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  1. Article: Probing cortical excitability using rapid frequency tagging

    Bergmann, Til Ole

    NeuroImage, 195:59-66

    2019  

    Abstract: Frequency tagging has been widely used to study the role of visual selective attention. Presenting a visual stimulus flickering at a specific frequency generates so-called steady-state visually evoked responses. However, frequency tagging is mostly done ... ...

    Institution Deutsches Resilienz Zentrum
    Abstract Frequency tagging has been widely used to study the role of visual selective attention. Presenting a visual stimulus flickering at a specific frequency generates so-called steady-state visually evoked responses. However, frequency tagging is mostly done at lower frequencies (<30 Hz). This produces a visible flicker, potentially interfering with both perception and neuronal oscillations in the theta, alpha and beta band. To overcome these problems, we used a newly developed projector with a 1440 Hz refresh rate allowing for frequency tagging at higher frequencies. We asked participants to perform a cued spatial attention task in which imperative pictorial stimuli were presented at 63 Hz or 78 Hz while measuring whole-head magnetoencephalography (MEG). We found posterior sensors to show a strong response at the tagged frequency. Importantly, this response was enhanced by spatial attention. Furthermore, we reproduced the typical modulations of alpha band oscillations, i.e., decrease in the alpha power contralateral to the attentional cue. The decrease in alpha power and increase in frequency tagged signal with attention correlated over subjects. We hereby provide proof-of-principle for the use of high-frequency tagging to study sensory processing and neuronal excitability associated with attention.
    Language English
    Document type Article
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  2. Article: Distilling the essence of TMS-evoked EEG potentials (TEPs): A call for securing mechanistic specificity and experimental rigor

    Bergmann, Til Ole

    Brain stimulation, 4(12):1051-1054

    2019  

    Institution Deutsches Resilienz Zentrum gGmbH
    Language English
    Document type Article
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  3. Article: Brain State-Dependent Brain Stimulation

    Bergmann, Til Ole

    Frontiers in psychology, 9:2108

    2018  

    Institution Deutsches Resilienz Zentrum gGmbH
    Keywords EEG ; real-time ; transcrancial magnetic stimulation (TMS) ; transcranial alternating current stimulation (tACS) ; transcranial direct current stimulation (tDCS)
    Language English
    Document type Article
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  4. Article: Pulsed Facilitation of Corticospinal Excitability by the Sensorimotor μ-Alpha Rhythm

    Bergmann, Til Ole / Ziemann, Ulf

    The journal of neuroscience, 50(39):10034-10043

    2019  

    Abstract: Alpha oscillations (8–14 Hz) are assumed to gate information flow in the brain by means of pulsed inhibition; that is, the phasic suppression of cortical excitability and information processing once per alpha cycle, resulting in stronger net suppression ... ...

    Institution Deutsches Resilienz Zentrum gGmbH
    Abstract Alpha oscillations (8–14 Hz) are assumed to gate information flow in the brain by means of pulsed inhibition; that is, the phasic suppression of cortical excitability and information processing once per alpha cycle, resulting in stronger net suppression for larger alpha amplitudes due to the assumed amplitude asymmetry of the oscillation. While there is evidence for this hypothesis regarding occipital alpha oscillations, it is less clear for the central sensorimotor μ-alpha rhythm. Probing corticospinal excitability via transcranial magnetic stimulation (TMS) of the primary motor cortex and the measurement of motor evoked potentials (MEPs), we have previously demonstrated that corticospinal excitability is modulated by both amplitude and phase of the sensorimotor μ-alpha rhythm. However, the direction of this modulation, its proposed asymmetry, and its underlying mechanisms remained unclear. We therefore used real-time EEG-triggered single- and paired-pulse TMS in healthy humans of both sexes to assess corticospinal excitability and GABA-A-receptor mediated short-latency intracortical inhibition (SICI) at rest during spontaneous high amplitude μ-alpha waves at different phase angles (peaks, troughs, rising and falling flanks) and compared them to periods of low amplitude (desynchronized) μ-alpha. MEP amplitude was facilitated during troughs and rising flanks, but no phasic suppression was observed at any time, nor any modulation of SICI. These results are best compatible with sensorimotor μ-alpha reflecting asymmetric pulsed facilitation but not pulsed inhibition of motor cortical excitability. The asymmetric excitability with respect to rising and falling flanks of the μ-alpha cycle further reveals that voltage differences alone cannot explain the impact of phase. SIGNIFICANCE STATEMENT: The pulsed inhibition hypothesis, which assumes that alpha oscillations actively inhibit neuronal processing in a phasic manner, is highly influential and has substantially shaped our understanding of these oscillations. However, some of its basic assumptions, in particular its asymmetry and inhibitory nature, have rarely been tested directly. Here, we explicitly investigated the asymmetry of modulation and its direction for the human sensorimotor μ-alpha rhythm. We found clear evidence of pulsed facilitation, but not inhibition, in the human motor cortex, challenging the generalizability of the pulsed inhibition hypothesis and advising caution when interpreting sensorimotor μ-alpha changes in the sensorimotor system. This study also demonstrates how specific assumptions about the neurophysiological underpinnings of cortical oscillations can be experimentally tested noninvasively in humans.
    Keywords alpha oscillation ; motor cortex ; motor evoked potential (MEP) ; short-interval intracortical inhibition (SICI) ; real-time EEG-TMS ; transcranial magnetic stimulation (TMS)
    Language English
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  5. Article ; Online: Network perturbation-based biomarkers of depression and treatment response.

