Publikationer från Linköpings universitet
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Sequences and animal intelligence
No full textHere, we explore some cognitive mechanisms that support and constrain sequential abilities in non-human animals (hereafter animals). By examining limits in memory for stimulus sequences and how behaviour sequences can be learned, we highlight the combinatorial costs that arise as sequences get increasingly longer, which may hinder the development of cognitive abilities that require faithful representation of sequences, like language. We discuss a trace memory model as a framework for understanding how animals represent stimulus sequences and suggest that animals represent sequences as unstructured collections of decaying memory traces rather than representing order faithfully. The implications of this model challenge traditional interpretations of declarative and rule-based learning in animals. In addition, we explore associative learning models that can account for how animals acquire behaviour sequences without precise memory of stimulus sequences. Current models have proven powerful in accounting for complex behaviour sequences. We end by asking what the value is of anthropocentric models in the study of animal intelligence, if other models provide more accurate predictions of animal behaviour. This article is part of the Theo Murphy meeting issue 'Selection shapes diverse animal minds'.Funding Agencies|Vetenskapsrdet</p
Single organic electrochemical neuron capable of anticoincidence detection
No full textEmulating complex neural computations like solving linearly inseparable tasks within single artificial neurons has remained an elusive goal in neuromorphic engineering. Here, we report a dendritic organic electrochemical neuron (d-OECN) capable of achieving anticoincidence detection by classifying the exclusive-OR (XOR) problem-a quintessential linearly inseparable task-within an individual neuron. Inspired by human cortical neurons that perform XOR through dendritic calcium spikes, the d-OECN leverages ion-tunable antiambipolarity in mixed ionic-electronic conducting polymers to mimic voltage-gated dendritic calcium dynamics. By integrating this dendritic component with a tunable spiking circuit representing the soma, the d-OECN achieves XOR classification through its inherent nonlinear activation profile, with decision boundaries that are both ionically and electrically tunable. Moreover, we demonstrate the d-OECN's ability to perform edge detection using XOR in a tactile sensing system, showcasing its potential for event-based sensing and processing. The d-OECNs, replicating key aspects of biological intelligence, pave the way for next-generation bioelectronics and robotics requiring complex neural computation.Funding Agencies|Knut and Alice Wallenberg Foundation [2021.0058]; Swedish Research council [2020- 03243, 2022- 04553]; European Research council through the eRc consolidator Grant project inFeR [101125879]; European commission [964677]; Pathfinder OPen project icOnic [101129638]; MScA- iF- 2020 project S-Oecn [101152690]; Swedish Foundation for Strategic Research [iS24- 0162, 2023- 01337]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at link oeping University (Faculty Grant SFO- Mat- liU) [2009- 00971]; Vinnova [2023-01337] Funding Source: Vinnova; Swedish Research Council [2022-04553, 2020-03243] Funding Source: Swedish Research Council</p
Chronic cOronary Syndrome in Swedish PRImary care (COSPRI)-a study protocol for a 5-year cluster randomized controlled trial on a novel package versus standard investigation in patients with suspected chronic coronary syndrome referred from primary health care
No full textBackground This trial aims to assess the effectiveness of a novel diagnostic package in the investigation of symptomatic chronic coronary artery disease (CAD), with a focus on reducing the time to diagnosis and improving risk assessment, compared to the current standard investigation approach. The package investigation is comprised of combined single photon emission computed tomography (SPECT), echocardiography, coronary artery calcification (CAC) scoring, not previously evaluated in Sweden for individual cardiovascular prevention, and CadScore, an acoustic risk score. The standard investigation is comprised of exercise bicycle stress testing and echocardiography. Methods The trial involves patients with a pre-test probability &gt; 15% for significant CAD referred from primary healthcare centers (PHCs) in Region & Ouml;sterg & ouml;tland (population 471,241 in March 2023) in south-east Sweden. All the 47 PHCs of the region will be invited to participate and will, after approval, be cluster randomized into two groups: package investigation versus standard investigation. The primary outcome is a composite measure comprised of waiting time to invasive coronary angiography or communication of non-invasive myocardial ischemia investigation results. Secondary outcomes include major adverse cardiovascular events (MACE), cost per patient, signs of reversible ischemia on any test, radiation exposure, and adherence to prescribed cardioprotective drugs. Discussion This trial addresses the urgent problem of chest pain and dyspnea assessment in primary care and aims to speed up diagnosis, reduce the need for specialist consultations, and potentially improve patient outcomes, with referral to SPECT directly from PHC in comparison with the widely used exercise test. The novel approach includes CAC scoring. Additionally, the utility of acoustic CadScore in reclassifying the risk of CAD is explored. Trial registration. The trial was registered on March 11, 2023, at ClinicalTrials.gov with the identifier: NCT05782582.Funding Agencies|Vetenskapsrdet</p
