communication;” “social environment;” “work;” and “errands/daily routines.” Notably, the sentiment analysis revealed that the “contacts/communication” group was characterized by a pronounced negative emotional tone underlying the text reports. This observed heterogeneity in emotional tonality underlying the reported experiences of the first COVID-19–related lockdown is likely to reflect differences in emotional burden, individual circumstances, and ways of coping with the pandemic, which is in line with previous research on this matter. ConclusionsThis study illustrates the timely and efficient applicability of an NLP pipeline and thereby serves as a precedent for applied researchers. Our study thereby contributes to both the dissemination of NLP techniques in applied health sciences and the identification of previously unknown experiences and burdens of persons with MS during the pandemic, which may be relevant for future treatment.

BackgroundElectronic health diaries hold promise in complementing standardized surveys in prospective health studies but are fraught with numerous methodological challenges. ObjectiveThe study aimed to investigate participant characteristics and other factors associated with response to an electronic health diary campaign in persons with multiple sclerosis, identify recurrent topics in free-text diary entries, and assess the added value of structured diary entries with regard to current symptoms and medication intake when compared with survey-collected information. MethodsData were collected by the Swiss Multiple Sclerosis Registry during a nested electronic health diary campaign and during a regular semiannual Swiss Multiple Sclerosis Registry follow-up survey serving as comparator. The characteristics of campaign participants were descriptively compared with those of nonparticipants. Diary content was analyzed using the Linguistic Inquiry and Word Count 2015 software (Pennebaker Conglomerates, Inc) and descriptive keyword analyses. The similarities between structured diary data and follow-up survey data on health-related quality of life, symptoms, and medication intake were examined using the Jaccard index. ResultsCampaign participants (n=134; diary entries: n=815) were more often women, were not working full time, did not have a higher education degree, had a more advanced gait impairment, and were on average 5 years older (median age 52.5, IQR 43.25-59.75 years) than eligible nonparticipants (median age 47, IQR 38-55 years; n=524). Diary free-text entries (n=632; participants: n=100) most often contained references to the following standard Linguistic Inquiry and Word Count word categories: negative emotion (193/632, 30.5%), body parts or body functioning (191/632, 30.2%), health (94/632, 14.9%), or work (67/632, 10.6%). Analogously, the most frequently mentioned keywords (diary entries: n=526; participants: n=93) were “good,” “day,” and “work.” Similarities between diary data and follow-up survey data, collected 14 months apart (median), were high for health-related quality of life and stable for slow-changing symptoms such as fatigue or gait disorder. Similarities were also comparatively high for drugs requiring a regular application, including interferon beta-1a (Avonex) and glatiramer acetate (Copaxone), and for modern oral therapies such as fingolimod (Gilenya) and teriflunomide (Aubagio). ConclusionsDiary campaign participation seemed dependent on time availability and symptom burden and was enhanced by reminder emails. Electronic health diaries are a meaningful complement to regular structured surveys and can provide more detailed information regarding medication use and symptoms. However, they should ideally be embedded into promotional activities or tied to concrete research study tasks to enhance regular and long-term participation.

Multiple Sclerosis (MS) and Rheumatoid Arthritis (RA) are common, chronic, autoimmune diseases affecting many people worldwide. While clinically very different in their phenotype, both diseases are thought to have an autoimmune-mediated origin. MS and RA share genetic similarities, and in both diseases, antibodies against host antigens can be found. Aside from the well-known somatic symptoms, many RA patients also show signs and symptoms of psychiatric illnesses, of which depression is the most common diagnosis. In this commentary, both diseases will be introduced and briefly characterized individually and then compared. Depression will be introduced as one of the most frequent psychiatric diseases in the general population. This paper focuses on presenting the possible causes, including psychosocial factors, genetics, and immunologic mechanisms. Hypotheses aimed to explain the higher incidence of depression in these two seemingly different autoimmune diseases will be discussed.

