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Adam Datta1, Agata Kulesza1, Sylwia Bednarek1, Marcello G. P. Rosa2, Piotr Majka1,2
1Laboratory of Neuroinformatics, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, Warsaw, Poland
2Department of Physiology and Neuroscience Program, Biomedicine Discovery Institute, Monash University, Clayton, Australia
Abstract: Understanding how the cerebral cortex processes information requires identifying and characterizing its areal and laminar cytoarchitecture. Deep learning offers a promising avenue to address these challenges by streamlining manual segmentation and offering observer-independent insights into cortical structure.
We propose a computational workflow for the segmentation of the cerebral cortex into layers and areas. The solution combines (1) estimation of the neuronal density and size, (2) extraction of one-dimensional cortical profiles starting from the pial surface and ending at the white matter, (3) a convolutional deep-learning model that segments the profiles into layers and assigns them to the respective cortical area.
We evaluated our solution on a dataset derived from a non-human primate - common marmoset monkey (Callithrix jacchus) brain. The model was trained to recognize the layers in cortical areas of a diverse cytoarchitecture. The evaluation revealed that the model’s performance increases when the neuronal density and size estimates contribute to the training process, compared to only using the image intensity. Furthermore, the model performs noticeably better when the classification of the profiles to cortical areas is enabled.
Beyond automating cortex segmentation into layers, our workflow offers possibilities for valuable insights into the cytoarchitectonic properties of the primate cerebral cortex
Funding: NCN SONATA 2019/35/D/NZ4/03031
Piotr Majka1, Nafiseh Atapour2, Marcello G.P. Rosa2, Shi Bai2, Sylwia Bednarek1,
Agata Kulesza1, Gabriela Saworska1, Katrina H. Worthy2
1Laboratory of Neuroinformatics, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, Warsaw, Poland
2Department of Physiology and Neuroscience Program, Biomedicine Discovery Institute,
Monash University, Clayton, Australia
Abstract: The calcium-binding protein calbindin is selectively expressed in specific neuronal populations of the cerebral cortex, including major classes of inhibitory interneurons. We have charted the distribution of calbindin-positive (CB+) neurons across areas and layers of the entire marmoset cortex using a combination of immunohistochemistry, deep-learning-based cell identification, 3-dimensional reconstruction, and cytoarchitecture-aware registration. CB+ neurons formed 10-20% of the cortical neuronal population, occurring in higher proportions in areas corresponding to low hierarchical levels of processing, such as sensory cortices. Although CB+ neurons concentrated in the supragranular layers, there were clear trends in laminar distribution: the relative density in infragranular layers increased with hierarchical level, and the density in layer 4 was lowest in areas involved in sensorimotor integration and action planning. These results reveal new aspects of the cytoarchitectural organization of the primate cortex and demonstrate an efficient approach to mapping the full distribution of neurochemically distinct cell types throughout the brain, readily applicable to most mammalian species and parts of the nervous system.
Funding: Funding was provided by the National Science Centre (2019/35/D/NZ4/03031 to Piotr Majka)
Julia Jakubowska1, Sylwia Bednarek1, Gabriela Saworska1,
Marcello G.P. Rosa2 and Piotr Majka1,2
1Laboratory of Neuroinformatics, Nencki Institute of Experimental Biology of the Polish Academy of Sciences, Warsaw, Poland
2Department of Physiology and Neuroscience Program, Biomedicine Discovery Institute, Monash University, Australia
Abstract: Deciphering complex rules and patterns behind high-level mammalian brain functions requires understanding their structural underpinnings, including the cytoarchitectural characterization of the cerebral cortex. Traditional manual approaches for addressing these tasks are time-consuming and subject to researcher bias. Consequently, there is a growing demand for automated, observer-independent tools and workflows capable of objectively describing voluminous microscopic brain imaging datasets.
We propose a general method based on a variational autoencoder (VAE), a generative model ensuring the continuity of its latent space, to (1) explore and characterize the cytoarchitecture and (2) generate synthetic images of neuronal cell somata following the identified properties. We demonstrate the feasibility of this approach using a dataset of images of neuronal cell bodies of the common marmoset monkey (Callithrix jacchus) brain.
Applying explainability methods, we explored the encoder’s latent space in the context of unsupervised clustering, where we observed cell segmentation according to their complex morphological features. We accessed the decoder part of the model, which generates neuron cells representatively reflecting their properties, such as shapes and intensities. We conclude that the proposed method may be suitable for characterizing the cytoarchitectural properties of large neuronal ensembles in various experimental contexts.
Funding: Funding was provided by the National Science Centre (2019/35/D/NZ4/03031 to Piotr Majka).
Marta Lotka1,2, Jeremi K. Ochab2
1Doctoral School of Exact and Natural Sciences, Jagiellonian University, Cracow, Poland
2Faculty of Physics, Astronomy and Computer Science, Jagiellonian University, Cracow, Poland
Abstract: The event-related potential technique is commonly used to assess the time course of cortical response to stimuli in studies utilizing electroencephalography. Yet it has inherent limitations, including sensitivity to specific pre-processing choices and reliance on averaging the signal over trials. We propose an alternative to the ERP technique, utilizing an algorithm introduced by Camargo et al. (2011), which recursively divides the EEG time series into quasi-stationary segments. To argue for the utility of this new method, it will be compared with the ERP technique. Method validation will be presented, including both theoretical results and application to the ERP Core dataset.
Piotr Biegański1and Marcin Syc1
1Biomedical Physics Division, Faculty of Physics, University of Warsaw, Warsaw, Poland
Abstract: Periodicity is one of the commonly estimated features of time series, recorded in a variety of fields, as potentially reflecting the feedback loops present in the signal. Exploratory assessment of the relative contributions of these oscillations is the goal of the spectral analysis. The most popular approach, based upon the Discrete Fourier Transform (DFT), assumes the presence of a fixed number of equally spaced frequencies, and estimates their relative weights. If the signal contains a frequency outside of the set probed by DFT, its power will be spread between adjacent frequency bins. Alternative approaches are based upon the least squares spectral analysis, including “Gauss-Vanicek method” or “Lomb-Scargle periodogram”.
In some cases, the assumed model may suggest a special role of particular frequencies. For example, in the actigraphic data (recordings of human activity from an accelerometer) we are often looking for the oscillations representing the circadian rhythms, with a period equal or close to 24 hours. For such cases there are specialized estimators, one of which is the method called “cosinor”.
We will discuss the mathematical properties of these methods; in particular, we will show that in some cases the cosinor can be treated as a special case of the DFT.
Funding: This research was supported by the Polish National Science Centre, grant number UMO-2018/31/B/ST7/01888.
Martyna Gorkowska1, Gniewosz Drwiega1, Lukasz Szumiec2, Jan Rodriguez Parkitna2, Przemyslaw E. Cieslak1
1Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Jagiellonian University, Krakow, Poland
2Department of Molecular Neuropharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland
Abstract: The motor cortex (MCtx) comprises circuits for voluntary movement control and motor skill learning.
The proposed mechanism for motor learning and updating is dopaminergic modulation of local neuronal activity. Our study focused on D1 and D2 receptor-expressing cells in the MCtx, revealing segregated populations. We then investigated if there is a causal relationship between dopamine (DA) release
and neuronal activity in these circuits during the development of skilled forelimb movements. We trained head-fixed mice to make self-initiated joystick movements to collect water rewards while simultaneously monitoring DA release and calcium dynamics in MCtx forelimb area using fiber photometry. We found that both DA fluorescence and neuronal calcium signals increased significantly after initiating joystick movement and receiving water rewards. Furthermore, animals’ performance adapted to changes in task parameters (e.g. reward threshold), which were followed by changes in calcium fluctuations and DA concentration recorded in MCtx dopaminoceptive circuits. Finally, we demonstrated that systemic injection of selective DA receptor antagonists or cell-type specific optogenetic perturbations of D1+ and D2+ neurons in MCtx impairs task performance. Overall, our findings revealed a link between DA release and neuronal activity in dopaminoceptive circuits within MCtx in the development of skilled forelimb movements and evaluating their outcomes.
Funding: National Science Centre Poland, SONATA_2020/39/D/NZ4/00503
Joanna Sadlak-Buda1,2, Anthony Kischel1, Przemysław Duda1, Tomasz Prószyński1
1Synaptogenesis Group, Life Science & Biotechnology Center, Łukasiewicz Research Network – PORT Polish Center for Technology Development, Wrocław, Poland
2Department of Molecular Physiology and Neurobiology, Faculty of Biological Sciences, University of Wroclaw, Wrocław, Poland
Abstract: AMOTL1, a member of the Angiomotin family of scaffolding proteins renowned for their pivotal roles in cytoskeletal organization, cancer progression, and angiogenesis, presents an intriguing yet enigmatic facet in neurobiology. Despite its expression in the brain and synaptic localization, its precise functions remain largely unknown. To study a potential function for AMOTL1 in the brain we engineered a systemic AMOTL1 knockout (KO) mice, revealing a spectrum of aberrations reminiscent of schizophrenia and mania models. Subsequently, we developed several conditional AMOTL1 mutants with deletions confined solely to neurons, specific neuronal subsets, or discrete brain regions. Detailed behavioral profiling of these strains, complemented by brain anatomical studies and analysis of cultured primary neurons, unveiled the indispensable functions of AMOTL1 in the central nervous system.
Funding: The research was supported by NCN grant OPUS 2019/33/B/NZ3/02528.
Ila Joshi1,2, Anthony Kischel1, Przemysław Kaczor1, Katarzyna O Rojek3 and Tomasz J. Prószyński1
1Laboratory of Synaptogenesis, Łukasiewicz Research Network – PORT Polish Center for Technology Development, Wrocław, Poland
2Ludwik Hirszfeld Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences, Wrocław, Poland
3Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
Abstract: Angiomotins, which include AMOT, AMOTL1, and AMOTL2, are scaffolding proteins mainly studied for their role in regulating the Hippo signaling pathway and cancer. However, the function of Angiomotins in the CNS is widely unknown. AMOT has been reported to regulate dendritic outgrowth and spine formation. Our unpublished project shows that AMOTL1 KO mice are a new model of psychiatric disorders involving impaired dopaminergic transmission. However, AMOTL2 functions within the brain remain unexplored. Our initial findings showed that AMOTL2 is expressed in both progenitors and differentiated neurons, which suggests that it might have different roles at different stages in the development. To study AMOTL2 functions, we perform conditional deletion at the early stage of development using the Nestin-CRE mouse line (deletions in progenitors that give rise to astrocytes and neurons) and observed increases in cortical thickness in newborns and adult mice. In parallel, our mass spectrometry analysis of the AMOTL2 protein complex from neurons uncovered interactions with several synaptic proteins, suggesting a possible role in synaptic organization. Moreover, AMOTL2 deletion in cultured hippocampal neurons decreased spine density and impaired spine maturation. We now use molecular, cellular, and behavioral tools to better understand AMOTL2's functions in the brain.
Funding: This research was supported by NCN grant Opus 2022/45/B/NZ3/03688.
Aleksandra Kaczmarska, Zuzanna Sulich, Jakub Bilnicki, Wojciech Solecki
Department of Neurobiology and Neuropsychology, Faculty of Management and Social Communication, Jagiellonian University, Krakow, Poland
Abstract: Ventral tegmental area (VTA) and locus coeruleus (LC) activity leads to dopamine (DA) and noradrenaline (NA) release in the forebrain, regulating similar physiological and behavioral functions. Interestingly, dopaminergic and noradrenergic systems display significant interplay at the level of both brain stem (LC-VTA) and forebrain. We aimed to identify the effects of VTA and LC activation on catecholamine release in the forebrain. We used fiber photometry to detect catecholamine release in the nucleus accumbens (NAc) and basolateral amygdala (BLA) in anesthetized male rats. To selectively detect DA and NA we used virally-induced expression of red fluorescent DA (rDA) and GPCR-activation-based NA (GRABNE) sensors in the NAc and BLA. To drive dopaminergic and noradrenergic activity we used electrical stimulation of the VTA and LC. Stimulation of the VTA induced robust phasic DA release in the NAc and BLA. Stimulation of the LC induced phasic NA signal in the BLA, with less significant NA release in the NAc. Surprisingly, activation of the VTA also evoked NA release, whereas LC activation led to robust phasic DA release in these structures. Here, we demonstrate that activation of the VTA or LC leads to both NA and DA release, suggesting complex LC-VTA-forebrain interplay.
Funding: National Science Centre Research grant no. UMO-2020/39/B/NZ7/03537
Maryna Myronets, Olga Pokotylo, Yaroslav Stepanyuk
Lesya Ukrainka Volyn National University, Lutsk, Volyns'ka Oblast', Ukraine
Abstract: The olfactory bulbs, among the brain's most ancient structures, are located rostrally and providing primary processing of olfactory information. They have a complex cytoarchitectonic organization.
The olfactory bulbs of mammals different ecological groups were studied: the European mole (Talpa europaea), noctule bats (Nyctalus noctula), house mouse (Mus musculus), and treeshrew (Tupaia glis). The histological sections (7-10 µ) were stained using the Nissl method (creosil violet or thionine).
The mitral layer (ML) is functionally important. It includes the largest neurons and is separated from the glomerular layer by the external plexiform layer. Axons and dendrites extend from the mitral cell (MC) perikaryon with a complex synaptic organization. Primary dendrites, in contact with axons of olfactory receptor cells, form glomeruli. Secondary dendrites branch laterally from the perikaryon.
