Journal: European Journal of Neuroscience

Abbreviation

Eur. j. neurosci.

Publisher

Wiley

Journal Volumes

ISSN

0953-816X
1460-9568

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2019 - 201922020 - 202514
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Publications 1 - 10 of 16
  • Switch costs in inhibitory control and voluntary behaviour: A computational study of the antisaccade task
    Item type: Journal Article
    Aponte, Eduardo A.; Stephan, Klaas; Heinzle, Jakob (2019)
    European Journal of Neuroscience
  • Hemodynamic modeling of long‐term aspirin effects on blood oxygenated level dependent responses at 7 Tesla in patients at cardiovascular risk
    Item type: Journal Article
    Do, Cao-Tri; Manjaly, Zina-Mary; Heinzle, Jakob; et al. (2021)
    European Journal of Neuroscience
    Aspirin is considered a potential confound for functional magnetic resonance imaging (fMRI) studies. This is because aspirin affects the synthesis of prostaglandin, a vasoactive mediator centrally involved in neurovascular coupling, a process underlying blood oxygenated level dependent (BOLD) responses. Aspirin‐induced changes in BOLD signal are a potential confound for fMRI studies of at‐risk individuals or patients (e.g. with cardiovascular conditions or stroke) who receive low‐dose aspirin prophylactically and are compared to healthy controls without aspirin. To examine the severity of this potential confound, we combined high field (7 Tesla) MRI during a simple hand movement task with a biophysically informed hemodynamic model. We compared elderly individuals receiving aspirin for primary or secondary prophylactic purposes versus age‐matched volunteers without aspirin medication, testing for putative differences in BOLD responses. Specifically, we fitted hemodynamic models to BOLD responses from 14 regions activated by the task and examined whether model parameter estimates were significantly altered by aspirin. While our analyses indicate that hemodynamics differed across regions, consistent with the known regional variability of BOLD responses, we neither found a significant main effect of aspirin (i.e., an average effect across brain regions) nor an expected drug × region interaction. While our sample size is not sufficiently large to rule out small‐to‐medium global effects of aspirin, we had adequate statistical power for detecting the expected interaction. Altogether, our analysis suggests that patients with cardiovascular risk receiving low‐dose aspirin for primary or secondary prophylactic purposes do not show strongly altered BOLD signals when compared to healthy controls without aspirin. © 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
  • Dopamine depletion induces neuron‐specific alterations of GABAergic transmission in the mouse striatum
    Item type: Journal Article
    Boccalaro, Ida Luisa; Schwerdel, Cornelia; Cristiá‐Lara, Leonardo; et al. (2020)
    European Journal of Neuroscience
    Lack of dopamine (DA) in the striatum and the consequential dysregulation of thalamocortical circuits are major causes of motor impairments in Parkinson's disease. The striatum receives multiple cortical and subcortical afferents. Its role in movement control and motor skills learning is regulated by DA from the nigrostriatal pathway. In Parkinson's disease, DA loss affects striatal network activity and induces a functional imbalance of its output pathways, impairing thalamocortical function. Striatal projection neurons are GABAergic and form two functionally antagonistic pathways: the direct pathway, originating from DA receptor type 1‐expressing medium spiny neurons (D1R‐MSN), and the indirect pathway, from D2R‐MSN. Here, we investigated whether DA depletion in mouse striatum also affects GABAergic function. We recorded GABAergic miniature IPSCs (mIPSC) and tonic inhibition from D1R‐ and D2R‐MSN and used immunohistochemical labeling to study GABAAR function and subcellular distribution in DA‐depleted and control mice. We observed slower decay kinetics and increased tonic inhibition in D1R‐MSN, while D2R‐MSN had increased mIPSC frequency after DA depletion. Perisomatic synapses containing the GABAAR subunits α1 or α2 were not affected, but there was a strong decrease in non‐synaptic GABAARs containing these subunits, suggesting altered receptor trafficking. To broaden these findings, we also investigated GABAARs in GABAergic and cholinergic interneurons and found cell type‐specific alterations in receptor distribution, likely reflecting changes in connectivity. Our results reveal that chronic DA depletion alters striatal GABAergic transmission, thereby affecting cellular and circuit activity. These alterations either result from pathological changes or represent a compensatory mechanism to counteract imbalance of output pathways. © 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
  • Timing of repetition suppression of event-related potentials to unattended objects
    Item type: Journal Article
    Stefanics, Gabor; Heinzle, Jakob; Czigler, István; et al. (2020)
    European Journal of Neuroscience
  • Alteration of brain dynamics during dual-task overground walking
    Item type: Journal Article
    Nenna, Federica; Do, Cao T.; Protzak, Janna; et al. (2021)
    European Journal of Neuroscience