Abstract We generalise the form factor bootstrap approach to integrable field theories with U(1) symmetry to derive matrix elements of composite branch-point twist fields associated with symmetry resolved entanglement entropies. The bootstrap equations are solved for the free massive Dirac and complex boson theories, which are the simplest theories with U(1) symmetry. We present the exact and complete solution for the bootstrap, including vacuum expectation values and form factors involving any type and arbitrarily number of particles. The non-trivial solutions are carefully cross-checked by performing various limits and by the application of the ∆-theorem. An alternative and compact determination of the novel form factors is also presented. Based on the form factors of the U(1) composite branch-point twist fields, we re-derive earlier results showing entanglement equipartition for an interval in the ground state of the two models.

Abstract Objective To determine the levels of brain‐derived neurotrophic factor (BDNF) in the serum of patients suffering from multiple sclerosis (MS) to evaluate the potential of serum BDNF as a biomarker for MS. Methods Using a recently validated enzyme‐linked immunoassay (ELISA) we measured BDNF in patients with MS (pwMS), diagnosed according to the 2001 McDonald criteria and aged between 18 and 70 years, participating in a long‐term cohort study with annual clinical visits, including blood sampling, neuropsychological testing, and brain magnetic resonance imaging (MRI). The results were compared with an age‐ and sex‐matched cohort of healthy controls (HC). Correlations between BDNF levels and a range of clinical and magnetic resonance imaging variables were assessed using an adjusted linear model. Results In total, 259 pwMS and 259 HC were included, with a mean age of 44.42 ± 11.06 and 44.31 ± 11.26 years respectively. Eleven had a clinically isolated syndrome (CIS), 178 relapsing remitting MS (RRMS), 56 secondary progressive MS (SPMS), and 14 primary progressive MS (PPMS). Compared with controls, mean BDNF levels were lower by 8 % (p˂0.001) in pwMS. The level of BDNF in patients with SPMS was lower than in RRMS (p = 0.004). Interpretation We conclude that while the use of comparatively large cohorts enables the detection of a significant difference in BDNF levels between pwMS and HC, the difference is small and unlikely to usefully inform decision‐making processes at an individual patient level.

Abstract We present a thorough analysis of the entanglement entropies related to different symmetry sectors of free quantum field theories (QFT) with an internal U(1) symmetry. We provide explicit analytic computations for the charged moments of Dirac and complex scalar fields in two spacetime dimensions, both in the massive and massless cases, using two different approaches. The first one is based on the replica trick, the computation of the partition function on Riemann surfaces with the insertion of a flux α, and the introduction of properly modified twist fields, whose two-point function directly gives the scaling limit of the charged moments. With the second method, the diagonalisation in replica space maps the problem to the computation of a partition function on a cut plane, that can be written exactly in terms of the solutions of non-linear differential equations of the Painlevé V type. Within this approach, we also derive an asymptotic expansion for the short and long distance behaviour of the charged moments. Finally, the Fourier transform provides the desired symmetry resolved entropies: at the leading order, they satisfy entanglement equipartition and we identify the subleading terms that break it. Our analytical findings are tested against exact numerical calculations in lattice models.

The operator entanglement (OE) is a key quantifier of the complexity of a reduced density matrix. In out-of-equilibrium situations, e.g., after a quantum quench of a product state, it is expected to exhibit an entanglement barrier. The OE of a reduced density matrix initially grows linearly as entanglement builds up between the local degrees of freedom; it then reaches a maximum and ultimately decays to a small finite value as the reduced density matrix converges to a simple stationary state through standard thermalization mechanisms. Here, by performing a new data analysis of the published experimental results of Brydges et al. [Science 364, 260 (2019)], we obtain the first experimental estimation of the OE of a subsystem reduced density matrix in a quantum many-body system. We employ the randomized-measurements toolbox and we introduce and develop a new efficient method to postprocess experimental data in order to extract higher-order density-matrix functionals and access the OE. The OE thus obtained displays the expected barrier as long as the experimental system is large enough. For smaller systems, we observe a barrier with a double-peak structure, the origin of which can be interpreted in terms of pairs of quasiparticles being reflected at the boundary of the qubit chain. As U(1) symmetry plays a key role in our analysis, we introduce the notion of symmetry-resolved operator entanglement (SROE), in addition to the total OE. To gain further insights into the SROE, we provide a thorough theoretical analysis of this new quantity in chains of noninteracting fermions, which, in spite of their simplicity, capture most of the main features of OE and SROE. In particular, we uncover three main physical effects: the presence of a barrier in any charge sector, a time delay for the onset of the growth of SROE, and an effective equipartition between charge sectors.