The ML is well-defined in all species studied. Noctule MC are arranged in 2-3 rows and cause the greatest thickness of the ML. Mole and mouse mitral cells are mostly in one or rarely two rows, resulting in a layer thickness less than that of the noctule. Тhe ML treeshrew has the largest neurons, which are arranged exclusively in a monolayer with the smallest thickness among the other species studied.
Jacek Wróbel, Daniel K. Wójcik, Mark J. Hunt
Laboratory of Neuroinformatics, Nencki Institute of Experimental Biology, Warsaw, Poland
Abstract: NMDA receptor antagonists, such as MK801, produce hyperlocomotion and enhance the power of high-frequency oscillations (HFO) in many regions, including the olfactory bulb (OB). The OB contains dopamine (DA) receptors (D1R/D2R) and DA neurons which can modulate sensory processing. This study explores the influence of DA in the OB on locomotion and HFO after systemic MK801 administration in rats. Male Wistar rats received 0.15mg/kg MK801 i.p. followed by local infusions of DA receptor agonists (SKF38393, quinpirole) or antagonists (SCH23390, eticlopride) into the OB. Effects on locomotion and HFO were recorded and analysed. Both DA agonists and antagonists elicited dose-dependent changes in MK801-induced locomotion. Although modulation of D1R/D2R did not significantly affect HFO power, a notable reduction in HFO frequency was observed after local infusion with a D2R agonist. Our findings reveal that DA receptors in the OB can modulate MK801-induced hyperactivation, with D2 receptor activation specifically reducing the frequency of HFO.
Funding: 2021/41/N/NZ4/04051
Jakub Bilnicki, Aleksandra Kaczmarska, Zuzanna Sulich, Wojciech Solecki
The Department of Neurobiology and Neuropsychology, Faculty of Management and Social Communication, Jagiellonian University, Krakow, Poland
Abstract: Reinforcing effects of opioids are associated with dopamine (DA) release in the forebrain resulting from disinhibition of the DA neurons in the ventral tegmental area (VTA) due to µ opioid receptors (MOR) activation on VTA-projecting and local GABA-ergic neurons. Indeed, systemic opioid administration increases dopaminergic activity, but this response is not uniform. In fact, MOR in the VTA are also expressed on some DA neurons as well as other cells. Such heterogeneity of VTA MOR expression is not well understood in context of DA release in the forebrain, as different DA neurons innervate different forebrain structures including nucleus accumbens (NAc) core and shell. We aimed to demonstrate the role of the MOR in the VTA in modulating phasic DA release in different subregions of the NAc.
We used fast-scan cyclic voltammetry (FSCV) in anesthetized male Sprague-Dawley rats to study electrically evoked DA release after intra-VTA micro-infusions of selective MOR agonist (DAMGO). Different sites of FSCV recordings were used to discriminate MOR effects on phasic DA release in NAc subregions. Intra-VTA DAMGO had limited effect on phasic DA release in the NAc. Several analysis were performed to demonstrate potential DAMGO effects depending on the recording site within the NAc.
Funding: National Science Centre Research grant no. UMO-2020/39/B/NZ7/03537.
Martyna Marzec, Karolina Nowalińska, Magdalena Walczak, Tomasz Błasiak
Department of Neurophysiology and Chronobiology, Faculty of Biology, Jagiellonian University, Cracow, Poland
Abstract: The midbrain dopaminergic system is involved in control of animals’ orienting movements and reactions to relevant environmental stimuli. The activity of midbrain dopaminergic neurons (DA) is influenced
by retinorecipient superior colliculus (SC), a structure engaged in visual processing and sensory integration. Previous studies neglected impact of SC on dopaminergic neuron activity and DA release on the contralateral side of the brain, focusing primarily on the ipsilateral side. To address this research gap, our group first sought to characterize how dopaminergic neurons in the VTA/SNc respond to asymmetric retinal stimulation during SC disinhibition. As a further step, we aimed to explore the resultant changes in dopamine release within the striatum, which are presented in the current study. Our approach combined in vivo fiber photometry recording of striatal dopamine release with SC pharmacological disinhibition and asymmetrical light stimulation of the animal’s eyes. Interestingly, we observed differences in both the level and dynamics of striatal dopamine release evoked by monocular stimulation between the hemispheres contralateral and ipsilateral to the stimulated eye. Our findings significantly broaden our understanding of sensory input lateralisation, and how it can modulate the activity of DA system, providing further information on learning, motivation, and decision-making processes.
Funding:National Science Centre, OPUS 17 2019/33/B/NZ4/03127
Karolina Nowalińska, Martyna Marzec, Tomasz Błasiak
Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Kraków, Poland
Abstract: Light affects animals’ circadian cycles, mood, perception and reactions to their environment. Retinal light information directly influences subcortical relay structures, which further distribute it within the brain. One example of such relay structures are the superior colliculi (SC), where information from various modalities is integrated and transmitted, among others, to the midbrain dopaminergic (DA) neurons within the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Interestingly, in species like mice and rats - with lateralized eyes - a greater proportion of visual input to SC originates from the contralateral eye due to eye placement.
Our study investigated VTA and SNc DA neurons activity, which is affected by lateralized illumination of the eyes of male albino rats anesthetized with urethane. After SC disinhibition with bicuculline microinjection, most of the recorded DA neurons exhibited responses to monocular light stimulation, showing differences when the ipsilateral or contralateral eye was stimulated in relation to the recording site. The proportion of excitatory and inhibitory responses, as well as the response dynamics (i.e. latency and duration), depended on whether the eye on the same or contralateral side to the recording site was stimulated.
Observed differences in DA neurons response proportions and dynamics to lateralized stimuli may influence DA release in the basal ganglia, potentially shaping animal behaviour and motivation.
Aleksandra Greggio1, Natalia Respekta-Długosz1,2, Oliwia Szkraba1, Pascal Froment3, Joelle Dupont3 and Agnieszka Rak1
1Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research,
Jagiellonian University, Krakow, Poland
2Doctoral School of Exact and Natural Sciences, Jagiellonian University, Krakow, Poland
3INRAE, Physiologie de la Reproduction et des Comportements, Nouzilly, France
Abstract: Resistin is an adipokine involved in the regulation of lipid and glucose metabolism, adipogenesis and reproduction. Recent studies indicated an important role of resistin in maintaining brain homeostasis, but its role in the hypothalamus secretory function is still unknown. The aim of the present study was to examined firstly gene and protein expression of resistin and its receptors ROR1, CAP1 and TLR4, and then the effect of resistin on the viability, levels of PCNA (proliferating cell nuclear antigen) and GnRH in the mouse hypothalamic GT1-7 cells (in vitro model of GnRH-secreting neurons). The gene and protein expression of resistin, ROR1, CAP1 and TLR4 were analysed by real-time PCR, Western blot, and immunocytochemistry, respectively. GT1-7 cells were treatment with resistin (0.1, 1, 10 ng/ml) and cell viability was analysed using alamarBlue®, PCNA transcript expression, as well as gene and protein levels of GnRH by real-time PCR, Western blot, and ELISA. Statistical analysis employed one-way ANOVA, followed by Tukey's test (n=5; p<0.05). The results showed the expression of gene and protein of resistin and its receptors as well as their co-localization with GnRH in GT1-7 cells. Additionally, the inhibitory effect of resistin on GT1-7 cells viability, PCNA transcript level and GnRH secretion were observed; with no effect on GnRH gene expression. Our results demonstrate for the first time expression of resistin system in mouse hypothalamic neuronal cells and its important role in the in vitro regulation of GnRH secretion.
Monika Żuwała, Marcelina Janik
Department of Glycoconjugate Biochemistry, Institute of Zoology and Biomedical Research, Jagiellonian University, Krakow, Poland
Abstract: Emerging evidence suggests a role for glutamate and orexins in cancer biology. The expression of nervous system-related receptors, including orexin receptors (OXR) and glutamate receptors (NMDA, AMPA), has been reported in several cancers. The effect of NMDA receptors has been shown to down-regulate the proliferation of lung cancer cells. In digestive cancers expressing OXR1, its activation has been shown to lead to cell apoptosis. On the other hand, a strong association between OXR2 expression and cervical cancer progression has been demonstrated, suggesting its potential as a therapeutic target. In this context, we aimed to determine the expression of OXR2 and AMPA receptors in selected melanoma (skin and uveal), thyroid and breast cancer cell lines. Melanoma cells are particularly predisposed to express these receptors as they originate from neural crest cells. Our results confirmed OXR2 expression in all melanoma, thyroid and breast cancer cell lines analysed. Expression of the AMPA receptor subunit - GluA1 was only detected in breast cancer cells and selected melanomas. To our knowledge, this is the first report of OXR2 expression in melanoma cells. As OXR2 expression has not been reported in melanocytes, it may play a role as a target in melanoma therapy.
Mariia Vashcheniuk¹, Yaroslav Stepanyuk²
¹Department of Normal Anatomy, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
²Department of Histology and Medical Biology, Lesya Ukrainka Volyn National University, Lutsk, Ukraine
Abstract: Background of the study: "Glutamate-induced obesity" is a term that has been causing scientists to debate for many years. Since the hypothalamic nuclei are responsible for energy and lipid metabolism, it was reasonable to analyze the morphological and morphometric changes in the hypothalamic nuclei under the influence of sodium glutamate and its absence (in an experiment of white rats).
Materials and Methods: The study material consisted of macro- and micropreparations of the hypothalamus of male Wistar rats. Sodium glutamate was administered orally to male rats once a day. Material sampling was carried out at 6, 8, 10, 12 weeks of the experiment. Analysis of histological sections stained with hematoxylin and eosin was performed.
Results: Large neurons were found in the dorsomedial and ventromedial nuclei of the hypothalamus with vacuolated perikaryon cytoplasm, hypochromic neurons and neurons with picnotic nuclei after prolonged administration of sodium glutamate. After discontinuation - the nuclei of certain neurons were picnotic, with some lysed nuclei.
Conclusions: Long-term administration of sodium glutamate leads to deep changes in the microstructural organization of the hypothalamic nuclei in experimental animals, which are not compensated by discontinuation of the specified dietary supplement.
Natalia Respekta-Długosz1,2, Jakub Chatys1, Karolina Pich1,2, Aleksandra Greggio1, Kamil Dobrzyń3, Nina Smolińska4, Joëlle Dupont5, Agnieszka Rak1
1Laboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, Poland
2Doctoral School of Exact and Natural Sciences, Jagiellonian University in Krakow, Krakow, Poland
3Department of Zoology, Faculty of Biology and Biotechnology, University of Warmia and Mazury, Olsztyn, Poland
4Department of Animal Anatomy and Physiology, Faculty of Biology and Biotechnology, University of Warmia and Mazury, Olsztyn, Poland
5INRAE, Physiologie de la Reproduction et des Comportements, Nouzilly, France
Abstract: OMENTIN-1 (OMNT1) is a novel adipokine that mediates important anti-inflammatory, antioxidative, and anti-apoptotic effects. It also regulates endothelial dysfunction and reproduction. Our previous study discovered the OMNT1 gene and protein expression in the porcine anterior pituitary (AP) cells. Nevertheless, OMNT1’s role in neurohormonal processes is unclear, so the present study aims
to investigate OMNT1 localization and its impact on tropic hormone (GH, PRL, ACTH, TSH, LH, FSH) secretion in porcine AP cells. APs were isolated from mature pigs to explore OMNT1 co-localization with tropic hormones using immunohistochemistry. In in vitro, AP cells were treated for 24 h with OMNT1 at increasing doses of 10, 50, and 100 ng/ml combined or not with hypothalamic liberins to study tropic hormones mRNA and protein expression by RT-qPCR and ELISA, respectively. Statistical analysis employed one-way ANOVA, followed by Tukey's test (n=5; p < 0.05). The results showed OMNT1 immunolocalization with tropic hormones (except ACTH) in AP cells. Also, OMNT1 (50 ng/ml) upregulated LH, FSH, PRL, and ACTH expression, while at 10 ng/ml, combined with TRH, it affected TSH, and at 100 ng/ml inhibited PRL expression. OMNT1 also modulated hormone secretion, stimulating LH (10 and 50 ng/ml) and inhibiting FSH (50 ng/ml) induced by GnRH. In conclusion, our study shows OMNT1 protein localization in pig's AP. Its regulatory role on tropic hormones suggests a potential neuromodulatory role of OMNT1 in the hypothalamic-pituitary axis, requiring further investigation into underlying molecular mechanisms.
Funding: National Science Centre, Poland, 2020/37/B/NZ9/01154
Anna Dyldina, Roman Myroniuk, Yaroslav Omelkovets
Medical Faculty, Lesia Ukrainka Volyn National University, Lutsk, Ukraine
Abstract: The cerebellum of Nyctalus noctula and Hirundo rustica was studied according to generally accepted methods.
It was found that the weight of the cerebellum of the common noctule is 16.2% of the brain weight, and that of the barn swallow is 15%. The relative volume of the cerebellum (in % of the cerebral volume) of the swallow is larger than that of the noctule (14.9% and 11%, respectively). Also, the relative area of the cerebellar cortex (as a percentage of the cerebral area) is larger in the bird than in the noctule, 31% and 23.6%, respectively.
At the same time, the average absolute and relative thickness of the cerebellar cortex and its individual layers in the common noctule (366±18.7 µm; 522) significantly exceeds that of the barn swallow (285±15.9 µm; 274).
