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Sander, T.

Publications and source records attributed to Sander, T..

9 recordsLinked to original sources

High frequency oscillations measured with optically pumped magnetometers from the human retina

Measurement of human neural activity with optically pumped magnetometers (OPMs) is rapidly proliferating, with sensitivity approaching that of cryogenic sensors. Most neuroscience research with OPMs to date has investigated neural responses below 70 Hz, but higher frequencies are also of interest. However, sensitivity to higher frequencies may be limited by both the inherent operating bandwidth of the current generation of zero-field OPMs as well as by their generally lower amplitude. To assess the upper bounds of OPM sensitivity we used the stereotypical retinal response to flashes of light. Retinal responses to light flashes characteristically exhibit a neural response above 70 Hz called the oscillatory potential (OP) when recorded with electroretinography (ERG). Here we adopt the term retinal high frequency oscillation (rHFO) to include measurement of similar activity with OPMs. Our comparison of magnetoretinography (MRG) and ERG shows that rHFO can be measured up to 140 Hz using rubidium-based zero-field OPMs.

neuroscience↗

OPM quantum sensors enhance non-invasive neuroimaging performance

Much of our understanding of how neural circuit activity relates to human behaviour as well as mental health stems from non-invasive assessments of the central nervous system. Further progress in key questions, however, requires a higher differentiation of circuit-level activity, which remains constrained by the sensitivity and resolution of existing instruments. Here we show that neural quantum sensing with optically pumped magnetometers (OPMs) addresses this issue by significantly outperforming EEG and conventional MEG in both signal-to-noise ratio (SNR) and signal coherence across trials. SNR for OPMs was increased by up to 205% compared to EEG and by up to 40% compared to conventional MEG. Likewise, the signal coherence across trials of OPMs was increased by up to 61% compared to EEG and by up to 23% compared to conventional MEG. Our data emphasize the important role of OPMs for non-invasive neuroimaging, paving the way for significant advances in basic research as well as translational applications.

neuroscience↗

Unleashing the potential of OPM-MEG to study event-related fields against low-frequency artifacts: the case of sentence processing

OPM-MEG (optically pumped magnetometers-magnetoencephalography) offers unprecedented opportunity in its proximity to the brain and in mobility, outperforming other human MEG systems. However, movements induce low-frequency artifacts (up to [~] 3 Hz) in this system, calling for pipelines that could efficiently reduce these low-frequency noises. Although a high-pass filter of e.g., 4 Hz may minimize these artifacts, it may also eliminate many event-related field (ERF) components, such as the N400 response in sentence processing studies. Moreover, as an emerging technology with expensive sensors, many labs are starting with an experimental setup with fewer sensors (e.g., [~] 10), making it challenging to reject principal components based on visually inspecting the topographic field maps. In the current paper, we show that a combination of moderate high-pass filtering (1 Hz) and evoked-biased denoising source separation (evoked-biased DSS) can effectively reveal typical N400 deflections and effects (between nouns and verbs), with a nine-sensor OPM-MEG setup. Our current pipeline paves the way to studying ERFs with OPM-MEG in more budget-friendly setups with a small number of sensors.

neuroscience↗

Deep brain stimulation device-specific artefacts in MEG recordings

BackgroundDeep brain stimulation (DBS) has strong beneficial effects for treating movement disorders. The related cortical mechanisms can be studied with magnetoencephalography (MEG) during active DBS. However, MEG is prone to artefacts induced by the electrical stimulation and the movement of ferromagnetic DBS components. Although artefacts might vary between DBS devices from different manufacturers, no such comparison has been performed. To date, no combined MEG-DBS studies have been conducted within Yokogawa MEG systems. ObjectiveThe aim of the present study was to compare DBS artefacts in MEG phantom recordings acquired with two MEG systems (Neuromag, Yokogawa) using DBS devices from three different manufacturers (Abbott, Boston Scientifc, Medtronic) and to test whether established cleaning methods can sufficiently reduce artefacts. MethodsDBS devices, electrodes, and extension cables were attached to a gelatine MEG phantom, and data was acquired in a Neuromag and a Yokogawa MEG system. ResultsThere are device-specific differences in movement-related artefacts with weaker artefacts for Boston Scientific (BSC) devices. Stimulation-, movement- and IPG-related artefacts are best cleaned when combining the ICA-MI and Hampel filter across recordings and DBS devices. However, the cleaning of movement-related artefacts can result in artefactual spectral peaks in physiologically relevant frequencies below 20 Hz. ConclusionsDevice-specific IPG-related artefacts have to be considered for MEG-DBS studies and can be cleaned with combinations of published cleaning methods for MEG and EEG data. Critically, cleaning movement-related artefacts can potentially result in spectral peaks, which resemble physiological activity. Finally, combined MEG-DBS recordings are feasible in Yokogawa-MEG systems.

