Biology subjects

Schwab, B. C.

Publications and source records attributed to Schwab, B. C..

12 recordsLinked to original sources

bioRxiv2026

Phase-lag-dependent modulation of interhemispheric β-band functional connectivity by dual-site tACS

Dual-site transcranial alternating current stimulation (ds-tACS) is a promising tool for causally manipulating interhemispheric communication; nevertheless, how different stimulation phase-lags selectively modulate functional connectivity (FC) remains unclear. We recruited 29 healthy participants and included 23 in the final analyses. Participants received 20 Hz ds-tACS over the bilateral primary motor cortices (M1s) using four phase-lags (0, pi/2, pi, 3pi/2) and sham stimulation, combined with recording of high-density EEG before and after stimulation. We quantified the interhemispheric FC using the debiased weighted phase-lag index. No significant differences were found in the average FC changes between overall active stimulation and sham. However, the phase-lag associated with maximum absolute FC changes varied substantially across participants. Accordingly, the assessment of phase-lag-dependency of FC using the Kullback-Leibler distance (DKL) revealed a significant phase-lag-dependent modulation of FC that was transient (limited to the first 5 s after stimulation), restricted to frequencies around the stimulation frequency (18-22 Hz), and occurred without corresponding phase-lag-dependent modulation of the spectral power. In an exploratory analysis, the modulation magnitude showed a quadratic relationship with the individual {beta}-peak FC frequency, where participants with {beta}-peak frequencies farther from the 20 Hz stimulation frequency exhibited stronger effects. These findings indicate that ds-tACS can induce time- and frequency-specific modulation of interhemispheric FC across phase-lags. Given the observed association with individual {beta}-peak connectivity frequency and the variability in the phase-lag associated with maximal FC change, our findings motivate further investigation of personalised neuromodulation protocols.

neuroscience↗

bioRxiv2026

Weak electric fields of deep brain stimulation can entrain spiking in multi-compartment cortical neuron models

Background: Deep brain stimulation (DBS) is widely used to treat neurological disorders, but how it exerts its therapeutic effects remains an open question. Although DBS primarily acts through stimulated subcortical structures and their networks, recent studies have demonstrated that cortical electric field (E-field) strengths generated during DBS are comparable to, and can exceed, those shown to modulate neuronal activity with transcranial alternating current stimulation. We therefore investigated whether and how these weak DBS fields can directly modulate cortical spike timing. Methods: We used multi-compartment computational models of five neuron types across all cortical layers and exposed them to E-fields modeled as DBS pulses. E-field amplitudes spanned the typical range of cortical E-field strengths during DBS, while frequency and orientation were varied. Entrainment was assessed using peri-stimulus time histograms and quantified by the phase locking value (PLV). Results: Weak DBS fields modulated spike timing of some neurons by either increasing or decreasing the likelihood of firing immediately following the stimulation pulse. This modulation reflected entrainment to the stimulation, with the PLV increasing with E-field amplitude and frequency. The magnitude and direction of spike-timing modulation varied across neuron types and depended on the orientation of the field. Conclusion: These findings suggest that cortical E-fields of DBS may directly influence activity of some cortical neurons, alongside the established indirect cortical effects mediated by subcortical targets and their networks. This provides a new perspective on how DBS may influence cortical activity and offers insights into its potential mechanisms of therapeutic and/or side effects.

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bioRxiv2026

Cortical E-fields of deep brain stimulation in Parkinson's disease patients exceed typical E-field magnitudes of transcranial electrical stimulation