Also, the bat has a higher CFI index, than the bird (23.55 and 3.28, respectively), which indicates a larger number of cerebellum lobes and is explained by the presence of hemispheres.
Thus, the swallow's cerebellum is characterized by more complex worm differentiation, larger relative area and volume, and less cortical thickness than that of the common noctule.
Grzegorz Olszak and Diana Legutko, Leszek Kaczmarek, Piotr Michaluk
Laboratory of Neurobiology, Nencki Institute of Experimental Biology, PAS, Warsaw, Poland
Abstract: Dendritic spines, small protrusions on neuronal dendrites, are crucial for the organization of excitatory synapses. Their structure and molecular composition evolve during development and undergo dynamic changes in response to learning. Matrix metalloproteinase 9 (MMP9) is a secretory gelatinase well-known for its involvement in affecting spine structure in response to learning. MMP9 is stored in synaptic vesicles, from which it is released into the extracellular space to digest proteins and orchestrate synaptic signaling cascades. However, the co-occurrence of MMP9 and its target proteins within these synaptic vesicles—critical for understanding the synchrony of their release and subsequent action—remains elusive, largely due to the limitations imposed by the small size of dendritic spines and the resolution of conventional light microscopy. To address this challenge, we utilized expansion microscopy, a super-resolution technique that physically enlarges specimens. This process entails embedding the specimen in a hydrogel, followed by digestion and isotropic expansion in an aqueous environment. Employing a combination of expansion microscopy and immunofluorescent staining enabled us to visualize the spatial distribution of MMP9 within dendritic spines using a conventional confocal microscope. Our ongoing research aims to explore the colocalization of MMP9 with potential targets, such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor binding protein 2 (IGFBP2).
Jadwiga Jabłońska, Grzegorz Wiera, Jerzy Mozrzymas
Department of Biophysics and Neurobiology, Wrocław Medical University, Wrocław, Poland
Abstract: The extracellular matrix (ECM) of the brain plays a pivotal role in regulating synaptic plasticity. The maturation of the ECM, particularly the formation of perineuronal nets enveloping parvalbumin (PV) interneurons, imposes constraints on excitatory synaptic plasticity in adulthood. Notably, these constraints can be reversed to a juvenile-like state by enzymatic treatment.
Our study utilized patch-clamp recordings to investigate the effects of hyaluronic acid or chondroitin sulphate digestion on GABAergic transmission in synapses connecting PV or somatostatin (SST) interneurons and CA1 pyramidal cells (PCs). We employed an optogenetic approach to selectively activate PV and SST inputs while synaptic currents (IPSCs) were measured from PCs.
Enzymatic removal of ECM constituents did not impact the amplitude or kinetic parameters of inhibitory transmission. However, it induced a subtle deepening of burst-induced depression in PV-PC synapses. We then analysed NMDA-dependent heterosynaptic long-term inhibitory plasticity. In SST-PC synapses, NMDA-iLTP was specifically impaired following chondroitinase treatment (sham: 125.9±7.6% , n=15 ; after digestion: 106.1±4.5%, n=16, p=0.03). Conversely, hyaluronidase treatment selectively impaired iLTP in PV-PC input (sham: 116.6±4.7% , n=16 ; after digestion: 100.4±5.3%, n=10, p=0.01). Collectively, these findings underscore the crucial role of the brain ECM in shaping inhibitory plasticity by exerting control over input-specific long-term modifications at distinct GABAergic synapses.
Funding:NCN grant 2021/43/B/NZ4/01675
Patrycja Brzdąk*, Katarzyna Lebida*, Jerzy W. Mozrzymas
Department of Biophysics and Neuroscience /Wroclaw Medical University, Wroclaw, Poland
*equal contribution
Abstract: Neuromodulation by dopamine is widely recognized as a key factor both in the regulation of hippocampal excitatory synaptic plasticity and in memory processes (Tsetsenis et al., 2023). However, the involvement of dopaminergic receptors signaling in the plasticity of GABAergic synapses is still unexplored. We therefore addressed the question whether dopamine D1-like receptors could modulate inhibitory synaptic transmission and plasticity in hippocampal brain slices. First, we performed recordings of miniature inhibitory postsynaptic currents (mIPSCs) using patch-clamp technique from pyramidal cells in the presence of dopamine D1/D5 receptors antagonist (SCH23390) or agonist (SKF38393) and we have revealed that usage of these compounds had opposite effects on the mIPSCs amplitude (SCH23390: 87±7 %, n = 7; SKF38393: 113±4 %, n = 6; relative to baseline). Then, we induced inhibitory LTP (iLTP) by NMDA treatment in control conditions (mIPSCs amplitude: 127 ± 4%, n = 9) and after blocking or enhancing the activity of dopamine D1/D5 receptors. Interestingly, we have observed that the application of SCH23390 led to conversion of iLTP to iLTD (84±5%, n = 7), while SKF38393 preserves iLTP (111±4%, n = 5). In conclusion, our data indicate that dopamine D1-like receptor signaling interfere with GABAergic transmission and plasticity in hippocampus.
Funding:The research was supported by Polish National Science Center (NCN) grants OPUS 2021/43/B/NZ4/01675, SONATINA 2023/48/C/NZ4/00072, MINIATURA 2023/07/X/NZ4/00687
Gabriela Stopka1, Aleksandra Trenk1, Anna Gugula1, Kinga Przybylska1, Aleksandra Nogaj1, Camila de Ávila2, Anthony J. Intorcia4, Geidy E. Serrano4, Thomas G. Beach4, Diego F. Mastroeni2, Andrew L. Gundlach3 and Anna Blasiak1
1Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Jagiellonian University, Krakow, Poland
2ASU-Banner Neurodegenerative Disease Research Center, Biodesign Institute, and School of Life Sciences, Tempe, Arizona, USA
3The Florey Institute of Neuroscience and Mental Health, and Florey Department of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia
4Neuropathology Laboratory, Banner Sun Health Research Institute, Sun City, Arizona, USA
Abstract: Alternations in the ventral hippocampus dentate gyrus (vDG) functioning are closely linked to anxiety disorders. vDG receives dense innervation from the nucleus incertus (NI), a stress-sensitive brainstem structure and a major source of relaxin-3 (RLN3) in the brain. RLN3, through its receptor, RXFP3, affects stress and anxiety-related behaviors. However, its impact on vDG neuronal activity remains unexplored. Therefore, we explored possible influence of RXFP3 activation on rat vDG neuronal activity ex vivo, and examined related neuroanatomical substrates, both in rats and humans.
Whole-cell patch-clamp recordings showed that RLN3 reduced vDG granule cell excitability. Viral vector based neural tract-tracing indicated similar innervation of the hilus and inner-molecular layer of vDG by NI-originating and RLN3-positive fibers, suggesting NI as a major source of this neuropeptide in vDG. HiPlex in situ hybridization (ISH) revealed RXFP3 mRNA expression in vDG hilar interneurons, but not in granule cells, in rats. Importantly, in human postmortem tissue, ISH also revealed RXFP3 mRNA expression in anterior DG GABA-ergic hilar interneurons.
Our findings suggest that NI-originating RLN3 innervation of vDG can directly activate RXFP3 on hilar interneurons, altering granule cell excitability. These effects of RLN3/RXFP3 signaling likely regulate stress and anxiety-related behaviors.
Funding: National Science Centre (UMO-2018/30/E/NZ4/00687, UMO-2023/49/B/NZ4/01885); MiniGrant2023-ID.UJ; BrightFocus Foundation A2021006; Alzheimer’s Association AARFD-22-972099.
Emilia Goszczyńska1, Aleksandra Trenk1, Anna Gugula1, Camila de Ávila2, Anthony J. Intorcia4, Geidy E. Serrano4, Thomas G. Beach4, Diego F. Mastroeni2, Andrew L. Gundlach3 and Anna Blasiak1
1Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Jagiellonian University, Krakow, Poland
2ASU-Banner Neurodegenerative Disease Research Center, Biodesign Institute, and School of Life Sciences, Tempe, Arizona, USA
3The Florey Institute of Neuroscience and Mental Health, and Florey Department of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia
4Neuropathology Laboratory, Banner Sun Health Research Institute, Sun City, Arizona, USA
Abstract: Somatostatin-expressing GABA-ergic interneurons (SOM) of dentate gyrus (DG) involve hilar interneurons (HILs) that innervate the medial septum (MS). Both DG and MS are heavily innervated by GABA-ergic neurons originating in the stress-sensitive brainstem nucleus incertus (NI), the main source of relaxin-3 (RLN3) in the brain. NI originating RLN3 innervation of DG is prominent in the ventral part of the DG (vDG), associated with anxiety behavior. Yet, the characteristics of NI-vDG-MS axis, as well as HILs involvement in this pathway remain unknown.
HiPlex in situ hybridization (ISH) studies revealed that neurons expressing RXFP3 mRNA in the rat vDG co-expressed vesicular GABA-transporter (vGAT) and SOM mRNA. Importantly, in human anterior hippocampal sections ISH also showed co-localization of vGAT, RXFP3 and SOM mRNA. Viral vector based neural tract-tracing studies confirmed that SOM DG neurons innervate MS. Additionally, tract-tracing results showed that single NI RLN3+ neurons innervate both MS and vHPC.
Our findings are first to show the involvement of SOM interneurons in RLN3 signaling in the vDG, and that MS and vDG are controlled by NI originating RLN3 innervation. Our research contributes to molecular characterization of SOM vDG interneurons, which are a crucial elements of the circuits engaged in stress and anxiety control.
Funding: National_Science_Centre_Poland: UMO-2023/49/B/NZ4/01885, UMO-2018/30/E/NZ4/00687; MiniGrant2023_ID.UJ
Gabriela Czerniak, Kinga Przybylska, Sylwia Drabik, Aleksandra Trenk, Patryk Sambak, Gabriela Stopka, Anna Guguła, Anna Blasiak
Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Jagiellonian University, Krakow, Poland
Abstract: Ventral hippocampal dentate gyrus (vDG) is strongly involved in the control of stress, anxiety and social interactions. vDG is densely innervated by highly stress sensitive brainstem nucleus incertus (NI) and midbrain interpeduncular nucleus (IPN). NI is the main source of relaxin-3 (RLN3) neuropeptide, and activation of RLN3 cognate receptor RXFP3 in the vDG, was shown to induce anxiety and social avoidance. However, the neuronal mechanisms underlying RLN3/RXFP3 signalling in the vHPC, as well as neurochemical characteristics of NI neurons innervating vDG are still not fully understood. Similarly, the nature of the IPN-vDG connection remains completely unknown.
Stereotaxic injections of fluorescent retrograde tracers into the vDG of Sprague Dawley rats revealed that NI neurons innervating vHPC are mainly RLN3-positive and their projections are mainly ipsilateral. At the same time vHPC-innervating neurons were observed in observed in the lateral, caudal, rostral and dorsomedial subnuclei of the IPN, remaining under NI control. Multi-electrode array (MEA) ex-vivo recordings unveiled both inhibitory and excitatory influence of RLN3 on the vDG network activity.
Taken together these observations shows that vDG remains under control of both NI and IPN, shedding light on the neurochemical and neurophysiological underpinnings of anxiety and social interactions.
Funding: National_Science_Centre_Poland: UMO-2023/49/B/NZ4/01885, UMO-2018/30/E/NZ4/00687;
Wiktoria Podolecka, Mark Jeremy Hunt
Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
Abstract: Olfactory sensory neurons deliver sensory input from the nasal epithelium to the olfactory bulb (OB). Our goal was to examine the role of sensory input from the nasal epithelia on electrophysiological activity in the OB. To accomplish this we developed a gadolinium model of anosmia. Rats (N=10/group) were bilaterally implanted with electrodes to the OB. Gadolinium (3 mg/side) or saline was infused to both nares. Anosmia was assessed using the hidden cookie test. Rats were tested every other day for 15 days. Local field potentials from the OB were recorded after each hidden cookie test. Gadolinium infusion increased time taken to find the hidden cookie compared to control rats. This lasted around 10 days. Electrophysiological recordings revealed gadolinium-infusion to the nares reduced the amplitudes of respiration rhythm (1-10 Hz) and gamma (40-80 Hz), compared to saline-infused rats. Hidden cookie test performance and changes in nasal respiration rhythm positively correlated. Together these findings demonstrate that intranasal gadolinium infusion can be used as a safe model to produce anosmia. Further we show that sensory input arising from the nasal epithelium is critical for the generation of respiratory and gamma rhythms in the OB.
Funding:Narodowe Centrum Nauki
Agnieszka Kania, Michał Kiełbiński, Marcin Siwiec, Grzegorz Hess
Department of Physiology, Maj Institute of Pharmacology, Polish Academy of Sciences, Cracow, Poland
Abstract: The 5-HT7 receptor is involved in many physiological and pathological processes, including spatial navigation, circadian rhythm regulation, pain perception and the development of mood disorders. Since the pathophysiology of major depressive disorder is thought to include disturbances in serotonin metabolism, it is of great interest to study the main site of serotonin production - the dorsal raphe nucleus (DRN), especially as the role of the 5HT7 receptor in this area remains largely obscure. In this study, we aimed to evaluate the effect of 5-HT7 receptor knock-out on cell membrane properties and excitatory synaptic activity in the DRN. Using whole-cell patch clamp electrophysiological protocols, we examined spontaneous excitatory synaptic currents and intrinsic excitability of serotonergic DRN cells of male 5-HT7 knockout and wild-type mice. The cells were identified by immunostaining for tryptophan hydroxylase II and each recorded neuron was filled with biocytin to allow examination of cell morphology using Sholl analysis. 5-HT7 receptor knockout increased the basal amplitude of sEPSCs and decreased the excitability of TPH+ neurons. In addition, a slight increase in the complexity of axodendritic arborizations was observed in 5HT7-KO mice. We hypothesize that these changes in DRN projection neurons may affect the release of serotonin in target structures.