Abstract We investigate the time evolution of the subsystem trace distance and Schatten distances after local operator quenches in two-dimensional conformal field theory (CFT) and in one-dimensional quantum spin chains. We focus on the case of a subsystem being an interval embedded in the infinite line. The initial state is prepared by inserting a local operator in the ground state of the theory. We only consider the cases in which the inserted local operator is a primary field or a sum of several primaries. While a nonchiral primary operator can excite both left-moving and right-moving quasiparticles, a holomorphic primary operator only excites a right-moving quasiparticle and an anti-holomorphic primary operator only excites a left-moving one. The reduced density matrix (RDM) of an interval hosting a quasiparticle is orthogonal to the RDM of the interval without any quasiparticles. Moreover, the RDMs of two intervals hosting quasiparticles at different positions are also orthogonal to each other. We calculate numerically the entanglement entropy, Rényi entropy, trace distance, and Schatten distances in time-dependent states excited by different local operators in the critical Ising and XX spin chains. These results match the CFT predictions in the proper limit.

Abstract We report on a systematic replica approach to calculate the subsystem trace distance for a quantum field theory. This method has been recently introduced in [J. Zhang, P. Ruggiero and P. Calabrese, Phys. Rev. Lett. 122 (2019) 141602 ], of which this work is a completion. The trace distance between two reduced density matrices ρ A and σ A is obtained from the moments tr(ρ A − σ A ) n and taking the limit n → 1 of the traces of the even powers. We focus here on the case of a subsystem consisting of a single interval of length ℓ embedded in the low lying eigenstates of a one-dimensional critical system of length L, a situation that can be studied exploiting the path integral form of the reduced density matrices of two-dimensional conformal field theories. The trace distance turns out to be a scale invariant universal function of ℓ/L. Here we complete our previous work by providing detailed derivations of all results and further new formulas for the distances between several low-lying states in two-dimensional free massless compact boson and fermion theories. Remarkably, for one special case in the bosonic theory and for another in the fermionic one, we obtain the exact trace distance, as well as the Schatten n-distance, for an interval of arbitrary length, while in generic case we have a general form for the first term in the expansion in powers of ℓ/L. The analytical predictions in conformal field theories are tested against exact numerical calculations in XX and Ising spin chains, finding perfect agreement. As a byproduct, new results in two-dimensional CFT are also obtained for other entanglement-related quantities, such as the relative entropy and the fidelity.

Background: Fatigue is a common non-motor symptom in Parkinson’s disease (PD) and is typically assessed via self-reported questionnaires such as the Parkinson’s Fatigue Scale (PFS). The PFS captures the presence of subjective experience of physical fatigue as well as its impact on daily functioning. Objectives: We aimed to investigate whether different variables (cognition, neuropsychiatric symptoms, disease-related measures) are associated with the experience of physical fatigue in comparison to fatigue affecting daily functioning. Method: Sixty-two non-demented PD patients were evaluated through questionnaires assessing fatigue, daytime sleepiness, apathy, depression, anxiety, and cognition. Items of fatigue were classified and summarized into two index variables measuring either the subjective experience of physical fatigue or the impact of fatigue on daily functioning. Linear regression with a stepwise elimination procedure was conducted to select the significant predictors for each index variable separately. Results: Subjective experience of physical fatigue (Model 1; r2 = 0.46; p 0.05), and lower motor functioning (b = 0.01; p = 0.05). Conclusions: In conclusion, our work supports associations between fatigue and other neuropsychiatric symptoms in PD and extends prior work suggesting that motor disturbances are specifically linked to fatigue-related impairment of daily functioning, but not to the subjective experience of physical fatigue.