Presence and Location of CatSper 1–4, Opioid (μ, δ and κ) and CD44 Receptors in Spermatozoa from Aoudad, Iberian Ibex and Mouflon
No full textDespite the apparent progress in reproductive technologies in wild ruminant species, healthy live births have been limited. Acquiring a sound knowledge of the molecular basis of most functional aspects of spermatozoa will improve the effectiveness of reproductive techniques and optimise conservation programs for threatened species. CatSper channels, opioid receptors and CD44 are involved in sperm capacitation of humans and domestic animals, but their presence in wild ruminants is yet undisclosed. The aim of this study was to determine the presence and localisation of CatSper 1-4, mu, delta and kappa-opioid receptors and CD44 in three wild ruminant species spermatozoa (aoudad [n = 5], Iberian ibex [n = 5], mouflon [n = 5]), which show different resistance to freezing-thawing processes. Western blotting (WB) and immunocytochemistry (ICC) performed with commercially available antibodies revealed that aoudad, Iberian ibex and mouflon are equipped with the aforementioned channels and receptors, sharing localisation with other domestic animals' spermatozoa but presenting species-particularities. WB revealed homogeneous results in CatSper 1, Catsper 2, Catsper 3 and CatSper 4 among the spermatozoa of the three species, unlike mu, delta and kappa-opioid and CD44 receptors that showed substantial inter-species differences in the number of bands. ICC showed inter-species differences in the location of CatSper 1-4, mu, delta and kappa-opioid and CD44 receptors. Data confirmed their presence and putative role on sperm function in wild ruminant species. Inter-species differences in the location of CatSper 1-4, mu, delta and kappa-opioid and CD44 receptors might underlie the variable response to reproductive technologies in these species.Funding Agencies|Fundacin Parques Reunidos-INIA-CSIC</p
Function and Anatomy of Fast Nociceptors
No full textPain, a fundamental and evolutionarily conserved physiological mechanism, allows organisms to detect and avoid potential harm. In the absence of pain perception (e.g. congenital insensitivity to pain), individuals face an increased risk of repeated injuries and even life-threatening situations. Conversely, when pain signalling becomes abnormal, as in chronic pain, it severely compromises quality of life and imposes substantial social and economic burdens. Chronic pain affects more than 20% of the global population, yet the biological mechanisms underlying its persistence remain incompletely understood. Current pharmacological treatments, such as opioids and nonsteroidal anti-inflammatory drugs, are often inadequate, providing only partial relief and carrying significant risks of adverse effects, including addiction and organ damage. Therefore, it is crucial to investigate and gain further insight into the underlying mechanisms of pain. At the peripheral level, painful stimuli are detected by specialized primary afferent fibers, nociceptors. While slow-conducting, unmyelinated C fiber nociceptors have been extensively studied, myelinated nociceptors—particularly fast nociceptors with conduction velocities within the Aδ and Aβ range—remain largely unexplored. One factor contributing to this knowledge gap is the lack of appropriate models to specifically target these neuron populations. Here, we generated two novel mouse models: NefhCreERT2, targeting myelinated fibers, and NaV1.8FlpO, targeting nociceptors. By combining these lines, we established an intersectional genetic strategy to selectively target myelinated nociceptors and characterize their functional and anatomical properties. Furthermore, using transcriptomic datasets, we identified Ntrk3 (encoding the TrkC growth factor receptor) as a potential genetic marker of a novel subpopulation of myelinated nociceptor. By combining TrkCCreERT2 and NaV1.8FlpO mouse lines, we were able to capture putative fast TrkC+;NaV1.8+ nociceptors. In this thesis, optogenetic activation of myelinated nociceptors elicited rapid paw withdrawal reflexes and nocifensive behaviors. Prolonged stimulation of these fibers induced central and peripheral sensitization, as well as mechanical allodynia. Putative fast TrkC+;NaV1.8+ nociceptors evoked rapid paw withdrawal reflexes upon optogenetic stimulation without causing overt pain behaviors, suggesting a role in mediating nociceptive withdrawal reflexes but not affective pain. Collectively, this work demonstrates that intersectional targeting strategies enable selective capture of neuronal subpopulations and advances our understanding of fast nociceptors in pain pathways.2025-10-03: The thesis was first published online. The online published version reflects the printed version. 2025-10-07: The thesis was updated with an errata list which is also downloadable from the DOI landing page. Before this date the PDF has been downloaded 14 times.</p