    When walking in our natural environment, we often solve additional cognitive tasks. This increases the demand of resources needed for both the cognitive and motor systems, resulting in Cognitive-Motor Interference (CMI). A large portion of neurophysiological investigations on CMI took place in static settings, emphasizing the experimental rigor but overshadowing the ecological validity. As a more ecologically valid alternative to treadmill and desktop-based setups to investigate CMI, we developed a dual-task walking scenario in virtual reality (VR) combined with Mobile Brain/Body Imaging (MoBI). We aimed at investigating how brain dynamics are modulated by dual-task overground walking with an additional task in the visual domain. Participants performed a visual discrimination task in VR while standing (single-task) and walking overground (dual-task). Even though walking had no impact on the performance in the visual discrimination task, a P3 amplitude reduction along with changes in power spectral densities (PSDs) were observed for discriminating visual stimuli during dual-task walking. These results reflect an impact of walking on the parallel processing of visual stimuli even when the cognitive task is particularly easy. This standardized and easy to modify VR paradigm helps to systematically study CMI, allowing researchers to control for the impact of additional task complexity of tasks in different sensory modalities. Future investigations implementing an improved virtual design with more challenging cognitive and motor tasks will have to investigate the roles of both cognition and motion, allowing for a better understanding of the functional architecture of attention reallocation between cognitive and motor systems during active behavior.
  • Maternal immune activation exerts long-term effects on activity and sleep in male offspring mice
    Item type: Journal Article
    ElGrawani, Waleed; Mueller, Flavia S.; Schalbetter, Sina M.; et al. (2024)
    European Journal of Neuroscience
    Exposure to infectious or non-infectious immune activation during early development is a serious risk factor for long-term behavioural dysfunctions. Mouse models of maternal immune activation (MIA) have increasingly been used to address neuronal and behavioural dysfunctions in response to prenatal infections. One commonly employed MIA model involves administering poly(I:C) (polyriboinosinic-polyribocytdilic acid), a synthetic analogue of double-stranded RNA, during gestation, which robustly induces an acute viral-like inflammatory response. Using electroencephalography (EEG) and infrared (IR) activity recordings, we explored alterations in sleep/wake, circadian and locomotor activity patterns on the adult male offspring of poly(I:C)-treated mothers. Our findings demonstrate that these offspring displayed reduced home cage activity during the (subjective) night under both light/dark or constant darkness conditions. In line with this finding, these mice exhibited an increase in non-rapid eye movement (NREM) sleep duration as well as an increase in sleep spindles density. Following sleep deprivation, poly(I:C)-exposed offspring extended NREM sleep duration and prolonged NREM sleep bouts during the dark phase as compared with non-exposed mice. Additionally, these mice exhibited a significant alteration in NREM sleep EEG spectral power under heightened sleep pressure. Together, our study highlights the lasting effects of infection and/or immune activation during pregnancy on circadian activity and sleep/wake patterns in the offspring.
  • Are language skills related to structural features in Broca's and Wernicke's area?
    Item type: Journal Article
    Jäncke, Lutz; Liem, Franz; Merillat, Susan (2021)
    European Journal of Neuroscience
    This study used structural magnetic resonance imaging to examine whether specific anatomical features of Broca's and Wernicke's areas are related to language functions in typically developing older subjects with no specific language expertize. Data from 231 subjects from the Zurich LHAB-study are used for this study. For these subjects, we obtained several psychometric measures from which we calculated performance measures reflecting specific psychological functions (language comprehension, verbal fluency, perceptual speed, visual memory, recognition of regularities, and logical thinking). From the MRI measurements, we calculated the cortical thickness and cortical surface of Broca's and Wernicke's areas. Applying multiple regression analyses, we identified a moderately strong relationship between language comprehension and the brain metrics from Broca's and Wernicke's areas and showed that approximately 10% of the variance in language comprehension performance is explained by the linear combination of all perisylvian brain metrics. The other psychological functions (verbal fluency, perceptual speed, visual memory, recognition of regularities, and logical thinking) are not related to these brain metrics. Subsequent detailed analyses revealed that the cortical thickness of Wernicke's area, in particular, contributed most to this structure-function relationship. The better performance in the language comprehension tests was related to a thicker cortex in Wernicke's area. Thus, this study demonstrates a structure-function relationship between the anatomical features of the perisylvian language areas and language comprehension, suggesting that particular anatomical features are associated with better language performance.
  • Anatomically Veridical On-Scalp Sensor Topographies
    Item type: Journal Article
    Alexander, Nicholas A.; Medrano, Johan; Seymour, Robert A.; et al. (2025)
    European Journal of Neuroscience