Migraine is a prevalent heterogeneous neurological disorder, enumerated as the eighth most disabling neurological disorder by the World Health Organization. The growing advancement in technology and investigation of various facets of cerebral metabolism in migraine has shed light to metabolic mechanisms in migraine pathophysiology. A growing number of clinical research postulates migraine as a reaction to oxidative stress levels that go beyond antioxidant capacity or cerebral energy deficiency. This has become an extremely attractive subject area and over the past years there has also been a sustained research activity in using ketone bodies (KB) as a novel potential migraine prophylaxis. Not much epidemiological research has been conducted to exhibit the efficacy of ketone bodies in abnormal metabolism in migraine pathophysiology. Therefore, a better understanding of ketone bodies in metabolic migraine may provide novel therapeutic opportunities. The goal of this review is to assess present understanding on potential migraine triggers, as well as how ketogenic interventions support metabolic disability in migraines and address the therapeutic importance of ketones in migraine treatment, accenting clinical studies (including neuroimaging and therapeutic studies). This review is intended to demonstrate existing literature on the effects of ketone bodies on metabolic migraine traits to guide the readership through current concepts and foster a perspective for future research.

Background: Multiple sclerosis (MS) symptoms are expected to aggregate in specific patterns across different stages of the disease. Here, we studied the clustering of onset symptoms and examined their characteristics, comorbidity patterns and associations with potential risk factors.Methods: Data stem from the Swiss Multiple Sclerosis Registry, a prospective study including 2,063 participants by November 2019. MS onset symptoms were clustered using latent class analysis (LCA). The latent classes were further examined using information on socio-demographic characteristics, MS-related features, potential risk factors, and comorbid diseases.Results: The LCA model with six classes (frequencies ranging from 12 to 24%) was selected for further analyses. The latent classes comprised a multiple symptoms class with high probabilities across several symptoms, contrasting with two classes with solitary onset symptoms: vision problems and paresthesia. Two gait classes emerged between these extremes: the gait-balance class and the gait-paralysis class. The last class was the fatigue-weakness-class, also accompanied by depression symptoms, memory, and gastro-intestinal problems. There was a moderate variation by sex and by MS types. The multiple symptoms class yielded increased comorbidity with other autoimmune disorders. Similar to the fatigue-weakness class, the multiple symptoms class showed associations with angina, skin diseases, migraine, and lifetime prevalence of smoking. Mononucleosis was more frequently reported in the fatigue-weakness and the paresthesia class. Familial aggregation did not differ among the classes.Conclusions: Clustering of MS onset symptoms provides new perspectives on the heterogeneity of MS. The clusters comprise different potential risk factors and comorbidities. They point toward different risk mechanisms.

Rényi entropies are conceptually valuable and experimentally relevant generalizations of the celebrated von Neumann entanglement entropy. After a quantum quench in a clean quantum many-body system they generically display a universal linear growth in time followed by saturation. While a finite subsystem is essentially at local equilibrium when the entanglement saturates, it is genuinely out of equilibrium in the growth phase. In particular, the slope of the growth carries vital information on the nature of the system’s dynamics, and its characterization is a key objective of current research. Here we show that the slope of Rényi entropies can be determined by means of a spacetime duality transformation. In essence, we argue that the slope coincides with the stationary density of entropy of the model obtained by exchanging the roles of space and time. Therefore, very surprisingly, the slope of the entanglement is expressed as an equilibrium quantity. We use this observation to find an explicit exact formula for the slope of Rényi entropies in all integrable models treatable by thermodynamic Bethe ansatz and evolving from integrable initial states. Interestingly, this formula can be understood in terms of a quasiparticle picture only in the von Neumann limit.