Funding:Supported by National Science Centre grant no: 2017/27/B/NZ4/01527
Agata Pytyś1, Domnic Colvin1, Rabia Ijaz1, Anna Buszka1, Izabela Figiel1, Jakub Włodarczyk1 and Tomasz Wójtowicz1
1Laboratory of Cell Biophysics, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
Abstract: S-palmitoylation (S-PALM) is a type of lipid posttranslational modification of proteins unique among other lipidations due to its reversible nature. It has been estimated that about 40% of synaptic proteins can undergo S-PALM. S-palmitoylation may modulate localization and function of synaptic proteins. However, the time-course of this process, protein-specificity and the role of S-PALM in scaling the efficacy of excitatory synapses remain largely unknown.
Here we studied dynamic changes of synaptic proteins’ S-PALM following pharmacological induction of long-term synaptic potentiation (LTP) in hippocampal neurons with either NMDAR co-agonist glycine or a mixture of rolipram, forskolin and picrotoxin. We employed Acyl-Biotin Exchange (ABE) assay and investigated the differences in S-PALM profiles of proteins at 20 min and 1h following LTP in in vitro and ex vivo preparations. Our results indicate that both palmitoylation and depalmitoylation occur post enhanced neuronal activity in time- and protein-dependent manner. Further research in this area may shed more light on the S-PALM’s role in healthy brain function and contribute to the understanding of diseases of the nervous system that negatively affect cognitive functioning in people.
Funding: Research funded by the Polish National Science Centre (grant 2019/34/E/NZ4/00387).
Agata Krużel, Marcin Siwiec, Krzysztof Tokarski
Department of Physiology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland
Abstract: Neuropathic pain remains one of the most challenging health issues nowadays. Complex etiology, chronic state and limited treatment options result in high demand for new, efficient therapies. 5-HT7R is a serotonin receptor subtype, localized in pathways connected to neuropathic pain and is shown to be involved in nociceptive mechanisms activated in animal models used to study chronic pain. In the present study, we aimed to determine the modulatory effects of 5-HT7 receptor activation on synaptic transmission in mouse dorsal horn spinal cord neurons, a region associated with pain transmission. Utilizing whole-cell patch clamp recordings, we assessed the effects of a new 5-HT7R agonist CPL 298 on inhibitory and excitatory synaptic transmission as well as intrinsic membrane properties of recorded neurons in lamina II of the dorsal horn. Our results suggest that activation of 5-HT7 receptors in the dorsal horn of the spinal cord modulates both inhibitory and excitatory neurotransmission, which may have therapeutic potential in the treatment and/or prevention of chronic pain.
Funding:POIR.01.01.01-00-0887/19 "Serotoninergic analgesic therapy based on a 5 HT7 receptor agonist (STEP7)" financed by NCBR
Rak Magdalena1, Białoń Magdalena1, Łażewska Dorota2, Kieć-Kononowicz Katarzyna2, Starowicz Katarzyna1, Popiołek-Barczyk Katarzyna1
1Department of Neurochemistry, Maj Institute of Pharmacology, Krakow, Poland
2Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College,
Krakow, Poland
Abstract: Neuropathic pain is caused by the lesion or disease of somatosensory nervous system and may be characterized by both sensory and affective impairments. Histamine H3 receptor (H3R) has been proven to play a role in cognition, mood disorders, and pain modulation. We aimed to assess the effect of a novel H3R antagonist (E-98), on pain (von Frey) anxiety (open field, OF) and memory performance (novel object recognition, NOR) in neuropathic mice. Mice underwent chronic constriction injury (CCI) (model of neuropathic pain) and received E-98 (10 mg/kg; twice daily, 7 days, following day 7th). We collected the hippocampus for high-performance liquid chromatography (HPLC) analysis of monoamines (NA, DA, 5-HT). E-98 produced an analgesic effect. Neuropathic mice exhibited lower rearings. In T2 (NOR), E-98-treated animals explored novel objects significantly longer. The time spent exploring a familiar object in T2 was higher in the vehicle-treated group, and E-98 did not influence this parameter. The HPLC analysis did not reveal any changes in monoamine levels. Our studies showed that CCI influenced animals’ locomotor activity and memory performance, and the E 98 treatment reversed this effect. The novel H3R antagonist did not affect hippocampal monoamine’s level, suggesting a different yet undefined mechanism of neuropathy-related affective impairment.
Funding:Work was financed by a grant from the National Science Centre, Poland, SONATA 2019/35/D/NZ7/01042.
Aleksandra Bober, Anna Piotrowska, Joanna Bogacka, Katarzyna Ciapała, Katarzyna Pawlik, Joanna Mika
Department of Pain Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland
Abstract: Chemokines and their ligands are known to be involved in nociceptive transmission in neuropathic pain including diabetic neuropathy. Among them CCR2 and CCR5 together with their ligands seem to be associated with pathomechanism of developing neuropathic pain. Therefore, our study aimed to examine the changes of these factors in parallel with hypersensitivity accompanying diabetic neuropathy. Moreover, we studied if and how cenicriviroc, a CCR2 and CCR5 antagonist, influences pain symptoms. The experiments were performed on male and female Swiss albino mice with streptozotocin (STZ; 200 mg/kg, intraperitoneally)-induced model of diabetic neuropathy. Pain-related behavior was assessed by the von Frey and cold plate tests. An analysis of the mRNA expression of CCR2 and CCR5 ligands was performed by qRT-PCR. Cenicriviroc was injected intraperitoneally 2h before behavioral tests on day 7 after STZ injection. The result shows that on day 7 after STZ administration, the blood glucose level was increased, and at the same time mechanical and thermal hypersensitivity developed. In male mice, we observed increased mRNA levels of Ccl2, Ccl5, and Ccl7 while in female mice additional Ccl8 and Ccl12 increased levels were noted. Moreover, we demonstrated that cenicriviroc alleviates STZ-induced hypersensitivity. Based on these results, we suggest that targeting CCR2 and CCR5 is a potent therapeutic solution in novel pain treatments for diabetic neuropathy.
Funding: The research was funded by the National Science Centre, Poland grant OPUS 22 2021/43/B/NZ7/00230, SONATA 17 2021/43/D/NZ5/02559 and statutory funds from the Maj Institute of Pharmacology Polish Academy of Sciences.
Anna Kusiak, Katarzyna Pawlik, Katarzyna Ciapała, Aleksandra Bober, Agata Ciechanowska, Wioletta Makuch and Joanna Mika
Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Pain Pharmacology, Krakow, Poland
Abstract: Recently, involvement of some chemokines in the development of neuropathic pain has been noted; however, participation of the CCR5 ligands in oxaliplatin-induced neuropathy still needs to be studied.
The goal of our study was to examine if CCR5 ligands (CCL3, CCL5, CCL7 and CCL8) evoked pain-related behavior and whether their levels are changed in oxaliplatin-induced neuropathy. The experiments were performed on male Swiss albino mice: naïve and with oxaliplatin (10 mg/kg, intraperitoneally)-induced model of peripheral neuropathy. The study was conducted using behavioral tests (von Frey/ cold plate) and RT-qPCR analysis of the spinal cords on day 7 and 14 after oxaliplatin administration in mice.
The results of our studies provide evidence that the intrathecal administration of CCL3, CCL5, CCL7 and CCL8 induces mechanical and thermal hypersensitivity in naïve mice. Importantly, the RT-qPCR analysis showed elevated levels of CCL5 and CCL7 mRNAs in the spinal cord on day 7 after oxaliplatin administration. Taken together, our results suggest an important role of two CCR5 ligands (CCL5 and CCL7) in the development of thermal and tactile hypersensitivity. Additionally, our biochemical studies revealed that they may also participate in hypersensitivity development observed in oxaliplatin-induced neuropathy. CCR5 may become a potential therapeutic target for pain management, but further research is necessary
Funding:The research was funded by the National Science Centre, Poland grant OPUS 22 2021/43/B/NZ7/00230 and statutory funds from the Maj Institute of Pharmacology Polish Academy of Sciences
Degutis M., Białoń M., Starowicz K., Popiołek-Barczyk K.
Department of Neurochemistry, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland
Abstract: Initiating and sustaining an inflammatory response largely depends on glial cell activation, which is a significant factor in the pathophysiology of chronic pain. Our study aimed to determine the analgesic effects of histamine H3 receptor (H3R) antagonist, pitolisant (PIT), in neuropathic mice and its influence on glial cells activation in primary cultures. The effect of a single intraperitoneal injection of PIT (1, 5, 10, 20 mg/kg) on mechanical stimuli (von Frey test) was assessed on mice subjected to chronic constriction injury (CCI) at day 14th after surgery. Anti-inflammatory effects of PIT were examined in LPS-treated (100 ng/mL) primary microglial and astrocyte cell cultures. Nitric oxide (NO) production was determined by Griess assay. Cytokine (IL-6, IL-1β, IL-10) and cell markers (Iba1, CD206) levels were quantified by ELISA and Western blot, respectively. We observed PIT's dose- and time-dependent analgesic effects. PIT (0.01, 0.1, 1.0, 10 µM) did not affect NO production by both cell types. PIT (10 µM) did not affect cytokine levels in microglia; however, it reduced the Iba1 level. We detected increased IL-1β and decreased IL-10 levels in astrocytes. The results demonstrate an analgesic property of PIT in neuropathic animals, while in cell cultures, modulation of glial cell activation.
Funding: This research was financed by grant SONATA 2019/35/D/NZ7/01042 from National Science Centre, Poland.
Bernard Kordas, Kamila Zglejc-Waszak, Judyta Juranek
Department of Human Physiology and Pathophysiology, School of Medicine, University of Warmia and Mazury in Olsztyn, Poland
Abstract: Background: This study compares biological (BR) and technical repetitions (TR) in assessing sciatic nerve morphometry in diabetic mice across wild-type (WT), Diaph1 knockout (DKO), and Diaph1-RAGE knockout (DRKO) models, examining statistical methodologies' impact on neuropathy interpretations.
Methods: Six months after the onset of streptozotocin-induced diabetes, WT, DKO, and DRKO mice were analyzed for nerve fiber metrics. BR used averages from individual animals; TR considered each measurement independently.
Results: TR underscored significant morphometric differences, particularly in axon and fiber diameters between diabetic DKO and diabetic WT. At the same time, BR illuminated diabetic DRKO's higher G-ratio versus diabetic WT, suggesting varied impact scales. Unlike BR's broader deformation analysis, TR revealed more structural deformations in diabetic DKO. Both acknowledged DRKO's neuroprotection via stabilized axon and fiber diameters, G-ratios, and fiber counts. Only TR analysis showed a difference in myelin-to-axon area ratio between diabetic WT and diabetic DRKO.
Conclusions: TRs offer a detailed lens for detecting minute morphometric differences and genotype-specific neuroprotective mechanisms against diabetic neuropathy, which BRs may not capture due to their aggregated data approach. However, BRs excel in elucidating inter-individual variability and broader genotype effects. Combining both methods could enhance understanding of neuropathic changes and gene-related neuroprotection in diabetes.
Funding:National Science Centre in Poland, Grant/Award Number: UMO-2018/30/E/NZ5/00458
Dominika Ciupek1, Jan Fiszer1,2, Maciej Malawski1,2, Tomasz Pięciak3,1
1Sano Centre for Computational Medicine, Kraków, Poland
2AGH University of Science and Technology, Kraków, Poland
3ETSI Telecomunicación, Universidad de Valladolid, Valladolid, Spain
Abstract: Medical data privacy concerns and heterogeneity in data acquisition protocols make creating and publishing large datasets for machine learning (ML) difficult. Federated learning (FL) allows separate institutions to train a common ML model without sharing data. This research examines the FL-based approach to estimate brain microstructural properties from diffusion magnetic resonance imaging (MRI) data. The study compares the performance of a traditional deep learning method with that supported with the FL technique. To estimate the diffusion tensor imaging (DTI) microstructural parameters (i.e., FA, MD), the U-Net model was used on three publicly available datasets (CamCan, HCP WU-Minn, and ZJU) and one private. Three FL algorithms were evaluated to improve the model's generalizability from different sources: the standard FedAvg and FedMedian, and the MRI data-specific FedCostWAvg. The ability of a network to generalize in traditional deep learning relies heavily on the dataset it was trained on. However, when using basic FL techniques, the model generalization is improved (MSE = 00381). Moreover, implementing FedCostWAvg significantly enhances the accuracy of the estimated FA parameter (the average MSE decreased from 0.00398 to 0.00361). These findings highlight the crucial role of FL in improving the security of medical data and the generalization of the model.
Funding:The numerical experiment was possible through computing allocation on the Ares and Athena systems at ACC Cyfronet AGH under the grants PLG/2023/016117 and PLG/2024/016945. This research is supported by the European Union’s Horizon 2020 research and innovation programme under grant agreement Sano No 857533 and the project of the Minister of Science and Higher Education "Support for the activity of Centers of Excellence established in Poland under Horizon 2020" on the basis of the contract number MEiN/2023/DIR/3796. Tomasz Pieciak acknowledges the Polish National Agency for Academic Exchange for grant PPN/BEK/2019/1/00421 under the Bekker programme and the Ministry of Science and Higher Education (Poland) under the scholarship for outstanding young scientists (692/STY/13/2018).
