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Bergmann, T. O.

Publications and source records attributed to Bergmann, T. O..

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Stimulus predictability rather than inter-trial interval itself affects motor evoked potential amplitudes

The inter-trial interval (ITI) of transcranial magnetic stimulation (TMS) can modulate motor-evoked potential (MEP) amplitude and may thus confound assessments of corticospinal excitability. We tested whether this effect depends on the ITI duration per se or the associated temporal predictability and whether intracortical inhibitory processes mediate these effects on. In 26 healthy participants, we recorded single-pulse MEPs and paired-pulse measures of short-interval intracortical inhibition (SICI; 2-ms interstimulus interval) and long-interval intracortical inhibition (LICI; 100-ms interstimulus interval) at ITIs of 2, 5, and 10 s. ITIs were presented in different Patterns, i.e., separate fixed blocks (FXD), randomly intermingled within blocks (RND), or randomly intermingled but auditorily cued at 950 ms pre-TMS (RNDC). MEPs showed significant effects of ITI, Pattern, and their interaction, being smaller at 2 s than at longer ITIs in FXD but not in RND and RNDC. However, RNDC produced marked MEP suppression across all ITI. SICI showed a Pattern x ITI interaction but no main effect of Pattern or between-pattern differences per ITI, whereas LICI showed complex Pattern x ITI interaction and both main effects. Notably, ITI affected SICI and LICI oppositely. While GABA-A-receptor mediated inhibition (SICI) showed an ITI dependency compatible with the ITI effects on single-pulse MEPs, it was unlikely mediating the predictability effects but may rather relate to an independent ITI driven suppression. In contrast, GABA-B-receptor mediated inhibition (LICI), was clearly modulated by predictability, but incompatible with the observed ITI effects on MEP amplitude. In summary, the effect of ITI duration on MEP amplitude seems to be largely explained by anticipatory suppression of corticospinal excitability based on the predictability of TMS pulses as derived from their temporal context, being easier for shorter and more regular ITIs and maximal for explicit cues immediately preceding the TMS pulse. SICI and LICI are modulated by ITI as well, with the latter affected by predictability, but neither can explain the observed predictability effects on single-pulse MEP amplitudes.

neuroscience↗

Suppression of corticospinal excitability by sleep spindles without increase in GABAergic inhibition

Thalamocortical sleep spindles are hypothesised to support memory consolidation during sleep by creating transient windows of enhanced hippocampal-neocortical communication and synaptic plasticity. A recent real-time electroencephalography (EEG)-triggered transcranial magnetic stimulation (TMS) study found a pulsed suppression of corticospinal excitability during spindles relative to spindle-free non-rapid eye movement (NREM) sleep, driven by the spindle falling phase. We hypothesised that this phasic suppression may reflect local inhibitory network dynamics, measurable as GABA-A receptor-mediated short-interval intracortical inhibition (SICI) using paired-pulse TMS. We applied real-time EEG-triggered single- and paired-pulse TMS over the primary motor cortex during pre-sleep wakefulness, spindle-free N2/N3 sleep, and at four sleep spindle phases (peak, falling, trough, and rising). Corticospinal excitability was strongly reduced from wakefulness to spindle-free N2/N3 sleep, and further suppressed during sleep spindles. Numerically, excitability was lowest during the falling phase and trough, although we found no significant modulation across spindle phases. Contrary to our hypothesis, neither spindle presence nor phase significantly modulated SICI. Secondary analyses provided preliminary evidence that slow oscillations present at stimulation increased excitability and reduced SICI, irrespective of spindle presence. Together, these findings indicate distinct contributions of sleep/wake vigilance states, sleep spindles, and slow oscillations to cortical network dynamics, and provide new insight into the transient modulation of corticospinal excitability and GABA-A-receptor mediated SICI during human NREM sleep.

neuroscience↗

Sleep spindle state-dependent motor cortical plasticity induction by EEG-triggered ripple burst TMS