Abstract Background Multiple sclerosis (MS) is one of the most frequently observed neurological conditions in Switzerland, but data sources for country-wide epidemiological trend monitoring are lacking. Moreover, while clinical and laboratory MS research are generally well established, there is a gap in patient-centered MS research to inform care management, or treatment decisions and policy making not only in Switzerland but worldwide. Methods In light of these research gaps, the Swiss Multiple Sclerosis Society initiated and funded the Swiss Multiple Sclerosis Registry (SMSR) an open-ended, longitudinal and prospective, nationwide, patient-centered study. The SMSR recruits adult persons with a suspected or confirmed MS diagnosis who reside or receive care in Switzerland. The SMSR has established a governance structure with clear rules and guidelines. It follows a citizen-science approach with direct involvement of persons with MS (PwMS), who contribute actively to registry development, operations, and research. Main scientific goals entail the study of MS epidemiology in Switzerland, health care access and provision, as well as life circumstances and wellbeing of persons with MS. The innovative study design (“layer model”) offers several participation options with different time commitments. Data collection is by means of regular surveys and medical record abstraction. Survey participation is offered in different modes (web, paper & pencil) and in the three main national languages (German, French, Italian). Participants also receive regular data feedbacks for personal use and self-monitoring, contextualized in the whole population of study participants. Data feedbacks are also used to solicit data corrections of key variables from participants. Discussion The SMSR combines the advantages of traditional and novel research methods in medical research and has recruited over 1600 PwMS in its first year. The future-oriented design and technology will enable a response not only to future technological innovations and research trends, but also to challenges in health care provision for MS. Trial registration ClinicalTrials.gov NCT02980640; December 6, 2016; retrospectively registered.

Background: Multiple sclerosis (MS) is the most common chronic, non-traumatic, neurologic disease in young adults. While approximate values of the disease burden of MS are known, individual drivers are unknown.Objective: To estimate the age-, sex-, and disease severity-specific contributions to the disease burden of MS.Methods: We estimated the disease burden of MS using disability-adjusted life years (DALYs) following the Global Burden of Disease study (GBD) methodology. The data sources consisted of the Swiss MS Registry, a recent prevalence estimation, and the Swiss mortality registry.Results: The disease burden of MS in Switzerland in 2016 was 6,938 DALYs (95%-interval: 6,018-7,955), which corresponds to 97 DALYs per 100,000 adult inhabitants. Morbidity contributed 59% of the disease burden. While persons in an asymptomatic (EDSS-proxy 0) and mild (EDSS-proxy >0–3.5) disease stage represent 68.4% of the population, they make up 39.8% of the MS-specific morbidity. The remaining 60.2% of the MS-specific morbidity stems from the 31.6% of persons in a moderate (EDSS-proxy 4–6.5) or severe (EDSS-proxy ≥7) disease stage.Conclusions: Morbidity has a larger influence on the disease burden of MS than mortality and is shared in a ratio of 2:3 between persons in an asymptomatic/mild and moderate/severe disease stage in Switzerland. Interventions to reduce severity worsening in combination with tailored, symptomatic treatments are important future paths to lower the disease burden of MS.

Background. Parkinson’s disease (PD) is associated with cognitive decline, progressing from subjective memory complaints (SMC) via mild cognitive impairment (MCI) to dementia. SMC are only measurable by an interview and thus rely on individuals reporting a subjectively perceived worsening of cognitive functioning. Cognitive decline is accompanied by a reduction in quality of life (QoL); however, the extent to which SMC manifest a reduction of QoL remains unclear. Objective. To determine the association between SMC and deterioration of QoL in patients suffering from PD. Methods. A total of 46 cognitively unimpaired PD patients (29 men and 17 women) completed PDQ-39, two assessments to measure SMC (Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and a Self-Assessment questionnaire), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). Multiple regression modelling was conducted to investigate the confounding effect of depression and anxiety. Results. The PDQ-39 domain cognitions, but not the PDQ-39 sum score, correlated significantly with the SMC Self-Assessment questionnaire (r = 0.57; p

