Biology subjects

Engel, A. K.

Publications and source records attributed to Engel, A. K..

At least 37 records · Page 2Linked to original sources

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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bioRxiv2020

BiPOLES: a tool for bidirectional dual-color optogenetic control of neurons

Optogenetic manipulation of neuronal activity has become an indispensable experimental strategy in neuroscience research. A large repertoire of excitatory and inhibitory tools allows precise activation or inhibition of genetically targetable neuronal populations. However, an optogenetic tool for reliable bidirectional control of neuronal activity allowing both up- and downregulation of the same neurons in a single experiment is still missing. Here we report BiPOLES, an optogenetic tool for potent excitation and inhibition of the same population of neurons with light of two different colors. BiPOLES consists of an inhibitory, blue-light-sensitive anion-conducting channelrhodopsin fused to an excitatory, red-light-sensitive cation-conducting channelrhodopsin in a single, trafficking-optimized tandem protein. BiPOLES enables multiple new applications including potent dual-color spiking and silencing of the same neurons in vivo and dual-color optogenetic control of two independent neuronal populations.

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bioRxiv2020

Dissociation between catecholamines and acetylcholine in the human cerebral cortex

Influential accounts postulate distinct roles of the catecholamine and acetylcholine neuromodulatory systems in cognition and behavior. But previous work found similar effects of these modulators on the response properties of individual cortical neurons. Here, we report a double dissociation between catecholamine and acetylcholine effects at the level of cortex-wide network interactions in humans. A pharmacological boost of catecholamine levels increased cortex-wide interactions during a visual task, but not rest. Conversely, an acetylcholine-boost decreased correlations during rest, but not task. Cortical circuit modeling explained this dissociation by differential changes in two circuit properties: the local excitation-inhibition balance (more strongly altered by catecholamines) and intracortical transmission (more strongly reduced by acetylcholine). The inferred catecholaminergic mechanism also predicted increased behavioral exploration, which we confirmed in human behavior during both a perceptual and value-based choice task. In sum, we identified specific circuit mechanisms for shaping cortex-wide network interactions and behavior by key neuromodulatory systems.

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bioRxiv2020

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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bioRxiv2019

Attention-dependent preparatory processing of naturalistic narratives is correlated with speech comprehension

While human speech comprehension is thought to be an active process that involves top-down predictions, it remains unclear how predictive information is used to prepare for the processing of upcoming speech information. We aimed to identify the neural signatures of the preparatory processing of upcoming speech. Participants selectively attended to one of two competing naturalistic, narrative speech streams, and a temporal response function (TRF) method was applied to derive event-related-like neural responses from electroencephalographic data. The phase responses to the attended speech at the delta band (1-4 Hz) were correlated with the comprehension performance of individual participants, with a latency of -200-0 ms before onset over the fronto-central and left-lateralized parietal regions. The phase responses to the attended speech at the alpha band also correlated with comprehension performance, but with a latency of 650-980 ms post-onset over fronto-central regions. Distinct neural signatures were found for the attentional modulation, taking the form of TRF-based amplitude responses at a latency of 240-320 ms post-onset over the left-lateralized fronto-central and occipital regions. Our findings reveal how the brain gets prepared to process an upcoming speech in a continuous, naturalistic speech context.

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bioRxiv2019

Data-driven classification of spectral profiles reveals brain region-specific plasticity

Congenital blindness has been shown to result in behavioral adaptation and neuronal reorganization, but the underlying neuronal mechanisms are largely unknown. Brain rhythms are characteristic for anatomically defined brain regions and provide a putative mechanistic link to cognitive processes. In a novel approach, using magnetoencephalography resting state data of congenitally blind and sighted humans, deprivation-related changes in spectral profiles were mapped to the cortex using clustering and classification procedures. Altered spectral profiles in visual areas suggest changes in visual alpha-gamma band inhibitory-excitatory circuits. Remarkably, spectral profiles were also altered in auditory and right frontal areas showing increased power in theta-to-beta frequency bands in blind compared to sighted individuals, possibly related to adaptive auditory and higher-cognitive processing. Moreover, occipital alpha correlated with microstructural white matter properties extending bilaterally across posterior parts of the brain. We provide evidence that visual deprivation selectively modulates spectral profiles, possibly reflecting structural and functional adaptation.