BackgroundDeep brain stimulation (DBS) is an established and effective intervention for Parkinsons disease. Although the exact mechanisms of action are still unclear, both therapeutic benefits and side effects are solely attributed to neuromodulation via strong electric fields (E-fields) in the surgical target. Nevertheless, DBS generates E-fields that extend beyond the stimulation site and can be detected throughout the brain. Recent evidence from transcranial electrical stimulation studies shows that weak cortical E-fields even below 1 V/m can have a neuromodulatory effect, raising the question of a physiological relevance of weak cortical fields of DBS. However, the strength of cortical E-fields of DBS is currently unknown. ObjectiveUsing a novel framework, we aimed to quantify the whole-brain E-field distribution in patients with Parkinsons disease receiving therapeutic DBS of the subthalamic nucleus (STN-DBS). MethodsIn this work, we developed a pipeline to simulate DBS E-field distributions throughout the brain, based on the existing open-source toolboxes Lead-DBS and SimNIBS. We constructed patient-specific whole-head models including electrode leads for 25 patients with Parkinsons disease receiving subthalamic DBS, and simulated E-fields using the patients clinical stimulation settings for 49 hemispheres. ResultsWe found that median peak E-field magnitudes exceeded 0.3 V/m in all cortical regions and were greater than 1 V/m in the orbital gyrus, superior temporal gyrus, fusiform gyrus, parahippocampal gyrus, insular gyrus, cingulate gyrus. Most prominently, the orbital and insular gyri showed peak magnitudes ranging from 0.81 to 8.61 V/m and 0.90 to 8.01 V/m. ConclusionsOur results indicate that the E-fields of STN-DBS reach cortical peak magnitudes that exceed typically reported values of transcranial electrical stimulation. This opens the possibility that weak E-fields of DBS could have a direct neuromodulatory effect in wider regions of the brain, for example in cortical regions.

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bioRxiv2025

Variable E-field properties of dual-site tACS

BackgroundDual-site transcranial alternating current stimulation (ds-tACS) enables the modulation of interregional functional connectivity by introducing a phase lag between the stimulating currents. However, overlapping electric fields (E-fields), particularly in closely spaced cortical targets like the primary motor cortices (M1s), may unintentionally alter E-field characteristics and confound the interpretation of functional connectivity modulation. ObjectiveWe aimed to systematically evaluate how different phase lags affect key E-field characteristics when using high-definition ds-tACS, particularly when targeting the M1s. We sought to determine which montage configuration best preserved stable E-field characteristics and investigated whether indi-vidualised montage selection could enhance control over E-field consistency. MethodsWe used individualised finite-element method simulations based on MRI-derived head models to quantify the effects of different phase lags on E-field characteristics. E-field magnitude, normal component, spatial distribution, directionality, and effective stimulation area were assessed for nine montages and eight phase lags. ResultsAll E-field properties, including E-field peak magnitude, peak magnitude of the normal component, redistribution, difference to optimal directionality, and effective area of stimulation, were modulated significantly across differ-ent phase lags for all tested montages. Furthermore, we found substantial inter-individual variability in all E-field properties. Individual selection of montages improved critical properties, particularly the E-field directionality. ConclusionsIn contrast to common assumptions, variations in the phase lag can significantly affect key E-field properties of high-definition ds-tACS. Therefore, we recommend considering modulations of the E-field characteristics when comparing physiological or behavioural effects of ds-tACS at different phase lags. Moreover, given the high inter-individual variability, we suggest the individualisation of montages to the most relevant E-field property. HighlightsO_LIDual-site tACS is often used to modulate functional connectivity. C_LIO_LIChanges in E-field characteristics with varying phase lags are undesirable. C_LIO_LIWe used FEM models to quantify these changes across arbitrary phase lags. C_LIO_LIE-field characteristics of all montages varied significantly with the phase lag. C_LIO_LIIndividualised montage selection was able to improve critical characteristics. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/668900v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@1c666baorg.highwire.dtl.DTLVardef@8257e4org.highwire.dtl.DTLVardef@1584d7corg.highwire.dtl.DTLVardef@472447_HPS_FORMAT_FIGEXP M_FIG C_FIG

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bioRxiv2025

Dual-site beta transcranial alternating current stimulation during a bimanual coordination task modulates functional connectivity between motor areas