    Müller-Dahlhaus, Florian / Bergmann, Til Ole

    Cell reports. Medicine

    2023  Volume 4, Issue 6, Page(s) 101086

    Abstract: Using concurrent TMS-EEG, Han et al. ...

    Abstract Using concurrent TMS-EEG, Han et al.
    MeSH term(s) Humans ; Prefrontal Cortex ; Depressive Disorder, Major/therapy ; Depression/diagnosis ; Depression/therapy ; Transcranial Magnetic Stimulation ; Hippocampus
    Language English
    Publishing date 2023-06-10
    Publishing country United States
    Document type Journal Article ; Comment
    ISSN 2666-3791
    ISSN (online) 2666-3791
    DOI 10.1016/j.xcrm.2023.101086
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  6. Article ; Online: Automated real-time EEG sleep spindle detection for brain-state-dependent brain stimulation.

    Hassan, Umair / Feld, Gordon B / Bergmann, Til Ole

    Journal of sleep research

    2022  Volume 31, Issue 6, Page(s) e13733

    Abstract: Sleep spindles are a hallmark electroencephalographic feature of non-rapid eye movement sleep, and are believed to be instrumental for sleep-dependent memory reactivation and consolidation. However, direct proof of their causal relevance is hard to ... ...

    Abstract Sleep spindles are a hallmark electroencephalographic feature of non-rapid eye movement sleep, and are believed to be instrumental for sleep-dependent memory reactivation and consolidation. However, direct proof of their causal relevance is hard to obtain, and our understanding of their immediate neurophysiological consequences is limited. To investigate their causal role, spindles need to be targeted in real-time with sensory or non-invasive brain-stimulation techniques. While fully automated offline detection algorithms are well established, spindle detection in real-time is highly challenging due to their spontaneous and transient nature. Here, we present the real-time spindle detector, a robust multi-channel electroencephalographic signal-processing algorithm that enables the automated triggering of stimulation during sleep spindles in a phase-specific manner. We validated the real-time spindle detection method by streaming pre-recorded sleep electroencephalographic datasets to a real-time computer system running a Simulink® Real-Time™ implementation of the algorithm. Sleep spindles were detected with high levels of Sensitivity (~83%), Precision (~78%) and a convincing F1-Score (~81%) in reference to state-of-the-art offline algorithms (which reached similar or lower levels when compared with each other), for both naps and full nights, and largely independent of sleep scoring information. Detected spindles were comparable in frequency, duration, amplitude and symmetry, and showed the typical time-frequency characteristics as well as a centroparietal topography. Spindles were detected close to their centre and reliably at the predefined target phase. The real-time spindle detection algorithm therefore empowers researchers to target spindles during human sleep, and apply the stimulation method and experimental paradigm of their choice.
    MeSH term(s) Humans ; Electroencephalography/methods ; Sleep/physiology ; Algorithms ; Brain/physiology ; Sleep Stages/physiology
    Language English
    Publishing date 2022-09-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 1122722-9
    ISSN 1365-2869 ; 0962-1105
    ISSN (online) 1365-2869
    ISSN 0962-1105
    DOI 10.1111/jsr.13733
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  7. Article ; Online: Inferring Causality from Noninvasive Brain Stimulation in Cognitive Neuroscience.