Background: When population-based databases are unavailable, nationwide assessments of the disease burden of multiple sclerosis (MS) resort to clinical, administrative or convenience-sampled data sources, which may produce results of limited external validity. Our aim was to develop a framework for estimating measures of occurrence of chronic diseases, and more broadly disease burden, that mitigate these limitations and to apply this framework to estimate the prevalence of multiple sclerosis (MS) in Switzerland.Methods: We developed a 7-step framework which implements the combination of several data sources together with a resampling and critical appraisal approach. The framework was applied to estimate the MS prevalence for 2016 in Switzerland, for which four distinct data sources (Swiss MS registry, Swiss national MS treatment registry, MediService database, and Swiss MS cohort study) were combined. Results were reviewed by disease experts and compared to earlier Swiss estimates and current prevalence estimates from other countries.Results: We estimate that in the year 2016 between 14,650 and 15,700 persons with MS have been living in Switzerland, yielding a period prevalence of 174–187/100,000 inhabitants. Compared to the last estimate in 1986, we detected a substantial increase of MS diagnoses which coincides with a higher number of diagnoses in women below the age of 65.Conclusions: Internationally, Switzerland is a high-prevalence country for MS, although estimates were somewhat lower than recent evaluations of Northern European countries. In addition, we corroborate previous reports that the prevalence increase coincides with a higher number of MS diagnoses among women. The proposed framework has wide applicability and the potential to place estimates of disease occurrence and burden with imperfect data availability on more solid grounds.

Background: Death and the anxiety of it becomes more apparent when confronted with a chronic disease. Even though multiple sclerosis (MS) is a treatable condition today, it is still accompanied by a multitude of impairments, which in turn may intensify of death anxiety. Objective: The aim of this study is to explore the relationship between depression, anxiety and death anxiety in individuals with MS. Methods: Fifty-six MS patients were recruited at the Department of Neurology of the University Clinic in Basel. Death anxiety was assessed using the Bochumer Questionnaire on attitude to death and death anxiety 2.0 (BOFRETTA 2.0). Results: Scores of death anxiety towards it in MS patients were low. Only disability (EDSS) was moderately correlated with death anxiety. Depression in MS was significantly correlated with fatigue and disability, but not with the BOFRETTA 2.0. Conclusion: Scores of death anxiety and the attitude towards death are low in this MS cohort. It was shown that both psychopathological and neurological deficits impact the subject of death with respect to multiple sclerosis.

The interrelations between fatigue, depression and health-related quality of life (HRQoL) in persons with multiple sclerosis (PwMS) are complex, and the directionality of the effects is unclear. To address this gap, the current study used a longitudinal design to assess direct and indirect effects of fatigue and depression on HRQoL in a one-year follow-up survey. A sample of 210 PwMS from the nationwide Swiss MS Registry was used. HRQoL was assessed using the European Quality of Life 5-Dimension 5-Level questionnaire. Path analysis on HRQoL, with fatigue and depression as predictors, was applied. Fatigue was measured by the Modified Fatigue Impact Scale (MFIS), including physical, cognitive and psychosocial subscales, and non-somatic depressive symptomatology was examined with the Beck Depression Inventory-Fast Screen (BDI-FS). Fatigue acted as a fully mediating variable (B = −0.718, SE = 0.253) between non-somatic depressive symptomatology and HRQoL. This indirect effect became apparent in the physical (B = −0.624, SE = 0.250), psychosocial (B = −0.538, SE = 0.256) and cognitive subscales (B = −0.485, SE = 0.192) of fatigue. In contrast, non-somatic depressive symptomatology did not act as a mediator. Our findings provide novel and clinically relevant longitudinal evidence showing that the debilitating effect of non-somatic aspects of depression on HRQoL was fully mediated and therefore explainable via fatigue.

These are lecture notes for a short course given at the Les Houches Summer School on ``Integrability in Atomic and Condensed Matter Physics'', in summer 2018. Here, I pedagogically discuss recent advances in the study of the entanglement spreading during the non-equilibrium dynamics of isolated integrable quantum systems. I first introduce the idea that the stationary thermodynamic entropy is the entanglement accumulated during the non-equilibrium dynamics and then join such an idea with the quasiparticle picture for the entanglement spreading to provide quantitive predictions for the time evolution of the entanglement entropy in arbitrary integrable models, regardless of the interaction strength.

