Biology subjects

Ziemann, U.

Publications and source records attributed to Ziemann, U..

25 records · Page 2Linked to original sources

bioRxiv2020

Specific induction of double negative B cells during protective and pathogenic immune responses

1Double negative (DN) (CD19+CD20lowCD27-IgD-) B cells are expanded in patients with autoimmune and infectious diseases; however their role in the humoral immune response remains unclear. Using systematic flow cytometric analyses of peripheral blood B cell subsets, we observed an inflated DN B cell population in patients with variety of active inflammatory conditions: myasthenia gravis, Guillain-Barre syndrome, neuromyelitis optica spectrum disorder, meningitis/encephalitis, and rheumatic disorders. Furthermore, we were able to induce DN B cells in healthy subjects following vaccination against influenza and tick borne encephalitis virus. Transcriptome analysis revealed a gene expression profile in DN B cells that clustered with naive B cells, memory B cells, and plasmablasts. Immunoglobulin VH transcriptome sequencing and analysis of recombinant antibodies revealed clonal expansion of DN B cells, that were targeted against the vaccine antigen. Our study suggests that DN B cells are expanded in multiple inflammatory neurologic diseases and represent an inducible B cell population that responds to antigenic stimulation, possibly through an extra-follicular maturation pathway.

immunology↗

bioRxiv2020

Non-invasive brain-spine interface: continuous brain control of trans-spinal magnetic stimulation using EEG

Brain-controlled neuromodulation therapies have emerged as a promising tool to promote functional recovery in patients with motor disabilities. This neuromodulatory strategy is exploited by brain-machine interfaces and could be used for restoring lower limb muscle activity or alleviating gait deficits. Towards a non-invasive approach for leg neurorehabilitation, we present a set-up that combines acquisition of electroencephalographic (EEG) activity to volitionally control trans-spinal magnetic stimulation (ts-MS). We engineered, for the first time, a non-invasive brain-spine interface (BSI) to contingently connect motor cortical activation during leg motor imagery with the activation of leg muscles via ts-MS. This novel brain-controlled stimulation was validated with 10 healthy participants who underwent one session including different ts-MS conditions. After a short screening of their cortical activation during lower limb motor imagery, the participants used the closed-loop system at different stimulation intensities and scored system usability and comfort. We demonstrate the efficiency and robustness of the developed system to remove online stimulation artifacts from EEG regardless of ts-MS intensity used. All the participants reported absence of pain due to ts-MS and good usability. Our results also revealed that ts-MS controlled afferent and efferent intensity-dependent modulation of the nervous system. The here presented system represents a novel non-invasive means to neuromodulate peripheral nerve activity of lower limb using brain-controlled spinal stimulation.

bioengineering↗

bioRxiv2019

TMS-EEG signatures of glutamatergic neurotransmission in human cortex

Neuronal activity in the brain is regulated by an excitation-inhibition balance. Glutamate is the main excitatory neurotransmitter. Transcranial magnetic stimulation (TMS) evoked electroencephalographic (EEG) potentials (TEPs) represent a novel way to quantify pharmacological effects on neuronal activity in the human cortex. Here we tested TEPs under the influence of a single oral dose of two anti-glutamatergic drugs, perampanel, an AMPA-receptor antagonist, and dextromethorphan, an NMDA-receptor antagonist, and nimodipine, an L-type voltage-gated calcium channel blocker in 16 healthy adults in a pseudorandomized, double-blinded, placebo-controlled, crossover design. Single-pulse TMS was delivered to the left motor cortex and TEPs were obtained pre-and post-drug intake. Dextromethorphan specifically increased the amplitude of the N45, a negative potential around 45 ms after the TMS pulse, while perampanel reduced the P70 amplitude in the non-stimulated hemisphere. Nimodipine and placebo had no effect on TEPs. These data extend previous pharmaco-TMS-EEG studies by demonstrating that the N45 is regulated by a balance of GABAAergic inhibition and NMDA-receptor-mediated glutamatergic excitation. In contrast, AMPA-receptor-mediated glutamatergic neurotransmission contributes to interhemispherically propagated activity reflected in the P70. These data are important to understand the physiology of TEPs as markers of excitability and propagated activity in the human cortex in health and disease.

neuroscience↗

bioRxiv2018

TMS-evoked EEG potentials from prefrontal and parietal cortex: reliability, site specificity, and effects of dextromethorphan

Measuring the brains response to transcranial magnetic stimulation (TMS) with electroencephalography (EEG) offers a unique insight into the local cortical circuits and networks activated following stimulation, particularly in non-motor regions where less is known about TMS physiology. However, the mechanisms underlying TMS-evoked EEG potentials (TEPs) remain largely unknown. We assessed TEP reliability, site-specificity, and sensitivity to changes in excitatory neurotransmission mediated by n-methyl-d-aspartate (NMDA) receptors following stimulation of non-motor regions. In fourteen male volunteers, resting EEG and TEPs from prefrontal (PFC) and parietal (PAR) cortex were measured before and after administration of either dextromethorphan (an NMDA receptor antagonist) or placebo across two sessions separated by at least a week in a double-blinded pseudo-randomised crossover design. At baseline, TEPs showed lower within-than between-subject variability for both stimulation sites across sessions, demonstrating the reliability of non-motor TEPs within individuals. There were differences in amplitude between PFC and PAR TEPs across a wide time range (15-250 ms), however the signals were correlated after ~80 ms, suggesting that early peaks reflect site-specific activity, whereas late peaks reflect activity patterns less dependent on the stimulated sites. TEPs were not altered following dextromethorphan compared to placebo, however low frequency resting oscillations were reduced in power. Our findings suggest that TEPs from PFC and PAR: 1) are reliable within and variable between individuals; 2) reflect stimulation site specific activity across early time periods (<80 ms); and 3) are not sensitive to changes in NMDA receptor-mediated neurotransmission.