BackgroundCommunication within brain networks depends on functional connectivity. One promising approach to modulate such connectivity between cortical areas is dual-site transcranial alternating current stimulation (tACS), which non-invasively applies weak alternating currents to two brain areas. Objectives/HypothesesIn the current study, we aimed to modulate inter-regional functional connectivity with dual-site tACS to bilateral primary motor cortices (M1s) during bimanual coordination and, in turn, alter behaviour. MethodsUsing functional magnetic resonance imaging (fMRI), we recorded participants brain responses during a bimanual coordination task in a concurrent tACS-fMRI design. While performing a slow and fast version of the task, participants received one of three types of beta (20 Hz) dual-site tACS over both M1s: in-phase, jittered-phase or sham, in a within-subject, repeated measures design. ResultsWhile we did not observe any significant tACS effects on behaviour, the study revealed a disruptive effect of in-phase tACS on interhemispheric connectivity. Additionally, the two active types of tACS (in-phase and jittered-phase) differed in the task-related M1 connectivity with other motor cortical regions, such as premotor cortex and supplementary motor area. Furthermore, individual E-field strengths were related to functional connectivity in the in-phase condition. ConclusionsDual-site beta tACS over both M1s altered functional connectivity between motor areas. However, this effect did not translate to the behavioural level, possibly due to compensatory mechanisms. HighlightsO_LIInterhemispheric connectivity between the primary motor cortices was targeted with dual-site beta tACS during bimanual coordination. C_LIO_LIIn-phase as compared to sham tACS disrupted interhemispheric connectivity during task performance. C_LIO_LIIn-phase and jittered-phase tACS led to different task-related functional connectivity patterns within the motor network. C_LIO_LIThe relationship between individual in-phase E-field strengths and interhemispheric connectivity depended on task demand. C_LIO_LIThere were no significant tACS effects on behavioural performance of bimanual coordination, possibly due to compensatory mechanisms. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=143 SRC="FIGDIR/small/647211v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@17ecdd8org.highwire.dtl.DTLVardef@1fc5b25org.highwire.dtl.DTLVardef@c3df42org.highwire.dtl.DTLVardef@17671bb_HPS_FORMAT_FIGEXP M_FIG C_FIG

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bioRxiv2023

Cortical high gamma power relates to movement speed and is disproportionately reduced after stroke

Motor cortical high-gamma oscillations (60 to 90 Hz) occur at the onset of movement and are spatially focused over the contralateral primary motor cortex. Although high-gamma oscillations are widely recognized for their significance in human motor control, their precise function on a cortical level remains elusive. Importantly, their relevance in human stroke pathophysiology is unknown. Understanding the neurophysiological processes of motor coding could be an important step in improving motor recovery after stroke. We recorded magnetoencephalography data during a thumb movement speed task in 14 chronic stroke survivors, 15 age-matched control participants and 29 healthy young participants. Motor cortical high-gamma oscillations showed a strong relation with movement speed as trials with higher movement speed were associated with greater high-gamma power. Stroke survivors showed reduced cortical high-gamma power, surpassing the effect attributable to decreased movement speed in these participants. Even though motor skill acquisition was evident in all groups, it was not linked to high-gamma power. Our study is, to our knowledge, the first to quantify high-gamma oscillations after stroke, revealing a reduction in movement-related high-gamma power. Moreover, we provide strong evidence for a pivotal role of motor cortical high-gamma oscillations in encoding movement speed.

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bioRxiv2021

Electrical neuromodulation biases brightness perception of flickering light

BackgroundVisual phenomena like brightness illusions impressively demonstrate the highly constructive nature of perception. In addition to physical illumination, the subjective experience of brightness is related to temporal neural dynamics in visual cortex. ObjectiveHere, we asked whether biasing the temporal pattern of neural excitability in visual cortex by transcranial alternating current stimulation (tACS) modulates brightness perception of concurrent rhythmic visual stimuli. MethodsParticipants performed a brightness discrimination task of two flickering lights, one of which was targeted by same-frequency electrical stimulation at varying phase shifts. tACS was applied with an occipital and a periorbital active control montage, based on simulations of electrical currents using finite-element head models. ResultsExperimental results reveal that flicker brightness perception is modulated dependent on the phase shift between sensory and electrical stimulation, solely under occipital tACS. Phase-specific modulatory effects by tACS were dependent on flicker-evoked neural phase stability at the tACS-targeted frequency, recorded prior to electrical stimulation. The optimal timing of tACS application leading to enhanced brightness perception was further correlated with the neural phase delay of the cortical flicker response. ConclusionsOur results corroborate the role of temporally coordinated neural activity in visual cortex for brightness perception of rhythmic visual input in humans. Phase-specific behavioral modulations by tACS emphasize its efficacy to transfer perceptually relevant temporal information to the cortex. These findings provide an important step towards understanding the basis of visual perception and further confirm electrical stimulation as a tool for advancing controlled modulations of neural activity and related behavior.