QUESTION UNDER STUDY Our aim was to assess whether a novel approach of digitally facilitated, citizen-science research, as followed by the Swiss Multiple Sclerosis Registry (Swiss MS Registry), leads to accelerated participant recruitment and more diverse study populations compared with traditional research studies where participants are mostly recruited in study centres without the use of digital technology. METHODS The Swiss MS Registry is a prospective, longitudinal, observational study covering all Switzerland. Participants actively contribute to the Swiss MS Registry, from defining research questions to providing data (online or on a paper form) and co-authoring papers. We compared the recruitment dynamics over the first 18 months with the a priori defined recruitment goals and assessed whether a priori defined groups were enrolled who are likely to be missed by traditional research studies. RESULTS The goal to recruit 400 participants in the first year was reached after only 20 days, and by the end of 18 months 1700 participants had enrolled in the Swiss MS Registry, vastly exceeding expectations. Of the a priori defined groups with potential underrepresentation in other studies, 645 participants (46.5%) received care at a private neurology practice, 167 participants (12%) did not report any use of healthcare services in the past 12 months, 32 (2.3%) participants lived in rural mountainous areas, and 20 (2.0% of the 1041 for whom this information was available) lived in a long-term care facility. Having both online and paper options increased diversity of the study population in terms of geographic origin and type and severity of disease, as well as use of health care services. In particular, paper enrolees tended to be older, more frequently affected by progressive MS types and more likely to have accessed healthcare services in the past 12 months. CONCLUSION Academic and industry-driven medical research faces substantial challenges in terms of patient involvement, recruitment, relevance and generalisability. Digital studies and stakeholder engagement may have enormous potential for medical research. But many digital studies are based on limited participant information and/or informed consent and unclear data ownership, and are subject to selection bias, confounding and information bias. The Swiss MS Registry serves as an example of a digitally enhanced, citizen-science study that leverages the advantages of both traditional medical research, with its established research methods, and novel societal and technological developments, while mitigating their ethical and legal disadvantages and risks. Trial registration number ClinicalTrials.gov identifier NCT02980640.

We describe a patient with persistent cerebral achromatopsia occurring after bilateral occipital strokes. Blinded color recognition was assessed with a computerized experimental paradigm and the patient reported the degree of confidence in the response exactness on a visual percent scale. Color recognition was accurate and above chance (Fisher's exact test, p < 0.002). The degree of confidence in the answers showed a significant correlation with recognition scores (Spearman rank order correlation, p < 0.0001). These findings constitute the exceptional condition of what we called color anopsognosia (not knowing of seeing colors) and recall the theoretic figure of the ‘philosophical zombie'. However, the cognitive mechanisms of the dissociation between a subjective colorless vision and good performance for color naming still remain poorly understood.

Background. Visuospatial dysfunction is among the first cognitive symptoms in Parkinson’s disease (PD) and is often predictive for PD-dementia. Furthermore, cognitive status in PD-patients correlates with quantitative EEG. This cross-sectional study aimed to investigate the correlation between EEG slowing and visuospatial ability in nondemented PD-patients. Methods. Fifty-seven nondemented PD-patients (17 females/40 males) were evaluated with a comprehensive neuropsychological test battery and a high-resolution 256-channel EEG was recorded. A median split was performed for each cognitive test dividing the patients sample into either a normal or lower performance group. The electrodes were split into five areas: frontal, central, temporal, parietal, and occipital. A linear mixed effects model (LME) was used for correlational analyses and to control for confounding factors. Results. Subsequently, for the lower performance, LME analysis showed a significant positive correlation between ROCF score and parietal alpha/theta ratio (b=.59, p=.012) and occipital alpha/theta ratio (b=0.50, p=.030). No correlations were found in the group of patients with normal visuospatial abilities. Conclusion. We conclude that a reduction of the parietal alpha/theta ratio is related to visuospatial impairments in PD-patients. These findings indicate that visuospatial impairment in PD-patients could be influenced by parietal dysfunction.