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bioRxiv2019

Dynamic Predictions: Oscillatory Mechanisms Underlying Multisensory Sequence Processing

Neural oscillations have been proposed to be involved in predictive processing, however less addressed in the multisensory context. In the present study, we recorded cortical activity using magnetoencephalography during an audiovisual serial prediction task in which participants had to acquire stimulus sequences and to monitor whether subsequent probe items complied with the sequence. In a given trial, either visual or auditory features of the bimodal stimuli were task-relevant. Task-related changes of power and coupling of neural oscillations were analyzed using a data-driven clustering approach. We observed prediction-related theta-band (5-7 Hz) coupling in a network involving the cingulate, premotor, prefrontal, and superior temporal regions. The behavioral performance of participants varied as a function of the phase delay of the coupling between different regions in this network. . Two additional spectro-temporal clusters were detected in which beta power (11-16 Hz and 16-22 Hz, respectively) was stronger if the previous or the following stimuli were the same as the current one in the sequence. These clusters spatially overlapped with the theta-band prediction cluster, and interacted with it through cross-frequency coupling. Our results offer novel insights into the multi-timescale neural dynamics underlying multisensory predictions, suggesting that oscillations in multiple frequency ranges, as well as coupling within and across frequencies, may be critical for multisensory sequence processing.

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bioRxiv2019

Simulating individually targeted transcranial electric stimulation for experimental application

Transcranial electric stimulation (tES) induces electric fields that are subject to a complex interaction with individual anatomical properties, such as the low-conducting human skull, the distribution of cerebrospinal fluid or the sulcal depth, as well as stimulation target location and orientation. This complex interaction might contribute to the heterogenous results that are commonly observed in applications of tES in humans. Targeted tES, on the other hand, might be able to account for some of these individual factors. In the present study, we used the finite-element method (FEM) and head models of twenty-one participants to evaluate the effect of individually targeted tES on simulated intracranial current densities. Head models were based on an automated segmentation algorithm to facilitate processing in experimental sample sizes. We compared a standard stimulation montage to two individually optimized tES montages using an Alternating Direction Method of Multipliers (ADMM) and a Constrained Maximum Intensity (CMI) approach. A right parietal target was defined with three different orientations. Individual current densities showed varying intensity and spatial extent near the lower limit at which physiological efficacy of electric fields can be assumed. Both individually optimized targeting algorithms were able to control the electric field properties, with respect to intensities and/or spatial extent of the electric fields. Still, across head models, intensity in the stimulation target was constrained by individual anatomical properties. Thus, our results underline the importance of targeted tES in enhancing the effectiveness of future tES applications and in elucidating the underlying mechanisms.

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bioRxiv2019

Mathematical relations between measures of brain connectivity estimated from electrophysiological recordings for Gaussian distributed data

A large variety of methods exist to estimate brain coupling in the frequency domain from electrophysiological data measured e.g. by EEG and MEG. Those data are to reasonable approximation, though certainly not perfectly, Gaussian distributed. This work is based on the well-known fact that for Gaussian distributed data, the cross-spectrum completely determines all statistical properties. In particular, for an infinite number of data, all normalized coupling measures at a given frequency are a function of complex coherency. However, it is largely unknown what the functional relations are. We here present those functional relations for six different measures: the weighted phase lag index, the phase lag index, the absolute value and imaginary part of the phase locking value (PLV), power envelope correlation, and power envelope correlation with correction for artifacts of volume conduction. With the exception of PLV, the final results are simple closed form formulas. We tested in simulations of linear and nonlinear dynamical systems and for empirical resting state EEG on sensor level to what extent a model, namely the respective function of coherency, can explain the observed couplings. For empirical data w e found that for measures of phase-phase coupling deviations from the model are in general minWor, while power envelope correlations systematically deviate from the model for all frequencies. For power envelope correlation with correction for artifacts of volume conduction the model cannot explain the observed couplings at all. We also analyzed power envelope correlation as a function of time and frequency in an event related experiment using a stroop reaction task and found significant event related deviations mostly in the alpha range.