Associations between physical activity and CVD-related metabolomic and proteomic biomarkers
No full textAim Habitual physical activity (PA) affects metabolism and homeostasis in various tissues and organs. However, detailed knowledge of associations between PA and cardiovascular disease (CVD) risk markers is limited. We sought to identify associations between accelerometer-assessed PA classes and 183 proteomic and 154 metabolomic CVD-related biomarkers.Method We utilized cross-sectional data from the main SCAPIS cohort (n = 4647, median age: 57.5 yrs, 50.5% female) as a discovery sample and the SCAPIS pilot cohort (n = 910, median age: 57.5 yrs, 50.3% female) as a validation sample. PA was assessed via hip-worn accelerometers, while plasma concentrations of proteomic biomarkers were measured using Olink CVD II and III panels. Metabolomic markers were assessed using the Nightingale NMR platform. We evaluated associations between four PA classes (moderate-to-vigorous PA [MVPA], low-intensity PA [LIPA], sedentary [SED], and prolonged SED [prolSED]) and biomarkers, controlling for potential confounders and applying a false discovery rate of 5% using multiple linear regressions.Results A total of eighty-five metabolomic markers and forty-three proteomic markers were validated and found to be significantly associated with one or more PA classes. LIPA and SED markers demonstrated significant mirroring or opposing relations to biomarkers, while prolSED mainly shared relations with SED. Notably, HDL species were predominantly negatively associated with SED, whereas LDL species were positively associated with SED and negatively associated with MVPA. Among the proteomic markers, eighteen were uniquely associated with MVPA (among those Interleukin - 6 [IL6] and Growth/differentiation factor 15 [GDF15] both negatively related), seven with SED (among those Metalloproteinase inhibitor 4 [TIMP4] and Tumor necrosis factor receptor 2 [TNFR2], both positively related), and eight were related to both SED/prolSED (among those Lipoprotein lipase [LPL] negatively related to SED and leptin [LEP] positively related to SED) and MVPA (with LPL positively related to MVPA and LEP negatively related to MVPA).Conclusion Our findings suggest the existence of specific associations between PA classes and metabolomic and cardiovascular protein biomarkers in a middle-aged population. Beyond validation of previous results, we identified new associations. This multitude of connections between PA and CVD-related markers may help elucidate the previously observed relationship between PA and CVD. The identified cross-sectional associations could inform the design of future experimental studies, serving as important outcome measures.Funding Agencies|Livfrskringsbolaget Skandia, RiskHlsa</p
Guided Internet-Based Cognitive Behavior Therapy for Women With Bulimia Nervosa : A Randomized Clinical Trial
No full textIMPORTANCE: Despite the rising prevalence of bulimia nervosa and the associated risks of chronicity and severe physical and psychological morbidity, access to effective treatment remains poor. The effectiveness and acceptability of internet-based cognitive behavior therapy (ICBT) for women with bulimia nervosa in clinical settings in East Asia remain unclear. OBJECTIVE: To determine the effectiveness and acceptability of a guided ICBT program to treat women with bulimia nervosa in Japan. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was conducted at 7 university hospitals in Japan between August 2022 and October 2024. This study enrolled female participants aged 13 to 65 years whose symptoms met the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for bulimia nervosa, had a body mass index (BMI) of 17.5 or greater, had internet access, and had no history of practicing CBT-related techniques within the past 2 years. INTERVENTIONS: Both the control and intervention groups received usual care. The intervention consisted of ICBT with additional guidance from a therapist. The therapy program was tailored to Japanese culture and grounded in a specific cognitive behavior model, and it was performed over a 12-week period. MAIN OUTCOMES AND MEASURES: Severity of bulimia nervosa, measured by the weekly combined frequency of episodes involving binge eating and compensatory behaviors, was assessed by a blinded, independent rating team at baseline and at the 12-week intervention end point. Intention-to-treat analyses were conducted using a linear mixed model with effect sizes calculated using Cohen d. RESULTS: A total of 61 women met the eligibility criteria and were randomized to the intervention group (n = 31) or the control group (n = 30). Participants were predominantly young (mean [SD] age, 27.8 [9.0] years), had normal weight (mean [SD] BMI, 21.1 [3.6]), and had a mean (SD) duration of illness of 9.3 (8.8) years; half (31 [50.8%]) were employed. Intent-to-treat analysis revealed that guided ICBT significantly reduced the weekly combined frequency of episodes involving binge eating and compensatory behaviors (by an adjusted mean difference of 9.84 episodes [95% CI, 2.49-17.18 episodes], P = .01; Cohen d = 0.73 [95% CI, 0.21-1.26]). Sensitivity analyses supported these findings. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the intervention group experienced a significant decrease in bulimia symptoms compared with the control group, supporting the effectiveness and acceptability of the therapist-guided ICBT program. These findings suggest that integration of therapist-guided ICBT in usual care has the potential to improve accessibility to efficacious treatment options for women with bulimia nervosa. TRIAL REGISTRATION: UMIN Clinical Trials Registry Identifier: UMIN00048732.Funding Agencies|Japan Society for the Promotion of Science [JP22H00985, JP23K22256]; Lotte Foundation</p