Background: Sleep spindles are fundamental for plasticity and memory consolidation. Here we sought to target different spindle states in sleeping healthy participants with real-time EEG-burst repetitive transcranial magnetic stimulation (rTMS) at hippocampal ripple frequency, and test the spindle state-dependent induction of corticospinal and sensorimotor cortical plasticity. We hypothesized that the spindle-trough is a particularly critical state for plasticity induction because hippocampal ripples are naturally nested in the spindle-trough, reflecting replay of memory traces and facilitating memory consolidation. Methods: Fourteen participants underwent four experimental nights, in which rTMS was applied either at the spindle-trough, spindle-peak, spindle random phase or during spindle-free epochs. Readouts of plasticity were changes in resting-state EEG (rsEEG) power, motor evoked potential (MEP) amplitude, local mean field amplitude (LMFA, for the N45 and P60 potential components), immediate response slope (IRS) and TMS-related time frequency response (TFR), tested 10 and 30 min after the end of the rTMS interventions upon awakening, and compared to pre-sleep baseline. Results: Spindle-trough rTMS resulted in pre- to post-sleep decreases of rsEEG beta-band power, MEP amplitude, P60-LMFA, IRS and TFR in the alpha-band, and an increase in the N45-LMFA. None of the other spindle state-dependent rTMS interventions resulted in consistent plastic changes. Conclusions: Targeting the spindle-trough with ripple-burst rTMS stands out in consistently leading to long-term depression-like changes across a broad array of corticospinal and sensorimotor cortical excitability readouts. This opens the intriguing opportunity of targeted manipulation of human sleep physiology for improving specific behavioral processes, such as memory consolidation.

neuroscience↗

Boredom and the representation of information content in the neocortex

Boredom - a pervasive mental state - promotes the pursuit of novel information by assigning negative value to monotonous conditions. Yet, how the brain extracts and represents the information content of ongoing sensory experience remains poorly understood. Here, we combine behavioral assays, neurophysiological recordings and computational modeling across humans and mice to investigate how sensory information shapes boredom-related behavior. In a cross-species choice task, both humans and mice robustly avoid monotonous sources of sensory stimulation. We formalize perceived monotony using empirical entropy as a measure of information content and show that monotony avoidance scales directly with low entropy and in humans correlates with boredom experience. Human electroencephalography and mesoscopic calcium imaging in mice reveal that the recruitment of neocortical activity tracks stimulus entropy. Two-photon calcium imaging in the auditory cortex of mice further uncovers a stimulus-invariant population code for entropy, supported by neurons tuned to information content. A recurrent network model reproduced this code through an interplay of afferent depression and recurrent facilitation. Together, we demonstrate how the information content of sensory experience is represented in cortical population activity, providing a basis for boredom-related avoidance behavior. Thus, our findings link synaptic and neuronal dynamics to boredom, acting as a safeguard mechanism to ensure high information input to the brain.

neuroscience↗

Optimizing Network-Level TMS-fMRI: Benchmarking a Novel TMS-Compatible "Sushi" MR Coil

Concurrent TMS-fMRI can map how stimulation affects both the targeted cortex and connected brain-wide networks, but this requires MR receive hardware that allows TMS coil placement while preserving reliable whole-brain BOLD sensitivity. We developed and benchmarked a practical TMS-compatible "Sushi" MR receive setup assembled from two flexible 18-channel body arrays. Across six experiments, we tested functional readout validity, signal quality, and active TMS-fMRI compatibility. Resting-state fMRI (n = 12) and verbal N-back task-fMRI (n = 8) were acquired with Sushi, a commercially available 2x7-channel Surface setup, and a standard 64-channel head/neck array. Functional similarity to the 64-channel reference was quantified with spatial overlap, and multi-echo combination (MEcomb) was tested as a post-acquisition signal optimization strategy. Sushi recovered subject-specific resting-state networks that more closely matched the 64-channel reference than Surface, with no significant difference from the 64-channel test-retest reference. For task-fMRI, MEcomb increased task-map similarity for Sushi, whereas setup comparisons within each pipeline were not significant. MEcomb also improved resting-state similarity and increased temporal signal-to-noise ratio (tSNR) across receive setups. In phantom measurements, TMS coil placement produced spatially graded tSNR reductions relative to the no-TMS-coil condition, strongest near the coil. In one participant, active interleaved single-pulse TMS-fMRI over two cortical sites showed no detectable pulse-locked image artifacts; whole-brain MEcomb tSNR during active TMS-fMRI was reduced by 2.6-6.9% relative to the no-coil/no-stimulation reference. Together, Sushi and MEcomb provide complementary hardware and processing tools for TMS-compatible whole-brain fMRI. This combination supports network-level functional readouts while preserving feasibility for active interleaved TMS-fMRI.