Fabian Bogusz
Department of Biocybernetics and Biomedical Engineering, AGH University of Krakow, Krakow, Poland
Abstract: The multiparametric magnetic resonance imaging allows to disentangle the different water microenvironments that contribute to the acquired signal. To analyze such multiparametric signals one can use the continuum modeling approach which transforms the signal into a set of coefficients corresponding to compartments characterized by different parameters. The possible compartments are described by the so-called kernels representing processes present during the signal evolution. Considering the diffusion-relaxometry acquisitions majority of the works use the one-dimensional first-order diffusion signal expansion represented by the apparent diffusion coefficient as the diffusion part of the kernel.
This work proposes the use of the three-dimensional simple harmonic oscillator-based reconstruction and estimation as the diffusion representation in the diffusion-relaxometry signal analysis. To define the objective function used in the coefficient estimation task the network least absolute shrinkage and selection operator and alternating direction method of multipliers were used. The proposed method was compared with the diffusion-relaxation correlation spectrum imaging and sparsity promoting iterative joint non-negative least squares approaches. A significant improvement in the signal approximation was achieved. The method allows to estimate the indices associated with the geometrical parameters of the nerve fibers and also separate the free water contribution in the orientation distribution function reconstruction.
Marcin Sińczuk¹, Rafał Rola², Nikodem Hryniewicz¹, Ewa Piątkowska-Janko¹, Piotr Bogorodzki¹
¹CNSLab, Nałęcz Institute of Biocybernetics and Biomedical Engineering PAS, Warsaw, Poland
²Neurology Department of The Military Institute of Aviation Medicine, Warsaw, Poland
Abstract: 1H Magnetic Resonance Spectroscopy (1HMRS) thermometry (MRSt) is an innovative method enabling localized non-invasive brain temperature measurements. However its use in brain temperature measurements in tumors has been scarce. MRS is a technique used for measuring metabolites levels in brain tumors as key biomarkers. In our study unsuppressed water peak in conjunction with metabolite peaks data from MRS spectrum was used in order to estimate temperature within brain tumors. Calibration datasets were generated using phantom filled with water solution of chosen metabolites (NAA 12.5mM, Creatine 10mM and Choline 3mM). In vivo data was collected from 10 preoperative adult patients with brain lesions with voxels placed both within lesioned tissue and contralaterally. Temperature measurements were calculated with individual metabolites as reference and with an amplitude weighted averaging combining all measurements. MRSt temperature measurement method demonstrated a similar overall temperature increase in the lesioned tissue compared to healthy tissue. Our findings suggest the feasibility of introducing temperature as a novel biomarker in MRS studies of brain tumors.
Antoni Cierniak1, Aleksandra Midro1, Borys M. Kwinta2, Kornelia M. Kliś2
1Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
2Department of Neurosurgery and Neurotraumatology, Jagiellonian University Medical College, Cracow, Poland
Abstract: Transcranial Doppler (TCD) examination of Middle Cerebral Artery (MCA) blood flow is frequently used in neurosurgery in multiple clinical scenarios concerning cerebrovascular diseases. However, a limited number of parameters are typically used in MCA waveform analysis. The aim of the study was to evaluate novel spectral parameters of the MCA waveform and assess their variability in terms of common cardiovascular risk factors. 80 patients’ (56.23% females) aged 57.21±13.61, admitted to the neurosurgery unit, were prospectively enrolled. A detailed medical history was collected. Each patient underwent TCD examination of the MCA bilaterally. Envelopes of 5 registered MCA flow waveforms were transformed into the frequency domains using the Fourier transform, and the following parameters were calculated: spectral coefficient, spectral entropy, and spectral spread. We found significant associations between spectral parameters of MCA waveform and diagnosed hypertension, smoking, and dyslipidemia. Patients with hypertension had significantly lower spectral coefficient (8.05±10.51 vs. 13.47±13.32; p=0.02). In the multivariate linear regression model, spectral entropy and spectral coefficient remained independently associated with hypertension (R=-0.97; 95%CI:[-1.83;-0.10]; p<0.01; R=-2.69 95%CI:[-5.39;-0.35]; p=0.04). Our findings suggest that traditionally used neurosonological parameters might be supplemented by an analysis of proposed spectral parameters. We also provide evidence of the clinical significance of these parameters.
Karolina Lorek1, Joanna Mączewska2, Leszek Królicki2, Małgorzata Chalimoniuk3, Józef Langfort4, Sławomir Budrewicz5, Magdalena Koszewicz5, Magdalena Siemiatycka1, Jarosław Marusiak1
1Department of Kinesiology, Faculty of Physiotherapy, Wroclaw University of Health and Sport Science, Wroclaw, Poland.
2Nuclear Medicine Department, Medical University of Warsaw, Warsaw, Poland.
3Department of Physical Education and Health in Biala Podlaska, Jozef Pilsudski University of Physical Education in Warsaw, Faculty in Biala Podlaska, Biala Podlaska, Poland.
4Institut of Sport Sciences, Jerzy Kukuczka Academy of Physical Education in Katowice, Katowice, Poland.
5Department of Neurology, Wroclaw Medical University, Wroclaw, Poland.
Abstract: The underlying mechanism of muscle stiffness in Parkinson's disease (PD) is poorly understood, and no direct relationship exists between dopamine deficiency and rigidity. The study involved fifteen patients with right-sided mild PD symptoms. All subjects were assessed by: (i) positron emission computed tomography with an estimation of striatal [18F]Fluorodopa uptake ratio ([18F]FDOPA PET/CT) to evaluate dopaminergic degeneration; (ii) resting EEG recorded after bimanual anti-phase index finger movement from which we calculated event-related synchronization of the beta band; and (iii) the resting muscle stiffness of upper extremity measured by myometry. Mediation analysis were conducted using structural equation models to examine the impact of motor cortex activation in putative associations between dopamine deficiency and upper extremity muscle stiffness. PD patients exhibited significantly lower muscle stiffness of right first dorsal interosseous (FDI) than the left FDI. The activation of the motor cortex was positively correlated with the muscle stiffness of the right FDI and also positively associated with putaminal dopaminergic dysfunction. Structural equation models indicated that motor cortex activation mediated the association between putaminal dopamine depletion and muscle stiffness of right FDI. The motor cortex did not significantly mediate associations between putaminal dopamine depletion and muscle stiffness of left FDI. Impaired muscle stiffness of the right upper extremity associated with putaminal dopaminergic deficiency seems to be mediated to some extent by the motor cortex, what might suggest cortical compensations.
Funding: The work was supported by the National Science Centre, Poland, under research project no. 2017/25/B/NZ7/02795, entitled ‘Effect of high intensity interval training on mechanisms of neuroplasticity and psychomotor behaviours in Parkinson's disease patients: a randomized study with 1-year follow up’, awarded to Jaroslaw Marusiak.
1Department of Behavioural Neuroscience, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia
2Department of Physical Medicine and Rehabilitation, University Hospital Bratislava, Bratislava, Slovakia
32nd Department of Neurology, Faculty of Medicine, Comenius University & University Hospital Bratislava, Bratislava, Slovakia
Abstract: In stroke patients with hemiparesis, the asymmetrical position of the trunk is often characterized by a one-sided tilt or impaired mobility to one side. Postural tilt and predominant loading can be seen on either the paretic side or non-paretic side. Dynamic sitting balance in the early post-stroke stages varies across cases and thus requires individualized intervention. Recent studies have shown that additional sensory input enhances rehabilitation when added to standard motor-skill training. Visual feedback and proprioceptive stimulation can positively modify neural mechanisms, facilitate the improvement of motor performance, and promote effective motor learning.
Two subacute stroke patients with cerebral lesions of vascular origin underwent personalized training (8 days, 20 min/day), which included 8 postural tasks based on visual biofeedback using the center of pressure position projected on a screen. The tasks were carried out while sitting on the force plate, and the patient trained trunk mobility in both frontal and sagittal planes, focusing on the paretic side. Unilateral vibration (80 Hz, 1 mm, 15 s) to the quadratus lumborum was applied in two tasks.
After 8 days of training, the functional limits of stability in the frontal plane were extended by approximately 53% on the paretic side in both stroke patients.
Funding: This work was supported by the grant APVV-20-0420.
Weronika Kleszczyńska, Anna Jamroz-Wiśniewska, Konrad Rejdak
Chair and Department of Neurology, Medical University of Lublin, Poland
Abstract: Background: Multiple sclerosis (MS) is an immune-mediated demyelinating disease, typically diagnosed among young adults. According to recent reports, the course of MS might be determined by age at disease onset. The aim of this study was to compare clinical picture in groups of adult patients with MS onset before and after 40 years of age.
Methods: The retrospective observational study included adult patients diagnosed with MS. The cohort was divided into two groups depending on the age of onset: 18-40 years (young-onset MS; YOMS) and at or later than age of 40 (late-onset MS; LOMS).
Results: Together 84 patients were included: with YOMS (n=70) and LOMS (n=14). Mean age at diagnosis was 29,47 ± 6,21 in YOMS and 43,93 ± 2,79 years in LOMS. There was dominance of women in YOMS (82,86% vs 64,29%), however with no statistical significance. In the YOMS group, most cases represented relapsing-remitting type of MS (RRMS) while in the LOMS group there was a predominance of primary-progressive MS. Later onset patients had significantly more frequent urination disorders (p=0,008).
Conclusions: Clinical picture of MS is different depending on the age of onset. Most cases of YOMS represent RRMS. LOMS is associated with more frequent urinary dysfunction.
Przemysław R. Kac, Fernando González Ortiz1,2, Andreja Emeršič3,4, Maciej Dulewicz1, Michael Turton5, Peter Harrison5, Nicholas J. Ashton1,6,7,8, Henrik Zetterberg1,2,9,10,11, Saša Čučnik3,4,12, Milica Gregorič Kramberger3,13,14,15, Uroš Rot3,13, Kaj Blennow1,2 and Thomas K. Karikari1,15
1Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
2Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Molndal, Sweden
3Department of Neurology, University Medical Centre Ljubljana, Slovenia
4Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia
5Bioventix Plc, Farnham, UK
6Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
7King’s College London, Institute of Psychiatry, Psychology& Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London, UK.
8NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK.
9Department of Neurodegenerative Disease, UCL Institute of Neurology,London, UK
10UK Dementia Research Institute at UCL, London, UK.
11Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.
12Department of Rheumatology, University Medical Center Ljubljana, Ljubljana, Slovenia
13Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
14Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Sweden
15Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Abstract: BACKGROUND: Plasma phosphorylated-tau (p-tau) biomarkers have found utility in clinical trials for anti-amyloid drug therapies for Alzheimer’s Disease (AD). Plasma p-tau levels are increased in AD, and their decrease is observed after drug treatment. However, it is unknown if p-tau212 is a useful biofluid-based biomarker for AD since no method exists for its quantification. Here, we developed and validated a novel blood p-tau212 assay and assessed its biomarker potential in cohort with in vivo diagnosis of AD neuropathology.
METHODS: Using in-house Simoa immunoassay we measured p-tau212 levels in plasma in Slovenia Memory Clinic Cohort n=149
RESULTS: Plasma p-tau212 and p-tau217 had statistically not different AUCs to distinguish Aβ- SCD from Aβ+ AD-dementia (AUC=92.5% [95% CI=87.0%-97.9%] versus 95.6% [95% CI=91.7%-99.4%]; DeLong test P=0.232) and to separate Aβ+ AD-dementia from Aβ- non-AD MCI (AUC =89.2% [95% CI=88.2%-96.2%] versus AUC= 87.8% [95% CI=78.2%-97.2]; De Long test p=0.8119;). Positive predictive value (PPV) for Aβ positivity versus SCD were 94.7% for p-tau212 and 98.1% for p-tau217. The negative predictive values (NPVs) were 72.4% and 74.2% respectively.
CONCLUSIONS: As the newest member of the plasma AD biomarker toolbox, plasma p-tau212 is useful for AD diagnosis and differentiation diagnosis. Blood-based p-tau212 will be a cost-effective and simple-to-implement alternative to in vivo and autopsy-based evaluations for AD neuropathological changes.
Fernando Gonzalez-Ortiz1, Kaj Blennow1, Thomas K. Karikari1, Tormod Fladby2, Bjørn-Eivind Kirsebom3, Marc Suarez-Calvet4
1Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden
2Department of Neurology, Akershus University Hospital, Lørenskog, Norway
3Department of Psychology, Faculty of Health Sciences, The Arctic University of Norway, Tromsø, Norway
4Barcelona βeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain
Abstract: Background: Among the fluid biomarkers for Alzheimer’s disease (AD) diagnosis, plasma p-tau markers, particularly p-tau217, have shown high accuracy for the differentiation of AD from healthy controls and other neurodegenerative conditions. In addition, findings that plasma p-tau217 is increased in amyloid PET positive, but tau PET negative, cases have led to the assumption that plasma p-tau primarily reflects brain amyloidosis, and therefore only is changed in AD. In this multicentre study, we aim to explore levels of plasma p-tau217 in different age groups and across diverse acute and chronic neurological conditions.