    When working with sensor-level data recorded using on-scalp neuroimaging methods such as electroencephalography (EEG), it is common practice to use two-dimensional (2D) representations of sensor positions to aid interpretation. Positioning of sensors relative to anatomy, as in the classic 10–20 system of EEG electrode placement, enables the use of 2D topographies that are familiar to many researchers and clinicians. However, when using another increasingly popular on-scalp neuroimaging method, optically pumped magnetometer–based magnetoencephalography (OP-MEG), bespoke sensor arrays are much more common, and these are not prepared according to any standard principle. Consequently, polar projection is often used to produce individual sensor topographies that are not directly related to anatomy and cannot be averaged across people simply. Given the current proliferation of OP-MEG facilities globally, this issue will become an increasing hindrance when visualising OP-MEG data, particularly for group studies. To address this problem, we adapted and extended the 10–20 system to build a flexible, anatomical projection method applied to digitised head shape, fiducials and sensor positions. We demonstrate that the method maintains spatially veridical representations across individuals improving on standard polar projections at varying OPM sensor array densities. By applying our projection method, the benefits of anatomically veridical 2D topographies can now be enjoyed when visualising data, such as those from OP-MEG, regardless of variation in sensor placement as in sparse or focal arrays.
  • Multi-omics correlates of insulin resistance and circadian parameters mapped directly from human serum
    Item type: Journal Article
    Du, Ngoc-Hien; Sinturel, Flore; Nowak, Nora; et al. (2024)
    European Journal of Neuroscience
    While it is generally known that metabolic disorders and circadian dysfunction are intertwined, how the two systems affect each other is not well understood, nor are the genetic factors that might exacerbate this pathological interaction. Blood chemistry is profoundly changed in metabolic disorders, and we have previously shown that serum factors change cellular clock properties. To investigate if circulating factors altered in metabolic disorders have circadian modifying effects, and whether these effects are of genetic origin, we measured circadian rhythms in U2OS cell in the presence of serum collected from diabetic, obese or control subjects. We observed that circadian period lengthening in U2OS cells was associated with serum chemistry that is characteristic of insulin resistance. Characterizing the genetic variants that altered circadian period length by genome-wide association analysis, we found that one of the top variants mapped to the E3 ubiquitin ligase MARCH1 involved in insulin sensitivity. Confirming our data, the serum circadian modifying variants were also enriched in type 2 diabetes and chronotype variants identified in the UK Biobank cohort. Finally, to identify serum factors that might be involved in period lengthening, we performed detailed metabolomics and found that the circadian modifying variants are particularly associated with branched chain amino acids, whose levels are known to correlate with diabetes and insulin resistance. Overall, our multi-omics data showed comprehensively that systemic factors serve as a path through which metabolic disorders influence circadian system, and these can be examined in human populations directly by simple cellular assays in common cultured cells.
  • Modulation of sleep/wake patterns by gephyrin phosphorylation status
    Item type: Journal Article
    Tsai, Yuan-Chen; Elgrawani, Waleed; Muheim, Christine; et al. (2024)
    European Journal of Neuroscience
    Sleep/wake cycles intricately shape physiological activities including cognitive brain functions, yet the precise molecular orchestrators of sleep remain elusive. Notably, the clinical impact of benzodiazepine drugs underscores the pivotal role of GABAergic neurotransmission in sleep regulation. However, the specific contributions of distinct GABAA receptor subtypes and their principal scaffolding protein, gephyrin, in sleep dynamics remain unclear. The evolving role of synaptic phospho-proteome alterations at excitatory and inhibitory synapses suggests a potential avenue for modulating gephyrin and, consequently, GABAARs for sleep through on-demand kinase recruitment. Our study unveils the distinctive roles of two prevalent GABAA receptor subtypes, alpha 1- and alpha 2-GABAARs, in influencing sleep duration and electrical sleep activity. Notably, the absence of alpha 1-GABAARs emerges as central in sleep regulation, manifesting significant alterations in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep during dark or active phases, accompanied by altered electroencephalogram (EEG) patterns across various frequencies. Gephyrin proteomics analysis reveals sleep/wake-dependent interactions with a repertoire of known and novel kinases. Crucially, we identify the regulation of gephyrin interaction with ERK1/2, and phosphorylations at serines 268 and 270 are dictated by sleep/wake cycles. Employing AAV-eGFP-gephyrin or its phospho-null variant (S268A/S270A), we disrupt sleep either globally or locally to demonstrate gephyrin phosphorylation as a sleep regulator. In summary, our findings support the local cortical sleep hypothesis and we unveil a molecular mechanism operating at GABAergic synapses, providing critical insights into the intricate regulation of sleep.
Publications 1 - 10 of 16