neuroscience↗

Modulating Brain Perfusion, Functional Connectivity, and Metabolite Patterns through Theta Burst Transcranial Focused Ultrasound Stimulation

BackgroundTranscranial ultrasonic stimulation (TUS) is an emerging non-invasive neuromodulation technique with the potential to target both cortical and subcortical brain regions. This study investigates the effects of theta-burst TUS (tb-TUS), a neuromodulatory pattern characterized by bursts of pulses repeated at a theta frequency, on cerebral blood flow, functional connectivity, and metabolite concentrations in the primary motor cortex (M1). The aim of this study is to take a first step towards the mechanistic and methodological feasibility of tb-TUS at the M1 using multimodal neuroimaging. MethodsSeventeen healthy participants underwent a double-blind, sham-controlled crossover design, receiving both active and sham tb-TUS to the left M1 over three days. Multimodal MRI, including pseudo-continuous arterial spin labeling (PCASL), resting-state functional MRI (rs-fMRI), and magnetic resonance spectroscopy (MRS), was conducted at baseline, pre-, and post-stimulation. Acoustic simulations and finger-tapping BOLD-peak signal guided individualized TUS targeting. ResultsActive tb-TUS significantly reduced cerebral blood flow (p < .001) and within-region functional connectivity (p < .001) in the M1 compared to sham stimulation. A non-significant trend towards decreased GABA was observed, with no significant session x condition interaction found for GABA, Glutamate, or Glx concentrations. ConclusionThis pilot study demonstrates that tb-TUS of the M1 induces reductions in cerebral blood flow and functional connectivity in healthy participants. Our findings indicate that tb-TUS may be mitigating neural hyperactivity patterns, but preliminary studies so far arrive at differing results, highlighting the need for further research to replicate our findings, elucidate the underlying mechanisms, and optimize stimulation protocols.

physiology↗

Spatiotemporal patterns of theta-band activity during rapid-eye movement sleep: a magnetoencephalography analysis

Theta oscillations (4-8 Hz) in frontal cortical regions are present to different degrees across states of consciousness. In sleep, theta is prominent in periods of rapid eye-movement (REM) sleep. Theta has been linked to processes of memory consolidation; however, its mechanistic contribution specifically during REM sleep is not well understood. Interestingly, in the wake state, frontal theta activity increases during effortful cognitive tasks involving executive functions such as working memory, hinting at similarities in circuitry, and potentially, function. The aim of the present work is to create a spatially resolved, whole-brain characterisation of REM oscillatory activity in healthy human subjects, distinguishing theta from neighbouring frequency bands, differentiating substages of REM sleep (phasic and tonic REM), and comparing REM theta to that which is evoked during a working memory task. To that end, we analysed magneto- and electroencephalography (M/EEG) data recorded during overnight sleep in 10 healthy subjects, and similar data from 17 healthy subjects who performed a working memory task, using a novel whole-brain, source-localised MEG approach. Our results show that (i) theta activity has a frontal midline topography that is distinct from those of other prominent frequency bands in REM (delta, alpha, beta), (ii) theta activity in frontal midline regions is best observed within a focused 5-7 Hz range, separating it from occipital alpha activity, (iii) REM theta is dominant over the frontal midline but is also observed in several sub-cortical areas, (iv) theta is more widespread in tonic than phasic REM sleep, and (v) the focused frontal midline theta pattern observed in REM phasic sleep is the most similar of all observed sleep substages to theta evoked by a working memory task. These results enhance our understanding of theta physiology in REM sleep and suggest future targets for research into REMs role in learning and memory.