neuroscience↗

bioRxiv2018

μ-rhythm extracted with personalized EEG filters correlates with corticospinal excitability in real-time phase-triggered EEG-TMS

Ongoing brain activity has been implicated in the modulation of cortical excitability. The combination of electroencephalography (EEG) and transcranial magnetic stimulation (TMS) in a real-time triggered setup is a novel method for testing hypotheses about the relationship between spontaneous neuronal oscillations, cortical excitability, and synaptic plasticity. For this method, a reliable real-time extraction of the neuronal signal of interest from scalp EEG with high signal-to-noise ratio (SNR) is of crucial importance. Here we compare individually tailored spatial filters as computed by spatial-spectral decomposition (SSD), which maximizes SNR in a frequency band of interest, against established local C3-centered Laplacian filters for the extraction of the sensorimotor -rhythm. Single-pulse TMS over the left primary motor cortex was synchronized with the surface positive or negative peak of the respective extracted signal, and motor evoked potentials (MEP) were recorded with electromyography (EMG) of a contralateral hand muscle. Both extraction methods led to a comparable degree of MEP amplitude modulation by phase of the sensorimotor -rhythm at the time of stimulation. This could be relevant for targeting other brain regions with no working benchmark such as the local C3-centered Laplacian filter, as sufficient SNR is an important prerequisite for reliable real-time single-trial detection of EEG features.

neuroscience↗

bioRxiv2018

EEG-triggered TMS reveals stronger brain state-dependent modulation of motor evoked potentials at weaker stimulation intensities

BackgroundCorticospinal excitability depends on the current brain state. The recent development of real-time EEG-triggered transcranial magnetic stimulation (EEG-TMS) allows studying this relationship in a causal fashion. Specifically, it has been shown that corticospinal excitability is higher during the scalp surface negative EEG peak compared to the positive peak of {micro}-oscillations in sensorimotor cortex, as indexed by larger motor evoked potentials (MEPs) for fixed stimulation intensity.\n\nObjectiveWe further characterize the effect of {micro}-rhythm phase on the MEP input-output (IO) curve by measuring the degree of excitability modulation across a range of stimulation intensities. We furthermore seek to optimize stimulation parameters to enable discrimination of functionally relevant EEG-defined brain states.\n\nMethodsA real-time EEG-TMS system was used to trigger MEPs during instantaneous brain-states corresponding to {micro}-rhythm surface positive and negative peaks with five different stimulation intensities covering an individually calibrated MEP IO curve in 15 healthy participants.\n\nResultsMEP amplitude is modulated by {micro}-phase across a wide range of stimulation intensities, with larger MEPs at the surface negative peak. The largest relative MEP-modulation was observed for weak intensities, the largest absolute MEP-modulation for intermediate intensities. These results indicate a leftward shift of the MEP IO curve during the {micro}-rhythm negative peak.\n\nConclusionThe choice of stimulation intensity influences the observed degree of corticospinal excitability modulation by {micro}-phase. Lower stimulation intensities enable more efficient differentiation of EEG {micro}-phase-defined brain states.

neuroscience↗

bioRxiv2017

The Spectral Features Of EEG Responses To Transcranial Magnetic Stimulation Of The Primary Motor Cortex Depend On The Amplitude Of The Motor Evoked Potentials

Transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) can excite both cortico-cortical and cortico-spinal axons resulting in TMS-evoked potentials (TEPs) and motor-evoked potentials (MEPs), respectively. Despite this remarkable difference with other cortical areas, the influence of motor output and its amplitude on TEPs is largely unknown. Here we studied TEPs resulting from M1 stimulation and assessed whether their waveform and spectral features depend on the MEP amplitude. To this aim, we performed two separate experiments. In experiment 1, single-pulse TMS was applied at the same supra-threshold intensity on primary motor, prefrontal, premotor and parietal cortices and the corresponding TEPs were compared by means of local mean field power and time-frequency spectral analysis. In experiment 2 we stimulated M1 at resting motor threshold in order to elicit MEPs characterized by a wide range of amplitudes. TEPs computed from high-MEP and low-MEP trials were then compared using the same methods applied in experiment 1. In line with previous studies, TMS of M1 produced larger TEPs compared to other cortical stimulations. Notably, we found that only TEPs produced by M1 stimulation were accompanied by a late ([~]300 ms after TMS) event-related desynchronization (ERD), whose magnitude was strongly dependent on the amplitude of MEPs. Overall, these results suggest that M1 produces peculiar responses to TMS possibly reflecting specific anatomo-functional properties, such as the re-entry of proprioceptive feedback associated with target muscle activation.

neuroscience↗