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bioRxiv2019

Congruency effects can compensate for deficits of healthy older adults in crossmodal integration

One of the pivotal challenges of aging is to maintain independence in the activities of daily life. In order to adapt to changes in the environment, it is crucial to continuously process and accurately combine simultaneous input from different sensory systems, i.e., crossmodal integration.\n\nWith aging, performance decreases in multiple cognitive domains. The processing of sensory stimuli constitutes one of the key features of this deterioration. Age-related sensory impairments affect all modalities, substantiated by decreased acuity in visual, auditory or tactile detection tasks.\n\nHowever, whether this decline of sensory processing leads to impairments in crossmodal integration remains an unresolved question. While some researchers propose that crossmodal integration degrades with age, others suggest that it is conserved or even gains compensatory importance.\n\nTo address this question, we compared behavioral performance of older and young participants in a well-established crossmodal matching task, requiring the evaluation of congruency in simultaneously presented visual and tactile patterns. Older participants performed significantly worse than young controls in the crossmodal task when being stimulated at their individual unimodal visual and tactile perception thresholds. Performance increased with adjustment of stimulus intensities. This improvement was driven by better detection of congruent stimulus pairs (p<0.01), while detection of incongruent pairs was not significantly enhanced (p=0.12).\n\nThese results indicate that age-related impairments lead to poor performance in complex crossmodal scenarios and demanding cognitive tasks. Performance is enhanced when inputs to the visual and tactile systems are congruent. Congruency effects might therefore be used to develop strategies for cognitive training and neurological rehabilitation.

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bioRxiv2019

An oscillator ensemble model of sequence learning

Learning and memorizing sequences of events is an important function of the human brain and the basis for forming expectations and making predictions. Learning is facilitated by repeating a sequence several times, causing rhythmic appearance of the individual sequence elements. This observation invites to consider the resulting multitude of rhythms as a spectral fingerprint which characterizes the respective sequence. Here we explore the implications of this perspective by developing a neurobiologically plausible computational model which captures this fingerprint by attuning an ensemble of neural oscillators. In our model, this attuning process is based on a number of oscillatory phenomena that have been observed in electrophysiological recordings of brain activity like synchronization, phase locking and reset as well as cross-frequency coupling. We compare the learning properties of the model with behavioral results from a study in human participants and observe good agreement of the errors for different levels of complexity of the sequence to be memorized. Finally, we suggest an extension of the model for processing sequences that extend over several sensory modalities.

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bioRxiv2019

Delta phase resetting mediates non-rhythmic temporal prediction

The phase of neural oscillatory activity aligns to the predicted onset of upcoming stimulation. Whether such phase alignments represent phase resets of underlying neural oscillations or just rhythmically evoked activity, and whether they can be observed in a rhythm-free visual context, however, remains unclear. Here, we recorded the magnetoencephalogram while participants were engaged in a temporal prediction task judging the visual or tactile reappearance of a uniformly moving stimulus. The prediction conditions were contrasted with a control condition to dissociate phase adjustments of neural oscillations from stimulus-driven activity. We observed stronger delta band inter-trial phase consistency (ITPC) in a network of sensory, parietal and frontal brain areas, but no power increase reflecting stimulus-driven or prediction-related processes. Delta ITPC further correlated with prediction performance in the cerebellum and visual cortex. Our results provide evidence that phase alignments of low-frequency neural oscillations underlie temporal predictions in a non-rhythmic visual and crossmodal context.