Method: Using the Simoa HD-X platform, we measured plasma p-tau217 in healthy newborns (n=55), healthy younger [n=60] and older [n=30] controls, AD (n=60), acute ischemic stroke, AIS [20], cardiac arrest [n=20] and traumatic brain injury, TBI [n=20].
Results: Across the different groups, newborns had the highest concentrations of plasma p-tau217 (10.19 +/- 3.92 pg/ml). There were no significant differences between young and older controls. Levels in AD were significantly higher than in the older control group (3.43 +/- 1.44 and 1.57 +/- 0.45 pg/ml, respectively) and showed a high diagnostic accuracy identifying AD (AUC: 0.92). Acute conditions such as cardiac arrest and TBI, but not AIS, had similar or higher levels of p-tau217 as in AD at admission. However, p-tau217 levels decreased rapidly in the first 24 hours after admission in patients with cardiac arrest and TBI.
Conclusions: Our findings suggest that tau phosphorylation is process present in both physiological and pathological processes across the lifespan. High plasma p-tau in newborns might indicate an important role of tau phosphorylation in neuronal plasticity in the earliest stages of brain development. High plasma p-tau in acute conditions may be due to a temporary opening of the blood-brain barrier, with release of p-tau from the extracellular space to blood. While plasma p-tau217 is a very efficient biomarker for detecting AD pathology, tau phosphorylation, secretion and clearance can be affected in a variety of physiological and pathological conditions, necessitating further investigations to identify a wider set of conditions worth considering in the impending clinical implementation of blood biomarkers.
Maciej Dulewicz1, Jörg Hanrieder1,2,3, Przemysław Radosław Kac1, Agnieszka Kulczyńska-Przybik4, Barbara Mroczko4, Manuel Maler5, Timo Oberstein5, Johannes Kornhuber5, Henrik Zetterberg1,2,7,8,9, Kaj Blennow1,7, Piotr Lewczuk4,5
1Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
2Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK
3UK Dementia Research Institute at UCL, London, UK
4Department of Neurodegeneration Diagnostics, Medical University of Białystok, Białystok, Poland
5Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany
6SciLifeLab, University of Gothenburg, Gothenburg, Sweden
7Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
8Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China
9Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, WI, USA
Abstract: Background: In the Alzheimer's disease (AD) biomarkers have become increasingly important for various clinical purposes tracking the progression of the disease. The GFAP is an astrocytic cytoskeleton intermediate filament protein and concentrations of GFAP are higher in areas surrounding Aβ plaques and increased with tau accumulation in the brains of patients with AD. Measuring levels of GFAP in the blood and CSF can provide insights into the extent of neurodegeneration pathology in AD. This study intends to evaluate how effectively the concentrations of GFAP in the blood and in CSF can differentiate individuals with CSF biomarker-confirmed AD in comparison to CSF biomarker-negative healthy control group.
Methods: Plasma and CSF concentrations of GFAP were measured by Single molecule array (Simoa) assay. The quantitative assessment of classical biomarkers (Aβ-42, Aβ-42/Aβ-40, tau, and pTau181) in the CSF of patients with possible AD according to the Erlangen Score algorithm (ER 2 and 3) and controls (ER 0) were performed by Lumipulse.
Results: Significantly higher plasma concentrations of GFAP in CSF and Plasma were noticed in AD patients compared to controls.
Conclusions: The results of the present study indicate that plasma GFAP has better diagnostic accuracy than CSF.
Diana Piotrowska1,2, Elena Camporesi1,2, Johan Gobom1,2, Kaj Blennow1,2, Henrik Zetterberg1,2,3,4,5,6,7, Gunnar Brinkmalm1,2
1Department of Psychiatry & Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
2Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
3Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King’s College London, London, United Kingdom
4Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, Queen Square, London, United Kingdom
5UK Dementia Research Institute, University College London, London, United Kingdom
6Hong Kong Center for Neurodegenerative Diseases, HKCeND, Hong Kong, China
7School of Medicine and Public Health, University of Wisconsin-Madison, Madison, USA
Abstract: Alzheimer’s disease (AD) originates from two major brain changes: extracellular plaques of amyloid beta, and intraneuronal tau protein accumulations called tangles. Our question is, if tau accumulations associated with amyloid beta plaques are different regarding their molecular composition when compared with tangles that form independently of amyloid beta. If our hypothesis is correct, we expect to find differences in the way tau is processed by pinpointing cleavage sites or modifications that are disease specific. Specific aims are to analyse brain material from AD and other tauopathies using immunoprecipitation-mass spectrometry (IP-MS) and different extraction methods.
Method optimisation is always the first step towards addressing the given research question. This step includes optimisation of tau protein digestion into peptides, by introducing different enzymes and finding the most optimal reaction time. Here, we report that the most optimal time for tau protein digestion is 18h when using trypsin. Next steps cover optimisation of the amount and ratio of labelled protein standards for tau protein isoforms for best MS readouts. We believe this work is essential to improve our understanding of why tau accumulations develop in neurodegenerative dementias, and the work should give clues on novel biomarkers and therapeutics.
Justyna Gerłowska
Faculty of Education and Psychology, UMCS, Lublin, Poland
Abstract: Understanding and using emotional communication is a complex task integrating the language and cognitive skills. The right hemisphere hypothesis focuses on the lateralization of emotion processing indicating the domination of the right hemisphere in the adequate emotion processing. Theory has been studied within different groups of subjects. Current research analyses understanding and communication of the emotional communicates within the group of elderly subjects (N=25). The relations between the cognitive capacity, language fluency and understanding of humour were analysed. The standardised methods of evaluation like: MMSE, verbal fluency tests and RHLB were used. The results show different patterns of humour understanding in group of healthy elderly persons, mild cognitive impairment (MCI) and Alzheimer Disease patients. The prosody of speech and emotional prosody shows different level among the above-mentioned groups. The education level and the cognitive abilities show corelations with the level of emotional prosody, humour understanding and prosody of speech. The capabilities of active emotional communication was investigated by observation of the facial expressions of the subjects. The relations between dominating emotion and the humour understanding and ability to differentiate the prosody were investigated.
Julia Bączek, Stanisław Karkosz, Marcin Hojan, Jarosław M. Michałowski
Poznan Laboratory of Affective Neuroscience, SWPS University in Poznan, Poland
Abstract: The sense of mental well-being is related to the activity of several biological systems. Investigating them allows us to define conditions needed to maintain an adequate mental health. The enzyme - Salivary alpha amylase (sAA), is considered a marker of the response of the autonomic nervous system which has a greater sensitivity than heart rate, blood pressure or cortisol. The sAA activity increases in the presence of a psychological stressor, especially of a psychosocial nature, and is related to the level of subjectively experienced anxiety. This study analyzed the characteristics and relationships of the enzyme with subjective measures describing the level of anxiety in a sample of 130 people. The subjects took part in a therapeutic intervention. Alpha amylase was tested before and after the intervention. The analyzes showed a relationship between the initial level of sAA activity and the level of physiological flexibility of the person. The initial level of sAA activity turned out to be a predictor of the future outcome of therapeutic interventions. ROC analysis indicated the possible future use of baseline sAA activity level as a diagnostic indicator. Analyzes also showed an association of sAA with generalized anxiety disorder. However, the method requires refinement in further research.
Funding: This work was supported by the National Science Centre [grant numbers 018/30/E/HS6/00703]
Świętek Anna, Godlewska Hanna
SWPS University
Abstract: Anxiety is a condition which is present in every student’s life due to a lot of exams, trying to manage academic and personal life and many others. Unfortunately, a large part of students do not lead a healthy lifestyle including nutritious food and sport. We perceive nutritious food as a high intake of fruits, vegetables, omega 3 acids, whole grains products and minimizing the consumption of processed meals with high fat and carbohydrates index. The analysis made by Aucoin et al. (2021) revealed the associations between more fruits and vegetables, omega 3 acids, vitamins, microelements consumption and less anxiety. In order to examine the potential role of healthy eating in students' anxiety level, we investigated the group of students (19-26 years old). To measure the consumption of roughage we used Dietary Screener Questionnaire (DSQ) and for the anxiety level - State-Trait Anxiety Inventory (STAI). Our study reveals a positive correlation between unhealthy food habits and the apprehension level. Although, more studies are needed to explore the impact of nourishment on anxiety.
Patrycja Czaj, Kacper Denisiuk, Blanka Dwojaczny
Department of Human Physiology, Collegium Medicum Nicolaus Copernicus University, Bydgoszcz, Poland
Abstract: Most studies focus on the analysis of cognitive function in older adults or in neurodegenerative diseases, paying little attention to the impairment of these functions in young people. In our study, we wanted to examine the effects of pro-inflammatory cytokines on cognitive function in young adults. We collected a group of 49 college students aged 20-25 and examined the following parameters: body fat, BMI, waist-to-hip ratio, il-6 and TNF-alpha blood levels. We also conducted cognitive tests: TMT, face association test, Stroop test. Among all the subjects, we identified a group of 13 women who had elevated levels of IL-6. Then, after processing the results, we found correlations between reduced cognitive test scores and an increase in the waist-hip ratio, and elevated levels of il-6. Based on the available literature and the results of our study, it can be assumed that interleukin-6 reduces cognitive function in young people. This study suggests that it would be appropriate to look more closely at other pro-inflammatory cytokines, as well as anti-inflammatory cytokines based on their effects on cognitive function in young individuals.
R. Krycinska1, M. Binder2, M. Wierzchon2, J. Wordliczek1
1Department of Interdisciplinary Intensive Care, Jagiellonian University Collegium Medicum, Krakow, Poland
2Institute of Psychology, Jagiellonian University, Krakow, Poland
Abstract: Previous studies found consistent attenuation of gamma-range responses to auditory stimulation during consciousness loss under general anesthesia. Our goal was to replicate and extend the assessment of 40-Hz auditory steady-state responses (ASSR) sensitivity to consciousness changes and exploring envelope following responses (EFR) to wide-band chirp modulated stimulation across various frequencies, including both low-gamma and high-gamma frequencies. We studied 26 patients undergoing propofol-remifentanil TIVA TCI. Auditory stimulation involved click-based 40-Hz and wide-band chirp-modulated protocols under three conditions: pre-anesthesia, anesthesia maintenance, and post-awakening. EEG data were recorded using a 64-channel amplifier system at 1024 Hz. Anesthetic agent concentrations and anesthesia depth were monitored with target-controlled infusion systems, and bispectral index (BIS). EEG analysis focused on inter-trial phase clustering (ITPC) from 7 fronto-central channels, using cluster-based nonparametric permutation testing on envelope curve data. Under constant 40-Hz stimulation, we found a significant difference in grand average ITPC responses between averaged pre-and post-anesthesia conditions and anesthesia (clusterstat = 602.2, p < 0.001, [-0.03-0.65 s]). In wide band stimulation, the ITPC response, particularly in the low-gamma range (28-50 Hz), indicated consciousness loss during anesthesia (clusterstat = 64.28, p < 0.001). Notably, the significant difference between averaged responses before and after anesthesia and anesthesia conditions held only for low-gamma frequencies, with no significant difference in the high-gamma range. Despite sensitivity of 40-Hz ASSR and low gamma EFR to consciousness loss, these measures appear insensitive to BIS and propofol concentration. We confirmed consistent attenuation of 40-Hz ASSR responses during general anaesthesia-induced consciousness loss. In wide-band stimulation, the most discriminative part of the EFR response was in the low-gamma range (28-50 Hz), emphasizing its selectivity for consciousness loss. However, no significant differences were found in BIS index or propofol concentration during deep anesthesia, indicating limited utility for anesthesia depth monitoring. This may be due to the marked reduction in ITPC parameter at the point of consciousness loss.
Suphicha Sirawattanakul, lek. Dominik Kobylarek
Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland
Abstract: Parsonage-Turner syndrome, a rare neuropathy characterized by brachial plexus inflammation potentially involving the phrenic nerve palsy resulting in diaphragmatic paralysis and pulmonary dysfunction, with 1.64 per 100,000 rate of incidence yearly. A 39-year-old patient was admitted to the Department of Neurology at to the Department of Neurology at Uniwersytecki Szpital Kliniczny w Poznaniu due to right brachial nerve inflammation complicated by phrenic nerve palsy, manifesting as right upper limb pain and breathing difficulty. An X-ray revealed a high-positioned left diaphragmatic dome on X-ray (2022). The patient's medical history indicated right brachial plexus inflammation complicated by phrenic nerve palsy eight years earlier (2013). On admission, the patient reported persistent fatigue and pain of the upper limb. Despite overall good physical condition, with intact upper and lower limb reflexes and normal neurological examination, atrophy of the right biceps, supraspinatus, and infraspinatus muscles was observed. Further imaging, including CT scan of the head, chest, and abdominal cavity and MRI of the cervical spine, was done to exclude proliferative processes, and blood tests to rule out malignancy. A diagnosis of Parsonage-Turner Syndrome complicated by phrenic nerve palsy was established based on clinical and imaging findings. The patient was discharged in a good condition with a planned treatment including Encorton. To our best knowledge, this is the only case that illustrates a rare instance of a long gap period relapse of Parsonage Turner Syndrome on the contralateral side of the body.
Nina Prucnal, Michał Kuniecki
Emotion and Perception Lab, Institute of Psychology, Faculty of Philosophy, Jagiellonian University, Krakow, Poland
Abstract: Clinical experience suggests that stroke may lead to impaired social cognition, including impaired affective and cognitive empathy. However, the available scientific information on this topic is inconclusive. It is unclear whether the impairment affects both types of empathy or only cognitive or affective empathy. The aim of this study was to use the Multifaced Empathy Test to investigate the extent to which stroke survivors show impairments in understanding the emotional states of others and in affective empathy.