    Bergmann, Til Ole / Hartwigsen, Gesa

    Journal of cognitive neuroscience

    2020  Volume 33, Issue 2, Page(s) 195–225

    Abstract: Noninvasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation or transcranial direct and alternating current stimulation, are advocated as measures to enable causal inference in cognitive neuroscience experiments. ... ...

    Abstract Noninvasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation or transcranial direct and alternating current stimulation, are advocated as measures to enable causal inference in cognitive neuroscience experiments. Transcending the limitations of purely correlative neuroimaging measures and experimental sensory stimulation, they allow to experimentally manipulate brain activity and study its consequences for perception, cognition, and eventually, behavior. Although this is true in principle, particular caution is advised when interpreting brain stimulation experiments in a causal manner. Research hypotheses are often oversimplified, disregarding the underlying (implicitly assumed) complex chain of causation, namely, that the stimulation technique has to generate an electric field in the brain tissue, which then evokes or modulates neuronal activity both locally in the target region and in connected remote sites of the network, which in consequence affects the cognitive function of interest and eventually results in a change of the behavioral measure. Importantly, every link in this causal chain of effects can be confounded by several factors that have to be experimentally eliminated or controlled to attribute the observed results to their assumed cause. This is complicated by the fact that many of the mediating and confounding variables are not directly observable and dose-response relationships are often nonlinear. We will walk the reader through the chain of causation for a generic cognitive neuroscience NIBS study, discuss possible confounds, and advise appropriate control conditions. If crucial assumptions are explicitly tested (where possible) and confounds are experimentally well controlled, NIBS can indeed reveal cause-effect relationships in cognitive neuroscience studies.
    MeSH term(s) Brain ; Cognition ; Cognitive Neuroscience ; Humans ; Neuroimaging ; Transcranial Direct Current Stimulation ; Transcranial Magnetic Stimulation
    Language English
    Publishing date 2020-06-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1007410-7
    ISSN 1530-8898 ; 0898-929X ; 1096-8857
    ISSN (online) 1530-8898
    ISSN 0898-929X ; 1096-8857
    DOI 10.1162/jocn_a_01591
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  8. Article: Inferring causality from noninvasive brain stimulation in cognitive neuroscience

    Bergmann, Til Ole / Hartwigsen, Gesa

    Journal of Cognitive Neuroscience

    2021  Volume 33, Issue 2, Page(s) 195–225

    Abstract: Noninvasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation or transcranial direct and alternating current stimulation, are advocated as measures to enable causal inference in cognitive neuroscience experiments. ... ...

    Title translation Ableitung von Kausalität aus nicht-invasiver Hirnstimulation in den kognitiven Neurowissenschaften
    Abstract Noninvasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation or transcranial direct and alternating current stimulation, are advocated as measures to enable causal inference in cognitive neuroscience experiments. Transcending the limitations of purely correlative neuroimaging measures and experimental sensory stimulation, they allow to experimentally manipulate brain activity and study its consequences for perception, cognition, and eventually, behavior. Although this is true in principle, particular caution is advised when interpreting brain stimulation experiments in a causal manner. Research hypotheses are often oversimplified, disregarding the underlying (implicitly assumed) complex chain of causation, namely, that the stimulation technique has to generate an electric field in the brain tissue, which then evokes or modulates neuronal activity both locally in the target region and in connected remote sites of the network, which in consequence affects the cognitive function of interest and eventually results in a change of the behavioral measure. Importantly, every link in this causal chain of effects can be confounded by several factors that have to be experimentally eliminated or controlled to attribute the observed results to their assumed cause. This is complicated by the fact that many of the mediating and confounding variables are not directly observable and dose - response relationships are often nonlinear. We will walk the reader through the chain of causation for a generic cognitive neuroscience NIBS study, discuss possible confounds, and advise appropriate control conditions. If crucial assumptions are explicitly tested (where possible) and confounds are experimentally well controlled, NIBS can indeed reveal cause-effect relationships in cognitive neuroscience studies.
    Keywords Bildgebende Verfahren ; Brain Stimulation ; Cognitive Neuroscience ; Electrical Brain Stimulation ; Elektrische Hirnstimulation ; Hirnstimulation ; Kognitive Neurowissenschaft ; Neuroimaging ; Transcranial Magnetic Stimulation ; Transkranielle Magnetstimulation
    Language English
    Document type Article
    ZDB-ID 1007410-7
    ISSN 1530-8898 ; 0898-929X ; 1096-8857
    ISSN (online) 1530-8898
    ISSN 0898-929X ; 1096-8857
    DOI 10.1162/jocn_a_01591
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  9. Article ; Online: Repetitive sensorimotor mu-alpha phase-targeted afferent stimulation produces no phase-dependent plasticity related changes in somatosensory evoked potentials or sensory thresholds.