neuroscience↗

Meta-analysis on reporting practices as a source of heterogeneity in in vitro cancer research

BackgroundHeterogeneity of results of exact same research experiments oppose a significant socio-economic burden. In vitro research presents the early step of basic science and drug development projects. Insufficient methodological reporting is likely to be one of the contributors to results heterogeneity, however, little knowledge on reporting habits of in vitro cancer research and their effects on results reproducibility is available. Glioblastoma is a form of brain cancer with largely unmet clinical need. MethodsHere we use systematic review to describe reporting practices in in vitro glioblastoma research using the U87-MG cell line and perform multilevel random-effects meta-analysis followed by meta-regression to explore sources of heterogeneity within that literature, and any associations between reporting characteristics and reported findings. ResultsIn 137 identified articles, the overall methodological reporting is disappointing, e.g., the control type, mediums glucose level and cell density are reported in only 36.5, 21.2 and 16.8 percent of the articles, respectively. After adjustments for different drug concentrations and treatment durations, a three-level meta-analysis proves meaningful results heterogeneity across the studies (I2 = 70.1%). ConclusionsOur results further support the ongoing efforts of establishing consensus reporting practices to elevate durability of results. By doing so, we hope that this work will raise awareness of how stricter reporting may help to improve the frequency of successful translation of preclinical results into human application, not only in neuro-oncology. FundingWe received no specific funding for this project.

cancer biology↗

Ultra-rare constrained missense variants in the epilepsies: Shared and specific enrichment patterns in neuronal gene-sets

BackgroundBurden analysis in epilepsy has shown an excess of deleterious ultra-rare variants (URVs) in few gene-sets, such as known epilepsy genes, constrained genes, ion channel or GABAA receptor genes. We set out to investigate the burden of URVs in a comprehensive range of gene-sets presumed to be implicated in epileptogenesis. MethodsWe investigated several constraint and conservation-based strategies to study whole exome sequencing data from European individuals with developmental and epileptic encephalopathies (DEE, n = 1,003), genetic generalized epilepsy (GGE, n = 3,064), and non-acquired focal epilepsy (NAFE, n = 3,522), collected by the Epi25 Collaborative, compared to 3,962 ancestry-matched controls. The burden of 12 non-synonymous URVs types in 92 gene-sets was compared between epilepsy cases (DDE, GGE, NAFE) and controls using logistic regression analysis. ResultsBurden analysis of brain-expressed genes revealed an excess of different URVs types in all three epilepsy categories which was largest for missense variants in highly constrained sites (constrained missense variants). The URVs burden was prominent in neuron-specific, synaptic and developmental genes as well as genes encoding ion channels and receptors, and it was generally higher for DEE and GGE compared to NAFE. The patterns of URVs burden in gene-sets expressed in inhibitory vs. excitatory neurons or receptors suggested a high burden in both groups in DEE but a differential involvement of inhibitory genes in GGE, while excitatory genes were predominantly affected in NAFE. Top ranking susceptibility genes from a recent genome-wide association study (GWAS) of generalized and focal epilepsies displayed a higher URVs burden in constrained coding regions in GGE and NAFE, respectively. ConclusionsUsing exome-based gene-set burden analysis, we demonstrate that missense URVs affecting mainly constrained sites are enriched in neuronal genes in both common and rare severe epilepsy syndromes. Our results indicate a differential impact of these URVs in genes expressed in inhibitory vs. excitatory neurons and receptors in generalized vs. focal epilepsies. The excess of URVs in top-ranking GWAS risk-genes suggests a convergence of rare deleterious and common risk-variants in the pathogenesis of generalized and focal epilepsies.