Fifty-one people in the subacute phase of their first stroke and 25 demographically matched people undergoing rehabilitation in five hospitals in Lesser Poland were studied.
Statistical analysis showed that post-stroke patients had statistically significantly lower affective empathy scores (M=5.49; SD=1.73) than controls (M=6.29; SD=1.31), t(74) = 2.42; p<0.05, especially for positive valence pictures t(74) = 3.16; p<0.01. There were no statistically significant differences between groups for cognitive empathy.
The study suggests that despite the cognitive understanding of another person's situation, the reported level of affective empathy may be weakened after the stroke.
Funding: Excellence Initative - Jagiellonian University, Fundacja Studentów i Absolwentów Uniwersytetu Jagiellońskiego „Bratniak”.
Monika Sypecka1, Sylwia Katarzyna Król2, Anna Sarnowska1
1Translational Platform for Regenerative Medicine, Mossakowski Medical Research Institute, PAS, Warsaw, Poland
2Department of Neurooncology, Mossakowski Medical Research Institute, PAS, Warsaw, Poland
Abstract: Mesenchymal stem/stromal cells derived from Wharton’s jelly of human umbilical cord (WJ-MSCs) exhibit unique immunomodulative and neuroprotective properties and are therefore considered as a potential tool in the treatment of various neurological disorders. Their therapeutic potential mostly relies on their secretome – WJ-MSCs secrete different factors that are either secreted into the environment as a soluble secretome or are encapsulated within extracellular vesicles (EVs), particularly exosomes. The ability to secrete immunomodulative and neuroprotective factors usually varies significantly between donors, which correlates with different numbers of released exosomes. Therefore, we performed a comparative study of the ability to secrete exosomes by WJ-MSCs obtained from different donors. Umbilical cords were obtained from full-term deliveries and MSCs were then mechanically isolated from Wharton’s jelly. The cells were then cultured until 3rd passage in standard culture medium. Next, the standard medium was removed, WJ-MSCs were rinsed with double-filtered PBS (0,1 μm) and a medium without platelet lysate was added for 24h. After 24h, cell culture medium containing exosomes secreted by WJ-MSCs was collected and exosomes were isolated by ultracentrifugation. The isolated exosomes were suspended in double-filtered PBS and NTA analysis was performed. The analysis revealed that WJ-MSCs obtained from different donors secrete different numbers of exosomes, which in the future may potentially have an impact on the efficiency of cell therapies dedicated for individual patients.
Funding: This research was funded by National Science Centre grant number 2022/47/O/NZ3/01739.
Justyna Kotowicz1*, Anna Banaszkiewicz3*, Gabriela Dzięgiel-Fivet3, Karen Emmorey4, Artur Marchewka2, Katarzyna Jednoróg3
1Institute of Pedagogy, University of Silesia, Katowice, Poland
2Laboratory of Brain Imaging, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
3Laboratory of Language Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
4Laboratory for Language and Cognitive Neuroscience, San Diego State University, San Diego, USA
* Equal contribution
Abstract:Deaf, native signers who use sign language on a daily basis have different language and sensory experience from hearing individuals, hence, reading processes are not the same in those two groups. Previously, the neuronal basis of the reading in deaf, native signers were mainly investigated at the word level and still relatively little is known about neural underpinnings of reading at the sentence level. Our study used functional magnetic resonance imaging (fMRI) to investigate brain activity while performing a sentence reading task (Semantic Judgment Task) in deaf, native signers and hearing adults. Similar activation in both groups were observed in the typical left perisylvian reading network areas: the left middle temporal gyrus (MTG) and the left inferior frontal gyrus (IFG). However, differences were also found: increased activity in left occipitotemporal and right frontal and temporal regions in deaf, relative to hearing readers. Functional connectivity analysis revealed enhanced coupling between the left IFG and the left MTG in hearing but not in deaf group. The analysis of lateralization indices showed more left-lateralized reading-related activation in the STG in the deaf readers. In conclusion, our study showed shared and distinct patterns in brain activity in deaf and hearing when reading sentences.
Piotr Górniak1, Agata Wolna1,2, Zofia Wodniecka1
1Language and Bilingualism Lab, Institute of Psychology, Jagiellonian University, Kraków, Poland
2 McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, United States
Abstract: Speech production is a complex process engaging both language-specific and domain-general resources. However, it is unclear to what extent increasing task difficulty affects engagement of language-specific or domain-general mechanisms. In this study, we addressed this question using a verbal fluency task (VF) in which participants are asked to generate words in response to either semantic or phonetic cue, with phonetic fluency being shown more difficult. Forty-one participants performed semantic and phonetic fluency in an fMRI experiment. Additionally, we used two functional localizer tasks to identify the language-specific and domain-general networks in the brain. For each subject, we created a set of functional ROIs and subsequently, we assessed the response of these two networks to both VF tasks. Our results showed that differences between conditions are linked mainly to the increased engagement of the left-lateralized language network. Although both conditions engaged the multiple-demand network, we found no differences between them in this network. Our support the claim, that differences in performance between the VF versions result from specific language requirements rather than general task demands. Altogether our results show that while (1) the multiple-demand network supports the execution of demanding speech production tasks, (2) the production demands reflect language-specific processing.
Funding: This research was possible thanks to the grant from National Science Centre awarded to Zofia Wodniecka (OPUS 2017/27/B/HS6/00959).
Agnieszka Glica1, Katarzyna Wasilewska1, Julia Jurkowska2, Jarosław Żygierewicz2, Bartosz Kossowski3, Katarzyna Jednoróg1
1Laboratory of Language Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Poland
2Faculty of Physics, University of Warsaw, Poland
3Laboratory of Brain Imaging, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Poland
Abstract: According to the neural noise hypothesis of dyslexia, reading difficulties stem from an imbalance between excitatory (glutamate, Glu) and inhibitory (gamma-aminobutyric acid, GABA) activity in neural networks. Specifically, increased Glu levels in dyslexia were suggested. In the current work, we tested both indirect measures of the excitatory-inhibitory ratio from the EEG power spectrum in 120 Polish adolescents and young adults (60 with dyslexia, 60 controls) and direct Glu and GABA concentrations from magnetic resonance spectroscopy (MRS) at a 7T MRI scanner in half of the EEG sample. Previous works have shown associations between flatter slope of the EEG power spectrum and greater dominance of excitation over inhibition, and between greater GABAergic activity and increased EEG beta power. Based on the Bayesian statistics, we have found no evidence for group differences in the indirect measures of the neural noise (exponent and offset of the signal's slope, as well as beta power) tested both at rest and during an auditory language task. Similarly, no evidence for group differences was found in Glu and GABA concetrations in the left superior temporal sulcus derived from MRS. Our results indicate poor adequacy of the neural noise hypothesis in dyslexia.
Funding: This study was supported by the National Science Centre grant OPUS (2019/35/B/HS6/01763) awarded to prof. Katarzyna Jednoróg
Katarzyna Wasilewska1, Agnieszka Glica1, Bartosz Kossowski2, Katarzyna Jednoróg1
1Laboratory of Language Neurobiology, Nencki Institute of Experimental Biology, Polish
Academy of Sciences, Warsaw, Poland
2Laboratory of Brain Imaging, Nencki Institute of Experimental Biology, Polish Academy of
Sciences, Warsaw, Poland
Abstract: Functional Magnetic Resonance Spectroscopy (fMRS) is a non-invasive technique used to measure changes in metabolite concentrations in response to various stimuli. While it is a powerful tool for gaining deeper insights into the mechanisms accompanying brain activations, it still remains relatively novel, lacking clear guidelines for optimal data acquisition and analysis. Most of existing studies have focused on changes in the visual cortex in response to simple visual stimuli. In our innovative approach, we focus on metabolite changes induced by reading-related stimuli within individually localised brain regions involved in the reading process. Moreover, we extend the investigation by incorporating fMRS data acquisition with varying delays between stimulation and signal acquisition, aiming to study the glutamate response function. 59 adolescents and young adults aged 15-24 years participated in fMRS experiment on a 7T scanner. In the superior temporal sulcus 500 and 1000 ms after stimulus presentation we observed changes in glutamate (for 500 ms t = -2,099, p = 0,041; for 1000 ms t = -2,114, p = 0,040). Additionally, N-acetylaspartate (NAA) changes were detected in the medial prefrontal cortex 500 ms and 1000 ms after stimulation (for 500 ms, t = -2.714, p = 0.009; for 1000 ms, t = -2.800, p = 0.007).
Funding: This study was funded by the Polish National Science Center OPUS grant (2019/35/B/HS6/01763) awarded to Katarzyna Jednoróg.
Jakub Szewczyk1, Micha Heilbron2, Floris de Lange3
1Institute of Psychology, Jagiellonian University, Poland
2Faculty of Social and Behavioural Sciences, University of Amsterdam, The Netherlands
3Donders Institute for Brain, Cognition and Behaviour, Radboud University, The Netherlands
Abstract: Explicit computation of prediction error has been proposed as a key element of predictive coding, an architecture that naturally integrates bottom-up and top-down information. It has been hypothesized that this could lead to increased stimulus representations when prior expectations conflicts with sensory input (Blank and Davis, 2016). In this fMRI study, we test this hypothesis within the context of visual word recognition. We manipulated the signal strength of visually presented words (low vs. high noise), as well as prior information (visual words were preceded by an auditory word that was unrelated, semantically related, or the same word). Using forward encoding models, we investigated whether stimulus information was stronger when the input was clear and mismatching with prior expectations, therefore generating a strong prediction error. Preliminary results do not directly confirm this hypothesis: stimulus information in the visual ventral stream was not stronger for mismatching than matching conditions. However, we did find stimulus information patterns consistent with prediction error coding in the inferior frontal lobes. The results show that findings from Blank and Davis do not generalize to visually presented stimuli and thereby challenge their prediction error coding model.
Funding: This research is part of the project No. 2022/47/P/HS6/02294 within the POLONEZ BIS programme co-funded by the National Science Centre and the European Union’s
Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 945339
Franceska Furik1, Kinga G. Tóth1,3, Boglárka Morvai1, Dorottya Rácz1, Raena Shaikh1, Ivaylo B. Iotchev1, Marianna Boros1, Attila Andics1,2
1Neuroethology of Communication Lab, Department of Ethology, Eötvös Loránd University, Budapest, Hungary
2ELTE NAP Canine Brain Research Group, Budapest, Hungary
3Doctoral School of Biology, ELTE Eötvös Loránd University, Budapest,
Abstract: Ethological works suggest that dogs outperform other species in their readiness to respond to human vocal communicative signals, including speech. But whether this readiness of dogs is supported by neural tuning to characteristic spectral or temporal properties of natural speech, is currently not understood. To test this, we conducted an auditory electroencephalography (EEG) study (N = 27), comparing dogs’ neural entrainment to auditory streams of intact speech vs. sine-wave replica with natural (4 Hz) vs. fast (9 Hz) syllable presentation rates, in a 2x2 design. We expected that tuning to spectral and temporal properties of natural speech would lead to higher inter-trial coherence (ITC) values for intact speech and 4 Hz streams, respectively. Dog brains exhibited higher ITC values for 4Hz than 9Hz streams (p=0.001), but ITC values did not differ for intact speech vs. sine-wave streams, and there was no spectral by temporal naturalness interaction. These results suggest that dog brains are tuned to a speech-typical auditory rhythm but not to the spectral properties of speech. Further studies with other species need to reveal whether this tuning to the 4 Hz rate in dogs is a consequence of domestication or of living with humans, or it is more general across vocal mammals.
Funding: The research project has been funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (Grant Agreement No. 950159) and the National Brain Program 3.0 of the Hungarian Academy of Sciences. Project no. C2304666 has been implemented with the support provided by the Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund, financed under the KDP-2023 funding scheme.
Gabriela Puchała1
1Eye Tracking Research Center, Department of Psychology, SWPS University, Warsaw, Poland
Abstract: Plenty of eye-tracking studies comparing experts and novices in a certain field of knowledge have shown significant differences between these two groups in the way they process the stimuli and distribute visual attention on them. This study aimed to investigate whether similar dependence occurs in the field of cynology - the knowledge of dogs. To accomplish this, we examined 33 individuals - 7 experts (experienced Judges, Canine Assistants or Breeders registered in the Canine Association in Poland) and 26 novices (individuals without professional experience in cynology). Each participant completed an information questionnaire and then underwent an eye-tracking examination. Every participant was presented with 20 images of silhouettes and heads of purebred dogs and dogs resembling purebred dogs. The participants were compared in terms of the distribution of attention to each stimulus, the duration of stimulus observation, as well as chosen eye-tracking indicators during the perception of these stimuli - the number of saccades and fixations. All participants directed most of their attention towards the dogs’ heads.
However, experts in cynology looked at the dogs much more holistically. They paid significant amount of attention to the areas of the front and rear legs, as well as the tail and torso. Their attention was also distributed more evenly on the dogs’ silhouettes.
Novices focused mainly on the area of the dogs’ heads. Depending on the specific silhouette of the dog, their attention also extended to the areas of the legs or torso of a certain dog, but it was distributed significantly less evenly.
We can clearly observe that experts in the field of cynology looked at the stimuli more holistically, paying attention to every element of the dogs’ silhouettes with their attention being relatively evenly distributed.
