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Misselhorn, J.

Publications and source records attributed to Misselhorn, J..

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Delta phase-dependent modulation of temporal predictions by parietal transcranial alternating current stimulation

BackgroundPrevious research has shown that temporal prediction processes are associated with phase resets of low-frequency delta oscillations in a network of parietal, sensory and frontal areas during non-rhythmic sensory stimulation. Transcranial alternating current stimulation (tACS) modulates perceptually relevant brain oscillations in a frequency and phase-specific manner, allowing the assessment of their functional qualities in certain cognitive functions like temporal prediction. ObjectiveWe addressed the relation between oscillatory activity and temporal prediction by using tACS to manipulate brain activity in a sinusoidal manner. This enables the investigation of the relevance of low-frequency oscillations phase for temporal prediction. MethodsDelta tACS was applied over the left and right parietal cortex in two separate unimodal and crossmodal experiments. Participants judged either the visual or the tactile reappearance of a uniformly moving visual stimulus, which shortly disappeared behind and occluder. Using an intermittent electrical stimulation protocol, tACS was applied with six different phase shifts relative to sensory stimulation in both experiments while participants performed a temporal prediction task. Additionally, a computational model was developed and analysed to elucidate oscillation-based functional principles for the generation of temporal predictions. ResultsOnly in the unimodal experiment, the application of delta tACS resulted in a phase-dependent modulation of temporal prediction performance. By considering the effect of sustained tACS in the computational model, we demonstrate that the entrained dynamics can phase-specifically modulate temporal prediction accuracy. ConclusionOur findings suggest that phase-specific neuromodulation through delta tACS can influence temporal prediction accuracy in a unimodal context. This provides support to the notion that low-frequency delta oscillations are of causal relevance for temporal prediction.

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Transcranial electrical stimulation over premotor cortex mimics attentional modulation of visual processing

Attentional control over sensory processing has been linked to neural alpha oscillations and related pulsed inhibition of the human cortex. Despite the wide consensus on the functional relevance of alpha oscillations for attention, precise neural mechanisms of how alpha oscillations shape perception and how this top-down modulation is implemented in cortical networks remain unclear. Here, we tested the hypothesis that alpha oscillations in premotor cortex are causally involved in top-down regulation of visual cortex responsivity to contrast. We applied intermittent transcranial alternating current stimulation (tACS) over bilateral premotor cortex to manipulate attentional preparation in a visual discrimination task. tACS was applied at 10 Hz (alpha) and controlled with 40 Hz (gamma) and sham stimulation. Importantly, we used a novel linear mixed modeling approach for statistical control of neurosensory side-effects of the electric stimulation. We found a frequency-specific effect of alpha tACS on the slope parameter, leading to enhanced low-contrast perception and decreased perception of high-contrast stimuli. Side-effects affected both threshold and slope parameters, leading to high variability in parameter estimates. Controlling the impact of side-effects on psychometric parameters by linear mixed model analysis reduced variability and clarified the existing effect. We conclude that alpha tACS over premotor cortex mimicked a state of increased endogenous attention potentially by modulation of fronto-occipital connectivity in the alpha band. We speculate that this network modulation allowed for improved sensory readout from visual cortex which led to a decrease in psychometric slope, effectively broadening the dynamic range for contrast perception. Significance statementAttention is fundamental to voluntary control of perception and behavior. Yet, despite extensive scientific efforts, precise underlying neural mechanisms remain elusive. We contribute to this ongoing discussion by providing evidence for a vital role of frontal alpha oscillations in regulating the responsivity of visual cortex. By controlled neuromodulation with intermittent transcranial alternating current stimulation (tACS), we show that alpha tACS modulates psychometric properties of visual contrast perception. This study fills an important gap between work on alpha oscillations in spatial attention and studies on the psychometrics of attention. Furthermore, we pioneered an approach for the statistical control of tACS side-effects with linear mixed modeling and thereby add to the ongoing debate on outcome variability in studies using transcranial neurostimulation methods.

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Personalized alpha-tACS targeting left posterior parietal cortex modulates visuo-spatial attention and posterior evoked EEG activity

BackgroundCovert visuo-spatial attention is marked by the anticipatory lateralization of neuronal alpha activity in the posterior parietal cortex. Previous applications of transcranial alternating current stimulation (tACS) at the alpha frequency, however, were inconclusive regarding the causal contribution of oscillatory activity during visuo-spatial attention. ObjectiveAttentional shifts of behavior and electroencephalography (EEG) after-effects were assessed in a cued visuo-spatial attention paradigm. We hypothesized that parietal alpha-tACS facilitates attention in the ipsilateral visual hemifield. Furthermore, we assumed that modulations of behavior and neurophysiology are related to individual electric field simulations. MethodsWe applied personalized tACS at alpha and gamma frequencies to elucidate the role of oscillatory neuronal activity for visuo-spatial attention. Personalized tACS montages were algorithmically optimized to target individual left and right parietal regions that were defined by an EEG localizer. ResultsBehavioral performance in the left hemifield was specifically increased by alpha-tACS compared to gamma-tACS targeting the left parietal cortex. This hemisphere-specific effect was observed despite the symmetry of simulated electric fields. In addition, visual event-related potential (ERP) amplitudes showed a reduced lateralization over posterior sites induced by left alpha-tACS. Neuronal sources of this effect were localized in the left premotor cortex. Interestingly, accuracy modulations induced by left parietal alpha-tACS were directly related to electric field magnitudes in the left premotor cortex. ConclusionOverall, results corroborate the notion that alpha lateralization plays a causal role in covert visuo-spatial attention and indicate an increased susceptibility of parietal and premotor brain regions of the left dorsal attention network to subtle tACS-neuromodulation.