genomics↗

Improved spatio-temporal measurements of visually evoked fields using optically-pumped magnetometers

Recent developments in performance and practicality of optically pumped magnetometers have enabled new capabilities in non-invasive brain function mapping through magnetoencephalography. In particular the lack of need of cryogenic operating conditions allows for more flexible placement of the sensor heads closer to the brain surface, leading to improved spatial measurement resolution and increased source localisation capabilities. Through the recording of visually evoked brain fields (VEF), we demonstrate that the closer sensor proximity can be further exploited to improve the temporal resolution. We use optically pumped magnetometers (OPMs), and for reference superconducting quantum interference devices (SQUIDs), to measure brain responses to standard flash and pattern reversal stimuli. We find highly reproducible signals with consistency across multiple healthy participants, stimulus paradigms and sensor modalities. The temporal resolution advantage of OPMs is manifest in a fourfold improvement of the ratio of magnetic signal peak height to temporal width, compared to SQUIDs. The resulting capability of improved spatio-temporal signal tracing is illustrated by simultaneous vector recordings of VEFs in the primary (V1) and associative (V2) visual cortex, where a time lag on the order of 10-20 ms is consistently found. This paves the way for further studies of spatio-temporal neurophysiological signal tracking in visual stimulus processing and other brain responses with potentially far-reaching consequences for time-critical mapping of functionality in the healthy and pathological brains.

neuroscience↗

Dissecting the impact of metabolic environment on three common cancer cell phenotypes

The impact of different metabolic environments on cancer cell behavior is poorly understood. Here, we systematically altered nutrient composition of cell culture media and examined the impact on three phenotypes—drug-treatment survival, cell migration, and lactate overflow—that are frequently studied in cancer cells. These perturbations across diverse metabolic environments revealed simple relationships between cell growth rate and drug-treatment survival or migration. In contrast, lactate overflow was highly sensitive to changes in sugar availability but largely insensitive to changes in amino acid availability, regardless of the growth rate. Further investigation suggested that the degree of lactate overflow across metabolic environments is largely determined by the cells’ ability to maintain high rates of sugar uptake. This study enabled us to elucidate quantitative relationships between metabolic environment and cancer cell phenotypes, which echo empirical growth laws discovered to govern analogous phenotypes in microbes.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cancer biology↗

Precision timing with alpha-beta oscillatory coupling: stopwatch or motor control?

Precise timing is crucial for many behaviors ranging from street crossing, conversational speech, to athletic performance. The precision of motor timing has been suggested to result from the strength of phase-amplitude coupling (PAC) between the phase of alpha oscillations (, 8-12 Hz) and the power of beta activity ({beta}, 14-30 Hz), herein referred to as -{beta} PAC. The amplitude of {beta} oscillations has been proposed to code for temporally relevant information, and the locking of {beta} power to the phase of oscillations to maintain timing precision. Motor timing precision has at least two sources of variability: variability of timekeeping mechanism and variability of motor control. There is ambiguity to with of these two factors -{beta} PAC could be ascribed to. Whether -{beta} PAC indexes precision of internal timekeeping mechanisms like a stopwatch, or -{beta} PAC indexes motor control precision is unclear. To disentangle these two hypotheses, we tested how oscillatory coupling at different stages of time reproduction related to temporal precision. Human participants perceived, and subsequently reproduced, a time interval while magnetoencephalography was recorded. The data show a robust -{beta} PAC during both the encoding and the reproduction of a temporal interval, a pattern which could not be predicted for by the motor control account. Specifically, we found that timing precision resulted from the tradeoff between the strength of -{beta} PAC during the encoding and during the reproduction of intervals. We interpret these results as supporting evidence for the hypothesis that -{beta} PAC codes for precision of temporal representations in the human brain.\n\nHighlights- Encoding and reproducing temporal intervals implicate -{beta} PAC.\n- -{beta} PAC does not represent solely motor control.\n- -{beta} PAC maintains the precision of temporal representations.

neuroscience↗