Novices, on the other hand, focused mainly on the dogs’ heads and certain elements characteristic of the particular silhouette of the dog.
Funding: SWPS University in Warsaw
Sadiye Cankurtaran1,2, Kalinka Timmer3, Agata Wolna2,4,5, Zofia Wodniecka2
1Doctoral School in the Social Sciences, Jagiellonian University, Cracow, Poland
2Faculty of Psychology, Jagiellonian University, Cracow, Poland
3Faculty of Psychology, University of Warsaw, Warsaw, Poland
4Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, United States
5McGovern Institute for Brain Research, MIT, Cambridge, MA, United States
Abstract: In bilingualism research, the "L2 after-effect" describes the challenge of native language (L1) lexical access following second language (L2) use. We explored the constraints of the L2 after-effect: (1) is it elicited only by production, or also comprehension, in L2, and (2) to what extent does the complexity of the L2 task modulate it? We analyzed how different L2 tasks—ranging from reading aloud to picture naming (i.e., single-word reading, narrative reading, and picture naming)—affect the subsequent L1 retrieval in a picture naming task in Polish-English bilinguals (n=149). Our findings revealed no significant effects of the reading tasks in L2 (compared to L1) on L1 production. In contrast, naming pictures in L2 (compared to L1) hindered the consecutive picture naming in L1. These results show that the L2 after-effect is elicited by an active production task but not the passive reading tasks in L2. The next step in exploring the boundaries of the L2 after-effect is to check whether it's affected by the complexity of an active production task in L2. These insights advance our understanding of bilingual language processing and inform theoretical models, highlighting the differential impact of various language tasks on language control.
Funding: Research Support Module – Faculty of Philosophy (WSPR.WFiloz.1.5.2022) – Sadiye Cankurtaran
National Science Center (Sonata BIS 015/18/E/HS6/00428) – Zofia Wodniecka
Katarina Stekić1, Anđela Šoškić2, Ljiljana Ranđić3, Emilija Lazarević4, Lazar Tenjović1, Vanja Ković1
1Laboratory for Neurocognition and Applied Cognition, Faculty of Philosophy, University of Belgrade, Serbia
2Faculty of Education, University of Belgrade, Serbia
3Algo Centar, Belgrade, Serbia
4Institute for Educational Research, Belgrade, Serbia
Abstract: The relationship between phoneme awareness and reading proficiency, particularly in pre-reading stages, is a complex and debated topic. This study focuses on exploring phoneme awareness by examining phonemic analysis in pre-reading children (N=250, aged 3.5-6.5, 48% girls) in a shallow orthography (Serbian) to determine the dynamics of its development. Three phonemic analysis tasks were explored - recognizing the first, second, and last letter in a word. These tasks are typically used to test phoneme awareness. Our results show significant developmental differences in phonemic analysis ability among pre-reading children. Success rates varied significantly between age groups, with the most substantial differences observed between the oldest (5.5-6.5) and youngest (3.5-4.5) groups. Success in identifying the first letter in a word predicted success in identifying the second letter, but not the last letter in a word. Task correctness in identifying the first letter was significantly greater than success in other tasks in all age groups, but age-specific variations were observed, showing that phonemic awareness tasks may measure different levels of phoneme awareness development. Patterns of developmental outcomes within age groups were analysed, suggesting that phonemic analysis is a continuous, rather than a discrete ability.
Funding: The realization of this project was financially supported by the Ministry of Science, Technological Development and Innovation of the Republic of Serbia as part of the financing of scientific research work at the University of Belgrade - Faculty of Philosophy (contract number 451-03-47/2023-01/ 200163).
University of Belgrade - Faculty of Education (contract number 451-03-65/2024-03/ 200138).
Institute for Educational Research (contract no. 451-03-66/2024-03/ 200018).
Anna Meliksetian, Agata Wolna, Zofia Wodniecka
Psychology of Language and Bilingualism Lab, Institute of Psychology, Jagiellonian University, Kraków, Poland
Abstract: Studies on bilingual language use demonstrate a difficulty in speech production in the native language (L1) following production in a second language (L2). This so-called L2 after-effect manifests itself in a picture naming paradigm through longer naming latencies for L1 following L2 naming and possibly reflects engagement of language control mechanisms. The effect has been reported in experiments on noncognates, as cognate presence could increase language co-activation. However, the exact impact of cognates on language control has not been studied. We investigated whether inclusion of cognates indeed impacts the magnitude of L2 after-effect. Two experimental groups completed two sessions of picture naming. In the exposure block, cognates constituted 80% of stimuli in one group and 20% of stimuli in another group. The measurement block remained the same across groups and did not include cognates. The preliminary results show a clear L2 after-effect in both groups. However, the magnitude of the effect is bigger in the 80% cognate stimuli group. Slower word retrieval after naming cognates could be explained by an increased language competition following the increased language co-activation. The results should inform our understanding of mechanisms underlying the L2 after-effect and have methodological implications for future studies investigating language control.
Akanksha Gupta1, Tomas Matthews2, Virginia Penhune3, Benjamin Morillon1
1Institut de Neurosciences des Systèmes (INS), Aix-Marseille University, Inserm, Marseille, France
2Center for Music in the Brain, Department of Clinical Medicine, Aarhus University and The Royal Academy of Music Aarhus, Aalborg, Aarhus, Denmark
3Department of Psychology, Concordia University, Montreal, Canada
Abstract: The dynamic attending theory suggests that the temporal regularities within behaviorally relevant sensory streams can be exploited to selectively direct our attention and enhance perception. It is proposed that attention operates in various modes of processing, contingent on the stimulus and task structure, as the continuous allocation of attentional resources is metabolically expensive. Recent evidence indicated that the "rhythmic mode" functions optimally at approximately 1.5 Hz in the auditory domain. However, some recent studies did not find any behavioral advantage of dynamic attending. Furthermore, it remains unclear how different modes of attention adjust with varying tasks and whether these modes are dependent on different processing stages (e.g., perceptual, or linguistic). To investigate this, we carried out a series of nine deviant detection experiments with short (<7 sec) or long (~1 min) auditory streams, consisting of pure tones or syllables, presented at rates ranging from 0.5 to 6.5 Hz. We identified a rhythmic mode of operation—characterized by optimal performance accuracy at ~1.5 Hz during perceptual tasks involving long auditory streams, irrespective of the attended perceptual feature. Conversely, we observed no such advantages for short auditory streams. We further generalized these results using a model of coupled oscillators. Additionally, these benefits were not evident in syllabic categorization tasks for either short or long streams. Our findings reveal that a rhythmic mode of operation at 1.5 Hz naturally arises during the perception of long auditory streams and is specific to the processing stage.
Rob van der Lubbe1,2 , Tobias Merkelbach1, Erwin Hofman1
1Faculty of Behavior, Management, and Social Sciences, University of Twente, Enschede, The Netherlands
2Faculty of Physics, Adam Mickiewicz University, Poznan, Poland
Abstract: Syllogisms have a long history of being used to test fluid intelligence but the ability to properly judge them is affected by language barriers and existing beliefs. Nonverbal syllogisms have been developed to avoid these issues. In two of our experiments with nonverbal syllogisms, participants were exposed to either two, three, or four premises about spatial relations between objects in different pictures, and then had to judge whether a picture with a conclusion aligned with these premises. We examined to what extent task performance related to fluid intelligence and measured the electroencephalogram to examine whether task complexity is reflected in midfrontal theta power. In the first experiment conclusions were always a direct combination of the presented premises, while in the second experiment, conclusions could also be based on indirect combinations of the presented premises. Together, the results indicated that the ability to properly judge nonverbal syllogisms is indeed related to fluid intelligence. Furthermore, increased midfrontal theta power was observed while evaluating the conclusions which increased as a function of task complexity. These findings indicate that tasks with nonverbal syllogisms provide us with a tool that may enhance our understanding of fluid intelligence and its underlying brain dynamics.
Stanisław Adamczyk1, Małgorzata Paczyńska1, Anastasia Ruban1,5, Jan Szczypiński2, Michał Bola4, Paweł Orłowski3,4
1Department of Psychology, SWPS University of Social Sciences and Humanities, Warsaw, Poland
2Department of Psychiatry, Medical University of Warsaw, Warsaw, Poland
3Doctoral School in the Social Sciences, Jagiellonian University, Kraków, Poland
4Centre for Brain Research, Jagiellonian University, Kraków, Poland
5Department of Psychology, Faculty of Social Sciences, Uniwersytet Jana Długosza , Częstochowa, Poland
Abstract: Psychedelic substances have the potential to induce profound alterations in cognition, emotionality, and sensory perception. However, the quality and intensity of their subjective effects exhibit high intra- and inter-individual variability. Therefore, the aim of this cross-sectional study was to investigate how internal and external contextual factors are related to the subjective effects of a psychedelic experience, specifically with the intensity of ego-dissolution. Participants of an online survey (1761 in total; 1495 LSD users and 1231 psilocybin mushrooms users) reported their motivations for past use of a given substance, frequency of use in different environments and social contexts, and filled out an Ego Dissolution Inventory. Robust linear regression analysis revealed that ego-dissolution experiences were more intense in participants using psychedelics for spiritual purposes and less intense in those reporting curiosity as a motivation. Moreover, the ego-dissolution was more intense when psychedelics were consumed in one's own home, in natural settings, at festivals, or during ceremonies. Furthermore, regarding social context, greater intensity of ego-dissolution was observed when psychedelics were used alone, with a partner, a friend, or a guide. Therefore, our study contributes to better understanding of how contextual factors shape subjective psychedelic experiences, which is essential for advancing the psychedelic-assisted therapies.
Funding: National Science Center Poland PRELUDIUM (grant no. 2020/37/N/HS6/02086) and PRELUDIUM BIS (2020/39/O/HS6/01545) grants.
Julia Jurkowska1, Jarosław Żygierewicz2
1Faculty of Physics, University of Warsaw, Warsaw, Poland
2Biomedical Physics Division, Faculty of Physics, University of Warsaw, Warsaw, Poland
Abstract: Dyslexia, a neurodevelopmental disorder characterized by reading and spelling difficulties, has been a topic of research for over a century. However, a clear-cut cause and an unambiguous diagnostic rule have yet to be established. The prevalence of dyslexia varies between 5% and 17.5% of the population, depending on the adopted diagnostic criteria. The impact of reading and writing difficulties extends beyond learning, affecting social development and the overall mental well-being of individuals. Machine-learning techniques are being presented as a potential way to automate the process of diagnosing many disorders. Here, we use electroencephalographic signals recorded during a listening task from both individuals diagnosed with dyslexia and typical readers, aiming to find the optimal algorithm that distinguishes between the two groups. Two approaches were employed for this purpose: end-to-end, in which two neural networks (EEGNet, Deep4Net) were trained independently, and feature-based classifiers, which received multiple features from three different domains (time, frequency, and connectivity) as input. Presented results reflect the exploration of a comprehensive set of input data and a comparison of the obtained outcomes.
D. Zaremba1, B. Kossowski1, M. Wypych1, K. Jednoróg2, J. M. Michałowski3, C.A. Klöckner4, M. Wierzba1*, A. Marchewka1*
1Laboratory of Brain Imaging, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
2Laboratory of Language Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
3Poznań Laboratory of Affective Neuroscience, University SWPS , Poznań, Poland
4Norwegian University of Science and Technology, Trondheim, Norway
*These authors share senior authorship.
Abstract:
It was previously shown that emotions can drive climate action. 160 participants read Emotional Climate Change Stories eliciting either anger, hope, or neutral state. Then, they made a series of decisions between monetary rewards (egoistic) and reducing CO2 emissions (climate-friendly) in the Carbon Emission Task.
Initial analyses showed no group differences in behaviour nor neuronal activity. However, pooling the data from all participants revealed that the number of climate-friendly choices decreased with the size of monetary rewards but increased with the level of CO2 emission reduction.
In general, egoistic choices lead to activations in brain areas associated with reward processing (caudate nuclei), self-awareness (precuneus), and emotion processing (cingulate gyrus, insula). Interestingly, previous research associated these regions with altruistic, not egoistic behaviours.
On the other hand, climate-friendly choices activated parts of the executive network, including MFG and angular gyrus, implicated in studies on delayed gratification and moral judgements.
We did not find evidence for the influence of emotional stories on behaviour and brain activity in climate action. Climate-friendly choices may not completely align with altruistic decisions, as they involve immediate personal loss but contribute to long-term gains for both individuals and society. We propose to position the topic of climate action at the intersection of prosocial and delayed gratification research.
Funding: The research leading to these results has received funding from the Norwegian Financial Mechanism 2014-2021, project: “Understanding patterns of emotional responses to climate change and their relation to mental health and climate action taking” No. 2019/34/H/HS6/00677.
Zofia Maciąg
Eye Tracking Research Center, Institute of Psychology, SWPS University, Warsaw, Poland
Abstract:
This study investigates the effects of two types of audio description - traditional and contextual - on the reception of four selected works of art, as well as the presentation method: listening during viewing, listening before viewing or reading the description before viewing the painting. The research involved 58 participants without a formal art education, using an eye-tracking methodology. Data were analyzed using a two-way analysis of variance in a 2x3 design. Results indicate that traditional audio description significantly increases fixations on areas of interest within the paintings. Furthermore, listening to audio descriptions while viewing the painting emerges as crucial. Our findings underscore potential disparities in art perception based on the type of audio description employed. These insights contribute to understanding the efficacy of audio descriptions in enhancing engagement with visual art.