Engineering Electrical Transport by Implantation-Induced Defects in CrN Films Without Affecting Thermal Conductivity
No full textThe transport properties of CrN thin films deposited on sapphire have been tailored through structural modifications induced by cumulative argon implantation. As-grown samples experience the typical structural transition in CrN films from orthorhombic at low temperature to cubic above the N & eacute;el temperature (approximate to 280 K) and exhibit a metallic-like conduction in both phases. With increasing implantation dose, the conduction mode shifts to a semiconductor-like behavior in both phases, albeit at different damage levels. Analysis of the results suggests that hopping conduction becomes dominant beyond a given damage threshold. The results highlight a promising correlation between defect engineering and conduction mechanisms, offering valuable insights into the versatile electrical properties of CrN films. These implantation-induced defects scatter carriers, leading to a decrease in their mobility. As the implantation dose increases, the defect landscape evolves, modifying the density of states. However, up to a dose of 0.050 dpa, no significant influence on phonon scattering is observed. This approach demonstrates that ion implantation enables precise tuning of CrN's electrical properties without affecting thermal conductivity, offering valuable insights into defect engineering in transition metal nitrides and underscoring its potential for transport properties decorrelation.Funding Agencies|Swedish Research Council VR-RFI</p
Chemical reaction mechanism between trimethylgallium and oxygen for ß-gallium oxide growth: Thermodynamic and experimental studies
No full textThe metalorganic chemical vapor deposition (MOCVD) dynamics of beta-gallium oxide (beta-Ga2O3) growth using trimethylgallium (TMGa) and oxygen as precursors were investigated through both theoretical thermodynamic analysis and experimental validation in a horizontal low-pressure hot-wall reactor. Thermodynamic analysis revealed that high-purity beta-Ga2O3 can be grown through the complete combustion of TMG-derived gallium and hydrocarbons. Furthermore, the complete combustion of intentionally supplied hydrogen into the growth system also prevents the degradation of beta-Ga2O3 growth. Therefore, a high input VI/III ratio that ensures full combustion of gaseous species in the growth system is preferred for beta-Ga2O3 MOCVD. The growth experiments were performed on 2-in. sapphire substrates under an input VI/III ratio of 250. beta-Ga2O3 growth was confirmed at growth temperatures between 740 and 950 degrees C, with the growth rate decreasing from 0.7 to 0.5 mu m/h as temperature increased. Thermodynamic analysis successfully reproduced this growth behavior under the effective VI/III ratio of 6.5. The results demonstrate that beta-Ga2O3 MOCVD occurred under thermal equilibrium conditions and was thermodynamically controllable. (c) 2025 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license.Funding Agencies|Swedish Governmental Agency for Innovation Systems (VINNOVA) under the Competence Center Program [2022-03139]; Lund University; Linkoeping University; Chalmers University of Technology; Hitachi Energy; Ericsson; FMV; Gotmic; Region Skane; Saab; SweGaN; Veeco; Volvo Cars; UMS; Knut and Alice Wallenberg Foundation; Swedish Research Council (VR) [2024.0121]; Swedish Government Strategic Research Area Nano Lund [2023-04993]; Knut and Alice Wallenberg Foundation for a Scholar award; Carl Trygger Foundation for Scientific Research [2023.0349]; [312449]</p
Students’ and teachers’ experiences of a novel feedforward pedagogical model in the context of problem-based learning
No full textFeedforward is a strategic approach in education, particularly within formative assessment and Problem-Based Learning (PBL), aimed at guiding students towards learning objectives. Although not a standalone model, it enhances decision-making and performance, especially in clinical education. This study presents a novel, formalised feedforward model designed for integration into medical PBL, evaluated through focus group interviews with 123 students and 8 teachers. A content analysis revealed that feedforward shifted students' focus from exam results to long-term professional development. It encouraged repeated articulation of learning through peer and teacher dialogue, deepening understanding. The learning environment played a key role, fostering student engagement and sustainable learning. Feedforward promoted a student-centred approach by helping learners set goals, reflect collaboratively, and prioritise lifelong learning over short-term achievement. However, its most significant impact appeared among moderately performing students. Overall, the model supports a more reflective, goal-oriented educational experience that aligns with professional growth in medical education.Funding Agencies|Linkoping University for Research into Higher Education</p