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bioRxiv2019

Parkin deficiency perturbs striatal circuit dynamics

Loss-of-function mutations in the parkin-encoding PARK2 gene cause young-onset, autosomal recessive Parkinsons disease (PD). Here, we investigated how parkin mutations affect cortico-basal ganglia circuit dynamics and cell-type-specific functional connectivity by recording simultaneously from motor cortex, striatum and globus pallidus (GP) in anesthetized parkin-mutant mice.\n\nWhile ongoing activity of presumed striatal spiny projection neurons and their downstream counterparts in the GP was not different from controls, parkin deficiency had a differential impact on striatal interneurons: In parkin-mutant mice, tonically active neurons displayed elevated activity levels. Baseline firing of transgenic striatal fast spiking interneurons (FSI), on the contrary, was reduced and the correlational structure of the FSI microcircuitry was disrupted. The entire transgenic striatal microcircuit showed enhanced and phase-shifted phase coupling to slow (1-3Hz) cortical population oscillations. Unexpectedly, local field potentials recorded from striatum and GP of parkin-mutant mice robustly displayed amplified beta oscillations ([~]22Hz), phase-coupled to cortex. Moreover, parkin deficiency selectively increased spike-field coupling of FSIs to beta oscillations.\n\nOur findings suggest that loss of parkin function leads to amplifications of synchronized cortico-striatal oscillations and intrastriatal reconfiguration of interneuronal circuits. This presymptomatic disarrangement of dynamic functional connectivity may precede nigro-striatal neurodegeneration and predispose to imbalance of striatal outflow accompanying symptomatic PD.

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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

Large-scale functional connectivity in multisensory cortex predicts performance

Complex behavior and task execution require fast changes of local activity and functional connectivity in cortical networks at multiple scales. The roles that changes of power and connectivity play during these processes are still not well understood. Here, we study how fluctuations of functional cortical coupling across different brain areas determine performance in an audiovisual, lateralized detection task in the ferret. We hypothesized that dynamic variations in the networks state determine the animals performance. We evaluated these by quantifying changes of local power and of phase coupling across visual, auditory and parietal regions. While power for hit and miss trials showed significant differences only during stimulus and response onset, phase coupling already differed before stimulus onset. An analysis of principal components in coupling at the single-trial level during this period allowed us to reveal the subnetworks that most strongly determined performance. Whereas higher global phase coupling of visual and auditory regions to parietal cortex was predictive of task performance, a second component revealed a reduction in coupling between subnetworks of different sensory modalities, probably to allow a better detection of the unimodal signals. Furthermore, we observed that long-range coupling became more predominant during the task period compared to the pre-stimulus baseline. Taken together, our results show that fluctuations in the network state, as reflected in large-scale coupling, are key determinants of the animals behavior.

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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.

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bioRxiv2019

Multi-frequency tACS has lasting effects on neural synchrony and audiovisual responses

BACKGROUND: In cortical networks, synchronized oscillatory activity of neuronal populations enables communication, and its disturbance is related to a range of pathologies. Transcranial alternating current stimulation (tACS) has been explored as a flexible, noninvasive tool for the modulation and restoration of synchronized oscillatory signals. While numerous studies have addressed cognitive or behavioural effects of electrical stimulation, the neural changes underlying the effects of tACS and their persistence after stimulation offset have remained unclear. OBJECTIVE: Here, we screened for lasting aftereffects of prolonged tACS on intrinsic network activity and audiovisual processing in the anesthetized ferret brain. METHODS: Electrical stimulation was applied via subcutaneous wire electrodes. Current waveforms were synthesized from two frequencies in the alpha or gamma range, respectively. Flashes and clicks were used for audiovisual stimulation. Electrocorticographic recordings from an extended network including occipital, temporal and parietal cortical areas were obtained before and after tACS. RESULTS: Changes in local synchrony (continuous and spike-triggered power of LFP), synchrony across recording sites (imaginary coherence) and altered dynamics of sensory response-features (peak-to-peak amplitude, extremum latency) following electrical stimulation consistently point to a synchronizing effect of tACS that can outlast stimulation offset by at least 10 min. Gamma-band tACS proved particularly effective. In line with previous reports on cross-frequency interactions, we observed effects on coherence and power of baseline activity at frequencies other than the ones targeted by tACS. These cross-frequency interactions appeared to underlie the strengthening and stabilizing effect on audiovisual responses. CONCLUSION: We demonstrate aftereffects of tACS on synchrony and stimulus processing in an extended cortical network, measured intracranially in a setting that resembles tACS stimulation in humans. The data provide direct evidence for the efficacy of tACS as a tool for sustained modulation of cortical network dynamics.

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