neuroscience↗

Pulsed inhibition of corticospinal excitability by the thalamocortical sleep spindle

Thalamocortical sleep spindles, i.e., oscillatory bursts at [~]12-15 Hz of waxing and waning amplitude, are a hallmark feature of non-rapid eye movement (NREM) sleep and believed to play a key role in sleep-dependent memory reactivation and consolidation. Generated in the thalamus and projecting to neocortex and hippocampus, they are phasically modulated by neocortical slow oscillations (<1 Hz) and in turn phasically modulate hippocampal sharp-wave ripples (>80 Hz). This hierarchical cross-frequency nesting may enable phase-dependent plasticity in the neocortex, and spindles have thus been considered windows of plasticity in the sleeping brain. However, the assumed phasic excitability modulation had not yet been demonstrated for spindles. Utilizing a recently developed real-time spindle detection algorithm, we applied spindle phase-triggered transcranial magnetic stimulation (TMS) to the primary motor cortex (M1) hand area and measured motor evoked potentials (MEP) to characterize corticospinal excitability during sleep spindles. We found a net suppression of MEP amplitudes during spindles, driven by selective inhibition during the falling flank of the spindle oscillation, but no inhibition during its peak, rising flank, and trough. Importantly, this phasic inhibition occurred on top of the general sleep-related inhibition observed during spindle-free NREM sleep and did not extend into the immediate refractory post-spindle periods. We conclude that spindles exert asymmetric "pulsed inhibition" of corticospinal excitability, which is assumedly relevant for processes of phase-dependent plasticity. These findings and the developed real-time spindle targeting methods will enable future studies to uncover the causal role of spindles in synaptic plasticity and systems memory consolidation.

neuroscience↗

Transcranial magnetic stimulation of primary motor cortex elicits a site-specific immediate transcranial evoked potential

BackgroundTranscranial evoked potentials (TEPs) measured via electroencephalography (EEG) are widely used to study the cortical responses to transcranial magnetic stimulation (TMS). Immediate transcranial evoked potentials (i-TEPs) have been obscured by pulse and muscular artifacts. Thus, the TEP peaks that are commonly reported have latencies that are too long to be caused by direct excitation of cortical neurons. MethodsIn 14 healthy individuals, we recorded i-TEPs evoked by a single biphasic TMS pulse targeting the primary motor hand area (M1HAND) or parietal or midline control sites. Sampling EEG at 50 kHz enabled us to reduce the duration of the TMS pulse artifact to a few milliseconds, while minor adjustments of the TMS coil tilt or position enabled us to avoid cranial muscular twitches during the experiment. ResultsWe observed an early positive EEG deflection starting after approx. 2 ms combined with a series of peaks with an inter-peak interval of [~]1.1-1.4 ms in electrodes overlying the stimulated sensorimotor region. This multi-peak i-TEP response was only evoked by TMS of the M1HAND region and was modified by changes in stimulation intensity and current direction. DiscussionSingle-pulse TMS of the M1HAND evokes an immediate local multi-peak response at the cortical site of stimulation. Our results suggest that the observed i-TEP patterns are genuine cortical responses evoked by TMS caused by synchronized excitation of pyramidal neurons in the targeted precentral cortex. This notion needs to be corroborated in future studies, including further investigations into the potential contribution of instrumental or physiological artifacts.

neuroscience↗

Auditory confounds can drive online effects of transcranial ultrasonic stimulation in humans