    Pillen, Steven / Shulga, Anastasia / Zrenner, Christoph / Ziemann, Ulf / Bergmann, Til Ole

    PloS one

    2023  Volume 18, Issue 10, Page(s) e0293546

    Abstract: Phase-dependent plasticity has been proposed as a neurobiological mechanism by which oscillatory phase-amplitude cross-frequency coupling mediates memory process in the brain. Mimicking this mechanism, real-time EEG oscillatory phase-triggered ... ...

    Abstract Phase-dependent plasticity has been proposed as a neurobiological mechanism by which oscillatory phase-amplitude cross-frequency coupling mediates memory process in the brain. Mimicking this mechanism, real-time EEG oscillatory phase-triggered transcranial magnetic stimulation (TMS) has successfully induced LTP-like changes in corticospinal excitability in the human motor cortex. Here we asked whether EEG phase-triggered afferent stimulation alone, if repetitively applied to the peaks, troughs, or random phases of the sensorimotor mu-alpha rhythm, would be sufficient to modulate the strength of thalamocortical synapses as assessed by changes in somatosensory evoked potential (SEP) N20 and P25 amplitudes and sensory thresholds (ST). Specifically, we applied 100 Hz triplets of peripheral electrical stimulation (PES) to the thumb, middle, and little finger of the right hand in pseudorandomized trials, with the afferent input from each finger repetitively and consistently arriving either during the cortical mu-alpha trough or peak or at random phases. No significant changes in SEP amplitudes or ST were observed across the phase-dependent PES intervention. We discuss potential limitations of the study and argue that suboptimal stimulation parameter choices rather than a general lack of phase-dependent plasticity in thalamocortical synapses are responsible for this null finding. Future studies should further explore the possibility of phase-dependent sensory stimulation.
    MeSH term(s) Humans ; Evoked Potentials, Motor/physiology ; Evoked Potentials, Somatosensory ; Motor Cortex/physiology ; Alpha Rhythm ; Transcranial Magnetic Stimulation ; Sensory Thresholds ; Electric Stimulation ; Somatosensory Cortex/physiology
    Language English
    Publishing date 2023-10-30
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0293546
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  10. Article ; Online: Real-time, closed-loop, or open-loop stimulation? Navigating a terminological jungle.

    Antony, James W / Ngo, Hong-Viet V / Bergmann, Til Ole / Rasch, Björn

    Journal of sleep research

    2022  Volume 31, Issue 6, Page(s) e13755

    Abstract: Recent advancements in real-time brain stimulation in the sleep field have led to many exciting findings. However, they have also opened up terminological ambiguities about what constitutes "open-loop", "closed-loop", and "real-time" designs. Here, we ... ...

    Abstract Recent advancements in real-time brain stimulation in the sleep field have led to many exciting findings. However, they have also opened up terminological ambiguities about what constitutes "open-loop", "closed-loop", and "real-time" designs. Here, we address core theoretical aspects of these terms in the hopes of strengthening future research on this topic.
    MeSH term(s) Humans ; Sleep/physiology
    Language English
    Publishing date 2022-10-26
    Publishing country England
    Document type Letter
    ZDB-ID 1122722-9
    ISSN 1365-2869 ; 0962-1105
    ISSN (online) 1365-2869
    ISSN 0962-1105
    DOI 10.1111/jsr.13755
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