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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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Sensory capability and information integration independently predict cognitive status in healthy older adults

Ageing is characterized by changes in sensory and cognitive abilities. While there is evidence that decline in sensory acuity and enhanced multisensory integration predict cognitive status in healthy older adults, potential mechanistic links between these age-related alterations remain unclear. In the current study, we assessed performance of younger and older healthy adults in a visuotactile delayed match-to-sample task and related indices of multisensory integration to unisensory perceptual thresholds and cognitive assessment data. Additionally, we applied transcranial alternating current stimulation (tACS) to modulate cortical networks found to underlie visuotactile interactions and working-memory matching in our previous work. Analysing response times and signal detection measures, we found older adults to show enhanced multisensory integration and benefit more from successful working memory matching. Both measures predicted cognitive status and correlated positively with each other, suggesting that they likely reflect a common underlying tendency to integrate information. Sensory capability, however, independently predicted cognitive status. tACS with beta frequency (20 Hz) accelerated task performance and this effect was more pronounced in the older group. We conclude that sensory capability and information integration represent independent predictors of cognitive status. Finally, we discuss a potential role of the parietal cortex in mediating augmented integration in older adults.

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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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Effects of transcranial alternating-current stimulation to secondary motor areas on cortical oscillations in stroke patients

BackgroundThere is growing evidence that secondary motor areas are relevant for recovery after motor stroke. Communication among brain areas occurs via synchronization of oscillatory activity which can potentially be modulated via transcranial alternating-current stimulation (tACS).\n\nHypothesisWe hypothesized that tACS to secondary motor areas of the stroke-lesioned hemisphere leads to modulation of task-related connectivity among primary and secondary motor areas, reflected in metrics of EEG coupling in the frequency domain.\n\nMethodsWe applied focal tACS at 1mA peak-to-peak intensity to ipsilesional ventral premotor cortex (PMv) and supplementary motor area (SMA) in chronic stroke patients while they moved their impaired hand. To probe effects of stimulation on cortical oscillations, several task-related EEG-based connectivity metrics (coherence, imaginary coherence, phase-locking value, mutual information) were assessed before and after each stimulation.\n\nResultsOverall, we found significant but weak modulations of the motor network by tACS. Stimulation of PMv reduced task-related coupling between (i) both primary motor cortices (M1) (coherence, -0.0514{+/-}0.0665 (mean{+/-}SD, active stimulation) vs. 0.0085{+/-}0.0888 (sham), p=0.0029) and (ii) between ipsilesional M1 and contralesional PMv (coherence, - 0.0386{+/-}0.0703 vs. 0.0226{+/-}0.0694, p=0.0283; phase-locking value, -0.0363{+/-}0.0581 vs. 0.0036{+/-}0.0497, p=0.0097) compared with sham stimulation.\n\nConclusionsIn this exploratory analysis, tACS to the ipsilesional PMv induced a weak decrease of task-related connectivity between ipsilesional M1 and contralesional M1 and PMv. As an excess of interhemispheric coupling is under discussion as maladaptive phenomenon of motor reorganization after stroke (e.g., bimodal balance-recovery model), tACS-induced reduction of coupling might be an interesting approach to assist re-normalization of the post-stroke motor network.

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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.

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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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Frontal and parietal alpha oscillations reflect attentional modulation of cross-modal matching

Multisensory perception is shaped by both attentional selection of relevant sensory inputs and exploitation of stimulus-driven factors that promote cross-modal binding. Underlying mechanisms of both top-down and bottom-up modulations have been linked to changes in alpha/gamma dynamics in primary sensory cortices and temporoparietal cortex. Accordingly, it has been proposed that alpha oscillations provide pulsed inhibition for gamma activity and thereby dynamically route cortical information flow. In this study, we employed a recently introduced multisensory paradigm incorporating both bottom-up and top-down aspects of cross-modal attention in an EEG study. The same trimodal stimuli were presented in two distinct attentional conditions, focused on visual-tactile or audio-visual components, for which cross-modal congruence of amplitude changes had to be evaluated. Neither top-down nor bottom-up cross-modal attention modulated alpha or gamma power in primary sensory cortices. Instead, we found alpha band effects in bilateral frontal and right parietal cortex. We propose that frontal alpha oscillations reflect the origin of top-down control regulating perceptual gains and that modulations of parietal alpha oscillations relates to intersensory re-orienting. Taken together, we suggest that the idea of selective cortical routing via alpha oscillations can be extended from sensory cortices to the frontoparietal attention network.

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