Transcranial ultrasonic stimulation (TUS) is rapidly emerging as a promising non-invasive neuromodulation technique. TUS is already well-established in animal models, providing foundations to now optimize neuromodulatory efficacy for human applications. Across multiple studies, one promising protocol, pulsed at 1000 Hz, has consistently resulted in motor cortical inhibition in humans (Fomenko et al., 2020). At the same time, a parallel research line has highlighted the potentially confounding influence of peripheral auditory stimulation arising from TUS pulsing at audible frequencies. In this study, we disentangle direct neuromodulatory and indirect auditory contributions to motor inhibitory effects of TUS. To this end, we include tightly matched control conditions across four experiments, one preregistered, conducted independently at three institutions. We employed a combined transcranial ultrasonic and magnetic stimulation paradigm, where TMS-elicited motor-evoked potentials (MEPs) served as an index of corticospinal excitability. First, we replicated motor inhibitory effects of TUS but showed through both tight controls and manipulation of stimulation intensity, duration, and auditory masking conditions that this inhibition was driven by peripheral auditory stimulation, not direct neuromodulation. Further, we consider neuromodulation beyond driving overall excitation/inhibition and show preliminary evidence of how TUS might interact with ongoing neural dynamics instead. Primarily, this study highlights the substantial shortcomings in accounting for the auditory confound in prior TUS-TMS work where only a flip-over sham and no active control was used. The field must critically reevaluate previous findings given the demonstrated impact of peripheral confounds. Further, rigorous experimental design via (in)active control conditions is required to make substantiated claims in future TUS studies. Only when direct effects are disentangled from those driven by peripheral confounds can TUS fully realize its potential for research and clinical applications.

neuroscience↗

Ramped V1 transcranial ultrasonic stimulation modulates but does not evoke visual evoked potentials

Transcranial ultrasonic stimulation (TUS), has been shown to evoke visual evoked potential (VEP)-like potentials on EEG recordings, and also to modulate sensory evoked potentials. However, pulsed TUS is accompanied by an auditory confound, and it is possible that any observed effects were, in-part, evoked by this confound. Therefore, we used ramped TUS pulses, which are not as easily audible, to examine whether primary visual cortex (V1) TUS evokes VEP-like potentials, and modulates VEPs elicited using a checkerboard stimulus. MethodsWe tested 14 healthy participants (31 {+/-} 4.3 yrs, 4 F and 10 M). TUS was applied to the left V1 using a 270 kHz transducer (H115-2AA, Sonic Concepts). Ramped pulses (1 ms ramp, 3.25 ms total pulse duration) were repeated at 250 Hz, with a pulse train duration of 300 ms, an effective duty cycle of 50%, and Isppa without ramping of 16 W/cm2 in water. EEG was recorded from 16 channels using the g.USBamp amplifier (g.tec medical engineering GmbH). In two blocks (TUS-only), real and sham (100 each) TUS trials were repeated every 2 s. In another two blocks (TUS+checkerboard), a checkerboard stimulus was flipped every 0.5 s, and every fourth stimulus was associated with either a real or sham (100 each) TUS trial. The TUS trial started approx. 130 ms (0-5 ms jitter) before the checkerboard flip. All EEG data were analysed using Fieldtrip, and cluster-based permutation tests were used to test for differences between conditions. Results and discussionIn the TUS-only condition, in contrast to a previous study, we found no evoked potentials using ramped pulses which minimised the auditory artifact. In the TUS+checkerboard condition, we observed a modulation of the early-component of the VEP in real TUS, relative to no TUS trials. This suggests that, in line with in-vitro and animal data, there is a direct neuromodulatory effect of ultrasound, in addition to any confounding effects. Moving forward, ramping offers a relatively easy approach to minimise the auditory confound.

neuroscience↗

Automated real-time EEG sleep spindle detection for brain state-dependent brain stimulation

Sleep spindles are a hallmark electroencephalographic (EEG) feature of non-rapid eye movement (NREM) sleep and 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 (RTSD), a robust multi-channel EEG signal processing algorithm that enables the automated triggering of stimulation during sleep spindles in a phase-specific manner. We validated the RTSD method by streaming pre-recorded sleep EEG datasets to a real-time computer system running a Simulink(R) Real-Time implementation of the algorithm. Sleep spindles were detected with high levels of sensitivity ([~]83%) and precision ([~]78%) and an F1-score of [~]0.81 in reference to state-of-the-art offline algorithms (which reached similar levels when compared to 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 center and reliably at the predefined target phase. The RTSD algorithm therefore empowers researchers to target spindles during human sleep and apply the stimulation method and experimental paradigm of their choice.