We describe the case of a 75-year-old woman who manifested persistent confabulations after two consecutive strokes encompassing the area of the lenticulostriate arteries territory on both hemispheres. Findings reported on this rare clinical syndrome suggest that fantastic confabulations and delusional thoughts may arise after bilateral damage of subcortical nonthalamic structures.

Extensive behavioural, pharmacological, and neurological research reports stress effects on mammalian memory processes. While stress effects on memory quantity have been known for decades, the influence of stress on multiple memory systems and their distinct contributions to the learning process have only recently been described. In this paper, after summarizing the fundamental biological aspects of stress/emotional arousal and recapitulating functionally and anatomically distinct memory systems, we review recent animal and human studies exploring the effects of stress on multiple memory systems. Apart from discussing the interaction between distinct memory systems in stressful situations, we will also outline the fundamental role of the amygdala in mediating such stress effects. Additionally, based on the methods applied in the herein discussed studies, we will discuss how memory translates into behaviour.

We performed extensive neuropsychological assessment of two male patients (matched for age and educational level) with similar (localization and size) unilateral paramedian ischemic thalamic lesions (AB on the left and SD on the right). Both patients showed severe memory impairments as well as other cognitive deficits. In comparison to SD, AB showed severe impairment of executive functions and a more severe deficit of episodic/anterograde memory, especially in the verbal modality. The findings of this single case study suggest the possibility that the profile and severity of the executive dysfunction are determinant for the memory deficits and depend on from the side of the lesion. In addition to a material-side-specific (verbal versus visual) deficit hypothesis, the differential diencephalo-prefrontal contributions in mnestic-processing, in case of paramedian thalamic stroke, might also be explained in terms of their stage-specificity (encoding versus retrieval).

Variables which are of influence in establishing clear predictions of neuropsychological alterations from neuroradiological data (and vice versa) are documented and discussed. It is concluded that personality factors and the kind and locus of brain lesions are the most crucial determinants. The locus of the brain damage may have cumulative effects either when it is situated in a strategic place (usually within the white matter, affecting interneuronal communication) or when various types of lesions appear superimposed (combination of focal and diffuse lesions). Consequently, the consideration of the patient's personality background and of as many neuropsychological facts as possible may considerably increase the validity of outcome predictions. When static or dynamic neuroimaging fails to show abnormalities in spite of obvious psychological alterations, an intensive neuropsychological documentation may even replace neuroradiology.

Sleep plays a pivotal role in normal biological functions. Sleep loss results in higher stress vulnerability and is often found in mental disorders. There is evidence that brain-derived neurotrophic factor (BDNF) could be a central player in this relationship. Recently, we could demonstrate that subjects suffering from current symptoms of insomnia exhibited significantly decreased serum BDNF levels compared with sleep-healthy controls. In accordance with the paradigm indicating a link between sleep and BDNF, we aimed to investigate if the stress system influences the association between sleep and BDNF.Participants with current symptoms of insomnia plus a former diagnosis of Restless Legs Syndrome (RLS) and/or Periodic Limb Movement (PLM) and sleep healthy controls were included in the study. They completed questionnaires on sleep (ISI, Insomnia Severity Index) and stress (PSS, Perceived Stress Scale) and provided a blood sample for determination of serum BDNF. We found a significant interaction between stress and insomnia with an impact on serum BDNF levels. Moreover, insomnia severity groups and score on the PSS each revealed a significant main effect on serum BDNF levels. Insomnia severity was associated with increased stress experience affecting serum BDNF levels. Of note, the association between stress and BDNF was only observed in subjects without insomnia. Using a mediation model, sleep was revealed as a mediator of the association between stress experience and serum BDNF levels.This is the first study to show that the interplay between stress and sleep impacts BDNF levels, suggesting an important role of this relationship in the pathogenesis of stress-associated mental disorders. Hence, we suggest sleep as a key mediator at the connection between stress and BDNF. Whether sleep is maintained or disturbed might explain why some individuals are able to handle a certain stress load while others develop a mental disorder.