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bioRxiv2020

Spike-timing-dependent plasticity can account for aftereffects of dual-site transcranial alternating current stimulation

Transcranial alternating current stimulation (tACS), applied to two brain sites with different phase lags, has been shown to modulate stimulation-outlasting functional EEG connectivity between the targeted regions. Given the lack of knowledge on mechanisms of tACS aftereffects, it is difficult to further enhance effect sizes and reduce variability in experiments. In this computational study, we tested if spike-timing-dependent plasticity (STDP) can explain stimulation-outlasting connectivity modulation by dual-site tACS and explored the effects of tACS parameter choices. Two populations of spiking neurons were coupled with synapses subject to STDP, and results were validated via a re-analysis of EEG data. Our simulations showed stimulation-outlasting connectivity changes between in- and anti-phase tACS, dependent on both tACS frequency and synaptic conduction delays. Importantly, both a simple network entraining to a wide range of tACS frequencies as well as a more realistic network that spontaneously oscillated at alpha frequency predicted that the largest effects would occur for short conduction delays between the stimulated regions. This finding agreed with experimental EEG connectivity modulation by 10 Hz tACS, showing a clear negative correlation of tACS effects with estimated conduction delays between regions. In conclusion, STDP can explain connectivity aftereffects of dual-site tACS. However, not all combinations of tACS frequency and application sites are expected to effectively modulate connectivity via STDP. We therefore suggest using appropriate computational models and/or EEG analysis for planning and interpretation of dual-site tACS studies relying on aftereffects. HighlightsO_LINetwork model with STDP explains EEG connectivity change after dual-site tACS C_LIO_LIEffects are predicted to depend on tACS frequency and conduction delays C_LIO_LIEEG data confirm dependence on conduction delays between regions C_LIO_LIModel can be used to estimate and maximize experimental effects C_LI

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bioRxiv2019

Manipulation of Oscillatory Phase by Transcranial Alternating Current Stimulation

BackgroundOscillatory phase has been proposed as a key parameter defining the spatiotemporal structure of neural activity. To enhance our understanding of brain rhythms and improve clinical outcomes in pathological conditions, phase-specific modulation of oscillations by transcranial alternating current stimulation (tACS) emerged as a promising approach. However, the effectiveness of tACS in humans is still critically debated. ObjectiveHere, we investigated the phase-specificity of tACS effects on visually evoked steady state responses (SSRs) in 24 healthy human participants of either sex. MethodsTo this end, we used an intermittent electrical stimulation protocol and assessed the influence of tACS on SSR amplitude in the interval immediately following tACS. ResultsWe observed that the phase shift between flicker and tACS modulates evoked SSR amplitudes. The tACS effect size was dependent on the strength of flicker-evoked oscillatory activity, with larger effects in participants showing weaker locking of neural responses to flicker phase. Neural sources of phase-specific effects were localized in the parieto-occipital cortex within flicker-entrained regions. Importantly, the optimal phase shift between flicker and tACS associated with strongest SSRs was correlated with cortical SSR onset delays over the visual cortex. ConclusionsOverall, our data provide electrophysiological evidence for phase-specific modulations of oscillatory activity by tACS in humans. As the optimal timing of tACS application was dependent on neural conduction times as measured by SSR onset delays, data suggest that the interaction between tACS effect and SSR was cortical in nature. These findings corroborate the physiological efficacy of tACS and highlight its potential for controlled modulations of brain signals.

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bioRxiv2019

Weak modulation of thalamic discharge by basal ganglia output in association with a reaching task

Task-related activity in the ventral thalamus, a major target of basal ganglia output, is often assumed to be permitted or triggered by changes in basal ganglia activity through gating- or rebound-like mechanisms. To test those hypotheses, we sampled single-unit activity from connected basal ganglia output and thalamic nuclei (globus pallidus-internus, GPi, and ventrolateral-anterior nucleus, VLa) in monkeys performing a reaching task. Rate increases were the most common peri-movement change in both nuclei. Moreover, peri-movement changes generally began earlier in VLa than in GPi. Simultaneously-recorded GPi-VLa pairs rarely showed short-timescale spike-to-spike correlations or slow across-trials covariations and both were equally positive and negative. Finally, spontaneous GPi bursts and pauses were both followed by small, slow reductions in VLa rate. These results appear incompatible with standard gating and rebound models. Still, gating or rebound may be possible in other physiological situations: Simulations show how GPi-VLa communication can scale with GPi synchrony and GPi-to-VLa convergence, illuminating how synchrony of basal ganglia output during motor learning or in pathological conditions may render this pathway effective. Thus, in the healthy state, basal ganglia-thalamic communication during learned movement is more subtle than expected, with changes in firing rates possibly being dominated by a common external source.