neuroscience↗

Transcranial Direct Current Stimulation Alters the Waveform Shape of Cortical Gamma Oscillations

Neuronal oscillations in different frequency bands have been linked to a wide variety of cognitive functions, and may even be a fundamental mechanism of inter-regional communication. For this reason, manipulation of oscillatory activity via brain stimulation is a central goal in neuroscience research. However, the vast majority of studies characterise oscillatory activity solely in terms of amplitude and frequency. Oscillations can also be characterised by their waveform shape; the degree to which they resemble or deviate from sinusoids. Here we exploit Empirical Mode Decomposition (EMD), a novel method that allows quantification of oscillatory waveform shape. We show for the first time that transcranial direct current stimulation (tDCS) alters the waveform shape of gamma oscillatory activity in the visual cortex. Notably, changes in waveform shape were limited to one half of the phase cycle; anodal stimulation led to a relatively slower, and cathodal to a relatively faster, descending half-wave. tDCS is generally believed to affect cortical excitability via alteration of resting membrane potential. Interestingly, simulations of altered cortical excitability in a gamma-generating neuronal population indicated the waveform shape changes observed experimentally likely stem from stimulation of pyramidal neurons. These findings have implications for understanding the neural consequences of tDCS at the level of neuronal population phenomena such as cortical oscillations and underscore the importance of waveform shape as an important feature of neuronal oscillations.

neuroscience↗

Online Closed-Loop Real-Time tES-fMRI for Brain Modulation: Feasibility, Noise/Safety and Pilot Study

Recent studies suggest that transcranial electrical stimulation (tES) can be performed during functional magnetic resonance imaging (fMRI). The novel approach of using concurrent tES-fMRI to modulate and measure targeted brain activity/connectivity may provide unique insights into the causal interactions between the brain neural responses and psychiatric/neurologic signs and symptoms, and importantly, guide the development of new treatments. However, tES stimulation parameters to optimally influence the underlying brain activity in health and disorder may vary with respect to phase, frequency, intensity and electrodes montage. Here, we delineate how a closed-loop tES-fMRI study of frontoparietal network modulation can be designed and performed. We also discuss the challenges of running a concurrent tES-fMRI, describing how we can distinguish clinically meaningful physiological changes caused by tES from tES-related artifacts. There is a large methodological parameter space including electrode types, electrolytes, electrode montages, concurrent tES-fMRI hardware, online fMRI processing pipelines and closed-loop optimization algorithms that should be carefully selected for closed-loop tES-fMRI brain modulation. We also provide technical details on how safety and quality of tES-fMRI settings can be tested, and how these settings can be monitored during the study to ensure they do not exceed safety standards. The initial results of feasibility and applicability of closed-loop tES-fMRI are reported and potential hypotheses for the outcomes are discussed. Highlight pointsO_LIMethodological details of a closed-loop tES-fMRI study protocol are provided. C_LIO_LIThe protocol is performed successfully on a frontoparietal network without side-effects. C_LIO_LIThe temperature of electrodes in concurrent tES-fMRI remains in the safe range. C_LIO_LIProperly setup concurrent tES does not introduce MRI artifacts and noise. C_LIO_LISimplex optimizer could be used to find an optimal tES stimulation parameter. C_LI

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Specific changes in sleep oscillations after blocking human metabotropic glutamate receptor 5 in the absence of altered memory function