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bioRxiv2019

Synchronization of sensory gamma oscillations promotes multisensory communication

Rhythmic neuronal activity in the gamma range is a signature of active cortical processing and its synchronization across distant sites has been proposed as a fundamental mechanism of network communication. While this has been shown within sensory modalities, we tested whether crosstalk between the senses relies on similar mechanisms. In two consecutive experiments, we used a task in which human participants (male and female) matched amplitude changes of concurrent visual, auditory and tactile stimuli. In this task, matching of congruent stimuli was associated with a behavioral benefit compared to matching of incongruent stimuli. In the first experiment, we used source-level analysis of high-density electroencephalography (EEG) and observed that cross-modal matching of congruent inputs was associated with relatively weaker coherence between gamma oscillations in early sensory regions. Next, we used bifocal high-definition transcranial alternating current stimulation (hd-tACS) to manipulate the strength of coupling between sensory cortices. Here, we used a lateralized version of the task in which hd-tACS was applied either ipsilateral or contralateral to the hemisphere receiving sensory stimuli. Ipsilateral gamma, but not alpha stimulation slowed responses to congruent trials whereas responding to incongruent trials was not changed by tACS. We speculate that fast responding to congruent stimuli involves decoupling of sensory gamma oscillations, which was prevented by tACS. These results indicate that synchronization of gamma oscillations promotes direct communication between sensory modalities. The framework of coupled gamma oscillations underlying cortical communication might thus be generalizable from processing within sensory streams to interactions between sensory networks. Significance statementCortical gamma oscillations structure segregated neural activity and were suggested to represent a fundamental mechanism of network communication. While there is ample evidence for the role of long-range gamma synchronization in unisensory processing, its significance in multisensory networks is still unclear. We show that direct interactions between sensory cortices rely on synchronization of gamma band activity. To that end, we carried out two consecutive experiments using state-of-the-art high-density electroencephalography (EEG) and high-definition transcranial alternating current stimulation (hd-tACS). By complementing an observational with an interventional method, we provide novel evidence for the role of synchronized gamma oscillations in multisensory communication.

neuroscience↗

bioRxiv2018

Modulation of interhemispheric alpha-band connectivity by transcranial alternating current stimulation

BackgroundLong-range functional connectivity in the brain is considered fundamental for cognition and is known to be altered in many neuropsychiatric disorders. To modify such coupling independent of sensory input, noninvasive brain stimulation could be of utmost value. ObjectiveFirst, we tested if transcranial alternating current stimulation (tACS) is able to influence functional connectivity in the human brain. Second, we investigated the specificity of effects in frequency and space. MethodsEEG aftereffects of bifocal high-definition tACS were analyzed systematically in sensor and source space. Participants were stimulated transcranially in counterbalanced order (1) in-phase, with identical electric fields in both hemispheres, (2) anti-phase, with phase-reversed electric fields in the two hemispheres, and (3) jittered-phase, generated by subtle frequency shifts continuously changing the phase relation between the two fields. ResultsWhile total power and spatial distribution of the fields were comparable between conditions, global pre-post stimulation changes in EEG connectivity were larger after in-phase stimulation than after anti-phase or jittered-phase stimulation. Those differences in connectivity were restricted to the stimulated frequency band and decayed within the first 120 s after stimulation offset. Source reconstruction localized the maximum effect between the stimulated occipitoparietal areas. ConclusionThe relative phase of bifocal alpha-tACS modulated alpha-band connectivity between the targeted regions. As side effects did not differ between stimulation conditions, we conclude that neural activity was phase-specifically influenced by the electric fields. We thus suggest bifocal high-definition tACS as a tool to manipulate long-range cortico-cortical coupling which outlasts the stimulation period.

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