BackgroundSleep consolidates declarative memory by repeated replay linked to the cardinal oscillations of NonREM sleep. However, there is so far little evidence of classical glutamatergic plasticity induced by this replay. Rather, we have previously reported that blocking NMDA or AMPA receptors does not affect sleep-dependent consolidation of declarative memory. AimsInvestigate the role of metabotropic glutamate receptor 5 (mGluR5) on memory processing during sleep. MethodsIn two placebo-controlled within-subject cross-over experiments with 20 healthy humans each, we used fenobam to block mGluR5 during sleep. In Experiment I, participants learned word-pairs (declarative task) and a finger sequence (procedural task) in the evening, then received the drug and recall was tested in the next morning. To cover possible effects on synaptic renormalization processes during sleep, in Experiment II, participants learned new word-pairs in the morning after sleep. Results/OutcomesSurprisingly, fenobam neither reduced retention of memory across sleep nor new learning after sleep, although it severely altered sleep architecture and memoryrelevant EEG oscillations. In NonREM sleep, fenobam suppressed 12-15 Hz spindles but augmented 2-4 Hz delta waves, whereas in REM sleep it suppressed 4-8 Hz theta and 16-22 Hz beta waves. Notably, under Fenobam NonREM spindles became more consistently phase-coupled to the slow oscillation. Conclusions/InterpretationsOur findings indicate that mGluR5-related plasticity is not essential for memory processing during sleep, even though mGlurR5 are strongly implicated in the regulation of the cardinal sleep oscillations. Declaration of interest/FundingThe authors have nothing to disclose and funders had no influence on the research presented here.

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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.

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The non-transcranial TMS-evoked potential is an inherent source of ambiguity in TMS-EEG studies

Transcranial Magnetic Stimulation (TMS) excites populations of neurons in the stimulated cortex, and the resulting activation may spread to connected brain regions. The distributed cortical response can be recorded with electroencephalography (EEG). Since TMS also stimulates peripheral sensory and motor axons and generates a loud \"click\" sound, the TMS-evoked EEG potential (TEP) not only reflects neural activity induced by transcranial neuronal excitation but also neural activity reflecting somatosensory and auditory processing. In 17 healthy young individuals, we systematically assessed the contribution of multisensory peripheral stimulation to TEPs using a TMS-compatible EEG system. Real TMS was delivered with a figure-of-eight coil over the left para-median posterior parietal cortex or superior frontal gyrus with the coil being oriented perpendicularly or in parallel to the target gyrus. We also recorded the EEG responses evoked by sham stimulation over the posterior parietal and superior frontal cortex, mimicking the auditory and somatosensory sensations evoked by real TMS. We applied state-of-the-art procedures to attenuate somatosensory and auditory confounds during real TMS, including the placement of a foam layer underneath the coil and auditory noise masking. Despite these precautions, the temporal and spatial features of the cortical potentials evoked by real TMS at the prefrontal and parietal site closely resembled the cortical potentials evoked by realistic sham TMS, both for early and late TEP components. Our findings stress the need to include a peripheral multisensory control stimulation in the study design to enable a dissociation between truly transcranial and non-transcranial components of TEPs.

neuroscience↗

Low-frequency alternating current stimulation rhythmically suppresses stimulus-induced gamma-band oscillations in visual cortex and impairs perceptual performance

Alpha oscillations (8-12 Hz) are hypothesized to rhythmically gate sensory processing, reflected by activity in the 40-100 Hz gamma band, via the mechanism of pulsed inhibition. We applied transcranial alternating current stimulation (TACS) at individual alpha frequency (IAF) and flanking frequencies (IAF-4 Hz, IAF+4 Hz) to the occipital cortex of healthy human volunteers during concurrent magnetoencephalography (MEG), while participants performed a visual detection task inducing strong gamma-band responses. Occipital (but not frontal) TACS phasically suppressed stimulus-induced gamma oscillations in the visual cortex and impaired target detection, with stronger phase-to-amplitude coupling predicting behavioral impairments. Frontal control TACS ruled out retino-thalamo-cortical entrainment resulting from (subthreshold) retinal stimulation. All TACS frequencies tested were effective, suggesting that visual gamma-band responses can be modulated by a range of low frequency oscillations. We propose that TACS-induced cortical excitability fluctuations mimic the mechanism of pulsed inhibition, which mediates the function of alpha oscillations in gating sensory processing.

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